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  Subjects -> ALTERNATIVE MEDICINE (Total: 111 journals)
Showing 1 - 15 of 15 Journals sorted alphabetically
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 8)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 10)
Acupuncture in Medicine     Hybrid Journal   (Followers: 19)
Advanced Herbal Medicine     Open Access   (Followers: 8)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 8)
African Journal of Traditional, Complementary and Alternative Medicines     Open Access   (Followers: 7)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 3)
Alternative & Integrative Medicine     Open Access   (Followers: 16)
Alternative and Complementary Therapies     Hybrid Journal   (Followers: 22)
Alternative Medicine     Full-text available via subscription   (Followers: 4)
Alternative Medicine Studies     Open Access   (Followers: 14)
Anales de Hidrología Médica     Open Access   (Followers: 2)
Ancient Science of Life     Open Access   (Followers: 6)
Arabian Journal of Medicinal and Aromatic Plants     Open Access   (Followers: 4)
Arteterapia. Papeles de arteterapia y educación artística para la inclusión social     Open Access   (Followers: 5)
Asian Journal of Plant Pathology     Open Access   (Followers: 4)
Australian Journal of Acupuncture and Chinese Medicine     Full-text available via subscription   (Followers: 4)
Australian Journal of Herbal Medicine     Full-text available via subscription   (Followers: 5)
Australian Journal of Music Therapy     Full-text available via subscription   (Followers: 11)
Avicenna Journal of Phytomedicine     Open Access   (Followers: 1)
AYU : An international quarterly journal of research in Ayurveda     Open Access   (Followers: 6)
BMC Complementary and Alternative Medicine     Open Access   (Followers: 23)
Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas     Open Access   (Followers: 2)
Botanics : Targets and Therapy     Open Access   (Followers: 6)
Cadernos de Naturologia e Terapias Complementares     Open Access   (Followers: 1)
Chinese Herbal Medicines     Full-text available via subscription   (Followers: 1)
Chinese Medicine     Open Access   (Followers: 5)
Cognitive Neuroscience     Hybrid Journal   (Followers: 31)
Complementary Therapies in Clinical Practice     Hybrid Journal   (Followers: 23)
Complementary Therapies in Medicine     Hybrid Journal   (Followers: 19)
Current Traditional Medicine     Hybrid Journal   (Followers: 5)
Deutsche Heilpraktiker-Zeitschrift     Hybrid Journal   (Followers: 3)
Deutsche Zeitschrift für Akupunktur     Full-text available via subscription   (Followers: 2)
Erfahrungsheilkunde     Hybrid Journal   (Followers: 1)
European Journal of Medicinal Plants     Open Access  
Evidence-based Complementary and Alternative Medicine     Open Access   (Followers: 30)
Experimental and Therapeutic Medicine     Full-text available via subscription   (Followers: 1)
Fitoterapia     Hybrid Journal   (Followers: 9)
Focus on Alternative and Complementary Therapies     Hybrid Journal   (Followers: 12)
Global Journal of Integrated Chinese Medicine and Western Medicine     Open Access   (Followers: 1)
Global Journal of Traditional Medicine     Open Access   (Followers: 2)
Herba Polonica     Open Access   (Followers: 1)
Herbal Medicines Journal     Open Access   (Followers: 1)
Indian Journal of Research in Homoeopathy     Open Access   (Followers: 2)
Indian Journal of Traditional Knowledge (IJTK)     Open Access   (Followers: 2)
Innovare Journal of Ayurvedic Sciences     Open Access   (Followers: 10)
Intas Polivet     Full-text available via subscription   (Followers: 5)
Integrative Medicine Research     Open Access   (Followers: 3)
International Journal of Health and Medicine     Open Access   (Followers: 1)
International Journal of High Dilution Research     Open Access  
International Journal of Qualitative Studies on Health and Well-Being     Open Access   (Followers: 22)
International Journal of Yoga     Open Access   (Followers: 17)
International Journal of Yoga : Philosophy, Psychology and Parapsychology     Open Access   (Followers: 7)
Ipnosi     Full-text available via subscription  
Journal of Acupuncture and Herbs     Open Access   (Followers: 3)
Journal of Acupuncture and Meridian Studies     Open Access   (Followers: 1)
Journal of Acupuncture and Tuina Science     Hybrid Journal   (Followers: 4)
Journal of Alternative and Complementary Medicine     Hybrid Journal   (Followers: 17)
Journal of Applied Arts and Health     Hybrid Journal   (Followers: 1)
Journal of Applied Research on Medicinal and Aromatic Plants     Hybrid Journal   (Followers: 1)
Journal of Asian Natural Products Research     Hybrid Journal   (Followers: 5)
Journal of Ayurveda and Integrative Medicine     Open Access   (Followers: 7)
Journal of AYUSH :- Ayurveda, Yoga, Unani, Siddha and Homeopathy     Full-text available via subscription   (Followers: 10)
Journal of Bodywork and Movement Therapies     Hybrid Journal   (Followers: 18)
Journal of Complementary and Alternative Medical Research     Open Access   (Followers: 1)
Journal of Complementary and Integrative Medicine     Hybrid Journal   (Followers: 12)
Journal of Dance Medicine & Science     Full-text available via subscription   (Followers: 14)
Journal of Evidence-Based Integrative Medicine     Open Access   (Followers: 18)
Journal of Fasting and Health     Open Access   (Followers: 1)
Journal of Ginseng Research     Open Access  
Journal of Health Science and Alternative Medicine     Open Access   (Followers: 1)
Journal of Health Sciences Scholarship     Open Access  
Journal of Herbal Drugs (An International Journal on Medicinal Herbs)     Open Access   (Followers: 1)
Journal of Herbal Medicine     Hybrid Journal   (Followers: 2)
Journal of Herbal Science     Full-text available via subscription   (Followers: 6)
Journal of Integrative Medicine     Full-text available via subscription   (Followers: 4)
Journal of Integrative Medicine & Therapy     Open Access   (Followers: 2)
Journal of Manual & Manipulative Therapy     Hybrid Journal   (Followers: 17)
Journal of Medicinal Plants for Economic Development     Open Access  
Journal of Medicinally Active Plants     Open Access   (Followers: 2)
Journal of Natural Remedies     Open Access   (Followers: 3)
Journal of Nutraceuticals and Herbal Medicine     Open Access   (Followers: 4)
Journal of Palliative Medicine     Hybrid Journal   (Followers: 48)
Journal of the Australian Traditional-Medicine Society     Full-text available via subscription   (Followers: 1)
Journal of Traditional and Complementary Medicine     Open Access   (Followers: 4)
Journal of Traditional Chinese Medical Sciences     Open Access   (Followers: 1)
Journal of Yoga & Physical Therapy     Open Access   (Followers: 9)
Lekovite Sirovine     Open Access  
Médecine Palliative : Soins de Support - Accompagnement - Éthique     Full-text available via subscription   (Followers: 2)
Medical Acupuncture     Hybrid Journal   (Followers: 6)
Medicines     Open Access   (Followers: 1)
Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi     Open Access  
Muller Journal of Medical Sciences and Research     Open Access  
Natural solutions     Full-text available via subscription  
Natural Volatiles & Essential Oils     Open Access   (Followers: 1)
Nigerian Journal of Natural Products and Medicine     Full-text available via subscription  
OA Alternative Medicine     Open Access   (Followers: 1)
Oriental Pharmacy and Experimental Medicine     Partially Free   (Followers: 3)
Research Journal of Medicinal Plant     Open Access   (Followers: 2)
Research Journal of Pharmacognosy     Open Access  
Revista Brasileira de Plantas Medicinais     Open Access   (Followers: 1)
Revista Internacional de Acupuntura     Full-text available via subscription  
South African Journal of Plant and Soil     Hybrid Journal   (Followers: 1)
Synfacts     Hybrid Journal   (Followers: 7)
Traditional & Kampo Medicine     Full-text available via subscription  
Traditional Medicine Journal     Open Access   (Followers: 2)
World Journal of Acupuncture - Moxibustion     Full-text available via subscription   (Followers: 1)
World Journal of Traditional Chinese Medicine     Open Access   (Followers: 1)
Yoga Mimamsa     Open Access   (Followers: 2)
Zeitschrift für Orthomolekulare Medizin     Hybrid Journal   (Followers: 2)

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Journal of Ginseng Research
Journal Prestige (SJR): 1.256
Citation Impact (citeScore): 4
Number of Followers: 0  

  This is an Open Access Journal Open Access journal
ISSN (Print) 1226-8453
Published by Elsevier Homepage  [3203 journals]
  • Korean red ginseng enhances cardiac hemodynamics on doxorubicin-induced
           toxicity in rats

    • Abstract: Publication date: Available online 14 March 2019Source: Journal of Ginseng ResearchAuthor(s): Young-Jin Jang, Dongbin Lee, Mohammad Amjad Hossain, Adithan Aravinthan, Chang-Won Kang, Nam Soo Kim, Jong-Hoon KimAbstractBackgroundKorean red ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for cure cardiovascular problems. The present study was displayed to the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, biochemical parameters, and histopathological findings.MethodsAnimals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n=9, each group). Animals were administered with KRG (250 and 500 mg/kg, respectively) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24 h interval) on the 8th and 9th day. Electrocardiography (ECG) and echocardiograpy were recorded to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. Also, the dose of troponin I (cTnI) and activity of myeloperoxidase (MPO) in serum and cardiac tussue were analyzed, and evalulated histopathological finding by light microscopy.ResultsAdminstration of KRG at a dose of 250 and 500 mg/kg, respectively, recovered ECG changes, ejection fraction, fractional shortening, left ventricle systolic pressure, the maximal rate of change in left ventricle contraction (+dP/dtmax) and left ventricle relaxation (-dP/dtmax). Additionally, KRG treatment significantly normalized the oxidative stress markers in plasma, dose-dependently. Also, the values of cTnI and MPO were ameliorated by KRG treatment, dose-dependly. And, KRG treatment showed better parameters for histopathological study when compared with DOX control group.ConclusionThese mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study showed protective effects for KRG on cardiac toxicity.
       
  • Fermented red ginseng and ginsenoside Rd alleviate ovalbumin-induced
           allergic rhinitis in mice by suppressing IgE, interleukin-4, and
           interleukin-5 expression

    • Abstract: Publication date: Available online 7 March 2019Source: Journal of Ginseng ResearchAuthor(s): Hye In Kim, Jeon-Kyung Kim, Jae-Young Kim, Myung Joo Han, Dong-Hyun KimAbstractBackgroundTo increase the pharmacological effects of red ginseng (RG, the steamed root of Panax ginseng Meyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the antiallergic arthritis (AR) effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo.MethodsRBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-α, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer.ResultsRG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice.ConclusionfRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.
       
  • Protein target identification of ginsenosides in skeletal muscle tissues:
           discovery of natural small-molecule activators of muscle-type creatine
           kinase

    • Abstract: Publication date: Available online 7 March 2019Source: Journal of Ginseng ResearchAuthor(s): Feiyan Chen, Kexuan Zhu, Lin Chen, Liufeng Ouyang, Cuihua Chen, Ling Gu, Yucui Jiang, Zhongli Wang, Zixuan Lin, Qiang Zhang, Xiao Shao, Jianguo Dai, Yunan ZhaoAbstractBackgroundGinseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown.MethodsBy screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues.ResultsBiolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice.ConclusionOur results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.
       
  • Panax ginseng–derived fraction BIOGF1K reduces atopic dermatitis
           responses via suppression of mitogen-activated protein kinase signaling
           pathway

    • Abstract: Publication date: Available online 28 February 2019Source: Journal of Ginseng ResearchAuthor(s): Laura Rojas Lorz, Donghyun Kim, Mi-Yeon Kim, Jae Youl ChoAbstractBackgroundBIOGF1K, a fraction of Panax ginseng, has desirable antimelanogenic, anti-inflammatory, and antiphotoaging properties that could be useful for treating skin conditions. Because its potential positive effects on allergic reactions in skin have not yet been described in detail, this study's main objective was to determine its efficacy in the treatment of atopic dermatitis (AD).MethodsHigh-performance liquid chromatography was used to verify the compounds in BIOGF1K, and we used the (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide method to determine its cytotoxicity in RBL-2H3 and HMC-1 cell lines. RBL-2H3 cells were induced using both anti–DNP-IgE/DNP-BSA and calcium ionophore (A2187) treatments, whereas HMC-1 cells were induced using A2187 alone. To measure mast cell degranulation, we performed histamine (enzyme-linked immunosorbent assay) and β-hexosaminidase assays. To quantify interleukin (IL)-4, IL-5, and IL-13 levels in RBL-2H3 cells, we performed quantitative polymerase chain reaction (PCR); to quantify expression levels of IL-4 and IL-13 in HMC-1 cells, we used semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Finally, we detected the total and phosphorylated forms of extracellular signal-regulated kinase, p-38, and c-Jun N-terminal kinase proteins by immunoblotting.ResultsBIOGF1K decreased the AD response by reducing both histamine and β-hexosaminidase release as well as reducing the secretion levels of IL-4, IL-5, and IL-13 in RBL-2H3 cells and IL-4 and IL-13 in HMC-1 cells. In addition, BIOGF1K decreased MAPK pathway activation in RBL-2H3 and HMC-1 cells.ConclusionsBIOGF1K attenuated the AD response, hence supporting its use as a promising and natural approach for treating AD.
       
  • Ginsenoside Rg3 and Korean red ginseng extract epigenetically regulate the
           tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1

    • Abstract: Publication date: Available online 28 February 2019Source: Journal of Ginseng ResearchAuthor(s): Juyeon Ham, Dawoon Jeong, Sungbin Park, Hyeon Woo Kim, Heejoo Kim, Sun Jung KimAbstractBackgroundGinsenoside Rg3, a derivative of steroidal saponins abundant in ginseng, has a range of effects on cancer cells, including anti-cell proliferation and anti-inflammation activity. Here, we investigate two long noncoding RNAs (lncRNAs), STXBP5-AS1 and RFX3-AS1, which are hypomethylated and hypermethylated in the promoter region by Rg3 in MCF-7 cancer cells.MethodsThe lncRNAs epigenetically regulated by Rg3 were mined using methylation array analysis. The effect of the lncRNAs on the apoptosis and proliferation of MCF-7 cells was monitored in the presence of Rg3 or Korean red ginseng (KRG) extract after deregulating the lncRNAs. The expression of the lncRNAs and their target genes was examined using qPCR and Western blot analysis. The association between the expression of the target genes and the survival rate of breast cancer patients was analyzed using the Kaplan-Meier Plotter platform.ResultsSTXBP5-AS1 and RFX3-AS1 exhibited anti- and pro-proliferation effects, respectively, in the cancer cells, and the effects of Rg3 and KRG extract on apoptosis and cell proliferation were weakened after deregulating the lncRNAs. Of the genes located close to STXBP5-AS1 and RFX3-AS1 on the chromosome, STXBP5, GRM1, RFX3, and SLC1A1 were regulated by the lncRNAs on the RNA and protein level. Breast cancer patients that exhibited a higher expression of the target genes of the lncRNAs had a higher metastasis-free survival rate.ConclusionThe current study is the first to identify lncRNAs that are regulated by the presence of Rg3 and KRG extract and that subsequently contribute to inhibiting the proliferation of cancer cells.
       
