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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  [1612 journals]
  • Characterization of Phase I and Phase II Hepatic Metabolism and Reactive
           Intermediates of Larrea nitida Cav. and Its Lignan Compounds
    • Authors: Hyesoo Jeong; Soolin Kim, Jimin Lee, Jin Young Park, Wenmei Zhou, Xiyuan Liu, So Dam Kim, Yun Seon Song, Chang-Young Jang, Sei-Ryang Oh, Sangho Choi, Minsun Chang
      Abstract: Larrea nitida Cav. (LNC), which belongs to the family Zygophyllaceae, is widely indigenous and used in South America to treat various pathological conditions. It contains the antioxidant and antiinflammatory but toxic nordihydroguaiaretic acid (NDGA) as well as O-methylated metabolite of NDGA (MNDGA) as bioactive compounds. The hepatic metabolism-based toxicological potential of extracts of LNC (LNE), NDGA, and MNDGA has not previously been reported. The present study aimed to characterize the phase I and phase II hepatic metabolism and reactive intermediates of LNE, NDGA, and MNDGA and their effects on the major drug-metabolizing enzymes in vitro and ex vivo. A methanol extract of LNC collected from Chile as well as NDGA and MNDGA isolated from LNE were subjected to metabolic stability assays in liver microsomes in the presence of the cofactors reduced nicotinamide dinucleotide phosphate (NADPH) and/or uridine 5′-diphosphoglucuronic acid (UDPGA). Cytochrome P450 (CYP) inhibition assays were performed using CYP isozyme-specific model substrates to examine the inhibitory activities of LNE, NDGA, and MNDGA, which were expressed as % inhibition and IC50 values. Ex vivo CYP induction potential was investigated in the liver microsomes prepared from the rats intraperitoneally administered with LNE. Glutathione (GSH) adduct formation was monitored by LC-MS3 analysis of the microsomal incubation samples with either NDGA or MNDGA and an excess of GSH to determine the formation of electrophilic reactive intermediates. Both NDGA and MNDGA were stable to NADPH-dependent phase I metabolism, but labile to glucuronide conjugation. LNE, NDGA, and MNDGA showed significant inhibitory effects on CYP1A2, 2C9, 2D6, and/or 3A4, with IC50 values in the micromolar range. LNE was found to be a CYP1A2 inducer in ex vivo rat experiments, and mono- and di-GSH adducts of both NDGA and MNDGA were identified by LC-MS3 analysis. Our study suggests that hepatic clearance is the major elimination route for the lignans NDGA and MNDGA present in LNE. These lignans may possess the ability to modify biomacromolecules via producing reactive intermediates. In addition, LNE, NDGA, and MNDGA are found to be inhibitors for various CYP isozymes such as CYP2C9 and 3A4. Thus, the consumption of LNC as an herbal preparation or NDGA may cause metabolism-driven herb–drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-11-07T05:07:43.144026-05:
      DOI: 10.1002/ptr.5742
  • Polysaccharide of Danggui Buxue Tang, an Ancient Chinese Herbal Decoction,
           Induces Expression of Pro-inflammatory Cytokines Possibly Via Activation
           of NFκB Signaling in Cultured RAW 264.7 Cells
    • Authors: Amy GW Gong; Laura ML Zhang, Candy TW Lam, Miranda L Xu, Huai Y Wang, HQ Lin, Tina TX Dong, Karl WK Tsim
      Abstract: Danggui Buxue Tang (DBT) is an ancient Chinese herbal decoction containing two herbs, Astragali Radix (AR) and Angelicae Sinensis Radix (ASR): this herbal decoction serves as dietary supplement for women during menopause. DBT has been known to modulate immune responses, and its polysaccharide is proposed to be one of the active components. However, the polysaccharide-induced signaling in immune activation is not revealed. Here, we are identifying that the immune activation, triggered by DBT, could be mediated by polysaccharide. In cultured macrophages (RAW 264.7 cells), the application of polysaccharide-enriched extract of DBT significantly increased the expressions of mRNA and protein levels of interleukin-1β, interleukin-6 and tumor necrosis factor. The induction was much stronger than the polysaccharide extract generated singly from AR, or from ASR, or from their simple mixture. The induced cytokine release in cultured macrophage was revealed to be triggered by activation of nuclear factor-kappa B (NF-κB) signaling, including (i) degradation of IkBα; (ii) translocation of NF-κB p65 from cytosol to nuclei; and (iii) activation of NF-κB transcriptional elements. These results verified the possible role of DBT polysaccharide in modulating immune responses. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-11-03T01:15:29.353662-05:
      DOI: 10.1002/ptr.5745
  • The Impact of Resveratrol Supplementation on Blood Glucose, Insulin,
           Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2
           Diabetic Patients with Chronic Periodontitis
    • Authors: Ahmad Zare Javid; Razie Hormoznejad, Hojat allah Yousefimanesh, Mehrnoosh Zakerkish, Mohammad Hosein Haghighi-zadeh, Parvin Dehghan, Maryam Ravanbakhsh
      Abstract: The aim of this study was to investigate the impact of resveratrol supplementation along with non-surgical periodontal treatment on blood glucose, insulin, insulin resistance, triglyceride (TG), and periodontal markers in patients with type 2 diabetes with periodontal disease. In this double-blind clinical trial study, 43 patients with diabetes with chronic periodontitis were participated. Subjects were randomly allocated to intervention and control groups. The intervention and control groups received either 480 mg/day of resveratrol or placebo capsules (two pills) for 4 weeks. Fasting blood glucose, insulin, insulin resistance (homeostasis model assessment of insulin resistance), TGs, and pocket depth were measured in all subjects' pre-intervention and post-intervention. The mean serum levels of fasting insulin and insulin resistance (homeostasis model assessment of insulin resistance) were significantly lower in the intervention group compared with control group (10.42 ± 0.28 and 10.92 ± 0.9; 3.66 ± 0.97 and 4.49 ± 1.56, respectively). There was a significant difference in the mean pocket depth between intervention and control groups (2.35 ± 0.6 and 3.38 ± 0.5, respectively) following intervention. No significant differences were observed in the mean levels of fasting blood glucose and TGs between two groups' post-intervention. It is recommended that resveratrol supplementation may be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease.
