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Journal Cover Phytotherapy Research
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   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
   Published by John Wiley and Sons Homepage  [1582 journals]
  • Resistance-modifying Activity in Vinblastine-resistant Human Breast Cancer
           Cells by Oligosaccharides Obtained from Mucilage of Chia Seeds (Salvia
    • Authors: Daniel G. Rosas-Ramírez; Mabel Fragoso-Serrano, Sonia Escandón-Rivera, Alba L. Vargas-Ramírez, Juan P. Reyes-Grajeda, Manuel Soriano-García
      Abstract: The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was used to purify the hydrolysis degradation products. All compounds were tested in eight different cancer cell lines and Vero cells. All compounds were noncytotoxic at the concentration tested against the drug-sensitive and multidrug-resistant cells (IC50 > 29.2 μM). For the all products, a moderate vinblastine-enhancing activity from 4.55-fold to 6.82-fold was observed. That could be significant from a therapeutic perspective. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-20T01:21:37.820246-05:
      DOI: 10.1002/ptr.5815
  • Hypoglycemic and Antihyperglycemic Activities of Nine Medicinal Herbs Used
           as Antidiabetic in the Region of Lubumbashi (DR Congo)
    • Authors: Bakari Amuri; Mwamba Maseho, Lumbu Simbi, Philippe Okusa, Pierre Duez, Kahumba Byanga
      Abstract: The aim of this study was to assess the hypoglycemic and antihyperglycemic activities of nine plants used as antidiabetic treatments in Lubumbashi and its surroundings. Those are Albizia adianthifolia, Azanza garckeana, Cassia occidentalis, Cassia sieberiana, Erythrina abyssinica, Gladiolus klattianus, Rauvolfia caffra, Strychnos spinosa, and Vitex madiensis. Aqueous extracts, obtained by decoction and maceration, were administered (500 mg/kg) per os to guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral glucose tolerance test (OGTT) conditions (glucose, 2 g/kg; follow-up over 210 min). For OGTT experiments, area under the curve of blood glucose levels, maximum glucose concentration (Cmax), and time to reach Cmax (Tmax) were used to compare test groups with the control conditions (glucose group). In hypoglycemic tests, only three species induced significant (p 
      PubDate: 2017-04-20T00:50:33.378578-05:
      DOI: 10.1002/ptr.5814
  • Effects of Avocado (Persea americana) on Metabolic Syndrome: A
           Comprehensive Systematic Review
    • Authors: Jamshid Tabeshpour; Bibi Marjan Razavi, Hossein Hosseinzadeh
      Abstract: Metabolic syndrome (MetS) is a clustering of risk factors including high blood glucose, dyslipidemia, hypertension, and obesity that lead to the increased risk of type 2 diabetes mellitus and cardiovascular diseases (CVDs), which are among leading causes of death in the world. Metabolic syndrome increases the risk of type 2 diabetes mellitus and CVDs by approximately five and three folds, respectively. Therefore, it is of vital importance to manage such conditions with herbal options which have less undesirable adverse effects and may be more efficacious in comparison with synthetic options. Avocado is a well-known source of carotenoids, minerals, phenolics, vitamins, and fatty acids. The lipid-lowering, antihypertensive, antidiabetic, anti-obesity, antithrombotic, antiatherosclerotic, and cardioprotective effects of avocado have been demonstrated in several studies. In this review, we aimed to find out avocado's pharmacological effects on different components of MetS. Moreover, this review report is performed on the MetS effects of peel, seed, flesh, and leaves of avocado. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-10T02:20:47.980408-05:
      DOI: 10.1002/ptr.5805
  • Effect of Natural β-Glucosidase Inhibitors in Reducing Toxicity of
           Amygdalin in Persicae Semen
    • Authors: Chao Liu; Xia Li, Honggai Yang, Xinhui Mao, Juan Wang, Wenyuan Gao
      Abstract: Amygdalin can be decomposed into hydrocyanic acid, which is the primary source of Persicae Semen toxicity, by gut flora. Here, the inhibitory activity of β-glucosidase for test herb extracts was first determined and compared. In turn, optimization of the ratio of substrate and inhibitor in vitro and LD50 values of extracts, serum and liver contents of amygdalin in vivo was measured. Lycii Cortex was found to be the best inhibitory activity for β-glucosidase. The ratio of amygdalin-to-Lycii Cortex extract of 7.19:8.18 (mmol L−1/mg mL−1) can be relatively suitable for inhibiting β-glucosidase activity in test in vitro reaction system. After mixed with Lycii Cortex extract, the toxicity of Persicae Semen ethanol extract in mice is significantly reduced and more amygdalin can be absorbed into the bloodstream. The study provides useful information for reducing toxicity of Persicae Semen and suggests how to better use these natural β-glucosidase inhibitors in the utilization of glycosides and aglycones. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-09T23:45:28.901816-05:
      DOI: 10.1002/ptr.5798
  • Auraptene Induces Apoptosis via Myeloid Cell Leukemia 1-Mediated
           Activation of Caspases in PC3 and DU145 Prostate Cancer Cells
    • Authors: Jae Chul Lee; Eun Ah Shin, Bonglee Kim, Bo-Im Kim, Mahsa Chitsazian-Yazdi, Mehrdad Iranshahi, Sung-Hoon Kim
      Abstract: Although auraptene, a prenyloxy coumarin from Citrus species, was known to have anti-oxidant, anti-bacterial, antiinflammatory, and anti-tumor activities, the underlying anti-tumor mechanism of auraptene in prostate cancers is not fully understood to date. Thus, in the present study, we have investigated the anti-tumor mechanism of auraptene mainly in PC3 and DU145 prostate cancer cells, because auraptene suppressed the viability of androgen-independent PC3 and DU145 prostate cancer cells better than androgen-sensitive LNCaP cells. Also, auraptene notably increased sub-G1 cell population and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells as features of apoptosis in two prostate cancer cells compared with untreated control. Consistently, auraptene cleaved poly(ADP-ribose) polymerase, activated caspase-9 and caspase-3, suppressed the expression of anti-apoptotic proteins, including Bcl-2 and myeloid cell leukemia 1 (Mcl-1), and also activated pro-apoptotic protein Bax in both prostate cancer cells. However, Mcl-1 overexpression reversed the apoptotic effect of auraptene to increase sub-G1 population and induce caspase-9/3 in both prostate cancer cells. Taken together, the results support scientific evidences that auraptene induces apoptosis in PC3 and DU145 prostate cancer cells via Mcl-1-mediated activation of caspases as a potent chemopreventive agent for prostate cancer prevention and treatment. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T05:41:46.587499-05:
      DOI: 10.1002/ptr.5810
  • Anticancer Properties of Solamargine: A Systematic Review
    • Authors: Fatemeh Kalalinia; Iman Karimi-Sani
      Abstract: Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and enough effective for cancer prevention. Solamargine, a steroidal alkaloid glycoside found in Solanum species such as Solanum nigrum, displayed several therapeutic activities. We aim to review the use of solamargine in experimental cancer studies. Articles published in biology journals between 1975 and 2017 were retrieved from PubMed, Scopus, and Web of Science using relevant keywords. The scientific papers mainly focusing on solamargine with therapeutic efficacies against cancers were identified and tabulated. In addition, the reliability of experimental findings was determined under “Risk of Bias” criteria. The author manually reviewed 33 articles; 27 articles were found concerning the anti-cancer potential in cancer cells. Solamargine has been found to possess anticancer activities via its effect on a variety of biological pathways including cell survival pathways, tumor suppressor pathways, caspase activation pathway, mitochondrial pathways, death receptor pathways, protein kinase pathways, and signal pathways, which promote invasion/migration and multi drug resistance. Solamargine can be an anticancer agent candidate when complementary scientific evidences become available. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T04:44:46.289808-05:
      DOI: 10.1002/ptr.5809
  • The Clinical Efficacy and Adverse Effects of Interferon Combined with
           Matrine in Chronic hepatitis B: A Systematic Review and Meta-Analysis.