  • Unraveling dynamic metabolomes underlying different maturation stages of
           berries harvested from Panax ginseng

    • Abstract: Publication date: Available online 20 February 2019Source: Journal of Ginseng ResearchAuthor(s): Mee Youn Lee, Han Sol Seo, Digar Singh, Sang Jun Lee, Choong Hwan LeeAbstractBackgroundGinseng berries (GBs) show temporal metabolic variations among different maturation stages, determining their organoleptic and functional properties.MethodsWe analyzed metabolic variations concomitant to five different maturation stages of GBs including immature green (IG), mature green (MG), partially red (PR), fully red (FR), and overmature red (OR) using mass spectrometry (MS)–based metabolomic profiling and multivariate analyses.ResultsThe partial least squares discriminant analysis score plot based on gas chromatography–MS datasets highlighted metabolic disparity between preharvest (IG and MG) and harvest/postharvest (PR, FR, and OR) GB extracts along PLS1 (34.9%) with MG distinctly segregated across PLS2 (18.2%). Forty-three significantly discriminant primary metabolites were identified encompassing five developmental stages (variable importance in projection > 1.0, p  1.0, p 
       
  • Pathogenesis strategies and regulation of ginsenosides by two species of
           Ilyonectria in Panax ginseng: power of speciation

    • Abstract: Publication date: Available online 19 February 2019Source: Journal of Ginseng ResearchAuthor(s): Mohamed El-Agamy Farh, Yu-Jin Kim, Ragavendran Abbai, Priyanka Singh, Ki-Hong Jung, Yeon-Ju Kim, Deok-Chun YangAbstractBackgroundThe valuable medicinal plant Panax ginseng has high pharmaceutical efficacy because it produces ginsenosides. However, its yields decline because of a root-rot disease caused by Ilyonectria mors-panacis. Because species within Ilyonectria showed variable aggressiveness by altering ginsenoside concentrations in inoculated plants, we investigated how such infections might regulate the biosynthesis of ginsenosides and their related signaling molecules.MethodsTwo-year-old ginseng seedlings were treated with I. mors-panacis and I. robusta. Roots from infected and pathogen-free plants were harvested at 4 and 16 days after inoculation. We then examined levels or/and expression of genes of ginsenosides, salicylic acid (SA), jasmonic acid (JA), and reactive oxygen species (ROS). We also checked the susceptibility of those pathogens to ROS.ResultsGinsenoside biosynthesis was significantly suppressed and increased in response to infection by I. mors-panacis and I. robusta, respectively. Regulation of JA was significantly higher in I. robusta–infected roots, while levels of SA and ROS were significantly higher in I. mors-panacis–infected roots. Catalase activity was significantly higher in I. robusta–infected roots followed in order by mock roots and those infected by I. mors-panacis. Moreover, I. mors-panacis was resistant to ROS compared with I. robusta.ConclusionInfection by the weakly aggressive I. robusta led to the upregulation of ginsenoside production and biosynthesis, probably because only a low level of ROS was induced. In contrast, the more aggressive I. mors-panacis suppressed ginsenoside biosynthesis, probably because of higher ROS levels and subsequent induction of programmed cell death pathways. Furthermore, I. mors-panacis may have increased its virulence by resisting the cytotoxicity of ROS.
       
  • New hydroperoxylated and 20,24-epoxylated dammarane triterpenes from the
           rot roots of Panax notoginseng

    • Abstract: Publication date: Available online 6 February 2019Source: Journal of Ginseng ResearchAuthor(s): Jia-Huan Shang, Wen-Jie Sun, Hong-Tao Zhu, Dong Wang, Chong-Ren Yang, Ying-Jun ZhangAbstractBackgroundRoot rot is a serious destructive disease of Panax notoginseng, a famous cultivated araliaceous herb called Sanqi or Tianqi in Southwest China.MethodsThe chemical substances of Sanqi rot roots were explored by chromatographic techniques. MS, 1D/2D-NMR, and single crystal X-ray diffraction were applied to determine the structures. Murine macrophage RAW264.7 and five human cancer cell lines were used separately for evaluating the antiinflammatory and cytotoxic activities.Results and ConclusionThirty dammarane-type triterpenes and saponins were isolated from the rot roots of P. notoginseng. Among them, seven triterpenes, namely, 20(S)-dammar-25-ene-24(S)-hydroperoxyl-3β,6α,12β,20-tetrol (1), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-6α,12β,20-triol (2), 20(S)-dammar-12-oxo-23-ene-25-hydroperoxyl-3β,6α,20-triol (3), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-12β,20-diol (4), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid (5), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid methyl ester (6), and 6α-hydroxy-22,23,24,25,26,27-hexanordammar-3,12,20-trione (7), are new compounds. In addition, 12 known ones (12–16 and 19–25) were reported in Sanqi for the first time. The new Compound 1 showed comparable antiinflammatory activity on inhibition of NO production to the positive control, whereas the known compounds 9, 12, 13, and 16 showed moderate cytotoxicities against five human cancer cell lines. The results will provide scientific basis for understanding the chemical constituents of Sanqi rot roots and new candidates for searching antiinflammatory and antitumor agents.
       
  • Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy
           and apoptosis in hippocampal neurons of mice with cognitive impairment
           induced by sleep deprivation

    • Abstract: Publication date: Available online 6 February 2019Source: Journal of Ginseng ResearchAuthor(s): Yin Cao, Yingbo Yang, Hui Wu, Yi Lu, Shuang Wu, Lulu Liu, Changhong Wang, Fei Huang, Hailian Shi, Beibei Zhang, Xiaojun Wu, Zhengtao WangAbstractBackgroudSleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem–leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD.MethodsMouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay.ResultsSLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line.ConclusionSLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD.
       
  • Taxonomy of fungal complex causing red-skin root of Panax ginseng
           in China

    • Abstract: Publication date: Available online 6 February 2019Source: Journal of Ginseng ResearchAuthor(s): Xiao H. Lu, Xi M. Zhang, Xiao L. Jiao, Jianjun J. Hao, Xue S. Zhang, Yi Luo, Wei W. GaoAbstractBackgroundRed-skin root of Asian ginseng (Panax ginseng) significantly reduces the quality and limits the production of ginseng in China. The disease has long been thought to be a noninfectious physiological disease, except one report that proved it was an infectious disease. However, the causal agents have not been successfully determined. In the present study, we were to reveal the pathogens that cause red-skin disease.MethodsGinseng roots with red-skin root symptoms were collected from commercial fields in Northeast China. Fungi were isolated from the lesion and identified based on morphological characters along with multilocus sequence analyses on internal transcription spacer, β-tubulin (tub2), histone H3 (his3), and translation elongation factor 1α (tef-1α). Pathogens were confirmed by inoculating the isolates in ginseng roots.ResultsA total of 230 isolates were obtained from 209 disease samples. These isolates were classified into 12 species, including Dactylonectria sp., D. hordeicola, Fusarium acuminatum, F. avenaceum, F. solani, F. torulosum, Ilyonectria mors-panacis, I. robusta, Rhexocercosporidium panacis, and three novel species I. changbaiensis, I. communis, and I. qitaiheensis. Among them, I. communis, I. robusta, and F. solani had the highest isolation frequencies, being 36.1%, 20.9%, and 23.9%, respectively. All these species isolated were pathogenic to ginseng roots and caused red-skin root disease under appropriate condition.ConclusionFungal complex is the causal agent of red-skin root in P. ginseng.
       
  • Ginsenoside Rb1 and Rb2 upregulate Akt/mTOR signaling–mediated muscular
           hypertrophy and myoblast differentiation

    • Abstract: Publication date: Available online 31 January 2019Source: Journal of Ginseng ResearchAuthor(s): Ga-Yeon Go, Ayoung Jo, Dong-Wan Seo, Woo-Young Kim, Yong Kee Kim, Eui-Young So, Qian Chen, Jong-Sun Kang, Gyu-Un Bae, Sang-Jin LeeAbstractBackgroundAs a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation.MethodsC2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins.ResultsRb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation.ConclusionRb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy.
       
  • Advances in the chemistry, pharmacological diversity, and metabolism of
           20(R)-ginseng saponins

    • Abstract: Publication date: Available online 31 January 2019Source: Journal of Ginseng ResearchAuthor(s): Chaoming Wang, Juan Liu, Jianqiang Deng, Jiazhen Wang, Weizhao Weng, Hongxia Chu, Qingguo MengAbstractGinseng has been used as a popular herbal medicine in East Asia for at least two millennia. However, 20(R)-ginseng saponins, one class of important rare ginsenosides, are rare in natural products. 20(R)-ginseng saponins are generally prepared by chemical epimerization and microbial transformation from 20(S)-isomers. The C20 configuration of 20(R)-ginseng saponins are usually determined by 13C NMR and X-ray single-crystal diffraction. 20(R)-ginseng saponins have antitumor, antioxidative, antifatigue, neuroprotective, and osteoclastogenesis inhibitory effects, among others. Owing to the chemical structure and pharmacological and stereoselective properties, 20(R)-ginseng saponins have attracted a great deal of attention in recent years. In this study, the discovery, identification, chemical epimerization, microbial transformation, pharmacological activities, and metabolism of 20(R)-ginseng saponins are summarized.
       
  • Overexpression of ginseng patatin-related phospholipase pPLAIIIβ alters
           the polarity of cell growth and decreases lignin content in Arabidopsis

    • Abstract: Publication date: Available online 23 January 2019Source: Journal of Ginseng ResearchAuthor(s): Jin Hoon Jang, Ok Ran LeeAbstractBackgroundThe patatin-related phospholipase AIII family (pPLAIIIs) genes alter cell elongation and cell wall composition in Arabidopsis and rice plant, suggesting diverse commercial purposes of the economically important medicinal ginseng plant. Herein, we show the functional characterization of a ginseng pPLAIII gene for the first time and discuss its potential applications.MethodspPLAIIIs were identified from ginseng expressed sequence tag clones and further confirmed by search against ginseng database and polymerase chain reaction. A clone showing the highest homology with pPLAIIIβ was shown to be overexpressed in Arabidopsis using Agrobacterium. Quantitative polymerase chain reaction was performed to analyze ginseng pPLAIIIβ expression. Phenotypes were observed using a low-vacuum scanning electron microscope. Lignin was stained using phloroglucinol and quantified using acetyl bromide.ResultsThe PgpPLAIIIβ transcripts were observed in all organs of 2-year-old ginseng. Overexpression of ginseng pPLAIIIβ (PgpPLAIIIβ-OE) in Arabidopsis resulted in small and stunted plants. It shortened the trichomes and decreased trichome number, indicating defects in cell polarity. Furthermore, OE lines exhibited enlarged seeds with less number per silique. The YUCCA9 gene was downregulated in the OE lines, which is reported to be associated with lignification. Accordingly, lignin was stained less in the OE lines, and the expression of two transcription factors related to lignin biosynthesis was also decreased significantly.ConclusionOverexpression of pPLAIIIβ retarded cell elongation in all the tested organs except seeds, which were longer and thicker than those of the controls. Shorter root length is related to auxin-responsive genes, and its stunted phenotype showed decreased lignin content.
       
  • Ginsenoside Rg3 protects against iE-DAP–induced
           endothelial-to-mesenchymal transition by regulating the
           miR-139-5p–NF-κB axis

    • Abstract: Publication date: Available online 21 January 2019Source: Journal of Ginseng ResearchAuthor(s): Aram Lee, Eunsik Yun, Woochul Chang, Jongmin KimAbstractBackgroundEmerging evidence suggests that endothelial-to-mesenchymal transition (EndMT) in endothelial dysfunction due to persistent inflammation is a key component and emerging concept in the pathogenesis of vascular diseases. Ginsenoside Rg3 (Rg3), an active compound from red ginseng, has been known to be important for vascular homeostasis. However, the effect of Rg3 on inflammation-induced EndMT has never been reported. Here, we hypothesize that Rg3 might reverse the inflammation-induced EndMT and serve as a novel therapeutic strategy for vascular diseases.MethodsEndMT was examined under an inflammatory condition mediated by the NOD1 agonist, γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), treatment in human umbilical vein endothelial cells. The expression of EndMT markers was determined by Western blot analysis, real-time polymerase chain reaction, and immunocytochemistry. The underlying mechanisms of Rg3-mediated EndMT regulation were investigated by modulating the microRNA expression.ResultsThe NOD1 agonist, iE-DAP, led to a fibroblast-like morphology change with a decrease in the expression of endothelial markers and an increase in the expression of the mesenchymal marker, namely EndMT. On the other hand, Rg3 markedly attenuated the iE-DAP–induced EndMT and preserved the endothelial phenotype. Mechanically, miR-139 was downregulated in cells with iE-DAP–induced EndMT and partly reversed in response to Rg3 via the regulation of NF-κB signaling, suggesting that the Rg3–miR-139-5p-NF-κB axis is a key mediator in iE-DAP-induced EndMT.ConclusionThese results suggest, for the first time, that Rg3 can be used to inhibit inflammation-induced EndMT and may be a novel therapeutic option against EndMT-associated vascular diseases.
       
  • Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on
           hematopoietic recovery in mice with cyclophosphamide-induced
           myelosuppression and its material basis

    • Abstract: Publication date: Available online 11 January 2019Source: Journal of Ginseng ResearchAuthor(s): Jiahong Han, Min Dai, Yan Zhao, Enbo Cai, Lianxue Zhang, Xiaohuan Jia, Nian Sun, Xuan Fei, Hui ShuAbstractBackgroundGinseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice.MethodsThe mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg1, Re, Rb1, Rc, Rb2, Rb3, Rd, Rk3, Rh4, 20 (S)-Rg3, 20 (R)-Rg3, Rk1, Rg5, salidroside, and so on.ResultsG, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P 
       
  • Medicinal potential of Panax ginseng and its ginsenosides in
           atopic dermatitis treatment

    • Abstract: Publication date: Available online 7 January 2019Source: Journal of Ginseng ResearchAuthor(s): Laura Rojas Lorz, Mi-Yeon Kim, Jae Youl ChoAbstractAtopic dermatitis (AD) is a chronic and relapsing inflammatory disease that affects 1%–20% of people worldwide. Despite affecting many people, AD current treatments, such as corticosteroids and calcineurin inhibitors, have not only harmful secondary effects but are also often ineffective. Therefore, natural nontoxic compounds are on high demand for developing new effective AD treatments. Panax ginseng Meyer has been used traditionally for its promising healing and restorative properties to treat many diseases including skin disorders, reason why in this review we want to explore the research performed with AD and P. ginseng as well as determining its potential for new drug development. Previous researches have shown that P. ginseng has positive effects in AD patients such as lower eczema area and severity index, transepidermal water loss, and immunoglobulin E levels and better quality of sleep. In vivo animal models, as well, have shown positive results to P. ginseng and derived ginsenosides, such as the decrease of transepidermal water loss, immunoglobulin E levels in serum, allergy-related cytokines, and downregulation of NF-κB, MAPK, and Ikaros pathways. All of these previous data suggest that P. ginseng and its derived ginsenosides are undoubtedly a nontoxic effective option to treat AD.
       
  • Transcriptome analysis of Panax ginseng response to high light
           stress

    • Abstract: Publication date: Available online 2 January 2019Source: Journal of Ginseng ResearchAuthor(s): Je Hyeong Jung, Ho-Youn Kim, Hyoung Seok Kim, Sang Hoon JungAbstractBackgroundGinseng (Panax ginseng Meyer) is an essential source of pharmaceuticals and functional foods. Ginseng productivity has been compromised by high light (HL) stress, which is one of the major abiotic stresses during the ginseng cultivation period. The genetic improvement for HL tolerance in ginseng could be facilitated by analyzing its genetic and molecular characteristics associated with HL stress.MethodsGenome-wide analysis of gene expression was performed under HL and recovery conditions in 1-year-old Korean ginseng (P. ginseng cv. Chunpoong) using the Illumina HiSeq platform. After de novo assembly of transcripts, we performed expression profiling and identified differentially expressed genes (DEGs). Furthermore, putative functions of identified DEGs were explored using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis.ResultsA total of 438 highly expressed DEGs in response to HL stress were identified and selected from 29,184 representative transcripts. Among the DEGs, 326 and 114 transcripts were upregulated and downregulated, respectively. Based on the functional analysis, most upregulated and a significant number of downregulated transcripts were related to stress responses and cellular metabolic processes, respectively.ConclusionTranscriptome profiling could be a strategy to comprehensively elucidate the genetic and molecular mechanisms of HL tolerance and susceptibility. This study would provide a foundation for developing breeding and metabolic engineering strategies to improve the environmental stress tolerance of ginseng.
       
  • Ginseng berry polysaccharides on inflammation-associated colon cancer:
           inhibiting T-cell differentiation, promoting apoptosis, and enhancing the
           effects of 5-fluorouracil

    • Abstract: Publication date: Available online 2 January 2019Source: Journal of Ginseng ResearchAuthor(s): Chong-Zhi Wang, Lifei Hou, Jin-Yi Wan, Haiqiang Yao, Jinbin Yuan, Jinxiang Zeng, Chan Woong Park, Su Hwan Kim, Dae Bang Seo, Kwang-Soon Shin, Chun-Feng Zhang, Lina Chen, Qi-Hui Zhang, Zhi Liu, Clara Sava-Segal, Chun-Su YuanAbstractBackgroundGinseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms.MethodsGinseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation.ResultsGBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4+IFN-γ+ cell (Th1) differentiation, and decreased CD4+FoxP3+ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil.ConclusionData from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.
       