      PubDate: 2016-11-03T00:41:03.374538-05:
      DOI: 10.1002/ptr.5737
  • Hovenia Dulcis Extract Reduces Lipid Accumulation in Oleic Acid-Induced
           Steatosis of Hep G2 Cells via Activation of AMPK and PPARα/CPT-1 Pathway
           and in Acute Hyperlipidemia Mouse Model
    • Authors: Bonglee Kim; Moon-Jea Woo, Chul-Soo Park, Sang-Hun Lee, Jin-Soo Kim, Boim Kim, Seho An, Sung-Hoon Kim
      Abstract: Hovenia dulcis Thunb. (HDT) was known to have anti-fatigue, anti-diabetes, neuroprotective, and hepatoprotective effects. In the present study, the anti-fatty liver mechanism of HDT was elucidated in oleic acid (OA)-treated Hep G2 cells and acute hyperlipidemia mouse model using Triton WR-1339. Here, HDT activated p-AMP-activated protein kinase (p-AMPK), proliferator activated receptor-α, carnitine palmitoyltransferase and also inhibited the expression of lipogenesis and cholesterol synthesis proteins, such as 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element binding protein-1c, SREBP-2, and fatty acid synthase in OA-treated Hep G2 cells. Conversely, AMPK inhibitor compound C blocked the anti-fatty liver effect of HDT to induce AMPK phosphorylation and decrease 3-hydroxy-3-methylglutaryl-CoA reductase and lipid accumulation by oil red O staining in OA-treated Hep G2 cells. Additionally, HDT pretreatment protected against the increase of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol and phospholipid in an acute hyperlipidemia mouse model with enhancement of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase activities. Taken together, HDT inhibits OA-induced hepatic lipid accumulation via activation of AMPK and proliferator activated receptor-α/carnitine palmitoyltransferase signaling and enhancement of antioxidant activity as a potent candidate for nonalcoholic fatty liver disease and hyperlipidemia. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-20T05:00:30.987137-05:
      DOI: 10.1002/ptr.5741
  • Role of Medicinal Plants for Liver-Qi Regulation Adjuvant Therapy in
           Post-stroke Depression: A Systematic Review of Literature
    • Authors: Ling-Feng Zeng; Ye Cao, Lu Wang, Yun-Kai Dai, Ling Hu, Qi Wang, Li-Ting Zhu, Wen-Hu Bao, Yuan-Ping Zou, Yun-Bo Chen, Wei-Hua Xu, Wei-Xiong Liang, Ning-Sheng Wang
      Abstract: Current evidence demonstrated certain beneficial effects of medicinal herbs as an adjuvant therapy for post-stroke depression (PSD) in China; Chai-hu (Chinese Thorowax Root, Radix Bupleuri) is an example of a medicinal plant for Liver-Qi regulation (MPLR) in the treatment of PSD. Despite several narrative reports on the antidepressant properties of MPLR, it appears that there are no systematic reviews to summarize its outcome effects. Therefore, the aim of this review was to assess the effectiveness and safety of MPLR adjuvant therapy in patients with PSD. Seven databases were extensively searched from January 2000 until July 2016. Randomized control trials (RCTs) involving patients with PSD that compared treatment with and without MPLR were taken into account. The pooled effect estimates were calculated based on Cochrane Collaboration's software RevMan 5.3. Finally, 42 eligible studies with 3612 participants were included. Overall, MPLR adjuvant therapy showed a significantly higher effective rate (RR = 1.23; 95% CI = 1.19, 1.27; p 
      PubDate: 2016-10-20T04:30:27.496107-05:
      DOI: 10.1002/ptr.5740
  • Effects of Ginsenoside Rg1 on Learning and Memory in a Reward-directed
           Instrumental Conditioning Task in Chronic Restraint Stressed Rats
    • Authors: Wang Kezhu; Xu Pan, Lu Cong, Dong Liming, Zhang Beiyue, Lu Jingwei, Yang Yanyan, Liu Xinmin
      Abstract: Ginsenoside Rg1 is one of the major active ingredients of Panax ginseng and has showed notable improving learning and memory effects in several behavioral tasks, such as water maze, shuttle-box, and step-through, based on avoidance. However, there was no report about the role of Rg1 on the performance of reward-directed instrumental conditioning, which could reflect the adaptive capacity to ever-changing environments. Thus, in this study, the reward devaluation test and conditional visual discrimination task were conducted to study the ameliorating effects of Rg1 on cognitive deficits, especially the loss of adaptation capacity in chronic restraint stress (CRS) rat model. Our results showed that rat subjected to CRS became insensitive to the changes in outcome value, and it significantly harmed the rat's performance in conditional visual discrimination task. Moreover, the levels of BDNF, TrkB, and Erk phosphorylation were decreased in the prefrontal cortex of CRS rats. However, these changes were effectively reversed by Rg1 (5 and 10 mg/kg, i.p.). Therefore, it demonstrated that Rg1 has a good ability to improve learning and memory and also ameliorate impaired adaptive capacity induced by CRS. This amelioration effect of Rg1 might be mediated partially by BDNF/TrkB/Erk pathway in prefrontal cortex. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-20T04:15:33.05086-05:0
      DOI: 10.1002/ptr.5733
  • Compendium of Indian Folk Medicine and Ethnobotany (1991–2015)
    • Authors: Elizabeth M Williamson
      PubDate: 2016-10-20T04:11:50.437004-05:
      DOI: 10.1002/ptr.5744
  • Clinical Pharmacology of Citrus bergamia: A Systematic Review
    • Authors: Carmen Mannucci; Michele Navarra, Fabrizio Calapai, Raffaele Squeri, Sebastiano Gangemi, Gioacchino Calapai
      Abstract: Citrus bergamia Risso et Poiteau (“Bergamot”) originated from the Mediterranean ecoregion (southern Italy, Calabria). Bergamot essential oil (BEO) is used in perfumes, cosmetics, and for stress reduction. Juice from C. bergamia has been used for hyperlipidemia. We evaluated literature published on C. bergamia clinical applications. Clinical trials on C. bergamia not combined with other substances, published in English, were searched. We selected ten articles, six describing BEO effects on stress, three reporting effects of polyphenolic fraction of C. bergamia juice in hyperlipidemia and the last describing BEO effects in chronic psoriasis. Clinical studies were analyzed following Consolidated Standards of Reporting Trials for herbal therapy. Studies were conducted on small sample sizes and not have high quality level. Analysis indicates that BEO aromatherapy could be safe and useful to reduce stress symptoms. One study suggests its potential supportive role in ultraviolet B therapy against psoriasis. Supplementation with polyphenols from bergamot juice reduces plasma lipids and improves lipoprotein profile in moderate hyperlipidemia. Effectiveness and safety of C. bergamia cannot be definitively drawn because of publication bias and low quality level of the majority of studies. Further large-scale trials with rigorous design are required to define the role of C. bergamia in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-17T03:17:30.801422-05:
      DOI: 10.1002/ptr.5734
  • Modulatory Effect of an Urera Aurantiaca Extract on Immune and Tumoral
           Cells During Inflammation
    • Authors: Carla Marrassini; Claudia Anesini
      Abstract: There is a well known link between inflammation and cancer during initiation, propagation and metastasis. Urera aurantiaca (UA) Wedd. (Urticaceae) is a medicinal plant used in traditional medicine to treat inflammatory processes with proven in vivo antiinflammatory and antinociceptive effects. The effects of a methanolic extract (UA) and a purified fraction (PF) on the proliferation of normal and tumoral lymphocytes under the effect of prostaglandin E2 (PGE2) and on nitric oxide production by lipopolysaccharide-stimulated macrophages was evaluated. Both UA and PF stimulated normal lymphocytes but, in presence of PGE2, a modulatory effect was observed. The normal lymphocyte proliferation induced by PGE2 was driven by pathways involving both PKC and H2O2. In macrophages, UA and PF did not modify cell viability and abrogated the synthesis of nitric oxide induced by lipopolysaccharide. In tumoral lymphocytes, the UA exerted a biphasic effect: at low concentrations it increased cell proliferation, while at high concentrations, it displayed an antiproliferative effect. UA and PF were capable of reverting the proliferative action of PGE2. The tumoral cell proliferation induced by PGE2 is related to PKC, ERK 1/2 and MAP Kinase P38 pathways. The observed effects could be attributed to polyphenols, flavonoids and tannins. This work demonstrates the modulatory effects of the UA on different cell types during inflammatory conditions, which reinforces its antiinflammatory action. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-17T02:25:30.521593-05:
      DOI: 10.1002/ptr.5743
  • Anti-Dermatophyte and Anti-Malassezia Activity of Extracts Rich in
           Polymeric Flavan-3-ols Obtained from Vitis vinifera Seeds
    • Authors: Giovanna Simonetti; Felicia Diodata D'Auria, Nadia Mulinacci, Marzia Innocenti, Donato Antonacci, Letizia Angiolella, Anna Rita Santamaria, Alessio Valletta, Livia Donati, Gabriella Pasqua
      Abstract: Several human skin diseases are associated with fungi as dermatophytes and Malassezia. Skin mycoses are increasing and new alternatives to conventional treatments with improved efficacy and/or safety profiles are desirable. For the first time, the anti-dermatophytes and the anti-Malassezia activities of Vitis vinifera seed extracts obtained from different table and wine cultivars have been evaluated. Geometric minimal inhibitory concentration ranged from 20 to 97 µg/mL for dermatophytes and from 32 to 161 µg/mL for Malassezia furfur. Dried grape seed extracts analyzed by HPLC/DAD/ESI/MS showed different quali–quantitative compositions in terms of monomeric and polymeric flavan-3-ols. The minimal inhibitory concentrations for Trichophyton mentagrophytes and for M. furfur were inversely correlated with the amount of the polymeric fraction (r = −0.7639 and r = −0.7228, respectively). Differently, the antifungal activity against T. mentagrophytes was not correlated to the content of flavan-3-ol monomers (r = 0.2920) and only weakly correlated for M. furfur (r = −0.53604). These results suggest that extracts rich in polymeric flavan-3-ols, recovered from V.  vinifera seeds, could be used for the treatment of skin fungal infections. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-13T23:41:03.447453-05:
      DOI: 10.1002/ptr.5739
  • Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and
           APCmin/+ Mouse Models of Experimental Colon Cancer
    • Authors: Takumu Hasebe; Jun Matsukawa, Daina Ringus, Jun Miyoshi, John Hart, Atsushi Kaneko, Masahiro Yamamoto, Toru Kono, Mikihiro Fujiya, Yutaka Kohgo, Chong-Zi Wang, Chun-Su Yuan, Marc Bissonnette, Mark W. Musch, Eugene B. Chang
      Abstract: Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-12T00:51:00.879141-05:
      DOI: 10.1002/ptr.5735
  • Novel Compounds with new Anti-Ulcergenic Activity from Convolvulus
           pilosellifolius Using Bio-Guided Fractionation.
    • Authors: Amani S. Awaad; Asmaa Al-Refaie, Reham El-Meligy, Mohamed Zain, Hesham Soliman, Mohamed S. Marzoke, Nabil El-Sayed
      Abstract: Oral administration of the total alcohol extract of Convolvulus pilosellifolius Desr. (250 and 500 md/kg) showed potent anti-ulcerogenic activity in absolute ethanol-induced ulcer model in rats; it showed percent protection of control ulcer by 69.2 and 84.6%, respectively, while standard ranitidine (100 mg/kg) exhibited 46.2%. Bio-guided work leads to isolation of two novel compounds (1 and 2), which were identified through 1H, 13C NMR, HMPC, HMQC and DEPT as: methyl 2-(hydroxymethyl) octanoate, named as amanitate, and 16-amino-9,13-dimethyl-17-(prop-1-en-2-yl)-hexadecahydro-1H-cyclopenta[a] phenanthren-3-ol, named as asmatol. Both compounds (50 mg/kg) possessed anti-ulcerogenic activity with 95.4% and 55.84% protection, respectively. Two known compounds (3 and 4) were also isolated and identified through comparison with authentic samples and confirmed through different NMR techniques as kampeferol and quercetin. These compounds also showed anti-ulcerogenic activity with 78.38% and 5.38% protection, respectively. The cytoprotective mechanism explains the potent anti-ulcerogenic activity of the total alcohol extract and the isolated compounds. The extract was highly safe as the LD50 was more than 5000 mg/kg. These results were well supported by the sub-chronic toxicity study, as the extract (500 mg/kg) administrated orally to rats for 35 consecutive days showed no alteration in the liver and kidney functions. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-12T00:10:55.498724-05:
      DOI: 10.1002/ptr.5730
  • Impact of Cocoa Flavanols on Cardiovascular Health: Additional
           Consideration of Dose and Food Matrix.