    • Authors: Xiaotong Wang; Haixiong Lin, Ren Zhang
      Abstract: Currently, many studies have demonstrated certain beneficial effects of interferon (IFN) combined with matrine (Mat) for chronic hepatitis B (CHB) in China. However, the evidence from these randomized control trials is still controversial. Therefore, the aim of this meta-analysis was to explore the efficacy and safety of Mat combined with IFN for CHB. We performed a systematic search of seven databases to identify all randomized controlled trials that treated CHB with IFN or IFN plus Mat from their start date to September 30, 2015. The clinical efficacy and adverse effects were evaluated. Nine studies involving 1089 participants were included. Compared with IFN monotherapy, IFN 5 MU combined with Mat 150 mg augmented the hepatitis B e-antigen negative conversion rate after 3-month treatment [relative ratio (RR) = 1.41; 95% confidence interval (CI) (1.18, 1.69), p = 0.0002] and after 12-month treatment [RR = 1.96; 95% CI (1.21, 3.19), p = 0.006], hepatitis B virus DNA negative conversion rate after 3-month treatment [RR = 1.37; 95% CI (1.16, 1.62), p = 0.0002] and after 12-month treatment [RR = 1.96; 95% CI (1.21, 3.19), p = 0.006], hepatitis B virus e antibody (anti-HBe) conversion rate after 3-month treatment [RR = 1.47; 95% CI (1.19, 1.81), p = 0.0003], and AST level after 3-week treatment [weighted mean difference = −22; 95% CI (−40.41, −3.59), p = 0.02]. Furthermore, IFN 3 MU 3 months combined with Mat 150 mg after 2-month treatment reduced the risk of leucopenia and thrombocytopenia [RR = 0.55; 95% CI (0.36, 0.85), p = 0.007]. Unfortunately, all of the included trials were not in favor of hepatitis B surface antigen (HBsAg) negative conversion rate or influenza-like symptoms. Combination therapy with IFN plus Mat exhibited better clinical efficacy and fewer adverse effects than did IFN monotherapy in patients with CHB, except in the improvement of HBsAg negative conversion rate and influenza-like symptoms. Given the poor methodological quality of the evidence currently available, future high-quality, three-blinded randomized control trials are necessary to confirm these results. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T04:00:47.789595-05:
      DOI: 10.1002/ptr.5808
  • Epimedii Herba: A Promising Herbal Medicine for Neuroplasticity
    • Authors: Jae-Heung Cho; Jae-Young Jung, Beom-Joon Lee, Kyungjin Lee, Jae-Woo Park, Youngmin Bu
      Abstract: Epimedii Herba (EH) is an herbal medicine originating from several plants of the genus Epimedium. It is a major therapeutic option for kidney yang deficiency syndrome, which is closely related to androgen hormones and also has been used to treat hemiplegia following a stroke in traditional medicine of Korea and PR China. To date, many clinical and basic researches of EH have shown the activities on functional recovery from brain diseases. Recently, neuroplasticity, which is the spontaneous reaction of the brain in response to diseases, has been shown to accelerate functional recovery. In addition, androgen hormones including testosterone are known to be the representative of neuroplasticity factors in the brain recovery processes. In this review, we described the neuro-pharmacological activities of EH, focusing on neuroplasticity. Thirty-three kinds of papers from MEDLINE/PubMed, EMBASE, and CNKI were identified and analyzed. We categorized the results into five types based on neuroplasticity mechanisms and presented the definition of each category and briefly described the results of these papers. Altogether, we can suggest that neuroplasticity is a novel viewpoint for guiding future brain research of EH and provide the evidence for the development of new clinical applications using EH in the treatment of brain diseases. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T02:58:33.631475-05:
      DOI: 10.1002/ptr.5807
  • Diterpenes and Their Derivatives as Potential Anticancer Agents
    • Authors: Muhammad Torequl Islam
      Abstract: As therapeutic tools, diterpenes and their derivatives have gained much attention of the medicinal scientists nowadays. It is due to their pledging and important biological activities. This review congregates the anticancer diterpenes. For this, a search was made with selected keywords in PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society and miscellaneous databases from January 2012 to January 2017 for the published articles. A total 28, 789 published articles were seen. Among them, 240 were included in this study. More than 250 important anticancer diterpenes and their derivatives were seen in the databases, acting in the different pathways. Some of them are already under clinical trials, while others are in the nonclinical and/or pre-clinical trials. In conclusion, diterpenes may be one of the lead molecules in the treatment of cancer. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-28T02:58:40.923387-05:
      DOI: 10.1002/ptr.5800
  • Bergamot (Citrus bergamia) Essential Oil Inhalation Improves Positive
           Feelings in the Waiting Room of a Mental Health Treatment Center: A Pilot
    • Authors: Xuesheng Han; Jacob Gibson, Dennis L. Eggett, Tory L. Parker
      Abstract: Mental health issues have been increasingly recognized as public health problems globally. Their burden is projected to increase over the next several decades. Additional therapies for mental problems are in urgent need worldwide due to the limitations and costs of existing healthcare approaches. Essential oil aromatherapy can provide a cost-effective and safe treatment for many mental problems. This pilot study observed the effects of bergamot essential oil inhalation on mental health and well-being, as measured by the Positive and Negative Affect Scale, in a mental-health treatment center located in Utah, USA. Fifty-seven eligible participants (50 women, age range: 23–70 years) were included for analysis. Fifteen minutes of bergamot essential oil exposure improved participants' positive feelings compared with the control group (17% higher). Unexpectedly, more participants participated in experimental periods rather than control periods, suggesting even brief exposure to essential oil aroma may make people more willing to enroll in clinical trials. This study provides preliminary evidence of the efficacy and safety of bergamot essential oil inhalation on mental well-being in a mental health treatment center, suggesting that bergamot essential oil aromatherapy can be an effective adjunct treatment to improve individuals' mental health and well-being. © 2017 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2017-03-24T02:21:18.615804-05:
      DOI: 10.1002/ptr.5806
  • Standardized Sophora pachycarpa Root Extract Enhances Osteogenic
           Differentiation in Adipose-derived Human Mesenchymal Stem Cells
    • Authors: Samaneh Mollazadeh; Vajiheh Neshati, Bibi Sedigheh Fazly Bazzaz, Mehrdad Iranshahi, Majid Mojarrad, Hojjat Naderi-Meshkin, Mohammad Amin Kerachian
      Abstract: Bone defect is an important topic in public health. Novel therapies are based on osteogenic induction by natural antiosteoporotic compounds including plant-derived estrogens. In the current study, the osteogenic potential of Sophora pachycarpa root extract (SPRE) was explored on human adipose-derived mesenchymal stem cells. Herein, adipose-derived mesenchymal stem cells were osteoinducted in the presence of increased concentrations of the extract for 21 days. Then, cell viability was evaluated by MTT assay, and the differentiated cells were stained by Alizarin Red S for calcium deposition and subjected to alkaline phosphatase (ALP) assay for enzymatic activity. To assess the expression of bone-related genes, treated cells were evaluated by real-time polymerase chain reaction. The MTT test demonstrated that SPRE had no toxic effects on the cell viability. Treating the cells with SPRE noticeably promoted ALP activity, mineralization, and mRNA expression of runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). Additionally, cells subjected to 0.1 μg/mL SPRE showed the highest osteogenic effects. According to high-performance liquid chromatography fingerprinting of SPRE, the osteoprotective effects of SPRE is probably due to presence of phytochemicals with estrogen-like activity in the extract. Thus, SPRE might be a suitable therapeutic agent for bone defects therapy in the future research. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-24T01:50:33.865979-05:
      DOI: 10.1002/ptr.5803
  • The Effect of Butin on the Vitiligo Mouse Model Induced by Hydroquinone
    • Authors: Shi-Xia Huo; Qiong Wang, Xin-Min Liu, Chun-Hui Ge, Li Gao, Xiao-Ming Peng, Ming Yan
      Abstract: Vernonia anthelmintica (L.) Willd has been traditionally used in the treatment of vitiligo in Uyghur medicine. This study used butin, the main component of V. anthelmintica, to study the influence on hydroquinone-induced vitiligo in mice. The animals were randomly divided into six groups: control, model, 8-methoxypsoralen (8-MOP, 4.25 mg/kg), and butin (0.425, 4.25, and 42.5 mg/kg) groups. The number of melanin-containing hair follicles, basal layer melanocytes, melanin-containing epidermal cells, the expression of tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1), the malondialdehyde (MDA), and cholinesterase (CHE) activity in serum were measured. Our results indicated that compared with the model group, the melanin-containing hair follicles, the expression of TYR and TRP-1 increased, the activity of CHE decreased after treatment with 8-MOP and all doses of butin (p 
      PubDate: 2017-03-21T02:35:42.507836-05:
      DOI: 10.1002/ptr.5794
  • Alantolactone and Isoalantolactone Prevent Amyloid β25–35-induced
           Toxicity in Mouse Cortical Neurons and Scopolamine-induced Cognitive
           Impairment in Mice
    • Authors: Ji Yeon Seo; Soon Sung Lim, Jiyoung Kim, Ki Won Lee, Jong-Sang Kim
      Abstract: Given the evidence for detoxifying/antioxidant enzyme-inducing activities by alantolactone (AL) and isoalantolactone (IAL), the purpose of this study was to investigate the effects of AL and IAL on Aβ25–35-induced cell death in mouse cortical neuron cells and to determine their effects on scopolamine-induced amnesia in mice. Our data demonstrated that both compounds effectively attenuated the cytotoxicity of Aβ25–35 (10 μM) in neuronal cells derived from the mouse cerebral cortex. It was also found that the production of intracellular reactive oxygen species, including superoxide anion induced by Aβ25–35, was inhibited. Moreover, the administration of the sesquiterpenes reversed scopolamine-induced cognitive impairments as assessed by Morris water, Y-maze, and the passive avoidance tests, and the compounds decreased acetylcholinesterase (AChE) activities in a dose-dependent manner. Interestingly, AL and IAL did not improve scopolamine-induced cognitive deficit in Nrf2−/− mice, suggesting that memory improvement by sesquiterpenes was mediated not only by the activation of the Nrf2 signaling pathway but also by their inhibitory activity against AChE. In conclusion, our results showed that AL and IAL had neuroprotective effects and reversed cognitive impairments induced by scopolamine in a mouse model. Therefore, AL and IAL deserve further study as potential therapeutic agents for reactive oxygen species-related neurodegenerative diseases. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-21T01:59:40.08499-05:0
      DOI: 10.1002/ptr.5804
  • Effectiveness of Ageratina pichinchensis Extract in Patients with
           Vulvovaginal Candidiasis. A Randomized, Double-Blind, and Controlled Pilot
    • Authors: Ofelia Romero-Cerecero; Ana Laura Islas-Garduño, Alejandro Zamilpa, Jaime Tortoriello
      Abstract: Previous clinical studies have demonstrated the antifungal effectiveness of Ageratina pichinchensis extracts when topically administered to patients with dermatomycosis. The objective of this study was to evaluate the effectiveness and tolerability of a 7% standardized extract of A. pichinchensis (intravaginal) in patients with vulvovaginal candidiasis. The extract was standardized in terms of its encecalin content and administered during 6 days to patients with Candida albicans-associated vulvovaginitis. The positive control group was treated with Clotrimazole (100 mg). On day 7 of the study, a partial evaluation was carried out; it demonstrated that 94.1% of patients treated with Clotrimazole and 100% of those treated with the A. pichinchensis extract referred a decrease or absence of signs and symptoms consistent with vulvovaginal candidiasis. In the final evaluation, 2 weeks after concluding administration, 86.6% of patients in the control group and 81.2% (p = 0.65) of those treated with the A. pichinchensis extract demonstrated therapeutic success. Statistical analysis evidenced no significant differences between the two treatment groups. With the results obtained, it is possible to conclude that the standardized extract from A. pichinchensis, intravaginally administered, showed therapeutic and mycological effectiveness, as well as tolerability, in patients with vulvovaginal candidiasis, without noting statistical differences in patients treated with Clotrimazole. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-16T03:41:56.934535-05:
      DOI: 10.1002/ptr.5802
  • Ethanol Extract of Pinus koraiensis Leaf Ameliorates Alcoholic Fatty Liver
           via the Activation of LKB1–AMPK Signaling In Vitro and In Vivo
    • Authors: Sang-Hyuk Hong; Hyemin Lee, Hyo-Jung Lee, Bonglee Kim, Min-Ho Nam, Bum-Sang Shim, Sung-Hoon Kim
      Abstract: Although Pinus koraiensis leaf (PKL) was reported for its anti-diabetes, anti-obesity and anticancer effects as a folk remedy, the inhibitory effect of PKL on alcoholic fatty liver has never been elucidated yet. This study investigated the molecular mechanisms of PKL on alcoholic fatty liver in HepG2 cells, Sprague Dawley (SD) rats and Imprinting Control Region (ICR) mice. Pinus koraiensis leaf increased phosphorylation of liver kinase B1 (LKB1)/AMP-activated protein kinase signaling, low-density lipoprotein receptor and decreased fatty acid biosynthesis-related proteins such as sterol regulatory element-binding protein 1c, fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase in HepG2 cells. In SD rats with 25% alcohol-induced fatty liver, PKL suppressed the levels of aspartate aminotransferase and triglyceride and also enhanced the activities of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione s-transferase compared with untreated control. Furthermore, PKL increased serum alcohol dehydrogenase and serum aldehyde dehydrogenase, but decreased serum alcohol concentration in ICR mice after alcohol administration. Consistently, histochemical analysis revealed that PKL attenuated alcohol-induced fatty liver in SD rats. Overall, these findings suggest that PKL ameliorates alcohol-induced fatty liver via activation of LKB1–AMP-activated protein kinase and modulation of proteins related to lipogenesis synthesis, cholesterol synthesis and fatty acid oxidation. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-16T02:11:09.2809-05:00
      DOI: 10.1002/ptr.5801
  • A Polyphenol-rich Pomegranate Fruit Extract Suppresses NF-κB and IL-6
           Expression by Blocking the Activation of IKKβ and NIK in Primary Human
    • Authors: Abdul Haseeb; Nazir M. Khan, Omer S. Ashruf, Tariq M. Haqqi
      Abstract: Pomegranate fruit extract (PE) rich in polyphenols has been shown to exert chondroprotective effects, but the mechanism is not established. Here, we used an in vitro model of inflammation in osteoarthritis (OA) to investigate the potential of PE to suppress interleukin 1 beta (IL-1β)-stimulated expression of inflammatory cytokine IL-6, generation of reactive oxygen species (ROS) levels, and investigated the mechanism of NF-κB inhibition by analyzing the activation of the kinases upstream of IκBα in primary human chondrocytes. Total and phosphorylated forms of kinases and expression of IL-6 were determined at protein and mRNA levels by western immunoblotting and Taqman assay, respectively. Dihydrorhodamine 123 staining estimated ROS generation. Pomegranate fruit extract inhibited the mRNA and protein expression of IL-6, generation of ROS, and inhibited the IL-1β-mediated phosphorylation of inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), expression of IKKβ mRNA, degradation of IκBα, and activation and nuclear translocation of NF-κB/p65 in human chondrocytes. Importantly, phosphorylation of NF-κB-inducing kinase was blocked by PE in IL-1β-treated human OA chondrocytes. Taken together, these data suggest that PE exerts the chondroprotective effect(s) by suppressing the production of IL-6 and ROS levels. Inhibition of NF-κB activation by PE was blocked via modulation of activation of upstream kinases in human OA chondrocytes. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-09T02:30:51.812358-05:
      DOI: 10.1002/ptr.5799
  • Effect of Ziziphus jujube Fruit Infusion on Lipid Profiles, Glycaemic
           Index and Antioxidant Status in Type 2 Diabetic Patients: A Randomized
           Controlled Clinical Trial
    • Authors: Zeinab Yazdanpanah; Akram Ghadiri-Anari, Alireza Vahidi Mehrjardi, Ali Dehghani, Hadi Zare Zardini, Azadeh Nadjarzadeh
      Abstract: This study was designed to assess the effects of Ziziphus jujube fruit (ZJF) infusion on lipid profiles, glycaemic control and antioxidant status in patients with type 2 diabetes mellitus (T2DM). In this randomized controlled clinical trial, 116 participants with T2DM (older than 30 years) were assigned to consume a balanced diet or diet plus ZJF infusion (10 g/100 mL boiling water) three times/day before main meals for 12 weeks. Diet was designed to be energy restricted (500 kcal/day deficit from estimated energy requirements), and macronutrient content was similar in both groups (55% carbohydrate, 15% protein and 30% fat). The consumption of ZJF infusion compared with the control group was associated with significant improvement in glycosylated haemoglobin (−0.68 ± 0.65 vs. −0.44 ± 0.55%; p = 0.03), total cholesterol (−24.29 ± 28.89 vs. −11.21 ± 29.98 mg/dL; p = 0.02), triglycerides (−43.3 ± 39.26 vs. −27.16 ± 46.84 mg/dL; p = 0.05), low-density lipoprotein cholesterol (−19.85 ± 27.62 vs. −6.55 ± 27.82 mg/dL; p = 0.01), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (−0.56 ± 0.80 vs. −0.2 ± 0.72; p = 0.01) and total cholesterol to high-density lipoprotein cholesterol ratios (−0.73 ± 0.94 vs. −0.35 ± 0.77; p = 0.02). ZJF had beneficial effects on glycosylated haemoglobin and lipid profile in T2DM patients. Further research is needed to identify the mechanism of ZJF action on glucose and lipid metabolism. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-07T21:25:27.243385-05:
      DOI: 10.1002/ptr.5796
  • The Impact of Green Tea Supplementation on Anthropometric Indices and
           Inflammatory Cytokines in Women with Polycystic Ovary Syndrome
    • Authors: Esmat Mombaini; Sima Jafarirad, Durdana Husain, Mohammad Hossein Haghighizadeh, Parivash Padfar