  • Autophagy and its regulation by ginseng components

    • Abstract: Publication date: Available online 2 January 2019Source: Journal of Ginseng ResearchAuthor(s): Nurinanda Prisky Qomaladewi, Mi-Yeon Kim, Jae Youl ChoAbstractAutophagy is the sequential process whereby cell components are degraded, which can occur due to nutrient deprivation. Its regulation has an essential role in many diseases, functioning in both cell survival and cell death. Autophagy starts when mTORC1 is inhibited, resulting in the activation of several complexes to form a cargo that fuses with a lysosome, where it undergoes degradation. In this review, we describe a plant extract that is well known in Korea, namely Korean ginseng extract; we studied how its derivatives and metabolites can regulate autophagy and thus mediate the pathogenesis of certain diseases.
       
  • Protective effects of Korean Red Ginseng against sub-acute immobilization
           stress-induced testicular damage in experimental rats

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Sang-Ho Lee, Kyung-Hwa Choi, Kyu-Min Cha, Seock-Yeon Hwang, Un-Kyu Park, Min-Sik Jeong, Jae-Yup Hong, Chang-Kyun Han, Gyo In, Spandana Rajendra Kopalli, Si-Kwan KimAbstractBackgroundExcessive stress causes varied physiological and psychological disorders including male reproductive problems. Here, we attempted to investigate the protective effects of Korean Red Ginseng (Panax ginseng Meyer; KRG) against sub-acute immobilization stress-induced testicular damage in experimental rats.MethodsMale rats (age, 4 wk; weight, 60–70 g) were divided into four groups (n = 8 in each group): normal control group, immobilization control group, immobilization group treated with 100 mg/kg of KRG daily, and immobilization group treated with 200 mg/kg of KRG daily. Normal control and immobilization control groups received vehicle only. KRG (100 mg/kg and 200 mg/kg) was mixed in the standard diet powder and fed daily for 6 mo. Parameters such as organ weight, blood chemistry, sperm kinematic values, and expression levels of testicular-related molecules were measured using commercially available kits, Western blotting, and reverse transcription polymerase chain reaction.ResultsData revealed that KRG restored the altered testis and epididymis weight in immobilization stress-induced rats significantly (p 
       
  • Biosynthesis of rare 20(R)-protopanaxadiol/protopanaxatriol type
           ginsenosides through Escherichia coli engineered with uridine diphosphate
           glycosyltransferase genes

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Lu Yu, Yuan Chen, Jie Shi, Rufeng Wang, Yingbo Yang, Li Yang, Shujuan Zhao, Zhengtao WangAbstractBackgroundGinsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes.MethodsSeven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes.ResultsE. coli engineered with GT95syn selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3OH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing p2GT95synK1, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20OH and C3OH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth.ConclusionThis study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.
       
  • Preparative separation of minor saponins from Panax notoginseng leaves
           using biotransformation, macroporous resins, and preparative
           high-performance liquid chromatography

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Fang Liu, Ni Ma, Fang-Bo Xia, Peng Li, Chengwei He, Zhenqiang Wu, Jian-Bo WanAbstractBackgroundGinsenosides with less sugar moieties may exhibit the better adsorptive capacity and more pharmacological activities.MethodsAn efficient method for the separation of four minor saponins, including gypenoside XVII, notoginsenoside Fe, ginsenoside Rd2, and notoginsenoside Fd, from Panax notoginseng leaves (PNL) was established using biotransformation, macroporous resins, and subsequent preparative high-performance liquid chromatography.ResultsThe dried PNL powder was immersed in the distilled water at 50°C for 30 min for converting the major saponins, ginsenosides Rb1, Rc, Rb2, and Rb3, to minor saponins, gypenoside XVII, notoginsenoside Fe, ginsenoside Rd2, and notoginsenoside Fd, respectively, by the enzymes present in PNL. The adsorption characteristics of these minor saponins on five types of macroporous resins, D-101, DA-201, DM-301, X-5, and S-8, were evaluated and compared. Among them, D-101 was selected due to the best adsorption and desorption properties. Under the optimized conditions, the fraction containing the four target saponins was separated by D-101 resin. Subsequently, the target minor saponins were individually separated and purified by preparative high-performance liquid chromatography with a reversed-phase column.ConclusionOur study provides a simple and efficient method for the preparation of these four minor saponins from PNL, which will be potential for industrial applications.
       
  • Label-free quantitative proteomic analysis of Panax ginseng leaves upon
           exposure to heat stress

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): So Wun Kim, Ravi Gupta, Cheol Woo Min, Seo Hyun Lee, Ye Eun Cheon, Qing Feng Meng, Jeong Woo Jang, Chi Eun Hong, Ji Yoon Lee, Ick Hyun Jo, Sun Tae KimAbstractBackgroundGinseng is one of the well-known medicinal plants, exhibiting diverse medicinal effects. Its roots possess anticancer and antiaging properties and are being used in the medical systems of East Asian countries. It is grown in low-light and low-temperature conditions, and its growth is strongly inhibited at temperatures above 25°C. However, the molecular responses of ginseng to heat stress are currently poorly understood, especially at the protein level.MethodsWe used a shotgun proteomics approach to investigate the effect of heat stress on ginseng leaves. We monitored their photosynthetic efficiency to confirm physiological responses to a high-temperature stress.ResultsThe results showed a reduction in photosynthetic efficiency on heat treatment (35°C) starting at 48 h. Label-free quantitative proteome analysis led to the identification of 3,332 proteins, of which 847 were differentially modulated in response to heat stress. The MapMan analysis showed that the proteins with increased abundance were mainly associated with antioxidant and translation-regulating activities, whereas the proteins related to the receptor and structural-binding activities exhibited decreased abundance. Several other proteins including chaperones, G-proteins, calcium-signaling proteins, transcription factors, and transfer/carrier proteins were specifically downregulated.ConclusionThese results increase our understanding of heat stress responses in the leaves of ginseng at the protein level, for the first time providing a resource for the scientific community.
       
  • Ginsenoside compound K protects human umbilical vein endothelial cells
           against oxidized low-density lipoprotein-induced injury via inhibition of
           nuclear factor-κB, p38, and JNK MAPK pathways

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Shan Lu, Yun Luo, Ping Zhou, Ke Yang, Guibo Sun, Xiaobo SunAbstractBackgroundOxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated.MethodsIn our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (ΔΨm) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting.ResultsOur results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, NF-κB nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK.ConclusionThese results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the NF-κB, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.
       
  • A formulated red ginseng extract inhibits autophagic flux and sensitizes
           to doxorubicin-induced cell death

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Han-Hee Park, Seung-Won Choi, Gwang Jin Lee, Young-Dae Kim, Hyun-Jin Noh, Seung-Jae Oh, Iseul Yoo, Yu-Jin Ha, Gi-Bang Koo, Soon-Sun Hong, Sung Won Kwon, You-Sun KimAbstractBackgroundGinseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin.MethodsThe cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)–monomeric red fluorescent protein (mRFP)–LC3.ResultsRGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP–mRFP–LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death.ConclusionOur data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.
       
  • The effect of Glomus intraradices on the physiological properties of Panax
           ginseng and on rhizospheric microbial diversity

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Lei Tian, Shaohua Shi, Lina Ma, Xue Zhou, Shasha Luo, Jianfeng Zhang, Baohui Lu, Chunjie TianAbstractBackgroundGlomus intraradices is a species of arbuscular mycorrhizal fungi that, as an obligate endomycorrhiza, can form mutually beneficial associations with plants. Panax ginseng is a popular traditional Chinese medicine; however, problems associated with ginseng planting, such as pesticide residues, reduce the ginseng quality.MethodsIn this experiment, we studied the effect of inoculating G. intraradices on several physiological properties and microbial communities of ginseng. UV-Visible Spectrum method was used to detect physical properties. Denaturing gradient gel electrophoresis method was used to analyze microbial communities.ResultsThe results indicated that inoculation with G. intraradices can improve the colonization rate of lateral ginseng roots, increase the levels of monomeric and total ginsenosides, and improve root activity as well as polyphenol oxidase and catalase activities. We also studied the bacterial and fungal communities in ginseng rhizospheric soil. In our study, G. intraradices inoculation improved the abundance and Shannon diversity of bacteria, whereas fungi showed a reciprocal effect. Furthermore, we found that G. intraradices inoculation might increase some beneficial bacterial species and decreased pathogenic fungi in rhizospheric soil of ginseng.ConclusionOur results showed that G. intraradices can benefit ginseng planting which may have some instructive and practical significance for planting ginseng in farmland.
       
  • Effect of Korean Red Ginseng extract on colorectal lung metastasis through
           inhibiting the epithelial–mesenchymal transition via transforming growth
           factor-β1/Smad-signaling-mediated Snail/E-cadherin expression

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Ji-Ye Kee, Yo-Han Han, Jeong-Geon Mun, Seong-Hwan Park, Hee Dong Jeon, Seung-Heon HongAbstractBackgroundIn colorectal cancer (CRC), 40–60% of patients develop metastasis. The epithelial–mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells.MethodsTo investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription–polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-β1 (TGF-β1)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells.ResultsRGE decreased the adhesion and migration ability of the CT26 cells and TGF-β1-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-β1-induced EMT via TGF-β1/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice.ConclusionOur results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.
       
  • GS-KG9 ameliorates diabetic neuropathic pain induced by streptozotocin in
           rats

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Jee Youn Lee, Hae Young Choi, Chan Sol Park, Mi Kyung Pyo, Tae Young Yune, Go Woon Kim, Sung Hyun ChungAbstractBackgroundDiabetic neuropathy is one of the most devastating ailments of the peripheral nervous system. Neuropathic pain develops in ∼30% of diabetics. Here, we examined the suppressive effect of GS-KG9 on neuropathic pain induced by streptozotocin (STZ).MethodsHyperglycemia was induced by intraperitoneal injection of STZ. Rats showing blood glucose level> 250 mg/dL were divided into five groups, and treatment groups received oral saline containing GS-KG9 (50 mg/kg, 150 mg/kg, or 300 mg/kg) twice daily for 4 wk. The effects of GS-KG9 on pain behavior, microglia activation in the lumbar spinal cord and ventral posterolateral (VPL) nucleus of the thalamus, and c-Fos expression in the dorsal horn of the lumbar spinal cord were examined.ResultsThe development of neuropathic pain began at Day 5 and peaked at Week 4 after STZ injection. Mechanical and thermal pains were both significantly attenuated in GS-KG9-treated groups from 10 d after STZ injection as compared to those in the STZ control. GS-KG9 also repressed microglia activation in L4 dorsal horn and VPL region of the thalamus. In addition, increase in c-Fos-positive cells within L4 dorsal horn lamina I and II of the STZ control group was markedly alleviated by GS-KG9.ConclusionThese results suggest that GS-KG9 effectively relieves STZ-induced neuropathic pain by inhibiting microglial activation in the spinal cord dorsal horn and VPL region of the thalamus.
       
  • Enhanced Rg3 negatively regulates Th1 cell responses

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Minkyoung Cho, Garam Choi, Inbo Shim, Yeonseok ChungAbstractBackgroundKorean Red Ginseng (KRG; Panax ginseng Meyer) is a widely used medicinal herb known to exert various immune modulatory functions. KRG and one of its purified components, ginsenoside Rg3, are known to possess anti-inflammatory activities. How they impact helper T cell-mediated responses is not fully explored. In this study, we attempted to evaluate the effect of KRG extract (KRGE) and ginsenoside Rg3 on Th1 cell responses.MethodsUsing well-characterized T cell in vitro differentiation systems, we examined the effects of KRGE or enhanced Rg3 on the Th1-inducing cytokine production from dendritic cells (DC) and the naïve CD4+ T cells differentiation to Th1 cells. Furthermore, we examined the change of Th1 cell population in the intestine after treatment of enhanced Rg3. The influence of KRGE or enhanced Rg3 on Th1 cell differentiation was evaluated by fluorescence-activated cell sorting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction.ResultsKRGE significantly inhibited the production level of IL-12 from DCs and subsequent Th1 cell differentiation. Similarly, enhanced Rg3 significantly suppressed the expression of interferon gamma (IFNγ) and T-bet in T cells under Th1-skewing condition. Consistent with these effects in vitro, oral administration of enhanced Rg3 suppressed the frequency of Th1 cells in the Peyer's patch and lamina propria cells in vivo.ConclusionEnhanced Rg3 negatively regulates the differentiation of Th1 cell in vitro and Th1 cell responses in the gut in vivo, providing fundamental basis for the use of this agent to treat Th1-related diseases.
       
  • High frequency somatic embryogenesis and plant regeneration of
           interspecific ginseng hybrid between Panax ginseng and Panax quinquefolius
           

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Jong Youn Kim, Prakash Babu Adhikari, Chang Ho Ahn, Dong Hwi Kim, Young Chang Kim, Jung Yeon Han, Subramanyam Kondeti, Yong Eui ChoiAbstractBackgroundInterspecific ginseng hybrid, Panax ginseng × Panax quenquifolius (Pgq) has vigorous growth and produces larger roots than its parents. However, F1 progenies are complete male sterile. Plant tissue culture technology can circumvent the issue and propagate the hybrid.MethodsMurashige and Skoog (MS) medium with different concentrations (0, 2, 4, and 6 mg/L) of 2,4-dichlorophenoxyacetic acid (2,4-D) was used for callus induction and somatic embryogenesis (SE). The embryos, after culturing on GA3 supplemented medium, were transferred to hormone free ½ Schenk and Hildebrandt (SH) medium. The developed taproots with dormant buds were treated with GA3 to break the bud dormancy, and transferred to soil. Hybrid Pgq plants were verified by random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) analyses and by LC-IT-TOF-MS.ResultsWe conducted a comparative study of somatic embryogenesis (SE) in Pgq and its parents, and attempted to establish the soil transfer of in vitro propagated Pgq tap roots. The Pgq explants showed higher rate of embryogenesis (~56% at 2 mg/L 2,4-D concentration) as well as higher number of embryos per explants (~7 at the same 2,4-D concentration) compared to its either parents. The germinated embryos, after culturing on GA3 supplemented medium, were transferred to hormone free ½ SH medium to support the continued growth and kept until nutrient depletion induced senescence (NuDIS) of leaf defoliation occurred (4 months). By that time, thickened tap roots with well-developed lateral roots and dormant buds were obtained. All Pgq tap roots pretreated with 20 mg/L GA3 for at least a week produced new shoots after soil transfer. We selected the discriminatory RAPD and ISSR markers to find the interspecific ginseng hybrid among its parents. The F1 hybrid (Pgq) contained species specific 2 ginsenosides (ginsenoside Rf in P. ginseng and pseudoginsenosides F11 in P. quinquefolius), and higher amount of other ginsenosides than its parents.ConclusionMicropropagation of interspecific hybrid ginseng can give an opportunity for continuous production of plants.
       
  • Multicomponent assessment and ginsenoside conversions of Panax
           quinquefolium L. roots before and after steaming by HPLC-MSn

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Xin Huang, Yan Liu, Yong Zhang, Shuai-Ping Li, Hao Yue, Chang-Bao Chen, Shu-Ying LiuAbstractBackgroundThe structural conversions in ginsenosides induced by steaming or heating or acidic condition could improve red ginseng bioactivities significantly. In this paper, the chemical transformations of red American ginseng from fresh Panax quinquefolium L. under steaming were investigated, and the possible mechanisms were discussed.MethodsA method with reversed-phase high-performance liquid chromatography coupled with linear ion trap mass spectrometry (HPLC-MSn)-equipped electrospray ionization ion source was developed for structural analysis and quantitation of ginsenosides in dried and red American ginseng.ResultsIn total, 59 ginsenosides of protopanaxadiol, protopanaxatriol, oleanane, and ocotillol types were identified in American ginseng before and after steaming process by matching the molecular weight and/or comparing MSn fragmentation with that of standards and/or known published compounds, and some of them were determined to be disappeared or newly generated under different steaming time and temperature. The specific fragments of each aglycone-type ginsenosides were determined as well as aglycone hydrated and dehydrated ones. The mechanisms were deduced as hydrolysis, hydration, dehydration, and isomerization of neutral and acidic ginsenosides. Furthermore, the relative peak areas of detected compounds were calculated based on peak areas ratio.ConclusionThe multicomponent assessment of American ginseng was conducted by HPLC-MSn. The result is expected to provide possibility for holistic evaluation of the processing procedures of red American ginseng and a scientific basis for the usage of American ginseng in prescription.
       