    • Authors: Kade Davison; Peter RC Howe
      PubDate: 2016-10-09T22:16:35.648596-05:
      DOI: 10.1002/ptr.5729
  • Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide and
           Standardized Extract of Andrographis paniculata (Nees) with Nabumetone in
           Wistar Rats
    • Authors: Aishwarya Balap; Sathiyanarayanan Lohidasan, Arulmozhi Sinnathambi, Kakasaheb Mahadik
      Abstract: The aim of the study was to investigate the herb–drug interaction of Andrographis paniculata Nees (Acanthaceae) and Andrographolide (AN) with nabumetone (NAB) in wistar rats. Pharmacokinetic and pharmacodynamic interactions were studied after co-administration of APE and AN with NAB in Wistar rats. In pharmacokinetic studies, significant decrease in Cmax, AUC0–t and AUC0–∞ of 6-MNA after co-administration with pure AN and APE has been observed. Tmax of 6-MNA has been increased to 2 h from 1.5 h in AN + NAB treated group. Changes in mean residential time, clearance and volume of distribution of 6-MNA in APE + NAB treated group and AN + NAB treated group indicated interference of other components of APE other than AN. In pharmacodynamic study, significant decrease in antiarthritic activity of NAB on concomitant administration with APE and AN has been observed. The study concludes that NAB exhibits pharmacokinetic and pharmacodynamic interactions with APE and AN in rats thus alarms the concomitant use of herbal preparations containing APE and AN with NAB. Further study is needed to understand the mechanism and predict the herb–drug interaction in humans.
      PubDate: 2016-10-07T04:16:16.647225-05:
      DOI: 10.1002/ptr.5731
  • Bilberry: Chemical Profiling, in Vitro and in Vivo Antioxidant Activity
           and Nephroprotective Effect against Gentamicin Toxicity in Rats
    • Authors: Milica Veljković; Dragana R. Pavlović, Nenad Stojiljković, Sonja Ilić, Ivan Jovanović, Nataša Poklar Ulrih, Violeta Rakić, Ljubinka Veličković, Dušan Sokolović
      Abstract: We assessed possible protective effect of bilberry diet in rat model of nephrotoxicity. In vivo and in vitro antioxidant activity and chemical profiling of this functional food was performed. With aid of HPLC-DAD and spectrophotometric method, 15 individual anthocyanins were quantified alongside total tannin, phenylpropanoid, and anthocyanin content. The study was conducted on four groups of rats: control, treated with only gentamicin, treated with only bilberry, and treated with both gentamicin and bilberry. Kidney function was evaluated by tracking urea and creatinine. Morphology of renal tissue and its changes were recorded pathohistologically and quantified morphometrically. Bilberry (100 mg/kg daily) showed strong nephroprotective effect against gentamicin toxicity in rats (as shown through MDA, AOPP, and catalase levels). In conclusion, the demonstrated protective activity of bilberry extract matched well with the assessed in vivo and in vitro antioxidant activity as well as with its polyphenolic content, particularly with high anthocyanin levels. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-06T21:50:40.006447-05:
      DOI: 10.1002/ptr.5738
  • Triterpenoids-Enriched Extract from the Aerial Parts of Salvia
           miltiorrhiza Regulates Macrophage Polarization and Ameliorates Insulin
           Resistance in High-Fat Fed Mice
    • Authors: Jing Leng; Mei-Hong Chen, Zhi-Hui Zhou, Ya-Wen Lu, Xiao-Dong Wen, Jie Yang
      Abstract: Adipose tissue inflammation and macrophage polarization are tightly associated with the development of obesity-associated insulin resistance. Our previous studies have demonstrated the triterpenoids-enriched extract from the aerial parts of Salvia miltiorrhiza (TTE) could significantly improve atherosclerosis in LDLR−/− mice. However, its molecular mechanisms of TTE ameliorating insulin resistance remain unclear. In the present study, obesity model with insulin resistance induced by feeding high-fat diet (HFD) was established. Dietary TTE attenuated hyperlipidemia, improved glucose intolerance in mice and mediated the activation of IRS-1/PI3K/Akt insulin signaling pathway. Meanwhile, dietary TTE also attenuated macrophage infiltrations into adipose tissue and modified the phenotype ratio of M1/M2 macrophages. Furthermore, our results showed that TTE regulated the polarization of macrophages partly via adenosine monophosphate-activated kinase (AMPK). Taken together, these findings suggested that TTE has a potential clinical utility in improving insulin resistance. Its mechanisms might be contributed to its beneficial effects on macrophage polarization via AMPK. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-10-06T21:37:17.477428-05:
      DOI: 10.1002/ptr.5736
  • Plants as Antileishmanial Agents: Current Scenario
    • Authors: Nazif Ullah; Akhtar Nadhman, Sumaira Siddiq, Shaila Mehwish, Arshad Islam, Laila Jafri, Muhammad Hamayun
      Abstract: Leishmaniasis is a clinical manifestation caused by the parasites of the genus Leishmania. Plants are reservoirs of bioactive compounds, which are known to be chemically balanced, effective and least injurious as compared with synthetic medicines. The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s, which are summarized in this review. Moreover, it also highlights various traditional remedies used by local healers against leishmaniasis. A systematic cross-sectional study for antileishmanial activity of natural products was carried out using multiple literature databases. The records retrieved since 2000 till year 2016 were analysed and summarized in the form of comprehensive tables and graphs. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of chemicals for the treatment of protozoan diseases like leishmaniasis. Where the researchers prefer to use alcoholic solvents for the extraction of antileishmanial agents from plants, most of the studies are limited to in vitro conditions majorly on using promastigote forms of Leishmania. Thus, there is a need to carry out such activities in vivo and in host macrophages. Further, there is a need of mechanistic studies that can help taking few of the promising pure compounds to clinical level. Copyright © 2016 John Wiley & Sons, Ltd.The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of available drugs for the treatment of protozoan diseases like leishmaniasis. However, to develop such compounds as next drug against leishmaniasis, it is very important to test natural agents both in in-vivo and in host macrophages.