      Abstract: The present study aimed to determine the effect of a green tea supplement on anthropometric indices and inflammatory factors in women with polycystic ovary syndrome (PCOS). In this randomized clinical trial, 45 women with PCOS were randomly allocated into two groups receiving green tea tablets or placebo. The period of intervention was 45 days. The serum levels of interleukin 6, high-sensitivity C-reactive protein, and tumor necrosis factor α were measured before and after intervention period using the related kits. Anthropometric indices also were measured. The mean of body mass index, weight, waist circumference, and body fat percentage in the green tea group were reduced significantly. However, no significant difference was observed between the two groups. Also, there was no significant effect on the levels of inflammatory factors. The present results suggest that daily consumption of green tea tablets did not cause any effect on inflammation biomarkers in PCOS women. However, it may be effective as a complementary treatment for weight control in these women. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-02-28T05:40:47.414511-05:
      DOI: 10.1002/ptr.5795
  • Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation-Induced
           Mouse Memory Impairment Model
    • Authors: Cong Lu; Zhe Shi, Liming Dong, Jingwei Lv, Pan Xu, Yinghui Li, Lina Qu, Xinmin Liu
      Abstract: Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory-improving effects in normal mice and scopolamine-induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 μmol/kg; 40 μmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14-day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homogenized, and levels and activities of antioxidant defense biomarkers were evaluated to determine the level of oxidative stress. The results revealed that Rh1 prevented cognitive impairment induced by SD, and its ability to reduce oxidative stress in cortex and hippocampus may contribute to the mechanism of action. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-02-28T01:15:50.141583-05:
      DOI: 10.1002/ptr.5797
  • Radicol, a Novel Trinorguaiane-Type Sesquiterpene, Induces
           Temozolomide-Resistant Glioma Cell Apoptosis via ER Stress and Akt/mTOR
           Pathway Blockade
    • Authors: Zong-Yang Li; Ce Zhang, Lei Chen, Bao-Dong Chen, Qing-Zhong Li, Xie-Jun Zhang, Wei-Ping Li
      Abstract: Glioblastoma multiforme (GBM) is the most frequent, lethal and aggressive tumour of the central nervous system (CNS) in adults. Multidrug resistance (MDR) results in undesirable prognosis during GBM chemotherapy. In this study, we determined that Radicol (RAD), a novel trinorguaiane-type sesquiterpene originally isolated from the root of Dictamnus radicis Cortex, exhibited potently cytotoxic effect on temozolomide (TMZ)-resistant GBM cell lines in a dose-dependent manner. Radicol-induced apoptosis was confirmed with Hoechst 33342/propidium iodide and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labelling (TUNEL) staining. Studies investigating the mechanism revealed that RAD triggered an attenuation of protein disulphide isomerase (PDI) and induced the unmitigated unfolded protein response (UPR) and lethal endoplasmic reticulum (ER) stress. Simultaneously, we further demonstrated that RAD suppressed the activation of Akt/mTOR/p70S6K phosphorylation by up-regulating the induction of glycogen synthase kinase-3β (GSK-3β). These results established a link between RAD-induced ER stress and inhibition of the Akt/mTOR/p70S6K pathway, and the attenuation of PDI and activation of GSK-3β might be the synergistic target of antineoplastic effects during RAD-induced apoptosis. These findings suggested that RAD, possessing multiple cytotoxicity targets, low molecular weight and high lipid solubility, could be a promising agent for the treatment of malignant gliomas. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-02-27T05:45:34.522716-05:
      DOI: 10.1002/ptr.5793
  • Phytochemical Characterization, Antibacterial, Acetylcholinesterase
           Inhibitory and Cytotoxic Properties of Cryptostephanus vansonii, an
           Endemic Amaryllid
    • Authors: Mack Moyo; Adeyemi O. Aremu, Jude C. Chukwujekwu, Jiri Gruz, Jiri Skorepa, Karel Doležal, Cuthbert A.T. Katsvanga, Johannes Van Staden
      Abstract: Cryptostephanus vansonii I. Verd., an endemic Amaryllidaceae species from Zimbabwe, was evaluated for its acetylcholinesterase (AChE) inhibitory and cytotoxicity properties using Ellman's colorimetric method and the tetrazolium-based colorimetric assay against Vero monkey kidney cells, respectively. The plant extracts were also evaluated for their antibacterial activity against five bacteria. Furthermore, phytochemical profiles of the extracts were determined using ultra-high performance liquid chromatography coupled with tandem mass spectrometry analysis. A plant part-dependent AChE inhibitory activity was observed, in the order, root > rhizome > basal leaf > leaf. Overall, C. vansonii extracts exhibited better antibacterial activity against Gram-negative compared with Gram-positive bacteria. Cytotoxic effects were not detected in Vero monkey kidney cell lines suggesting the possible absence of toxophores in C. vansonii extracts. Similar to the trend in biological activity, a distinct plant part-dependent variation in hydroxybenzoates, hydroxycinnamates and flavonoids was observed in the plant extracts. In addition, 5-hydroxymetylfurfural and eucomic acid were detected in the different plant parts of C. vansonii. The results of the present study provide valuable AChE inhibition activity, toxicological and phytochemical profiles of C. vansonii. Further studies on isolation of bioactive compounds and their subsequent evaluation in other pharmacological and toxicological model systems are required. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-02-20T02:55:24.917042-05:
      DOI: 10.1002/ptr.5788
  • Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates
           Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated
           Reactive Oxygen Generation
    • Authors: Chan Hum Park; Sung Ho Shin, Eun Kyeong Lee, Dae Hyun Kim, Min-Jo Kim, Seong-Soo Roh, Takako Yokozawa, Hae Young Chung
      Abstract: The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-02-16T22:30:39.994464-05:
      DOI: 10.1002/ptr.5789
  • Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib
           through Abrogation of CREB and c-Jun Activation in Renal Cell Carcinoma
    • Abstract: Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase-3; caused poly(ADP-ribose) polymerase cleavage; abrogated the expression of B-cell lymphoma 2, B-cell lymphoma extra large, survivin, inhibitors of apoptosis proteins-1/2, cyclooxygenase-2, cyclin D1, matrix metallopeptidase-9, and vascular endothelial growth factor; and upregulated pro-apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element-binding protein and c-Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.