  • Fermentation of red ginseng extract by the probiotic Lactobacillus
           plantarum KCCM 11613P: ginsenoside conversion and antioxidant effects

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Jieun Jung, Hye Ji Jang, Su Jin Eom, Nam Soon Choi, Na-Kyoung Lee, Hyun-Dong PaikAbstractBackgroundGinsenosides, which are bioactive components in ginseng, can be converted to smaller compounds for improvement of their pharmacological activities. The conversion methods include heating; acid, alkali, and enzymatic treatment; and microbial conversion. The aim of this study was to determine the bioconversion of ginsenosides in fermented red ginseng extract (FRGE).MethodsRed ginseng extract (RGE) was fermented using Lactobacillus plantarum KCCM 11613P. This study investigated the ginsenosides and their antioxidant capacity in FRGE using diverse methods.ResultsProperties of RGE were changed upon fermentation. Fermentation reduced the pH value, but increased the titratable acidity and viable cell counts of lactic acid bacteria. L. plantarum KCCM 11613P converted ginsenosides Rb2 and Rb3 to ginsenoside Rd in RGE. Fermentation also enhanced the antioxidant effects of RGE. FRGE reduced 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and reducing power; however, it improved the inhibition of β-carotene and linoleic acid oxidation and the lipid peroxidation. This suggested that the fermentation of RGE is effective for producing ginsenoside Rd as precursor of ginsenoside compound K and inhibition of lipid oxidation.ConclusionThis study showed that RGE fermented by L. plantarum KCCM 11613P may contribute to the development of functional food materials.
       
  • Ginsenoside Rk1 ameliorates paracetamol-induced hepatotoxicity in mice
           through inhibition of inflammation, oxidative stress, nitrative stress and
           apoptosis

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Jun-Nan Hu, Xing-Yue Xu, Wei Li, Yi-Ming Wang, Ying Liu, Zi Wang, Ying-Ping WangAbstractBackgroundFrequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time.MethodsMice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treated with 250 mg/kg APAP exhibited severe liver injury after 24 h, and hepatotoxicity was assessed.ResultsOur results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1β compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group.ConclusionThe results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.
       
  • Discovery of a new primer set for detection and quantification of
           Ilyonectria mors-panacis in soils for ginseng cultivation

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Mohamed El-Agamy Farh, Jeong A. Han, Yeon-Ju Kim, Jae Chun Kim, Priyanka Singh, Deok-Chun YangAbstractBackgroundKorean ginseng is an important cash crop in Asian countries. However, plant yield is reduced by pathogens. Among the Ilyonectria radicicola-species complex, I. mors-panacis is responsible for root-rot and replant failure of ginseng in Asia. The development of new methods to reveal the existence of the pathogen before cultivation is started is essential. Therefore, a quantitative real-time polymerase chain reaction method was developed to detect and quantify the pathogen in ginseng soils.MethodsIn this study, a species-specific histone H3 primer set was developed for the quantification of I. mors-panacis. The primer set was used on DNA from other microbes to evaluate its sensitivity and selectivity for I. mors-panacis DNA. Sterilized soil samples artificially infected with the pathogen at different concentrations were used to evaluate the ability of the primer set to detect the pathogen population in the soil DNA. Finally, the pathogen was quantified in many natural soil samples.ResultsThe designed primer set was found to be sensitive and selective for I. mors-panacis DNA. In artificially infected sterilized soil samples, using quantitative real-time polymerase chain reaction the estimated amount of template was positively correlated with the pathogen concentration in soil samples (R2 = 0.95), disease severity index (R2 = 0.99), and colony-forming units (R2 = 0.87). In natural soils, the pathogen was recorded in most fields producing bad yields at a range of 5.82 ± 2.35 pg/g to 892.34 ± 103.70 pg/g of soil.ConclusionAccording to these results, the proposed primer set is applicable for estimating soil quality before ginseng cultivation. This will contribute to disease management and crop protection in the future.
       
  • Compound K, a ginsenoside metabolite, plays an antiinflammatory role in
           macrophages by targeting the AKT1-mediated signaling pathway

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Jeong-Oog Lee, Eunju Choi, Kon Kuk Shin, Yo Han Hong, Han Gyung Kim, Deok Jeong, Mohammad Amjad Hossain, Hyun Soo Kim, Young-Su Yi, Donghyun Kim, Eunji Kim, Jae Youl ChoAbstractBackgroundCompound K (CK) is an active metabolite of ginseng saponin, ginsenoside Rb1, that has been shown to have ameliorative properties in various diseases. However, its role in inflammation and the underlying mechanisms are poorly understood. In this report, the antiinflammatory role of CK was investigated in macrophage-like cells.MethodsThe CK-mediated antiinflammatory mechanism was explored in RAW264.7 and HEK293 cells that were activated by lipopolysaccharide (LPS) or exhibited overexpression of known activation proteins. The mRNA levels of inflammatory genes and the activation levels of target proteins were identified by quantitative and semiquantitative reverse transcription polymerase chain reaction and Western blot analysis.ResultsCK significantly inhibited the mRNA expression of inducible nitric oxide synthase and tumor necrosis factor-α and morphological changes in LPS-activated RAW264.7 cells under noncytotoxic concentrations. CK downregulated the phosphorylation of AKT1, but not AKT2, in LPS-activated RAW264.7 cells. Similarly, CK reduced the AKT1 overexpression-induced expression of aldehyde oxidase 1, interleukin-1β, interferon-β, and tumor necrosis factor-α in a dose-dependent manner.ConclusionOur results suggest that CK plays an antiinflammatory role during macrophage-mediated inflammatory actions by specifically targeting the AKT1-mediated signaling pathway.
       
  • Erratum to ‘Antistress effect of red ginseng in brain cells is mediated
           by TACE repression via PADI4’ [J Ginseng Res 37 (3) (2013) 315–323]

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Eun-Hye Kim, In-Hye Kim, Jung-Ah Ha, Kwang-Tae Choi, Suhkneung Pyo, Dong-Kwon Rhee
       
  • Korean Red Ginseng (Panax ginseng Meyer) with enriched Rg3 ameliorates
           chronic intermittent heat stress–induced testicular damage in rats via
           multifunctional approach

    • Abstract: Publication date: January 2019Source: Journal of Ginseng Research, Volume 43, Issue 1Author(s): Spandana Rajendra Kopalli, Kyu-Min Cha, Seock-Yeon Hwang, Min-Sik Jeong, Si-Kwan KimAbstractBackgroundPanax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3-enriched KRG extract (KGC04P) on heat stress–induced testicular damage in experimental rats was evaluated.MethodsMale rats (Sprague-Dawley) were divided into four groups (n = 10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures (32 ± 1°C, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction.ResultsSignificant (p 
       
  • Six new dammarane-type triterpene saponins from Panax ginseng flower buds
           and their cytotoxicity

    • Abstract: Publication date: Available online 30 December 2018Source: Journal of Ginseng ResearchAuthor(s): Ke-Ke Li, Sha-Sha Li, Fei Xu, Xiao-Jie GongAbstractBackgroundPanax ginseng has been used for a variety of medical purposes in eastern countries for more than two thousand years. From the extensive experiences accumulated in its long medication use history and the substantial strong evidence in modern research studies, we know that ginseng has various pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascular system–protective effects. The active chemical constituents of ginseng, ginsenosides, are rich in structural diversity and exhibit a wide range of biological activities.MethodsGinsenoside constituents from P. ginseng flower buds were isolated and purified by various chromatographic methods, and their structures were identified by spectroscopic analysis and comparison with the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide method was used to test their cytotoxic effects on three human cancer cell lines.ResultsSix ginsenosides, namely 6'–malonyl formyl ginsenoside F1 (1), 3β–acetoxyl ginsenoside F1 (2), ginsenoside Rh24 (6), ginsenoside Rh25 (7), 7β–hydroxyl ginsenoside Rd (8) and ginsenoside Rh26 (10) were isolated and elucidated as new compounds, together with four known compounds (3–5 and 9). In addition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values, a tentative structure–activity relationship was also discussed based on the results of our bioassay.ConclusionThe study of chemical constituents was useful for the quality control of P. ginseng flower buds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxic activities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51 and 20.48 μM, respectively.
       
  • Inhibitory mechanism of ginsenoside Rh3 on granulocyte–macrophage
           colony-stimulating factor expression in UV-B–irradiated murine SP-1
           keratinocytes

    • Abstract: Publication date: Available online 24 December 2018Source: Journal of Ginseng ResearchAuthor(s): Young Sun Park, Ji Eun Lee, Jong Il Park, Cheol hwan Myung, Young-Ho Lim, Chae Kyu Park, Jae Sung HwangAbstractBackgroundUltraviolet (UV) goes through the epidermis and promotes release of inflammatory cytokines in keratinocytes. Granulocyte–macrophage colony-stimulating factor (GM-CSF), one of the keratinocyte-derived cytokines, regulates proliferation and differentiation of melanocytes. Extracellular signal–regulated kinase (ERK1/2) and protein kinase C (PKC) signaling pathways regulate expression of GM-CSF. Based on these results, we found that ginsenoside Rh3 prevented GM-CSF production and release in UV-B–exposed SP-1 keratinocytes and that this inhibitory effect resulted from the reduction of PKCδ and ERK phosphorylation.MethodsWe investigated the mechanism by which ginsenoside Rh3 from Panax ginseng inhibited GM-CSF release from UV-B–irradiated keratinocytes.ResultsTreatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or UV-B induced release of GM-CSF in the SP-1 keratinocytes. To elucidate whether the change in GM-CSF expression could be related to PKC signaling, the cells were pretreated with H7, an inhibitor of PKC, and irradiated with UV-B. GM-CSF was decreased by H7 in a dose-dependent manner. When we analyzed which ginsenosides repressed GM-CSF expression among 15 ginsenosides, ginsenoside Rh3 showed the largest decline to 40% of GM-CSF expression in enzyme-linked immunosorbent assay. Western blot analysis showed that TPA enhanced the phosphorylation of PKCδ and ERK in the keratinocytes. When we examined the effect of ginsenoside Rh3, we identified that ginsenoside Rh3 inhibited the TPA-induced phosphorylation levels of PKCδ and ERK.ConclusionIn summary, we found that ginsenoside Rh3 impeded UV-B–induced GM-CSF production through repression of PKCδ and ERK phosphorylation in SP-1 keratinocytes.
       
  • The role of ginsenoside Rb1, a potential natural glutathione reductase
           agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells

    • Abstract: Publication date: Available online 16 December 2018Source: Journal of Ginseng ResearchAuthor(s): Hui-Jie Fan, Zhang-Bin Tan, Yu-Ting Wu, Xiao-Reng Feng, Yi-Ming Bi, Ling-Peng Xie, Wen-Tong Zhang, Zhi Ming, Bin Liu, Ying-Chun ZhouAbstractBackgroundOxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study.MethodsThe antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein.ResultsGRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (−6.426 kcal/mol), and the binding was stable. GRb1 significantly reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells.ConclusionGRb1 is a potential natural GR agonist that protects against oxidative stress–induced apoptosis of H9C2 cells.
       
  • Korean red ginseng and Korean black ginseng extracts, JP5 and BG1, prevent
           hepatic oxidative stress and inflammation induced by environmental heat
           stress

    • Abstract: Publication date: Available online 16 December 2018Source: Journal of Ginseng ResearchAuthor(s): Ji-Hyeon Song, Kui-Jin Kim, Sungwoo Chei, Young-Jin Seo, Kippeum Lee, Boo-Yong LeeAbstractBackgroundContinuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress.MethodsWe investigated the ability of Korean red ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model.ResultsHeat stress significantly increased gene and protein expression of oxidative stress–related factors such as catalase and SOD2, but treatment with JP5 (Korean red ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation.ConclusionsJP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.
       
  • Korean Red Ginseng attenuates type 2 diabetic cardiovascular dysfunction
           in Otsuka Long-Evans Tokushima Fatty rats

    • Abstract: Publication date: Available online 16 December 2018Source: Journal of Ginseng ResearchAuthor(s): Mohammad Amjad Hossain, Dongbin Lee, Chang-Won Kang, Nam Soo Kim, Jong-Hoon KimAbstractExtracts of ginseng species show antihyperglycemic activity. We evaluated the inhibitory effects of diabetic complications for Korean Red Ginseng (KRG), which is enriched in ginsenosides using Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The animals were divided into one of four groups (n = 6∼9): Long–Evans–Tokushima–Otsuka rats (control rats), OLETF rats, rats given 200 mg/kg KRG, and rats given 400 mg/kg KRG. We examined the protective potential of KRG against type 2 diabetic illnesses. The results exhibited that KRG showed significant antihyperglycemic and antioxidative effects in KRG-treated OLETF rats. And, our results proposed the amelioration of cardiac function through normalized ejection fraction, fractional shortening, and vascular reactivity. Furthermore, histopathological abnormalities in the OLETF rats were prevented by KRG treatment.
       
  • Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and
           neuronal cell death in HT22 cells

    • Abstract: Publication date: Available online 15 December 2018Source: Journal of Ginseng ResearchAuthor(s): Dong Hoi Kim, Dae Won Kim, Bo Hyun Jung, Jong Hun Lee, Heesu Lee, Gwi Seo Hwang, Ki Sung Kang, Jae Wook LeeAbstractBackgroundThe objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells.MethodsThe neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of Ca2+ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2′,7′-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model.ResultReduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 (25.7 μM). Cellular Ca2+ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons.ConclusionOur results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation.
       
  • New dammarane-type triterpenoid saponins from Panax notoginseng
           saponins

    • Abstract: Publication date: Available online 13 December 2018Source: Journal of Ginseng ResearchAuthor(s): Qian Li, Mingrui Yuan, Xiaohui Li, Jinyu Li, Ming Xu, Di Wei, Desong Wu, Jinfu Wan, Shuangxi Mei, Tao Cui, Jingkun Wang, Zhaoyun ZhuAbstractBackgroundPanax notoginseng saponin (PNS) is the extraction from the roots and rhizomes of Panaxnotoginseng (Burk.) F. H. Chen. PNS is the main bioactive component of Xuesaitong, Xueshuantong, and other Chinese patent medicines, which are all bestselling prescriptions in China to treat cardiocerebrovascular diseases. Notoginsenoside R1 and ginsenoside Rg1, Rd, Re, and Rb1 are the principal effective constituents of PNS, but a systematic research on the rare saponin compositions has not been conducted.ObjectiveThe objective of this study was to conduct a systematic chemical study on PNS and establish the HPLC fingerprint of PNS to provide scientific evidence in quality control. In addition, the cytotoxicity of the new compounds was tested.MethodsPure saponins from PNS were isolated by means of many chromatographic methods, and their structures were determined by extensive analyses of NMR and HR-ESI-MS studies. The fingerprint was established by HPLC-UV method. The cytotoxicity of the compounds was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide assay.Results and ConclusionThree new triterpenoid saponins (1–3) together with 25 known rare saponins (4–28) were isolated from PNS, except for the five main compounds (notoginsenoside R1 and ginsenoside Rg1, Rd, Re, and Rb1). In addition, the HPLC fingerprint of PNS was established, and the peaks of the isolated compounds were marked. The study of chemical constituents and fingerprint was useful for the quality control of PNS. The study on antitumor activities showed that new Compound 2 exhibited significant inhibitory activity against the tested cell lines.
       
  • Ginsenoside Rf inhibits cyclooxygenase-2 induction via peroxisome
           proliferator–activated receptor gamma in A549 cells

    • Abstract: Publication date: Available online 30 November 2018Source: Journal of Ginseng ResearchAuthor(s): Heewon Song, Joonwoo Park, KeunOh Choi, Jeonggeun Lee, Jie Chen, Hyun-Ju Park, Byeung-Il Yu, Mitsuru Iida, Mee-Ra Rhyu, YoungJoo LeeAbstractBackgroundGinsenoside Rf is a ginseng saponin found only in Panax ginseng that affects lipid metabolism. It also has neuroprotective and antiinflammatory properties. We previously showed that Korean Red Ginseng (KRG) inhibited the expression of cyclooxygenase-2 (COX-2) by hypoxia via peroxisome proliferator–activated receptor gamma (PPARγ). The aim of the current study was to evaluate the possibility of ginsenoside Rf as an active ingredient of KRG in the inhibition of hypoxia-induced COX-2 via PPARγ.MethodsThe effects of ginsenoside Rf on the upregulation of COX-2 by hypoxia and its antimigration effects were evaluated in A549 cells. Docking of ginsenoside Rf was performed with the PPARγ structure using Surflex-Dock in Sybyl-X 2.1.1.ResultsPPARγ protein levels and peroxisome proliferator response element promoter activities were promoted by ginsenoside Rf. Inhibition of COX-2 expression by ginsenoside Rf was blocked by the PPARγ-specific inhibitor, T0070907. The PPARγ inhibitor also blocked the ability of ginsenoside Rf to suppress cell migration under hypoxia. The docking simulation results indicate that ginsenoside Rf binds to the active site of PPARγ.ConclusionsOur results demonstrate that ginsenoside Rf inhibits hypoxia induced-COX-2 expression and cellular migration, which are dependent on PPARγ activation. These results suggest that ginsenoside Rf has an antiinflammatory effect under hypoxic conditions. Moreover, docking analysis of ginsenoside Rf into the active site of PPARγ suggests that the compound binds to PPARγ in a position similar to that of known agonists.
       