      PubDate: 2016-10-05T04:09:27.517761-05:
      DOI: 10.1002/ptr.5710
  • Antiinflammatory Effects of Functionally Active Compounds Isolated from
           Aged Black Garlic
    • Authors: Dong-gyu Kim; Min Jung Kang, Seong Su Hong, Yun-Hyeok Choi, Jung Hye Shin
      Abstract: The antiinflammatory effects of functionally active compounds isolated from aged black garlic (AGE-1 and AGE-2) were investigated using a lipopolysaccharide-induced inflammatory response model. To examine the potential antiinflammatory properties of AGE-1 and AGE-2, cell viability as well as nitric oxide, prostaglandin E2, and pro-inflammatory cytokine [interleukin-6 (IL-6), TNF-α, and IL-1β] levels were measured. The mRNA and protein expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were detected by reverse transcription polymerase chain reaction and western blotting. The results indicated that AGE-1 and AGE-2 were not cytotoxic to macrophages. Nitric oxide and prostaglandin E2 levels decreased significantly with increasing concentration of AGE-1 (IC50 = 29.6 and 1.41 µg/mL, respectively), but not AGE-2. The secretion of IL-6, TNF-α, and IL-1β was also suppressed by AGE-1 in a dose-dependent manner, and inducible nitric oxide synthase and cyclooxygenase-2 mRNA, and protein expression decreased with AGE-1 treatment. Furthermore, AGE-1 attenuated the phosphorylation of the extracellular signal-regulated kinase, p38, and c-Jun terminal kinase in lipopolysaccharide-induced RAW264.7 cells. These results suggested that compound AGE-1 may have significant effects on inflammatory factors and could potentially be used as an antiinflammatory therapeutic agent. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-30T03:15:40.061318-05:
      DOI: 10.1002/ptr.5726
  • Inhibitory Effects of Multiple-Dose Treatment with Baicalein on the
           Pharmacokinetics of Ciprofloxacin in Rats
    • Authors: Youn-Hwan Hwang; Hye Jin Yang, Dong-Gun Kim, Jin Yeul Ma
      Abstract: Ciprofloxacin is used as a treatment for urinary and respiratory tract infections in clinical practice. Baicalein, a major flavonoid present in Scutellaria baicalensis, is a well-known and potent antibacterial compound used in complementary and alternative medicine practices. The present study aimed to clarify the effects of multiple-dose treatment with baicalein on the pharmacokinetics of ciprofloxacin in rats. Following the oral administration of baicalein (20, 40, or 80 mg/kg) for five consecutive days, the rats received an oral administration of ciprofloxacin (20 mg/kg). Blood samples were collected at specific time points, and the plasma concentrations of ciprofloxacin were determined by using high-performance liquid chromatography. To evaluate the mechanisms underlying the interaction between baicalein and ciprofloxacin, a rhodamine 123 accumulation assay was performed in LS-180 cells. A pharmacokinetic study revealed that multiple-dose treatment with baicalein significantly decreased the peak serum concentration (Cmax), area under the curve (AUC0  480 min), and relative bioavailability (Frel) of ciprofloxacin (p 
      PubDate: 2016-09-26T20:40:26.83898-05:0
      DOI: 10.1002/ptr.5728
  • A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera:
           Potential for Drug Development
    • Authors: Bhesh Raj Sharma; Lekh Nath S. Gautam, Deepak Adhikari, Rajendra Karki
      Abstract: Nelumbo nucifera, also known as sacred lotus, has primarily been used as food throughout the Asian continent, and its medicinal values have been described in Ayurvedic and Traditional Chinese Medicine. The purpose of this study is to systematically characterize the chemical profiling and pharmacological activities of N. nucifera. Herein, we critically reviewed and analysed the phytochemical and pharmacological reports of N. nucifera. Our search for the keyword ‘Nelumbo nucifera pharmacology’ in all databases reported in Web of Science yielded 373 results excluding reviews and abstracts in document types. Two hundred and forty‐three spectrum natural compounds from different parts of N. nucifera belonging to diverse chemical groups, including alkaloids, flavonoids, glycosides, terpenoids, steroids, fatty acids, proteins, minerals, and vitamins have been reported. In addition, distinct pharmacological activities, mainly against cancer, microbial infection, diabetes, inflammation, atherosclerosis, and obesity, have been associated with crude extracts, fractions, and isolated compounds. This review highlights potential use of neferine, liensinine, isoliensinine, and nuciferine in clinical trials. In depth, mechanism of the potential chemical entities from N. nucifera via structure activity relationship needs to be explored to guarantee the stability and safety for the clinical use. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-26T00:41:26.53895-05:0
      DOI: 10.1002/ptr.5732
  • THC (Δ9‐Tetrahydrocannabinol) Exerts Neuroprotective Effect in
           Glutamate‐affected Murine Primary Mesencephalic Cultures Through
           Restoring Mitochondrial Membrane Potential and Anti‐apoptosis Involving
           CB1 Receptor‐dependent Mechanism
    • Authors: Chi Huu Nguyen; Christopher Krewenka, Khaled Radad, Barbara Kranner, Alexandra Huber, Johanna Catharina Duvigneau, Ingrid Miller, Rudolf Moldzio
      Abstract: Aging‐related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. Δ9‐Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate‐induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48 h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase‐3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate‐induced neurotoxicity. Moreover, THC significantly counteracted the glutamate‐induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB1 receptor antagonist, concentration‐dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti‐apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB1 receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-22T04:30:32.606126-05:
      DOI: 10.1002/ptr.5712
  • Antimycobacterial Activity and Low Cytotoxicity of Leaf Extracts of Some
           African Anacardiaceae Tree Species
    • Authors: Prudence N. Kabongo-Kayoka; Jacobus N. Eloff, Chikwelu L. Obi, Lyndy J. McGaw