  • Supplementation with Herbal Extracts to Promote Behavioral and
           Neuroprotective Effects in Experimental Models of Parkinson's Disease: A
           Systematic Review
    • Abstract: Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti-apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antifungal Activity of Gallic Acid In Vitro and In Vivo
    • Abstract: Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.
  • One Plant, Many Uses: A Review of the Pharmacological Applications of
           Morinda citrifolia
    • Abstract: Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.
  • Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly
           Through Regulation of the TLR4/MAPK/NF-κB Axis via AMPK Activation
    • Abstract: Acute lung injury (ALI) often leads to high mortality, and there is as yet no effective drug treatment. The present study aimed to investigate protective effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1, 10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose-dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1β, IL-6, TNF-α and HMGB1) release and higher MPO activity in lung tissues induced by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not only increased the phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also inhibited the activation of MAPKs and nuclear factor κB (NF-κB) signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down-regulating TLR4/MAPK/NF-κB signalling pathways. Copyright © 2017 John Wiley & Sons, Ltd.
  • Phytochemistry and Pharmacology of Phyllanthus niruri L.: A Review
    • Abstract: Phyllanthus niruri, a typical member of family Euphorbiaceae, is a small annual herb found throughout the tropical and subtropical regions of both hemispheres. The genus Phyllanthus has been used in traditional medicine for its wide range of pharmacological activities like antimicrobial, antioxidant, anticancer, antiinflammatory, antiplasmodial, antiviral, diuretic and hepatoprotective. This review summarizes the information about morphological, biochemical, ethanobotanical, pharmacological, biological and toxicological activities with special emphasis on mechanism of anticancer activity of P. niruri. Gaps in previous studies such as taxonomic inconsistency of P. niruri, novel phytochemicals and their therapeutic properties, especially mechanisms of anticancerous activity and market products available, have been looked into and addressed. Scientific information related to 83 phytochemicals (including many novel compounds detected recently by the authors) has been provided in a very comprehensive manner. Copyright © 2017 John Wiley & Sons, Ltd.
  • Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P-gp
           In Vitro
    • Abstract: Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process. An ultra performance liquid chromatography–electrospray ionization–mass spectrometry (UPLC-ESI-MS) analytical method was established to determine the intracellular concentration of TP. In order to study the role of efflux transporters of P-gp and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results showed that GA could enhance the elimination of TP and reduce the TP accumulation in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration of TP; in addition, GA co-incubation with verapamil significantly increased the TP cellular concentration compared with the control group. In conclusion, GA could reduce the accumulation of TP in HK-2 cells, which was related to P-gp. This is probably one of the mechanisms that TP combined with GA to detoxify its toxicity. Copyright © 2017 John Wiley & Sons, Ltd.
  • Inhibition of Prion Propagation by 3,4-Dimethoxycinnamic Acid
    • Abstract: Neurodegenerative diseases are associated with accumulation of amyloid-type protein misfolding products. Prion protein (PrP) is known for its ability to aggregate into soluble oligomers that in turn associate into amyloid fibrils. Preventing the formation of these infective and neurotoxic entities represents a viable strategy to control prion diseases. Numerous attempts to find dietary compounds with anti-prion properties have been made; however, the most promising agent found so far was curcumin, which is poorly soluble and merely bioavailable. In the present work, we identify 3,4-dimethoxycinnamic acid (DMCA) which is a bioavailable coffee component as a perspective anti-prion compound. 3,4-Dimethoxycinnamic acid was found to bind potently to prion protein with a Kd of 405 nM. An in vitro study of DMCA effect on PrP oligomerization and fibrillization was undertaken using isothermal titration calorimetry (ITC), dynamic light scattering (DLS) and circular dichroism (CD) methodologies. We demonstrated that DMCA affects PrP oligomer formation reducing the oligomer content by 30–40%, and enhancing SH-SY5Y cell viability treated with prion oligomers. Molecular docking studies allowed to suggest a site where DMCA is able to bind stabilizing PrP tertiary structure. We suggest that DMCA is a perspective dietary compound for prophylaxis of neurodegenerative diseases that needs further research. Copyright © 2017 John Wiley & Sons, Ltd.
  • Evaluation of Benefit and Tolerability of IQP-CL-101 (Xanthofen) in the
           Symptomatic Improvement of Irritable Bowel Syndrome: A Double-Blinded,
           Randomised, Placebo-Controlled Clinical Trial
    • Abstract: Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown aetiology. There is currently no known cure, and pharmacological interventions are usually targeting symptomatic relief, where natural and herbal remedies also play a role. This study aimed to evaluate the benefit and tolerability of IQP-CL-101 in symptomatic IBS relief. A double-blinded, randomised, placebo-controlled trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME-III criteria for IBS were randomised into two groups, given either two IQP-CL-101 softgels or matching placebo twice daily before main meals. The primary endpoint was the difference in change of IBS Symptom Severity Score (IBS-SSS) after an 8-week intake of IQP-CL-101 compared to placebo. After 8 weeks, subjects on IQP-CL-101 showed a significant reduction in IBS-SSS (113.0 ± 64.9-point reduction) compared to subjects on placebo (38.7 ± 64.5-point reduction) (p 
  • Neuroprotective Natural Products for the Treatment of Parkinson's Disease
           by Targeting the Autophagy–Lysosome Pathway: A Systematic Review
    • Abstract: The autophagy–lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.