  • Ginseng for an eye: effects of ginseng on ocular diseases

    • Abstract: Publication date: Available online 30 November 2018Source: Journal of Ginseng ResearchAuthor(s): Jisu Kim, Su-Young Han, Hyeyoung MinAbstractThe sense of vision is the primary means by which we gather information from our surroundings, and vision loss, therefore, severely compromises the life of the affected individuals, their families, and society. Loss of vision becomes more frequent with age, and diabetic retinopathy, age-related macular degeneration, cataracts, and glaucoma are the major causes of vision impairment. To find active pharmacological compounds that might prevent or ameliorate the vision-threatening eye diseases, numerous studies have been performed, and some botanical compounds, including those extracted from ginseng, have been shown to possess beneficial effects in the treatment or prevention of common ocular diseases. In this review, we summarize the recent reports investigating the therapeutic effects of ginseng and ginsenosides on diverse ocular diseases and discuss their therapeutic potential.
       
  • Transcriptome analyses of the ginseng root rot pathogens Cylindrocarpon
           destructans and Fusarium solani to identify radicicol resistance
           mechanisms

    • Abstract: Publication date: Available online 23 November 2018Source: Journal of Ginseng ResearchAuthor(s): Taiying Li, Jin-Hyun Kim, Boknam Jung, Sungyeon Ji, Mun Won Seo, You Kyoung Han, Sung Woo Lee, Yeoung Seuk Bae, Hong-Gyu Choi, Seung-Ho Lee, Jungkwan LeeAbstractBackgroundThe ascomycete fungi Cylindrocarpon destructans (Cd) and Fusarium solani (Fs) cause ginseng root rot and significantly reduce the quality and yield of ginseng. Cd produces the secondary metabolite radicicol, which targets the molecular chaperone Hsp90. Fs is resistant to radicicol, whereas other fungal genera associated with ginseng disease are sensitive to it. Radicicol resistance mechanisms have not yet been elucidated.MethodsTranscriptome analyses of Fs and Cd mycelia treated with or without radicicol were conducted using RNA-seq. All of the differentially expressed genes (DEGs) were functionally annotated using the Fusarium graminearum transcript database. In addition, deletions of two transporter genes identified by RNA-seq were created to confirm their contributions to radicicol resistance.ResultsTreatment with radicicol resulted in upregulation of chitin synthase and cell wall integrity genes in Fs and upregulation of nicotinamide adenine dinucleotide dehydrogenase and sugar transporter genes in Cd. Genes encoding an ATP-binding cassette transporter, an aflatoxin efflux pump, ammonium permease 1 (mep1), and nitrilase were differentially expressed in both Fs and Cd. Among these four genes, only the ABC transporter was upregulated in both Fs and Cd. The aflatoxin efflux pump and mep1 were upregulated in Cd, but downregulated in Fs, whereas nitrilase was downregulated in both Fs and Cd.ConclusionThe transcriptome analyses suggested radicicol resistance pathways, and deletions of the transporter genes indicated that they contribute to radicicol resistance.
       
  • Development of ginseng powder using high hydrostatic pressure treatment
           combined with UV-TiO2 photocatalysis

    • Abstract: Publication date: Available online 23 November 2018Source: Journal of Ginseng ResearchAuthor(s): Hyunah Lee, Hafiz Muhammad Shahbaz, Namho Ha, Jeong Un Kim, Sang Jun Lee, Jiyong ParkAbstractBackgroundKorean ginseng (Panax ginseng Meyer) powder is in rising demand because powder forms of foods are convenient to handle and are highly preservable. However, ginseng powder (GP) manufactured using the conventional process of air drying and dry milling suffers nutrient destruction and a lack of microbiological safety. The objective of this study was to prepare GP using a novel process comprised of UV-TiO2 photocatalysis (UVTP) as a prewashing step, wet grinding, high hydrostatic pressure (HHP), and freeze-drying treatments.MethodsThe effects of UVTP and HHP treatments on the microbial population, ginsenoside concentration, and physiological characteristics of GP were evaluated.ResultsWhen UVTP for 10 min and HHP at 600 MPa for 5 min were combined, initial 4.95 log CFU/g-fw counts of total aerobes in fresh ginseng were reduced to lower than the detection limit. The levels of 7 major ginsenosides in UVTP-HHP–treated GP were significantly higher than in untreated control samples. Stronger inhibitory effects against inflammatory mediator production and antioxidant activity were observed in UVTP-HHP–treated GP than in untreated samples. There were also no significant differences in CIELAB color values of UVTP-HHP–treated GP compared with untreated control samples.ConclusionCombined processing of UVTP and HHP increased ginsenoside levels and enhanced the microbiological safety and physiological activity of GP.
       
  • Synergistic anticancer effects of timosaponin AIII and ginsenosides in
           MG63 human osteosarcoma cells

    • Abstract: Publication date: Available online 16 November 2018Source: Journal of Ginseng ResearchAuthor(s): Okkeun Jung, Sang Yeol LeeAbstractBackgroundTimosaponin AIII (TA3) is a steroidal saponin extracted from Anemarrhena asphodeloides. Here, we investigated the anticancer effects of TA3 in MG63 human osteosarcoma cells. TA3 attenuates migration and invasion of MG63 cells via regulations of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, which are involved with cancer metastasis in various cancer cells. TA3 reduced enzymatic activities and transcriptional expressions of MMP-2 and MMP-9 in MG63 cells. TA3 also inhibited Src, focal adhesion kinase, extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), p38, β-catenin, and cAMP response element binding signaling, which regulate migration and invasion of cells. TA3 induced apoptosis of MG63 cells via regulations of caspase-3, caspase-7, and poly(ADP-ribose) polymerase (PARP). Then, we tested several ginsenosides to be used in combination with TA3 for the synergistic anticancer effects. We found that ginsenosides Rb1 and Rc have synergistic effects on TA3-induced apoptosis in MG63 cells.MethodsWe investigated the anticancer effects of TA3 and synergistic effects of various ginseng saponins on TA3-induced apoptosis in MG63 cells. To test antimetastatic effects, we performed wound healing migration assay, Boyden chamber invasion assays, gelatin zymography assay, and Western blot analysis. Annexin V/PI staining apoptosis assay was performed to determine the apoptotic effect of TA3 and ginsenosides.ResultsTA3 attenuated migration and invasion of MG63 cells and induced apoptosis of MG63 cells. Ginsenosides Rb1 and Rc showed the synergistic effects on TA3-induced apoptosis in MG63 cells.ConclusionsThe results strongly suggest that the combination of TA3 and the two ginsenosides Rb1 and Rc may be a strong candidate for the effective antiosteosarcoma agent.
       
  • Identification of a novel triterpene saponin from Panax ginseng seeds,
           pseudoginsenoside RT8, and its antiinflammatory activity

    • Abstract: Publication date: Available online 10 November 2018Source: Journal of Ginseng ResearchAuthor(s): Taewoong Rho, Hyun Woo Jeong, Yong Deog Hong, Keejung Yoon, Jae Youl Cho, Kee Dong YoonAbstractBackgroundPanax ginseng Meyer (Araliaceae) is a highly valued medicinal plant in Asian regions, especially in Korea, China, and Japan. Chemical and biological studies on P. ginseng have focused primarily on its roots, whereas the seeds remain poorly understood. This study explores the phytochemical and biological properties of compounds from P. ginseng seeds.MethodsP. ginseng seeds were extracted with methanol, and 16 compounds were isolated using various chromatographic methods. The chemical structures of the isolates were determined by spectroscopic data. Antiinflammatory activities were evaluated for triterpene and steroidal saponins using lipopolysaccharide-stimulated RAW264.7 macrophages and THP-1 monocyte leukemia cells.ResultsPhytochemical investigation of P. ginseng seeds led to the isolation of a novel triterpene saponin, pseudoginsenoside RT8, along with 15 known compounds. Pseudoginsenoside RT8 exhibited more potent antiinflammatory activity than the other saponins, attenuating lipopolysaccharide-mediated induction of proinflammatory genes such as interleukin-1β, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-9, and suppressed reactive oxygen species and nitric oxide generation in a dose-dependent manner.ConclusionThese findings indicate that pseudoginsenoside RT8 has a pharmaceutical potential as an antiinflammatory agent and that P. ginseng seeds are a good natural source for discovering novel bioactive molecules.
       
  • Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated
           by ABCB1 transporter: in vitro and in vivo study

    • Abstract: Publication date: Available online 8 November 2018Source: Journal of Ginseng ResearchAuthor(s): Sen-Ling Feng, Hai-Bin Luo, Liang Cai, Jie Zhang, Dan Wang, Ying-Jiang Chen, Huan-Xing Zhan, Zhi-Hong Jiang, Ying XieAbstractBackgroundMultidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo.MethodsCytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo.ResultsRg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose.ConclusionTherefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.
       
  • Ginseng-plus-Bai-Hu-Tang ameliorates diet-induced obesity, hepatic
           steatosis, and insulin resistance in mice

    • Abstract: Publication date: Available online 27 October 2018Source: Journal of Ginseng ResearchAuthor(s): Hsu-Feng Lu, Yu-Heng Lai, Hsiu-Chen Huang, I-Jung Lee, Lie-Chwen Lin, Hui-Kang Liu, Hsiao-Hsuan Tien, Cheng HuangAbstractBackgroundDietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear.MethodsThis study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice.ResultsGBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT.ConclusionGBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.
       
  • Tolerability and pharmacokinetics of ginsenosides Rb1, Rb2, Rc, Rd, and
           compound K after single or multiple administration of red ginseng extract
           in human beings

    • Abstract: Publication date: Available online 27 October 2018Source: Journal of Ginseng ResearchAuthor(s): Min-Koo Choi, Sojeong Jin, Ji-Hyeon Jeon, Woo Youl Kang, Sook Jin Seong, Young-Ran Yoon, Yong-Hae Han, Im-Sook SongAbstractBackgroundWe investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings.MethodsRed ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods.ResultsRepeated administration of high-dose red ginseng for 15 days was well tolerated and did not produce significant changes in body temperature or blood pressure. The plasma concentrations of Rb1, Rb2, and Rc were stable and showed similar area under the plasma concentration-time curve (AUC) values after 15 days of repeated administration. Their AUC values after repeated administration of red ginseng extract for 15 days accumulated 4.5- to 6.7-fold compared with single-dose AUC. However, the plasma concentrations of Rd and compound K showed large interindividual variations but correlated well between AUC of Rd and compound K. Compound K did not accumulate after 15 days of repeated administration of red ginseng extract.ConclusionA good correlation between the AUC values of Rd and compound K might be the result of intestinal biotransformation of Rb1, Rb2, and Rc to Rd and subsequently to compound K, rather than the intestinal permeability of these ginsenosides. A strategy to increase biotransformation or reduce metabolic intersubject variability may increase the plasma concentrations of Rd and compound K.
       
  • Panax ginseng: a candidate herbal medicine for autoimmune disease

    • Abstract: Publication date: Available online 26 October 2018Source: Journal of Ginseng ResearchAuthor(s): Joon-Il Lee, Kyoung Sun Park, Ik-Hyun ChoAbstractPanax ginseng Meyer (P. ginseng; Korean ginseng) is well known for its medicinal properties. It can alleviate pathological symptoms, promote health, and prevent potential diseases via its anti-inflammatory, antioxidant, homeostatic, and other positive effects on biological metabolism. Although many studies have determined effects of P. ginseng on various diseases, such as cardiovascular, neurological, and immunological diseases, little is known about the effect of P. ginseng on autoimmune diseases. Here, we review a few reports about effects of P. ginseng on autoimmune diseases (e.g., multiple sclerosis, Crohn's disease, ulcerative colitis, atopic dermatitis, and rheumatoid arthritis) and suggest the possibility of P. ginseng as a candidate herbal medicine to prevent and treat autoimmune diseases as well as the need to study it.
       
  • The adventure of a lifetime: kids, entertainment, and an endangered root

    • Abstract: Publication date: Available online 26 October 2018Source: Journal of Ginseng ResearchAuthor(s): George Lindemann
       
  • Acute and repeated dose 26-week oral toxicity study of 20(S)-ginsenoside
           Rg3 in Kunming mice and Sprague–Dawley rats

    • Abstract: Publication date: Available online 19 October 2018Source: Journal of Ginseng ResearchAuthor(s): Chunmei Li, Zhezhe Wang, Guisheng Li, Zhenhua Wang, Jianrong Yang, Yanshen Li, Hongtao Wang, Haizhu Jin, Junhua Qiao, Hongbo Wang, Jingwei Tian, Albert W. Lee, Yonglin GaoAbstractBackground20(S)-ginsenoside-Rg3 (C42H72O13), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns.MethodsIn acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague–Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects.ResultsThe result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings.ConclusionThe mean oral lethal dose (LD50) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.
       
  • Putative multiple reaction monitoring strategy for the comparative
           pharmacokinetics of postoral administration Renshen–Yuanzhi
           compatibility through liquid chromatography–tandem mass spectrometry

    • Abstract: Publication date: Available online 9 October 2018Source: Journal of Ginseng ResearchAuthor(s): Yufei Sun, Guifang Feng, Yan Zheng, Shu Liu, Yan Zhang, Zifeng Pi, Fengrui Song, Zhiqiang LiuAbstractBackgroundExploring the pharmacokinetic (PK) changes of various active components of single herbs and their combinations is necessary to elucidate the compatibility mechanism. However, the lack of chemical standards and low concentrations of multiple active ingredients in the biological matrix restrict PK studies.MethodsA putative multiple reaction monitoring strategy based on liquid chromatography coupled with mass spectrometry (LC–MS) was developed to extend the PK scopes of quantification without resorting to the use of chemical standards. First, the compounds studied, including components with available reference standard (ARS) and components lacking reference standard (LRS), were preclassified to several groups according to their chemical structures. Herb decoctions were then subjected to ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis with appropriate collision energy (CE) in MS2 mode. Finally, multiple reaction monitoring transitions transformed from MS2 of ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used for ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry to obtain the mass responses of LRS components. LRS components quantification was further performed by developing an assistive group-dependent semiquantitative method.ResultsThe developed method was exemplified by the comparative PK process of single herbs Radix Ginseng (RG), Radix Polygala (RP), and their combinations (RG–RP). Significant changes in PK parameters were observed before and after combination.ConclusionResults indicated that Traditional Chinese Medicine combinations can produce synergistic effects and diminish possible toxic effects, thereby reflecting the advantages of compatibility. The proposed strategy can solve the quantitative problem of LRS and extend the scopes of PK studies.
       
  • Effect of red ginseng NaturalGEL on skin aging

    • Abstract: Publication date: Available online 6 October 2018Source: Journal of Ginseng ResearchAuthor(s): Ye Hyang Kim, Hye Rim Park, So Yoon Cha, So Hun Lee, Jung Wung Jo, Jung Nam Go, Kang Hyuk Lee, Su Yeon Lee, Song Seok ShinAbstractBackgroundIn aged skin, degradation of collagen fibers, which occupy the majority of the extracellular matrix in the dermis, and changes of aquaporin 3 (AQP3) and skin constituents, such as hyaluronic acid and ceramide, cause wrinkles and decrease skin moisturization to contribute to dryness and lower elasticity skin. Red ginseng (RG) is used as a cosmetic and food material and is known to protect from UVB-induced cell death, increase skin hydration, prevent wrinkles, and have an antioxidative effect. But, in general, RG used as a material is the soluble liquid portion in the solvent, and the part that is not soluble in the solvent is discarded. Thus, we made the whole RG into microgranulation and dispersed in water to produce gel form for using entire RG, and it was named red ginseng NaturalGEL (RG NGEL).MethodsRG NGEL was investigated for matrix metalloproteinases inhibitory activity, induction of Type I collagen, AQP3, hyaluronan synthetase 2, serine palmitoyl transferase, ceramide synthase 3, and filaggrin expression and compared with RG water extract.ResultsRG NGEL reduced the levels of UV-induced matrix metalloproteinases and increased Type I collagen in human fibroblast cells and upregulated AQP3, hyaluronan synthetase 2, serine palmitoyl transferase, ceramide synthase 3, and filaggrin expressions in human keratinocytes compared with RG water extract.ConclusionRG NGEL has the potential as an effective reagent for antiaging cosmetics to improve wrinkle formation and skin hydration.
       