      Abstract: Treatment of tuberculosis (TB) is a challenge because of multidrug‐resistant and extremely drug‐resistant strains of Mycobacterium tuberculosis. Plant species contain antimicrobial compounds that may lead to new anti‐TB drugs. Previous screening of some tree species from the Anacardiaceae family revealed the presence of antimicrobial activity, justifying further investigations. Leaf extracts of 15 Anacardiaceae tree species were screened for antimycobacterial activity using a twofold serial microdilution assay against the pathogenic Mycobacterium bovis and multidrug resistant M. tuberculosis and rapidly growing mycobacteria, Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium aurum. The vaccine strain, M. bovis and an avirulent strain, H37Ra M. tuberculosis, were also used. Cytotoxicity was assessed using a colorimetric assay against Vero kidney, human hepatoma and murine macrophage cells. Four out of 15 crude acetone extracts showed significant antimycobacterial activity with minimum inhibitory concentration varying from 50 to 100 µg/mL. Searsia undulata had the highest activity against most mycobacteria, followed by Protorhus longifolia. M. fortuitum was the strongest predictor of activity against multidrug‐resistant TB (correlation coefficient = 0.65). Bioautography against M. aurum and M. fortuitum worked well as indicators of the Rf values of active compounds yielding strong zones of inhibition. The leaf extracts of S. undulata and P. longifolia had more than ten different antimycobacterial compounds and had low cytotoxicity with LC50 values above 100 µg/mL. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-13T01:05:56.767078-05:
      DOI: 10.1002/ptr.5706
  • Characterization of Phloroglucinol‐enriched Fractions of Brazilian
           Hypericum Species and Evaluation of Their Effect on Human Keratinocytes
    • Authors: Henrique Bridi; Aline Beckenkamp, Gari Vidal Ccana-Ccapatinta, Sérgio Augusto Loreto Bordignon, Andréia Buffon, Gilsane Lino Poser
      Abstract: In this study, a phytochemical and biological investigation on five South Brazilian Hypericum species (Hypericum caprifoliatum, Hypericum carinatum, Hypericum connatum, Hypericum myrianthum, and Hypericum polyanthemum) was carried out. The phloroglucinol‐enriched fractions (PEF) of the flowering aerial parts were analyzed by high‐performance liquid chromatography for the content of uliginosin A (1), japonicin A (2), uliginosin B (3), hyperbrasilol B (4), and the three benzopyrans, that is, 6‐isobutyryl‐5,7‐dimethoxy‐2,2‐dimethyl‐benzopyran (HP1) (5), 7‐hydroxy‐6‐isobutyryl‐5‐methoxy‐2,2‐dimethyl‐benzopyran (HP2) (6), and 5‐hydroxy‐6‐isobutyryl‐7‐methoxy‐2,2‐dimethyl‐benzopyran (HP3) (7). After chemical characterization, the PEF were assayed for cell proliferation on human keratinocyte cell line by MTT. The H. carinatum and H. polyanthemum PEF demonstrated better results with an increase in cell proliferation (138.7% and 120.6%, respectively). The cell counting and Ki‐67 assay with H. carinatum PEF confirmed the MTT results. The cell cycle distribution indicates an increase in the cells at S and G2/M phases, which is indicative of proliferation induction. In summary, the results indicate an induction of HaCaT proliferation by the treatment with H. carinatum PEF (at 10 and 15 µg/mL), suggesting a possible use as wound healing agent. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-13T00:46:29.674453-05:
      DOI: 10.1002/ptr.5727
  • Efficacy of Trans‐cinnamaldehyde and Eugenol in Reducing Acinetobacter
           baumannii Adhesion to and Invasion of Human Keratinocytes and Controlling
           Wound Infection In Vitro
    • Authors: Deepti P. Karumathil; Meera Surendran-Nair, Kumar Venkitanarayanan
      Abstract: The study investigated the efficacy of two natural, plant‐derived antimicrobials (PDAs), namely trans‐cinnamaldehyde (TC), and eugenol (EG) for decreasing Acinetobacter baumannii adhesion to and invasion of human keratinocytes (HEK001). Moreover, the efficacy of two PDAs for inhibiting A. baumannii biofilm formation was determined using an in vitro collagen matrix wound model. Additionally, the effect of TC and EG on A. baumannii biofilm architecture was visualized using confocal scanning microscopy. Further the effect of both PDAs on genes critical for biofilm synthesis was determined using real‐time quantitative polymerase chain reaction. Both TC and EG significantly reduced A. baumannii adhesion and invasion to HEK001 by ~2 to 3 log10 CFU/mL (p 
      PubDate: 2016-09-13T00:05:33.548159-05:
      DOI: 10.1002/ptr.5713
  • Decursin in Angelica gigas Nakai (AGN) Enhances Doxorubicin
           Chemosensitivity in NCI/ADR‐RES Ovarian Cancer Cells via Inhibition of
           P‐glycoprotein Expression
    • Authors: Hyeong Sim Choi; Sung-Gook Cho, Min Kyoung Kim, Min Soo Kim, Seung Hee Moon, Il Hwan Kim, Seong-Gyu Ko
      Abstract: Angelica gigas Nakai (AGN, Korean Dang‐gui) is traditionally used for the treatment of various diseases including cancer. Here, we investigated multidrug‐resistant phenotype‐reversal activities of AGN and its compounds (decursin, ferulic acid, and nodakenin) in doxorubicin‐resistant NCI/ADR‐RES ovarian cancer cells. Our results showed that a combination of doxorubicin with either AGN or decursin inhibited a proliferation of NCI/ADR‐RES cells. These combinations increased the number of cells at sub‐G1 phase when cells were stained with Annexin V‐fluorescein isothiocyanate. We also found that these combinations activated caspase‐9, caspase‐8, and caspase‐3 and increased cleaved PARP level. Moreover, an inhibition of P‐glycoprotein expression by either AGN or decursin resulted in a reduction of its activity in NCI/ADR‐RES cells. Therefore, our data demonstrate that decursin in AGN inhibits doxorubicin‐resistant ovarian cancer cell proliferation and induces apoptosis in the presence of doxorubicin via blocking P‐glycoprotein expression. Therefore, AGN would be a potentially novel treatment option for multidrug‐resistant tumors by sensitizing to anticancer agents. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-08T02:05:24.139613-05:
      DOI: 10.1002/ptr.5708
  • Perioperative Bromelain Therapy after Wisdom Teeth Extraction – A
           Randomized, Placebo‐Controlled, Double‐Blinded, Three‐Armed,
           Cross‐Over Dose‐Finding Study
    • Authors: Kai-Hendrik Bormann; Kristina Weber, Heike Kloppenburg, Armin Koch, Peter Meiser, Nils-Claudius Gellrich
      Abstract: Reduction in postoperative edema and inflammatory reactions is the key to the posttraumatic regeneration process. Use of bromelain is well established in this indication, but there is some controversy with regard to the optimal dosing of this drug. The aim of our study was therefore to investigate the efficacy of dosage‐dependent therapy with bromelain in patients after wisdom teeth extraction by comparing the registered dosage 1000 FIP (Fédération Internationale Pharmaceutique) against higher dosages of 3000 FIP and 4500 FIP. A total of 75 patients were randomized to one of the three dosage arms, and 68 of these patients were finally analyzed in the modified intention‐to‐treat population. Patients involved underwent two surgery sessions: one study period being conducted under treatment with bromelain and the other with placebo. Postoperative swelling determined by a 3D face scanning system was defined as the primary endpoint; further efficacy parameters were maximum swelling, pain, difficulty in swallowing, and use of analgesics. A superiority of treatment with 3000 FIP and 4500 FIP versus 1000 FIP could not be demonstrated. The analysis of pooled bromelain treatments versus placebo did, however, show a clear trend in favor of bromelain for all assessments. Adverse events did not occur more frequently under bromelain therapy compared with placebo. This study thus clearly supports the clinical relevance of treatment of postoperative conditions with bromelain, and the recommended daily dose was sufficiently effective in this trial and indication. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-09-06T22:30:38.304535-05:
      DOI: 10.1002/ptr.5707
  • Germacrone Inhibits Estrogen Receptor α‐Mediated Transcription in
           MCF‐7 Breast Cancer Cells
    • Authors: Mi-Sun Lim; Se-Young Choung, Kwang Won Jeong
      Abstract: Estrogen receptor (ER)α‐positive breast cancer cells regulate the expression of estrogen‐responsive genes, which are involved in cell proliferation, differentiation, and cell cycle progression. Clinically, the inhibition of ERα‐mediated gene expression in breast cancer cells has long been considered an effective way to prevent the development and progression of cancer. Germacrone, a terpenoid compound isolated from Rhizoma curcuma, has been known to have antitumor activity in various human cancer cell lines. However, the mechanism by which germacrone inhibits the proliferation of breast cancer cells is still unclear. Here, we demonstrated that germacrone inhibits ERα‐mediated gene expression at the transcriptional level in MCF‐7 cells. Germacrone inhibits the recruitment of ERα to the estrogen response element on chromatin and consequently compromises the binding of switch/sucrose non‐fermentable chromatin remodeling complex and RNA polymerase II to target gene promoter, thereby inhibiting the estrogen‐induced chromatin accessibility. In addition, germacrone efficiently potentiates the antitumor activity of methotrexate and 5‐fluorouracil. Our results not only provide substantial molecular mechanism of germacrone on ERα‐mediated signaling in breast cancer cells but also demonstrate the benefits of germacrone as a combination therapy with other drugs for the treatment of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-30T03:30:27.593445-05:
      DOI: 10.1002/ptr.5711
  • Folic Acid and Grape Seed Extract Prevent Azathioprine‐induced Fetal
           Malformations and Renal Toxicity in Rats
    • Authors: Ibrahim M. El-Ashmawy; Aida E. Bayad
      Abstract: Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co‐administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co‐treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co‐administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA‐induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA‐induced oxidative renal damages. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-26T00:15:32.231425-05:
      DOI: 10.1002/ptr.5709
  • Cinnamaldehyde, Carvacrol and Organic Acids Affect Gene Expression of
           Selected Oxidative Stress and Inflammation Markers in IPEC‐J2 Cells
           Exposed to Salmonella typhimurium
    • Authors: Sara A. Burt; Simone J.M. Adolfse, Dina S.A. Ahad, Monique H.G. Tersteeg-Zijderveld, Betty G.M. Jongerius-Gortemaker, Jan A. Post, Holger Brüggemann, Regiane R. Santos
      Abstract: Essential oils and organic acids are used as feed additives to improve health status and reduce colonization with pathogens. Although bactericidal in vitro, concentrations achieved in the animal gut are probably not lethal to pathogens. The aim of this study was to investigate the effects of cinnamaldehyde, carvacrol and cinnamic, lactic and propionic acids on the ability of Salmonella typhimurium ATCC 14028 (ST) to invade intestinal epithelial cells (IPEC‐J2) and on the expression levels of immune related genes in the cells. The minimum inhibitory concentration (MIC) and non‐inhibitory concentration (NIC) were determined and influence on the invasion capacity of ST was investigated. The structure of fimbriae and flagella was analysed by electron microscopy, and expression levels of HSP70, IkBa, IL‐8 and IL‐10 in the IPEC‐J2 cells were carried out by q‐PCR. Cinnamaldehyde, carvacrol and cinnamic and propionic acids inhibited ST invasion but not cell viability, bacterial viability and motility or the development of flagella. Propionic acid and cinnamaldehyde in combination with cinnamic acid caused structural impairment of fimbriae. Cinnamaldehyde up‐regulated expression of HSP70 irrespective of the presence of organic acids or ST; exposure to carvacrol induced HSP70 only in the presence of propionic acid and ST. © 2016 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2016-08-25T23:55:36.368279-05:
      DOI: 10.1002/ptr.5705
  • Ramalin Isolated from Ramalina Terebrata Attenuates Atopic
           Dermatitis‐like Skin Lesions in Balb/c Mice and Cutaneous Immune
           Responses in Keratinocytes and Mast Cells
    • Authors: Hye-Jin Park; Yeon Jeong Jang, Joung-Han Yim, Hong-Kum Lee, Suhkneung Pyo
      Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease that involves eczematous skin lesions with pruritic erythematous papules. In this study, we investigated the mitigating effects of ramalin, a component of the Antarctic lichen Ramalina terebrata against AD in vivo and in vitro. Oral administration of ramalin lessened scratching behaviors and significantly reduced both serum immunoglobulin E and IL‐4 levels, and mRNA levels of IL‐4 and IL‐10 in AD‐induced Balb/c mice. In vitro, treatment with ramalin produced significantly less inflammatory chemokines and cytokines, including TARC, MCP‐1, RANTES, and IL‐8 in TNF‐α‐stimulated HaCaT cells. In addition, ramalin inhibited the activation of nuclear factor‐kappa B as well as the phosphorylation of mitogen‐activated protein kinases (MAPK). Furthermore, ramalin treatment resulted in decreased production of β‐hexosaminidase and proinflammatory cytokines IL‐4, IL‐6, and TNF‐α in 2,4 dinitrophenyl‐human serum albumin‐stimulated RBL‐2H3 cells through blocking MAPK signaling pathways. The results suggest that ramalin modulates the production of immune mediators by inhibiting the nuclear factor‐kappa B and MAPK signaling pathways. Taken together, ramalin effectively attenuated the development of AD and promoted the mitigating effects on Th2 cell‐mediated immune responses and the production of inflammatory mediators in mast cells and keratinocytes. Thus, ramalin may be a potential therapeutic agent for AD. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-25T01:20:47.370476-05:
      DOI: 10.1002/ptr.5703
  • Inulin‐Type Oligosaccharides Extracted from Yacon Produce
           Antidepressant‐Like Effects in Behavioral Models of Depression
    • Authors: Lei An; Ji-Chu Yang, Hang Yin, Rui Xue, Qiong Wang, Yu Chen Sun, You-Zhi Zhang, Ming Yang