  • Nepetoidin B, a Natural Product, Inhibits LPS-stimulated Nitric Oxide
           Production via Modulation of iNOS Mediated by NF-κB/MKP-5 Pathways
    • Abstract: Previous reports showed that nepetoidin B (NTB), a natural product isolated from many herbs, has anti-fungal and anti-bacterial effects. In this study, the antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was determined by MTT assay. The nitric oxide (NO) production was detected by Griess assay. The TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay kits. Protein expressions were tested by western blotting. The transcription activity of inducible nitric oxide synthase (iNOS) was detected by luciferase assay. Immunofluorescence assay was used to observe the visualization of NF-κB/p65 nuclear translocation. NTB and LPS showed no obvious cytotoxic effect on RAW 264.7 cells. NTB remarkably inhibited LPS-induced NO and TNF-α secretion in a concentration-dependent manner while showed no significant effect on IL-6 secretion. NTB inhibited LPS-induced iNOS protein expression and transcription activity without affecting cyclooxygenase-2. Furthermore, NTB suppressed LPS-stimulated NF-κB/p65 phosphorylation and nuclear translocation. In addition, NTB significantly inhibited LPS-induced phosphorylation of JNK1/2 and p38MAPK without affecting ERK1/2. LPS-induced inhibition of mitogen-activated protein kinase phosphatase-5 (MKP-5) was completely reversed by NTB. In conclusion, these results suggested that NTB inhibited LPS-stimulated NO production possibly via modulation of iNOS mediated by MKP-5/NF-κB pathways in RAW 264.7 cells. Copyright © 2017 John Wiley & Sons, Ltd.
  • Polyphenols and Their Role in Obesity Management: A Systematic Review of
           Randomized Clinical Trials
    • Abstract: Polyphenols have been suggested to reduce body weight and modify body composition through different mechanisms. These effects have been extensively studied in animals and in vitro and to a lesser extent in humans. The aim of this review is to consider the association between polyphenols and body weight status by focusing on human intervention studies. We conducted a systematic literature search in MEDLINE (via EBSCOhost), ProQuest CENTRAL, and Cochrane CENTRAL without time restrictions. Randomized controlled trials assessing the effect of polyphenols on weight and/or body composition in the overweight and/or obese population were included. Nineteen studies met our inclusion criteria. Results suggest that further research is required before supporting a potential role of polyphenols in reducing weight in overweight and obese individuals (nine studies showed a significant decrease in weight by a mean of 1.47 ± 0.58 kg). Nevertheless, several studies indicated that polyphenols might be effective in preventing small increases in weight during periods of overfeeding rather than reducing weight as such. The outcomes noted do not yet support polyphenol supplementation as a complementary approach in weight loss diets. Further larger trials with a duration of 12 months or more are needed to elucidate the effect of polyphenols on body weight status. Copyright © 2017 John Wiley & Sons, Ltd.
  • Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the
           Trigeminovascular System
    • Abstract: Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus. As a result, baicalin administration (0.22 mm/kg) alleviated pain responses of migraine rats. It profoundly decreased NO and calcitonin gene-related peptide levels, increased ET levels, and rebuilt the NO/ET balance in migraine rats. Besides, baicalin pretreatment significantly reduced the number, the stained area size, and integrated optical density value of C-fos positive cells. In brief, this paper supports the possibility of baicalin as a potential migraine pharmacotherapy. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf
           Extract. Part I – Preclinical Studies
    • Abstract: One of the Brazilians medicinal plants most cited in ethnopharmacological surveys for the treatment of ulcers and gastric diseases was evaluated for its efficacy and toxicity. Maytenus ilicifolia leaf extract (MIE) was acutely and chronically (180 days) administered to rats, mice, and dogs. Acute tests were antiulcer effect and toxicological trials (observational pharmacological screening, LD50, motor coordination, sleeping time and motor activity). Chronic tests were the following: weight gain/loss and behavioral parameters in rats and mice; estrus cycle, effects on fertility, and teratogenic studies in rats and mutagenic features in mice, in addition to the Ames and micronucleus test. The following parameters were assessed in dogs: weight gain/loss, general physical conditions, water/food consumption, and anatomopathological examination of the organs subsequent to the 180-day treatment. The results showed a clear antiulcer activity for MIE from 70 mg/kg and an absence of toxicological effects in the three animal species, even if given in high doses or over a long period. The present results confirm the antiulcer property and absence of toxicological effects in three animal species of MIE, which is in line with its current popular medicinal use. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf
           Extract Part II—Clinical Study (Phase I)
    • Abstract: Maytenus ilicifolia is a plant widely used in South American folk medicine as an effective anti-dyspeptic agent, and the aim of this study was to evaluate their clinical and toxicological effects in healthy volunteers in order to establish its maximum safe dose. We selected 24 volunteers (12 women and 12 men) between 20 and 40 years of age and put them through clinical/laboratory screening and testing to ascertain their psychomotor functions (simple visual reaction, speed and accuracy, finger tapping tests). M. ilicifolia tablets were administered in increasing weekly dosages, from an initial dose of 100 mg to a final dose of 2000 mg. The volunteers' clinical and biochemical profiles and psychomotor functions were evaluated weekly, and they also completed a questionnaire about any adverse reactions. All subjects completed the study without significant changes in the evaluated parameters. The most cited adverse reactions were xerostomia (dry mouth syndrome) (16.7%) and polyuria (20.8%), with reversal of these symptoms without any intervention during the study. The clinical Phase I study showed that the administration of up to 2000 mg of the extract was well tolerated, with few changes in biochemical, hematological or psychomotor function parameters, and no significant adverse reactions. Copyright © 2017 John Wiley & Sons, Ltd.