  • Two new triterpenoid saponins derived from the leaves of Panax ginseng and
           their antiinflammatory activity

    • Abstract: Publication date: Available online 4 October 2018Source: Journal of Ginseng ResearchAuthor(s): Fu Li, Yufeng Cao, Yanyan Luo, Tingwu Liu, Guilong Yan, Liang Chen, Lilian Ji, Lun Wang, Bin Chen, Aftab Yaseen, Ashfaq A. Khan, Guolin Zhang, Yunyao Jiang, Jianxun Liu, Gongcheng Wang, Ming-Kui Wang, Weicheng HuAbstractBackgroundThe leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro.MethodsVarious chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells.Results and conclusionsTwo novel, minor triterpenoid saponins, ginsenoside LS1 (1) and 5,6-didehydroginsenoside Rg3 (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with IC50 of 37.38 μM compared with that of NG-monomethyl-L-arginine (IC50 = 90.76 μM). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin E2 and tumor necrosis factor-α. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration.
       
  • Highly regioselective biotransformation of ginsenoside Rb2 into compound Y
           and compound K by β-glycosidase purified from Armillaria mellea mycelia

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Min-Ji Kim, Jitendra Upadhyaya, Min-Sun Yoon, Nam Soo Ryu, Young Eun Song, Hee-Won Park, Young-Hoi Kim, Myung-Kon KimAbstractBackgroundThe biological activities of ginseng saponins (ginsenosides) are associated with type, number, and position of sugar moieties linked to aglycone skeletons. Deglycosylated minor ginsenosides are known to be more biologically active than major ginsenosides. Accordingly, the deglycosylation of major ginsenosides can provide the multibioactive effects of ginsenosides. The purpose of this study was to transform ginsenoside Rb2, one of the protopanaxadiol-type major ginsenosides, into minor ginsenosides using β-glycosidase (BG-1) purified from Armillaria mellea mycelium.MethodsGinsenoside Rb2 was hydrolyzed by using BG-1; the hydrolytic properties of Rb2 by BG-1 were also characterized. In addition, the influence of reaction conditions such as reaction time, pH, and temperature, and transformation pathways of Rb2, Rd, F2, compound O (C-O), and C-Y by treatment with BG-1 were investigated.ResultsBG-1 first hydrolyzes 3-O-outer β-d-glucoside of Rb2, then 3-O-β-d-glucoside of C-O into C-Y. C-Y was gradually converted into C-K with a prolonged reaction time, but the pathway of Rb2 → Rd → F2 → C-K was not observed. The optimum reaction conditions for C-Y and C-K formation from Rb2 by BG-1 were pH 4.0–4.5, temperature 45–60°C, and reaction time 72–96 h.Conclusionβ-Glycosidase purified from A. mellea mycelium can be efficiently used to transform Rb2 into C-Y and C-K. To our best knowledge, this is the first result of transformation from Rb2 into C-Y and C-K by basidiomycete mushroom enzyme.
       
  • Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of
           topically administered 20(S)-protopanaxadiol: in vitro and in vivo
           evaluation studies

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Ki-Taek Kim, Min-Hwan Kim, Ju-Hwan Park, Jae-Young Lee, Hyun-Jong Cho, In-Soo Yoon, Dae-Duk KimAbstractBackground20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD.MethodsMEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model.ResultsA Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient r2 = 0.929‒0.947).ConclusionThe MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.
       
  • Effects of fermented black ginseng on wound healing mediated by
           angiogenesis through the mitogen-activated protein kinase pathway in human
           umbilical vein endothelial cells

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Jun Yeon Park, Dong-Soo Lee, Chang-Eop Kim, Myoung-Sook Shin, Chang-Seob Seo, Hyeun-Kyoo Shin, Gwi Seo Hwang, Jun Min An, Su-Nam Kim, Ki Sung KangAbstractBackgroundFermented black ginseng (FBG) is produced through several cycles of steam treatment of raw ginseng, at which point its color turns black. During this process, the original ginsenoside components of raw ginseng (e.g., Re, Rg1, Rb1, Rc, and Rb2) are altered, and less-polar ginsenosides are generated (e.g., Rg3, Rg5, Rk1, and Rh4). The aim of this study was to determine the effect of FBG on wound healing.MethodsThe effects of FBG on tube formation and on scratch wound healing were measured using human umbilical vein endothelial cells (HUVECs) and HaCaT cells, respectively. Protein phosphorylation of mitogen-activated protein kinase was evaluated via Western blotting. Finally, the wound-healing effects of FBG were assessed using an experimental cutaneous wounds model in mice.Results and ConclusionThe results showed that FBG enhanced the tube formation in HUVECs and migration in HaCaT cells. Western blot analysis revealed that FBG stimulated the phosphorylation of p38 and extracellular signal-regulated kinase in HaCaT cells. Moreover, mice treated with 25 μg/mL of FBG exhibited faster wound closure than the control mice did in the experimental cutaneous wounds model in mice.
       
  • Influence of organic acids and heat treatment on ginsenoside conversion

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Gwi Yeong Jang, Min Young Kim, Yoon Jeong Lee, Meishan Li, Yu Su Shin, Junsoo Lee, Heon Sang JeongAbstractBackgroundHeat treatments are applied to ginseng products in order to improve physiological activities through the conversion of ginsenosides, which are key bioactive components. During heat treatment, organic acids can affect ginsenoside conversion. Therefore, the influence of organic acids during heat treatment should be considered.MethodsRaw ginseng, crude saponin, and ginsenoside Rb1 standard with different organic acids were treated at 130°C, and the chemical components, including ginsenosides and organic acids, were analyzed.ResultsThe organic acid content in raw ginseng was 5.55%. Organic acids were not detected in crude saponin that was not subjected to heat treatment, whereas organic acids were found in crude saponin subjected to heat treatment. Major ginsenosides (Rb1, Re, and Rg1) in ginseng and crude saponin were converted to minor ginsenosides at 130°C; the ginsenoside Rb1 standard was very stable in the absence of organic acids and was converted into minor ginsenosides in the presence of organic acids at high temperatures.ConclusionThe major factor affecting ginsenoside conversion was organic acids in ginseng. Therefore, the organic acid content as well as ginsenoside content and processing conditions should be considered important factors affecting the quality of ginseng products.
       
  • Protective effect of ultrasonication-processed ginseng berry extract on
           

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Yoonjin Nam, Jinhyung Bae, Ji Hoon Jeong, Sung Kwon Ko, Uy Dong SohnAbstractBackgroundAcute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats.MethodsGinseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS).ResultsAfter ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group.ConclusionUGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway.
       
  • Red ginseng monograph

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Seung-Ho So, Jong Won Lee, Young-Sook Kim, Sun Hee Hyun, Chang-Kyun HanAbstractGinseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.
       
  • Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with
           cytotoxic activity against human lung adenocarcinoma cells

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Jae Sik Yu, Hyun-Soo Roh, Kwan-Hyuck Baek, Seul Lee, Sil Kim, Hae Min So, Eunjung Moon, Changhyun Pang, Tae Su Jang, Ki Hyun KimAbstractBackgroundLung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells.MethodsBioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively.Results and conclusionBioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate–soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with IC50 values ranging from 161.1 μM to 264.6 μM. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.
       
  • Safety and tolerability of Korean Red Ginseng in healthy adults: a
           multicenter, double-blind, randomized, placebo-controlled trial

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Sang-Wook Song, Ha-Na Kim, Jae-Yong Shim, Byeong-Yeon Yoo, Dae-Hyun Kim, Sang-Hyun Lee, Joo-Sung Park, Moon-Jong Kim, Jun-Hyun Yoo, BeLong Cho, Hee-Cheol Kang, Kwang-Min Kim, Sung-Soo Kim, Kyung-Soo KimAbstractBackgroundKorean Red Ginseng (KRG) has been used in Asia for its various biological effects, but no studies have investigated the safety of its long-term intake. Therefore, the present study evaluated the safety of KRG intake for 24 weeks.MethodsWe randomized 1,000 participants in a 1:1 ratio into two groups, which were treated daily with 2 g of KRG or a placebo for 24 weeks. The primary endpoint was all adverse events and adverse drug reactions (ADRs) that occurred after KRG or placebo administration, which were reported at week 4, 12, and 24 after the baseline visit.ResultsIn total, 192 and 211 participants experienced adverse events in the KRG and placebo groups (39.2% and 42.0%, respectively; p = 0.361), and 59 and 57 KRG- and placebo-treated individuals reported ADRs (12.0% and 11.4%, respectively; p = 0.737). The frequently occurring ADRs were pruritus (2.0%), headache (1.6%), diarrhea (1.4%), and dizziness (1.2%) in the KRG group and pruritus (2.0%), headache (1.8%), dizziness (1.6%), rash (1.4%), and diarrhea (1.2%) in the placebo group. Discontinuation of drug administration due to ADRs was reported in 13 participants, six (1.2%) and seven (1.4%) in the KRG and placebo groups, respectively (p = 0.814). No significant abnormal changes were revealed by anthropometric, laboratory, and vital sign measurements in the KRG group compared with those in the placebo group.ConclusionThe present study confirms the safety and tolerability of daily intake of 2 g of KRG for 24 weeks by healthy adults.
       
  • A comparative study on immune-stimulatory and antioxidant activities of
           various types of ginseng extracts in murine and rodent models

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Evelyn Saba, Yuan Yee Lee, Minki Kim, Seung-Hyung Kim, Seung-Bok Hong, Man Hee RheeAbstractBackgroundGinseng (Panax ginseng) is a widely used traditional herbal supplement that possesses various health-enhancing efficacies. Various ginseng products are available in market, especially in the Korean peninsula, in the form of drinks, tablets, and capsules. The different ginseng types include the traditional red ginseng extract (RGE), white ginseng, and black red ginseng extract (BRGE). Their fermented and enzyme-treated products are also available. Different treatment regimens alter the bioavailability of certain compounds present in the respective ginseng extracts. Therefore, in this study, we aimed to compare the antioxidant and immune-stimulating activities of RGE, BRGE, and fermented red ginseng extract (FRGE).MethodsWe used an acetaminophen-induced oxidative stress model for investigating the reduction of oxidative stress by RGE, BRGE, and FRGE in Sprague Dawley rats. A cyclophosphamide-induced immunosuppression model was used to evaluate the immune-stimulating activities of these ginseng extracts in BALB/c mice.ResultsOur results showed that most prominently, RGE (in almost all experiments) exhibited excellent antioxidant effects via increasing superoxide dismutase, catalase, and glutathione peroxidase activities in the liver and decreasing serum 8-hydroxy-2′-deoxyguanosine, aspartate aminotransferase, and lactate dehydrogenase levels compared with the groups treated with FRGE and BRGE. Moreover, RGE significantly increased the number of white blood cells, especially T and B lymphocytes, and antibody-forming cells in the spleen and thymus, and it also activated a number of immune cell subtypes.ConclusionTaken together, these results indicate that RGE is the best supplement for consumption in everyday life for overall health-enhancing properties.
       
  • Panax ginseng as an adjuvant treatment for Alzheimer's disease

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Hyeon-Joong Kim, Seok-Won Jung, Seog-Young Kim, Ik-Hyun Cho, Hyoung-Chun Kim, Hyewhon Rhim, Manho Kim, Seung-Yeol NahAbstractLongevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid β-protein (Aβ) formation by inhibiting β- and γ-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Aβ-induced neurotoxicity, and decrease Aβ-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Aβ-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Aβ-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce Aβ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.
       
  • Proteomic change by Korean Red Ginseng in the substantia nigra of a
           Parkinson's disease mouse model

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Dongsoo Kim, Sunoh Kwon, Hyongjun Jeon, Sun Ryu, Ki-Tae Ha, Seungtae KimAbstractBackgroundRecent studies have shown that Korean Red Ginseng (KRG) successfully protects against dopaminergic neuronal death in the nigrostriatal pathway of a Parkinson's disease (PD) mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration; however, the mechanism has yet to be identified. Therefore, in this study we used two-dimensional electrophoresis to investigate the effects of KRG on the changes in protein expression in the substantia nigra (SN) of MPTP-treated mice.MethodsMale C57BL/6 mice (9 wk old) were intraperitoneally administered MPTP (20 mg/kg) four times at 2-h intervals, after which KRG (100 mg/kg) was orally administered once a day for 5 d. Two hours after the fifth KRG administration, a pole test was conducted to evaluate motor function, after which the brains were immediately collected. Survival of dopaminergic neurons was measured by immunohistochemistry, and protein expression was measured by two-dimensional electrophoresis and Western blotting.ResultsKRG alleviated MPTP-induced behavioral dysfunction and neuronal toxicity in the SN. Additionally, the expression of eight proteins related to neuronal formation and energy metabolism for survival were shown to have changed significantly in response to MPTP treatment or KRG administration. KRG alleviated the downregulated protein expression following MPTP administration, indicating that it may enhance neuronal development and survival in the SN of MPTP-treated mice.ConclusionThese findings indicate that KRG may have therapeutic potential for the treatment of patients with PD.
       
  • Ginseng seed oil ameliorates hepatic lipid accumulation in vitro and
           in vivo

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Go Woon Kim, Hee Kyung Jo, Sung Hyun ChungAbstractBackgroundDespite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models.MethodsIn vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague–Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk.ResultsOil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with β-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction.ConclusionThese findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.
       
  • Korean Red Ginseng mitigates spinal demyelination in a model of acute
           multiple sclerosis by downregulating p38 mitogen-activated protein kinase
           and nuclear factor-κB signaling pathways

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Min Jung Lee, Byung Joon Chang, Seikwan Oh, Seung-Yeol Nah, Ik-Hyun ChoAbstractBackgroundThe potential therapeutic values of Korean Red Ginseng extract (KRGE) in autoimmune disorders of nervous system have not been fully investigated.MethodsWe used an acute experimental autoimmune encephalomyelitis animal model of multiple sclerosis and determined the effects and mechanism of KRGE on spinal myelination.ResultsPretreatment with KRGE (100 mg/kg, orally) for 10 days before immunization with myelin basic protein (MBP)68–82 peptide exerted a protective effect against demyelination in the spinal cord, with inhibited recruitment and activation of immune cells including microglia, decreased mRNA expression of detrimental inflammatory mediators (interleukin-6, interferon-γ, and cyclooxygenase-2), but increased mRNA expression of protective inflammatory mediators (insulin-like growth factor β1, transforming growth factor β, and vascular endothelial growth factor-1). These results were associated with significant downregulation of p38 mitogen-activated protein kinase and nuclear factor-κB signaling pathways in microglia/macrophages, T cells, and astrocytes.ConclusionOur findings suggest that KRGE alleviates spinal demyelination in acute experimental autoimmune encephalomyelitis through inhibiting the activation of the p38 mitogen-activated protein kinase/nuclear factor-κB signaling pathway. Therefore, KRGE might be used as a new therapeutic for autoimmune disorders such as multiple sclerosis, although further investigation is needed.
       
  • Effect of polysaccharides from a Korean ginseng berry on the
           immunosenescence of aged mice

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Miseon Kim, Young-Su Yi, Juewon Kim, Sang Yun Han, Su Hwan Kim, Dae Bang Seo, Jae Youl Cho, Song Seok ShinAbstractBackgroundKorean ginseng has been widely evaluated to treat human diseases; however, most studies on Korean ginseng have focused on its root. In this study, polysaccharides [acidic-polysaccharide-linked glycopeptide (APGP) extracted with 90% ethanol and hot water] were prepared from Korean ginseng berries, and their effect on immunosenescence was explored.MethodsThe effect of APGP on thymic involution was evaluated by measuring the size of thymi dissected from aged mice. The effect of APGP on populations of immune cells, including natural killer (NK) cells, dendritic cells, age-correlated CD11c-positive B cells, and several subtypes of T cells [CD4-positive, CD8-positive, and regulatory (Treg) T cells] in the thymi and spleens of aged mice was analyzed by fluorescence-activated cell sorting analysis. Serum levels of interleukin (IL)-2 and IL-6 were evaluated by enzyme-linked immunosorbent assay analysis. Profiles of APGP components were evaluated by high-performance liquid chromatography (HPLC) analysis.ResultsAPGP suppressed thymic involution by increasing the weight and areas of thymi in aged mice. APGP increased the population of NK cells, but showed no effect on the population of dendritic cells in the thymi and spleens of aged mice. APGP decreased the population of age-correlated CD11c-positive B cells in the spleens of aged mice. APGP showed no effect on the populations of CD4- and CD8-positive T cells in the thymi of aged mice, whereas it increased the population of Treg cells in the spleens of aged mice. APGP further decreased the reduced serum levels of IL-2 in aged mice, but serum levels of IL-6 were not statistically changed by APGP in aged mice. Finally, HPLC analysis showed that APGP had one major peak at 15 min (a main type of polysaccharide) and a long tail up to 35 min (a mixture of a variety of types of polysaccharides).ConclusionThese results suggested that APGP exerted an anti-immunosenescent effect by suppressing thymic involution and modulating several types of immune cells.
       
  • Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to
           inhibit proliferation of MCF-7 breast cancer cells

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Hyunkyung Lee, Seungyeon Lee, Dawoon Jeong, Sun Jung KimAbstractBackgroundGinsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes.MethodsThe effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2.ResultsLINE1 showed induction of hypomethylation at specific CpGs by 1.6–9.1% (p 
       
  • Influence of phytochemical composition on in vitro antioxidant and
           reducing activities of Indian ginseng [Withania somnifera (L.) Dunal] root
           extracts

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Bhaskar Ganguly, Nirbhay Kumar, Abul H. Ahmad, Sunil K. RastogiAbstractBackgroundRoots of Withania somnifera (WS) are a celebrated medicinal ingredient in Ayurvedic and many other indigenous systems of medicine. The present study investigates the effect of the phytochemical composition of the extracts on their antioxidant and reducing activities.MethodsWS roots were extracted with water, acetone, aqueous methanol (1:1), and methanol:chloroform:water (1:1:1) to obtain aqueous, acetone, hydro-methanolic, and methanol–chloroform–water extracts. Thereafter, phytochemical constitution and antioxidant and reducing activities of the extracts were compared using different qualitative and quantitative tests.ResultsMaximum extraction recovery was obtained with 50% aqueous methanol whereas extraction with acetone yielded the poorest recovery. Methanol–chloroform–water extract had the highest content of phytochemical constituents, except tannins, and also exhibited the highest antioxidant and reducing activities.ConclusionPhytochemical composition and antioxidant and reducing activities of the extracts were positively associated with the use of organic solvents during the extraction process. Alkaloids and flavonoids were the most important contributors in the antioxidant and reducing activities of the extracts.
       
  • Korean Red Ginseng extract and ginsenoside Rg3 have anti-pruritic effects
           on chloroquine-induced itch by inhibition of MrgprA3/TRPA1-mediated
           pathway

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Wook-Joo Lee, Young-Sik Kim, Won-Sik ShimAbstractBackgroundIt was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1.MethodsIntracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 (“MrgprA3/TRPA1”), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3.ResultsCQ-induced Ca2+ influx was strongly inhibited by KRGE (10 μg/mL) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced Ca2+ influx in MrgprA3/TRPA1. Moreover, both KRGE (10 μg/mL) and Rg3 (100 μM) suppressed CQ-induced Ca2+ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: 274.0 ± 51.47 (control) vs. 104.7 ± 17.39 (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: 216.8 ± 33.73 (control) vs. 115.7 ± 20.94 (Rg3)].ConclusionThe present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.
       
  • Ginsenosides from Korean Red Ginseng ameliorate lung inflammatory
           responses: inhibition of the MAPKs/NF-κB/c-Fos pathways

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Ju Hee Lee, Dong Suk Min, Chan Woo Lee, Kwang Ho Song, Yeong Shik Kim, Hyun Pyo KimAbstractBackgroundKorean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response.MethodsFrom Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S).ResultsAll ginsenosides orally administered at 20 mg/kg showed 11.5–51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1–51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-κB, and the c-Fos component in the lung tissue (n = 3).ConclusionCertain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.
       
  • C/N/O/S stable isotopic and chemometric analyses for determining the
           geographical origin of Panax ginseng cultivated in Korea

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Ill-Min Chung, Jae-Kwang Kim, Ji-Hee Lee, Min-Jeong An, Kyoung-Jin Lee, Sung-Kyu Park, Jang-Uk Kim, Mi-Jung Kim, Seung-Hyun KimAbstractBackgroundThe geographical origin of Panax ginseng Meyer, a valuable medicinal plant, is important to both ginseng producers and consumers in the context of economic profit and human health benefits. We, therefore, aimed to discriminate between the cultivation regions of ginseng using the stable isotope ratios of C, N, O, and S, which are abundant bioelements in living organisms.MethodsSix Korean ginseng cultivars (3-yr-old roots) were collected from five different regions in Korea. The C, N, O, and S stable isotope ratios in ginseng roots were measured by isotope ratio mass spectrometry, and then these isotope ratio profiles were statistically analyzed using chemometrics.ResultsThe various isotope ratios found in P. ginseng roots were significantly influenced by region, cultivar, and the interactions between these two factors (p ≤ 0.001). The variation in δ15N and δ13C in ginseng roots was significant for discriminating between different ginseng cultivation regions, and δ18O and δ34S were also affected by both altitude and proximity to coastal areas. Chemometric model results tested in this study provided discrimination between the majority of different cultivation regions. Based on the external validation, this chemometric model also showed good model performance (R2 = 0.853 and Q2 = 0.738).ConclusionOur case study elucidates the variation of C, N, O, and S stable isotope ratios in ginseng root depending on cultivation region. Hence, the analysis of stable isotope ratios is a suitable tool for discrimination between the regional origins of ginseng samples from Korea, with potential application to other countries.
       
  • AKT-targeted anti-inflammatory activity of Panax ginseng calyx
           ethanolic extract

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Sang Yun Han, Juewon Kim, Eunji Kim, Su Hwan Kim, Dae Bang Seo, Jong-Hoon Kim, Song Seok Shin, Jae Youl ChoAbstractBackgroundKorean ginseng (Panax ginseng) plays an anti-inflammatory role in a variety of inflammatory diseases such as gastritis, hepatitis, and colitis. However, inflammation-regulatory activity of the calyx of the P. ginseng berry has not been thoroughly evaluated. To understand whether the calyx portion of the P. ginseng berry is able to ameliorate inflammatory processes, an ethanolic extract of P. ginseng berry calyx (Pg-C-EE) was prepared, and lipopolysaccharide-activated macrophages and HEK293 cells transfected with inflammation-regulatory proteins were used to test the anti-inflammatory action of Pg-C-EE.MethodsThe ginsenoside contents of Pg-C-EE were analyzed by HPLC. Suppressive activity of Pg-C-EE on NO production, inflammatory gene expression, transcriptional activation, and inflammation signaling events were examined using the Griess assay, reverse transcription-polymerization chain reaction, luciferase activity reporter gene assay, and immunoblotting analysis.ResultsPg-C-EE reduced NO production and diminished mRNA expression of inflammatory genes such as cyclooxygenase-2, inducible NO synthase, and tumor necrosis factor-α in a dose-dependent manner. This extract suppressed luciferase activity induced only by nuclear factor-κB. Interestingly, immunoblotting analysis results demonstrated that Pg-C-EE reduced the activities of protein kinase B (AKT)1 and AKT2.ConclusionThese results suggest that Pg-C-EE may have nuclear-factor-κB-targeted anti-inflammatory properties through suppression of AKT. The calyx of the P. ginseng berry is an underused part of the ginseng plant, and development of calyx-derived extracts may be useful for treatment of inflammatory diseases.
       
  • Production of bioactive ginsenoside Rg3(S) and compound K using
           recombinant Lactococcus lactis

    • Abstract: Publication date: October 2018Source: Journal of Ginseng Research, Volume 42, Issue 4Author(s): Ling Li, Soo Jin Lee, Qiu Ping Yuan, Wan Taek Im, Sun Chang Kim, Nam Soo HanAbstractBackgroundGinsenoside Rg3(S) and compound K (C-K) are pharmacologically active components of ginseng that promote human health and improve quality of life. The aim of this study was to produce Rg3(S) and C-K from ginseng extract using recombinant Lactococcus lactis.MethodsL. lactis subsp. cremoris NZ9000 (L. lactis NZ9000), which harbors β-glucosidase genes (BglPm and BglBX10) from Paenibacillus mucilaginosus and Flavobacterium johnsoniae, respectively, was reacted with ginseng extract (protopanaxadiol-type ginsenoside mixture).ResultsCrude enzyme activity of BglBX10 values comprised 0.001 unit/mL and 0.003 unit/mL in uninduced and induced preparations, respectively. When whole cells of L. lactis harboring pNZBglBX10 were treated with ginseng extract, after permeabilization of cells by xylene, Rb1 and Rd were converted into Rg3(S) with a conversion yield of 61%. C-K was also produced by sequential reactions of the permeabilized cells harboring each pNZBgl and pNZBglBX10, resulting in a 70% maximum conversion yield.ConclusionThis study demonstrates that the lactic acid bacteria having specific β-glucosidase activity can be used to enhance the health benefits of Panax ginseng in either fermented foods or bioconversion processes.
       
  • Oleanolic acid 3-acetate, a minor element of ginsenosides, induces
           apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells
           via the involvement of a reactive oxygen species–independent
           mitochondrial pathway

    • Abstract: Publication date: Available online 19 September 2018Source: Journal of Ginseng ResearchAuthor(s): Hantae Jo, Jeong-Hyun Oh, Dong-Wook Park, Changho Lee, Churl K. MinAbstractObjectivesOleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms.MethodsCytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (ΔΨm), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice.ResultsOleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ΔΨm, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate–induced apoptosis in SKOV3 and HEC-1A cells.ConclusionThese findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.
       
  • Ginsenoside Rb1 exerts neuroprotective effects through regulation of
           Lactobacillus helveticus abundance and GABAA receptor expression

    • Abstract: Publication date: Available online 19 September 2018Source: Journal of Ginseng ResearchAuthor(s): Huimin Chen, Jiajia Shen, Haofeng Li, Xiao Zheng, Dian Kang, Yangfan Xu, Chong Chen, Huimin Guo, Lin Xie, Guangji Wang, Yan LiangAbstractBackgroundGinsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure.PurposeThe present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora.MethodsA pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1.ResultsThe results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 109 CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABAA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H.ConclusionIn sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.
       
  • Ginsenosides: the need to move forward from bench to clinical trials

    • Abstract: Publication date: Available online 7 September 2018Source: Journal of Ginseng ResearchAuthor(s): Seung Eun Yu, Benjamin Mwesige, Young-Su Yi, Byong Chul YooAbstractPanax ginseng, known as Koran ginseng, one of the most commonly used traditional plants, has been demonstrated to show a wide range of pharmacological applications. Ginsenosides are the major active ingredients found in ginseng and are responsible for the biological and pharmacological activities, such as antioxidation, antiinflammation, vasorelaxation, and anticancer actions. Existing studies have mostly focused on identifying and purifying single ginsenosides and investigating pharmacological activities and molecular mechanisms in cells and animal models. However, ginsenoside studies based on clinical trials have been very limited. Therefore, this review aimed to discuss the currently available clinical trials on ginsenosides and provide insights and future directions for developing ginsenosides as efficacious and safe drugs for human disease.
       
  • Studies of the effects and mechanisms of ginsenoside Re and Rk3 on
           myelosuppression induced by cyclophosphamide

    • Abstract: Publication date: Available online 30 August 2018Source: Journal of Ginseng ResearchAuthor(s): Jiahong Han, Jing Xia, Lianxue Zhang, Enbo Cai, Yan Zhao, Xuan Fei, Xiaohuan Jia, He Yang, Shuangli LiuAbstractBackgroundGinsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk3 (Rk3) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk3 on cyclophosphamide-induced myelosuppression.MethodsThe mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting.ResultsBoth Re and Rk3 could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G0/G1 phase cells, and increase the proliferation index. Finally, Re and Rk3 could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3.ConclusionRe and Rk3 could improve the hematopoietic function of myelosuppressed mice. The effect of Rk3 was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk3 on myelosuppression.
       
  • Gintonin stimulates autophagic flux in primary cortical astrocytes

    • Abstract: Publication date: Available online 27 August 2018Source: Journal of Ginseng ResearchAuthor(s): Md. Ataur Rahman, Hongik Hwang, Seung-Yeol Nah, Hyewhon RhimAbstractBackgroundGintonin (GT), a novel ginseng-derived exogenous ligand of lysophosphatidic acid (LPA) receptors, has been shown to induce cell proliferation and migration in the hippocampus, regulate calcium-dependent ion channels in the astrocytes, and reduce β-amyloid plaque in the brain. However, whether GT influences autophagy in cortical astrocytes is not yet investigated.MethodsWe examined the effect of GT on autophagy in primary cortical astrocytes using immunoblot and immunocytochemistry assays. Suppression of specific proteins was performed via siRNA. LC3 puncta was determined using confocal microscopy.ResultsGT strongly upregulated autophagy marker LC3 by a concentration- as well as time-dependent manner via G protein–coupled LPA receptors. GT-induced autophagy was further confirmed by the formation of LC3 puncta. Interestingly, on pretreatment with an mammalian target of rapamycin (mTOR) inhibitor, rapamycin, GT further enhanced LC3-II and LC3 puncta expression. However, GT-induced autophagy was significantly attenuated by inhibition of autophagy by 3-methyladenine and knockdown Beclin-1, Atg5, and Atg7 gene expression. Importantly, when pretreated with a lysosomotropic agent, E-64d/peps A or bafilomycin A1, GT significantly increased the levels of LC3-II along with the formation of LC3 puncta. In addition, GT treatment enhanced autophagic flux, which led to an increase in lysosome-associated membrane protein 1 and degradation of ubiquitinated p62/SQSTM1.ConclusionGT induces autophagy via mTOR-mediated pathway and elevates autophagic flux. This study demonstrates that GT can be used as an autophagy-inducing agent in cortical astrocytes.
       
  • Inhibitory effect of Korean Red Ginseng extract on DNA damage response and
           apoptosis in Helicobacter pylori–infected gastric epithelial cells

    • Abstract: Publication date: Available online 14 August 2018Source: Journal of Ginseng ResearchAuthor(s): Hyunju Kang, Joo Weon Lim, Hyeyoung KimAbstractBackgroundHelicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori–induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori–infected gastric epithelial cells.MethodsWe determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori–infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined.ResultsH. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori–infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori–infected gastric epithelial cells, similar to KRG.ConclusionKRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori–infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.
       
  • Proteomic analyses reveal that ginsenoside Rg3(S) partially reverses
           

    • Abstract: Publication date: Available online 13 August 2018Source: Journal of Ginseng ResearchAuthor(s): Ik-Soon Jang, Eunbi Jo, Soo Jung Park, In-Hu Hwang, Hyun Mi Kang, Je-Ho Lee, Joseph Kwon, Junik Son, Ho Jeong Kwon, Jong-Soon ChoiAbstractBackgroundThe cellular senescence of primary cultured cells is an irreversible process characterized by growth arrest. Restoration of senescence by ginsenosides has not been explored so far. Rg3(S) treatment markedly decreased senescence-associated β-galactosidase activity and intracellular reactive oxygen species levels in senescent human dermal fibroblasts (HDFs). However, the underlying mechanism of this effect of Rg3(S) on the senescent HDFs remains unknown.MethodsWe performed a label-free quantitative proteomics to identify the altered proteins in Rg3(S)-treated senescent HDFs. Upregulated proteins induced by Rg3(S) were validated by real-time polymerase chain reaction and immunoblot analyses.ResultsFinally, 157 human proteins were identified, and variable peroxiredoxin (PRDX) isotypes were highly implicated by network analyses. Among them, the mitochondrial PRDX3 was transcriptionally and translationally increased in response to Rg3(S) treatment in senescent HDFs in a time-dependent manner.ConclusionOur proteomic approach provides insights into the partial reversing effect of Rg3 on senescent HDFs through induction of antioxidant enzymes, particularly PRDX3.
       
  • Hepatoprotective effect of ultrasonicated ginseng berry extract on a rat
           mild bile duct ligation model

    • Abstract: Publication date: Available online 10 August 2018Source: Journal of Ginseng ResearchAuthor(s): Yoonjin Nam, Sung Kwon Ko, Uy Dong SohnAbstractBackgroundThe Panax ginseng berry extract (GBE) is well known to have an antidiabetic effect. The aim of this study is to evaluate and investigate the protective effect of ultrasonication-processed P. ginseng berry extract (UGBE) compared with GBE on liver fibrosis induced by mild bile duct ligation (MBDL) model in rats. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenosides Rh1, Rh4, Rg2, Rg3, Rk1, Rk3, and F4 in the extract was elevated.MethodsIn this study, the protective effect of the newly developed UGBE was evaluated on hepatotoxicity and neuronal damage in MBDL model. Silymarin (150 mg/kg) was used for positive control. UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg), GBE (250 mg/kg), and silymarin (150 mg/kg) were orally administered for 6 weeks after MBDL surgery.ResultsThe MBDL surgery induced severe hepatotoxicity that leads to liver inflammation in rats. Also, the serum ammonia level was increased by MBDL surgery. However, the liver dysfunction of MBDL surgery–operated rats was attenuated by UGBE treatment via myeloid differentiation factor 88-dependent Toll-like receptor 4 signaling pathways.ConclusionUGBE has a protective effect on liver fibrosis induced by MBDL in rats through inhibition of the TLR4 signaling pathway in liver.
       
  • Salting-out extraction of ginsenosides from the enzymatic hydrolysates of
           Panax quinquefolium based on ethanol/sodium carbonate system

    • Abstract: Publication date: Available online 8 August 2018Source: Journal of Ginseng ResearchAuthor(s): Yingqin Wei, Baojuan Hou, Haiyan Fang, Xinjie Sun, Feng MaAbstractBackgroundSalting-out extraction (SOE) had been developed as a special branch of aqueous two-phase system recently. So far as we know, few reports involved in extracting ginsenosides with SOE because of the lower recovery caused by the unique solubility and surface activity of ginsenosides. A new SOE method for rapid pretreatment of ginsenosides from the enzymatic hydrolysates of Panax quinquefolium was established in this article.MethodsThe SOE system comprising ethanol and sodium carbonate was selected to extract ginsenosides from the enzymatic hydrolysates of Panax quinquefolium, and HPLC was applied to analyze the ginsenosides.ResultsThe optimized extraction conditions were as follows: the aqueous two-phase extraction system comprising ethanol, sodium carbonate, ethanol concentration of 41.51%, and the mass percent of sodium carbonate of 7.9% in the extraction system under the experimental condition. Extraction time had minor influence on extraction efficiency of ginsenosides. The results also showed that the extraction efficiencies of three ginsenosides were all more than 90.0% only in a single step.ConclusionThe proposed method had been successfully applied to determine ginsenosides in enzymatic hydrolysate and demonstrated as a powerful technique for separating and purifying ginsenosides in complex samples.
       
  • Fermented ginseng extract, BST204, disturbs adipogenesis of mesenchymal
           stem cells through inhibition of S6 kinase 1 signaling

    • Abstract: Publication date: Available online 8 August 2018Source: Journal of Ginseng ResearchAuthor(s): Sang Ah Yi, Jieun Lee, Sun Kyu Park, Jeom Yong Kim, Jong Woo Park, Min Gyu Lee, Ki Hong Nam, Jee Hun Park, Hwamok Oh, Saetbyul Kim, Jihoon Han, Bo Kyung Kim, Dong-Gyu Jo, Jeung-Whan HanAbstractBackgroundThe biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway.MethodsThe inhibitory effects of BST204 on S6K1 signaling were investigated by immunoblot, nuclear fractionation, immunoprecipitation analyses. The antiadipogenic effect of BST204 was evaluated by measuring mRNA levels of adipogenic genes and by chromatin immunoprecipitation and quantitative real-time polymerase chain reaction analysis.ResultsTreatment with BST204 inhibited activation and nuclear translocation of S6K1, further decreasing the interaction between S6K1 and histone H2B in 10T1/2 mesenchymal stem cells. Subsequently, phosphorylation of H2B at serine 36 (H2BS36p) by S6K1 was reduced by BST204, inducing an increase in the mRNA expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation and promoted myogenic and early osteogenic gene expression. Consistently, BST204 treatment during adipogenic commitment suppressed the expression of adipogenic marker genes and lipid drop formation.ConclusionOur results indicate that BST204 blocks adipogenesis of mesenchymal stem cells through the inhibition of S6K1-mediated histone phosphorylation. This study suggests the potential therapeutic strategy using BST204 to combat obesity and musculoskeletal diseases.
       
  • A new role for the ginsenoside RG3 in antiaging via mitochondria function
           in ultraviolet-irradiated human dermal fibroblasts

    • Abstract: Publication date: Available online 31 July 2018Source: Journal of Ginseng ResearchAuthor(s): Hyunji Lee, Youngeun Hong, Quangdon Tran, Hyeonjeong Cho, Minhee Kim, Chaeyeong Kim, So Hee Kwon, SungJin Park, Jongsun Park, Jisoo ParkAbstractBackgroundThe efficacy of ginseng, the representative product of Korea, and its chemical effects have been well investigated. The ginsenoside RG3 has been reported to exhibit apoptotic, anticancer, and antidepressant-like effects.MethodsIn this report, the putative effect of RG3 on several cellular function including cell survival, differentiation, development and aging process were evaluated by monitoring each specific marker. Also, mitochondrial morphology and function were investigated in ultraviolet (UV)-irradiated normal human dermal fibroblast cells.ResultsRG3 treatment increased the expression of extracellular matrix proteins, growth-associated immediate-early genes, and cell proliferation genes in UV-irradiated normal human dermal fibroblast cells. And, RG3 also resulted in enhanced expression of antioxidant proteins such as nuclear factor erythroid 2–related factor-2 and heme oxygenase-1. In addition, RG3 affects the morphology of UV-induced mitochondria and plays a role in protecting mitochondrial dysfunction.ConclusioinRG3 restores mitochondrial adenosine triphosphate (ATP) and membrane potential via its antioxidant effects in skin cells damaged by UV irradiation, leading to an increase in proteins linked with the extracellular matrix, cell proliferation, and antioxidant activity.
       
  • Impact of HIV-1 subtype and Korean Red Ginseng on AIDS progression:
           comparison of subtype B and subtype D

    • Abstract: Publication date: Available online 20 July 2018Source: Journal of Ginseng ResearchAuthor(s): Young-Keol Cho, Jung-Eun Kim, Sun-Hee Lee, Brian T. Foley, Byeong-Sun ChoiAbstractBackgroundTo date, no study has described disease progression in Asian patients infected with HIV-1 subtype D.MethodsTo determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in CD4+ T cell counts over 96 ± 59 months was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene.ResultsCD4+ T cell AD was significantly higher in the six subtype D–infected patients than in the 157 subtype B–infected patients irrespective of Korean Red Ginseng (KRG) treatment (p 
       
  • Ginsenoside Rg1 promotes browning by inducing UCP1 expression and
           mitochondrial activity in 3T3-L1 and subcutaneous white adipocytes

    • Abstract: Publication date: Available online 18 July 2018Source: Journal of Ginseng ResearchAuthor(s): Kippeum Lee, Young-Jin Seo, Ji-Hyoen Song, Boo-Yong LeeAbstractBackgroundPanax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated.Methods3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and real-time polymerase chain reaction, respectively.ResultsRg1 dramatically enhanced expression of brown adipocyte–specific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5′ adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion.ConclusionsRg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway.
       
  • Mediation of antiinflammatory effects of Rg3-enriched red ginseng extract
           from Korean red ginseng via retinoid X receptor
           α–peroxisome-proliferating receptor γ nuclear receptors

    • Abstract: Publication date: Available online 17 July 2018Source: Journal of Ginseng ResearchAuthor(s): Evelyn Saba, Muhammad Irfan, Dahye Jeong, Kashif Ameer, Yuan Yee Lee, Chae-Kyu Park, Seung-Bok Hong, Man Hee RheeAbstractBackgroundGinseng has a wide range of beneficial effects on health, such as the mitigation of minor and major inflammatory diseases, cancer, and cardiovascular diseases. There are abundant data regarding the health-enhancing properties of whole ginseng extracts and single ginsenosides; however, no study to date has determined the receptors that mediate the effects of ginseng extracts. In this study, for the first time, we explored whether the antiinflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE) are mediated by retinoid X receptor α–peroxisome-proliferating receptor γ (RXRα-PPARγ) heterodimer nuclear receptors.MethodsNitric oxide assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, quantitative reverse transcription polymerase chain reaction, nuclear hormone receptor–binding assay, and molecular docking analyses were used for this study.ResultsRg3-RGE exerted antiinflammatory effects via nuclear receptor heterodimers between RXRα and PPARγ agonists and antagonists.ConclusionThese findings indicate that Rg3-RGE can be considered a potent antiinflammatory agent, and these effects are likely mediated by the nuclear receptor RXRα-PPARγ heterodimer.
       
  • Molecular discrimination of Panax ginseng cultivar K-1 using
           pathogenesis-related protein 5 gene

    • Abstract: Publication date: Available online 9 July 2018Source: Journal of Ginseng ResearchAuthor(s): Hongtao Wang, Fengjiao Xu, Xinqi Wang, Woo-Saeng Kwon, Deok-Chun YangAbstractBackgroundThe mixed-cultivation of different Panax ginseng cultivars can cause adverse effects on stability of yield and quality. K-1 is a superior cultivar with good root shape and stronger disease resistance. DNA markers mined from functional genes are clearly desirable for K-1, as they may associate with major traits and can be used for marker-assisted selection to maintain the high quality of Korean ginseng.MethodsFive genes encoding pathogenesis-related (PR) proteins of P. ginseng were amplified and compared for polymorphism mining. Primary, secondary, and tertiary structures of PR5 protein were analyzed by ExPASy-ProtParam, PSSpred, and I-TASSER methods, respectively. A coding single nucleotide polymorphism (SNP)–based specific primer was designed for K-1 by introducing a destabilizing mismatch within the 3′ end. Allele-specific polymerase chain reaction (PCR) and real-time allele-specific PCR assays were conducted for molecular discrimination of K-1 from other cultivars and landraces.ResultsA coding SNP leading to the modification of amino acid residue from aspartic acid to asparagine was exploited in PR5 gene of K-1 cultivar. Bioinformatics analysis showed that the modification of amino acid residue changed the secondary and tertiary structures of the PR5 protein. Primer KSR was designed for specific discrimination of K-1 from other ginseng cultivars and landraces. The developed real-time allele-specific PCR assay enabled easier automation and accurate genotyping of K-1 from a large number of ginseng samples.ConclusionThe SNP marker and the developed real-time allele-specific PCR assay will be useful not only for marker-assisted selection of K-1 cultivar but also for quality control in breeding and seed programs of P. ginseng.
       
  • Comprehensive comparative analysis of chloroplast genomes from seven Panax
           species and development of an authentication system based on
           species-unique single nucleotide polymorphism markers

    • Abstract: Publication date: Available online 22 June 2018Source: Journal of Ginseng ResearchAuthor(s): Van Binh Nguyen, Vo Ngoc Linh Giang, Nomar Espinosa Waminal, Hyun-Seung Park, Nam-Hoon Kim, Woojong Jang, Junki Lee, Tae-Jin YangAbstractBackgroundPanax species are important herbal medicinal plants in the Araliaceae family. Recently, we reported the complete chloroplast genomes and 45S nuclear ribosomal DNA sequences from seven Panax species, two (P.quinquefolius and P.trifolius) from North America and five (P.ginseng, P.notoginseng, P.japonicus, P.vietnamensis, and P.stipuleanatus) from Asia.MethodsWe conducted phylogenetic analysis of these chloroplast sequences with 12 other Araliaceae species and comprehensive comparative analysis among the seven Panax whole chloroplast genomes.ResultsWe identified 1,128 single nucleotide polymorphisms (SNP) in coding gene sequences, distributed among 72 of the 79 protein-coding genes in the chloroplast genomes of the seven Panax species. The other seven genes (including psaJ, psbN, rpl23, psbF, psbL, rps18, and rps7) were identical among the Panax species. We also discovered that 12 large chloroplast genome fragments were transferred into the mitochondrial genome based on sharing of more than 90% sequence similarity. The total size of transferred fragments was 60,331 bp, corresponding to approximately 38.6% of chloroplast genome. We developed 18 SNP markers from the chloroplast genic coding sequence regions that were not similar to regions in the mitochondrial genome. These markers included two or three species-specific markers for each species and can be used to authenticate all the seven Panax species from the others.ConclusionThe comparative analysis of chloroplast genomes from seven Panax species elucidated their genetic diversity and evolutionary relationships, and 18 species-specific markers were able to discriminate among these species, thereby furthering efforts to protect the ginseng industry from economically motivated adulteration.
       
  • Ginsenoside Rg1 supplementation clears senescence-associated
           β-galactosidase in exercising human skeletal muscle

    • Abstract: Publication date: Available online 21 June 2018Source: Journal of Ginseng ResearchAuthor(s): Jinfu Wu, Suchada Saovieng, I-Shiung Cheng, Tiemin Liu, Shangyu Hong, Chang-Yu Lin, I-Chen Su, Chih-Yang Huang, Chia-Hua KuoAbstractBackgroundGinsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-β-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-β-gal in exercising human skeletal muscle.MethodsTo examine SA-β-gal change, 12 young men (age 21 ± 0.2 years) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% VO2max). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% VO2max) was conducted on another 12 participants (age 23 ± 0.5 years) with the same experimental design.ResultsNo changes of SA-β-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-β-gal in exercised muscle after cycling in the Rg1 trial (p 
       
  • Non-clinical pharmacokinetic behavior of ginsenosides

    • Abstract: Publication date: Available online 18 June 2018Source: Journal of Ginseng ResearchAuthor(s): Hyo-Joong Won, Hyun Il Kim, Taejun Park, Hyeongmin Kim, Kanghee Jo, Hyojin Jeon, Seo Jun Ha, Jung Min Hyun, Aeri Jeong, Jung Sik Kim, Ye Jin Park, Yun Ho Eo, Jaehwi LeeAbstractGinsenosides, the major active ingredients of ginseng and other plants of the genus Panax, have been used as natural medicines in the East for a long time; in addition, their popularity in the West has increased owing to their various beneficial pharmacological effects. There is therefore a wealth of literature regarding the pharmacological effects of ginsenosides. In contrast, there are few comprehensive studies that investigate their pharmacokinetic behaviors. This is because ginseng contains the complicated mixture of herbal materials as well as thousands of constituents with complex chemical properties, and ginsenosides undergo multiple biotransformation processes after administration. This is a significant issue as pharmacokinetic studies provide crucial data regarding the efficacy and safety of compounds. Moreover, there have been many difficulties in the development of the optimal dosage regimens of ginsenosides and the evaluation of their interactions with other drugs. Therefore, this review details the pharmacokinetic properties and profiles of ginsenosides determined in various animal models administered through different routes of administration. Such information is valuable for designing specialized delivery systems and determining optimal dosing strategies for ginsenosides.
       
  • Comparative transcriptome analysis of heat stress responsiveness between
           two contrasting ginseng cultivars

    • Abstract: Publication date: Available online 7 June 2018Source: Journal of Ginseng ResearchAuthor(s): Murukarthick Jayakodi, Sang-Choon Lee, Tae-Jin YangAbstractBackgroundPanax ginseng has been used in traditional medicine to strengthen the body and mental well-being of humans for thousands of years. Many elite ginseng cultivars have been developed, and ginseng cultivation has become well established during the last century. However, heat stress poses an important threat to the growth and sustainable production of ginseng. Efforts have been made to study the effects of high temperature on ginseng physiology, but knowledge of the molecular responses to heat stress is still limited.MethodsWe sequenced the transcriptomes (RNA-Seq) of two ginseng cultivars, Chunpoong (CP) and Yunpoong (YP), which are sensitive and resistant to heat stress, respectively, after 1- and 3-week heat treatments. Differential gene expression and gene ontology enrichment along with profiled chlorophyll contents were performed.ResultsCP is more sensitive to heat stress than YP and exhibited a lower chlorophyll content than YP. Moreover, heat stress reduced the chlorophyll content more rapidly in CP than in YP. A total of 329 heat-responsive genes were identified. Intriguingly, genes encoding chlorophyll a/b–binding proteins, WRKY transcription factors, and fatty acid desaturase were predominantly responsive during heat stress and appeared to regulate photosynthesis. In addition, a genome-wide scan of photosynthetic and sugar metabolic genes revealed reduced transcription levels for ribulose 1,5-bisphosphate carboxylase/oxygenase under heat stress, especially in CP, possibly attributable to elevated levels of soluble sugars.ConclusionOur comprehensive genomic analysis reveals candidate loci/gene targets for breeding and functional studies related to developing high temperature–tolerant ginseng varieties.
       
 
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