  • C-Glycosyl Flavonoids from Beta vulgaris Cicla and Betalains from Beta
           vulgaris rubra: Antioxidant, Anticancer and Antiinflammatory
           Activities—A Review
    • Abstract: The green beet (Beta vulgaris var. cicla L.) and red beetroot (B. vulgaris var. rubra L.) contain phytochemicals that have beneficial effects on human health. Specifically, the green beet contains apigenin, vitexin, vitexin-2-O-xyloside and vitexin-2-O-rhamnoside, while the red beetroot is a source of betaxanthins and betacyanins. These phytochemicals show considerable antioxidant activity, as well as antiinflammatory and antiproliferative activities. Vitexin-2-O-xyloside, in combination with betaxanthins and betacyanins, exerts antiproliferative activity in breast, liver, colon and bladder cancer cell lines, through the induction of both intrinsic and extrinsic apoptotic pathways. A significant body of evidence also points to the role of these phytochemicals in the downregulation of the pro-survival genes, baculoviral inhibitor of apoptosis repeat-containing 5 and catenin beta-1, as well as the genes controlling angiogenesis, hypoxia inducible factor 1A and vascular endothelial growth factor A. The multi-target action of these phytochemicals enhances their anticancer activity. Vitexin-2-O-xyloside, betaxanthins and betacyanins can be used in combination with conventional anticancer drugs to reduce their toxicity and overcome the multidrug resistance of cancer cells. In this review, we describe the molecular mechanisms that enable these dietary phytochemicals to block the proliferation of tumor cells and inhibit their pro-survival pathways. Copyright © 2017 John Wiley & Sons, Ltd.
  • Optimization of Aqueous Extraction and Biological Activity of
           Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model
    • Abstract: Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave-assisted aqueous Harpagophytum extract (1–1000 μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis. In this context, we evaluated the effects on C2C12 and HCT116 viability, and on LPS-induced production of serotonin (5-HT), tumor necrosis factor (TNF)-α, prostaglandin (PG)E2 and 8-iso-prostaglandin (8-iso-PG)F2α. Harpagophytum extract was well tolerated by C2C12 cells, while reduced HCT116 colon cancer cell viability. On the other hand, Harpagophytum extract reduced H2O2-induced (1 mM) reactive oxygen species (ROS) production, in both cell lines, and inhibited LPS-induced colon production of PGE2, 8-iso-PGF2α, 5-HT and TNFα. Concluding, we demonstrated the efficacy of a microwave-assisted Harpagophytum aqueous extract in modulating the inflammatory, oxidative stress and immune response in an experimental model of inflammatory bowel diseases (IBD), thus suggesting a rational use of Harpagophytum in the management and prevention of ulcerative colitis in humans. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antiinflammatory Activity of Cinnamon (Cinnamomum zeylanicum) Bark
           Essential Oil in a Human Skin Disease Model
    • Abstract: The effect of cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) on human skin cells has not been elucidated. Therefore, we investigated the activity of a commercially available CBEO in a validated human dermal fibroblast system, a model of chronic inflammation and fibrosis. We first evaluated the impact of CBEO on 17 protein biomarkers that play critical roles in inflammation and tissue remodeling. The impact of CBEO on genome-wide gene expression was also evaluated. CBEO showed strong anti-proliferative effects on skin cells and significantly inhibited the production of several inflammatory biomarkers, including vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interferon gamma-induced protein 10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by gamma interferon. In addition, CBEO significantly inhibited the production of several tissue remodeling molecules, including epidermal growth factor receptor, matrix metalloproteinase-1, and plasminogen activator inhibitor-1. Macrophage colony-stimulating factor, which is an immunomodulatory protein molecule, was also significantly inhibited by CBEO. Furthermore, CBEO significantly modulated global gene expression and altered signaling pathways, many of which are important in inflammation, tissue remodeling, and cancer biology. The study shows that CBEO is a promising antiinflammatory agent; however, further research is required to clarify its clinical efficacy. © 2017 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
  • Aloe-emodin Induces Apoptosis in Human Liver HL-7702 Cells through Fas
           Death Pathway and the Mitochondrial Pathway by Generating Reactive Oxygen
    • Abstract: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe-emodin on human normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin decreased the viability of HL-7702 cells in a dose-dependent and time-dependent manner. Aloe-emodin induced S and G2/M phase cell cycle arrest in HL-7702 cells. This apoptosis was further investigated by flow cytometry and nuclear morphological changes by DAPI staining, respectively. Moreover, aloe-emodin provoked the production of intracellular reactive oxygen species and the depolarization of mitochondrial membrane potential (MMP). Further studies by western blot indicated that aloe-emodin dose-dependently up-regulated the levels of Fas, p53, p21, Bax/Bcl-2 ratio, and cleaved caspase-3, -8, -9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). Taken together, these results suggest that aloe-emodin inhibits cell proliferation of HL-7702 cells and induces cell cycle arrest and caspase-dependent apoptosis via both Fas death pathway and the mitochondrial pathway by generating reactive oxygen species, indicating that aloe-emodin should be taken into account in the risk assessment for human exposure. Copyright © 2017 John Wiley & Sons, Ltd.
  • The effects of chosen plant extracts and compounds on mesenchymal stem
           cells—a bridge between molecular nutrition and regenerative medicine-
           concise review
    • Abstract: Mesenchymal stem cells (MSC) stand as a promising tool in regenerative medicine because of their high therapeutic potential in treatment of degenerative, metabolic and other types of diseases. The cellular therapies involving MSCs include their isolation mainly from the bone marrow, adipose tissue or umbilical cord and in vitro expansion for further autologous or allogeneic transplantation. Recent studies revealed, that bioactive compounds, naturally occurring in seaweeds, herbs, fruits and vegetables, possess the ability to modulate self-renewal and differentiation potential of adult stem cells, targeting a broad range of intracellular signal transduction pathways. Number of ongoing trials aim to find a herbal extract that may become less toxic and affordable natural therapeutic. Mesenchymal stem cells are treated with crude extracts or individual compounds to investigate its effects and mechanism on stem cells proliferation and differentiation. Deeply investigated, herbal extract which increases tissue regeneration and promotes stem cell growth may be successfully applied in the field of biomaterials. Promoting the endogenous stem cell multipotency and their differentiation potential may additionally support the regenerative processes after MSCs transplantation. The review focuses on the beneficial effects of chosen plant derived substances on MSCs proliferative activity and their osteogenic differentiation potential. Copyright © 2017 John Wiley & Sons, Ltd.
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    • Abstract: No abstract is available for this article.
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