      Abstract: Yacon (Smallanthus sonchifolius), a traditional food in the Andean diet, is attracting global attention for its medicinal properties, which are mainly because of its high content of non‐digestible oligosaccharides. The purpose of this study is to evaluate the antidepressant‐like effects of inulin‐type oligosaccharides extracted from yacon (YOs) in behavioral models of depression. Behavioral despair models in mice including the tail suspension test (TST) and the forced swimming test (FST) were used to determine the effects of acute YOs administration. The locomotor activity was also explored to eliminate any false‐positive activity. In addition, to further investigate the antidepressant‐like effects of subchronic YOs administration, the learned helplessness (LH) paradigm in rats was performed. The results demonstrated that YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reduced the immobility time in the mouse TST and FST in a U‐shaped, dose‐dependent manner, and showed no stimulatory effect on the locomotor activity. Furthermore, subchronic YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reversed the escape deficits in LH rats, including an increased number of escape failures and prolonged escape latency. These findings suggest that the inulin‐type oligosaccharides extracted from yacon may be a prospective natural source for antidepressants. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-19T02:56:25.641669-05:
      DOI: 10.1002/ptr.5698
  • Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during
           Alcohol Consumption: A Randomized, Double‐Blind, Placebo‐Controlled,
           Crossover Study
    • Authors: Harsha Chigurupati; Biswajit Auddy, M. Biyani, Sidney J. Stohs
      Abstract: Traditionally, licorice has been used to treat liver problems. Glycyrrhizin, the primary active compound, has been shown to suppress elevations in liver enzymes that occur when the liver becomes diseased or damaged. This randomized, double‐blind, placebo‐controlled, crossover study evaluated the hepatoprotective effects of a proprietary glycyrrhizin product during alcohol consumption. Twelve healthy individuals (six male and six female subjects) in a clinic setting consumed vodka nightly for 12 days with the glycyrrhizin product or placebo (blank control), achieving a blood alcohol level of 0.12%. Liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), and alkaline phosphatase and serum reduced glutathione were measured at overnight visits 1, 6, and 12. In the alcohol only group, AST, ALT, and GGT significantly increased from baseline (overnight visit 1) to overnight visit 12. In the active group, no statistically significant increases were observed for AST, ALT, and GGT, while alkaline phosphatase significantly decreased and plasma glutathione decreased relative to the alcohol control group. These results suggest that consumption of the proprietary glycyrrhizin study product during alcohol consumption may support improved liver health compared with drinking alcohol alone. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-19T01:55:34.841077-05:
      DOI: 10.1002/ptr.5699
  • Plumbagin Enhances Tamoxifen Sensitivity and Inhibits Tumor Invasion in
           Endocrine Resistant Breast Cancer through EMT Regulation
    • Authors: Nithidol Sakunrangsit; Nuttiya Kalpongnukul, Trairak Pisitkun, Wannarasmi Ketchart
      Abstract: Tamoxifen is widely used as the first line drug for estrogen receptor‐positive subtype which is expressed in 70% of overall breast cancer patients. However, approximately 50% of these patients develop acquired resistance after 5 years of treatment, which is characterized by tumor recurrence and metastasis. The epithelial mesenchymal transition (EMT) is an important process in breast cancer invasion. Fundamentally, targeting the EMT represents a crucial therapeutic strategy for preventing or treating breast cancer metastasis. Plumbagin (PLB) is a natural naphthoquinone with significant anticancer effects against several types of tumor cells including breast cancer. In this study, we investigated the effect of PLB on human endocrine‐resistant breast cancer cell growth, invasion and the possible mechanisms underlying such actions. PLB exhibited potent cytotoxic activity at a micromolar concentration against endocrine‐resistant breast cancer cells. Interestingly, a fixed low concentration of PLB and tamoxifen combination resulted in an increase in growth inhibition in endocrine‐resistant cells. In addition, PLB also significantly suppressed mesenchymal biomarker expressions that govern the EMT process, resulting in attenuated metastatic capabilities. In conclusion, PLB should be developed as a pharmacological agent for the use as a single treatment or in combination for endocrine‐resistant breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-17T01:15:29.721779-05:
      DOI: 10.1002/ptr.5702
  • Progress in the Development and Applicability of Potential Medicinal Plant
           Extract‐Conjugated Polymeric Constructs for Wound Healing and Tissue
    • Authors: Urmimala Das; Sudhanshu Shekhar Behera, Sandeep Singh, Syed Ibrahim Rizvi, Abhishek Kumar Singh
      Abstract: Wound, burn and tissue related diseases are the most common and devastating forms of trauma worldwide and thousands are still dying each year when they are left untreated. The traditional treatments for wound infection using medicinal plant extracts in hydrogels and ointment formulations have several disadvantages, delicate shape and dry up quickly upon exposure to air. Indeed, there is need for the development of an alternative form of dressing material for wound healing applications. Because the medicinal plant products are economical, researchers have adopted a novel approach of complexing the active components of plants with various groups of polymers to develop biodegradable fabrications. Moreover, fabricated constructs are very extremely useful as scaffold in tissue regeneration with known successes in wound healing/ dressing applications that the fabricated substitutes mimic the extracellular matrix of tissue. In this review, we give an extensive overview on scientifically evaluated bioactive molecules of medicinal plants as well as plant extract blended polymeric constructs for the possible treatment of various skin injuries. In addition, the technological challenges and future trends for recent developments of the treatments of wound infections are extensively summarized. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-17T00:55:39.246155-05:
      DOI: 10.1002/ptr.5700
  • Aqueous and Ethanolic Extracts of Boswellia serrata Protect Against Focal
           Cerebral Ischemia and Reperfusion Injury in Rats
    • Authors: Fatemeh Forouzanfar; Hossein Hosseinzadeh, Alireza Ebrahimzadeh Bideskan, Hamid R. Sadeghnia
      Abstract: Oxidative stress and cell apoptosis play major roles in neuronal injury after ischemia–reperfusion (I‐R) injury. Boswellia serrata is a medicinal plant with antioxidant properties. Acetyl‐11‐keto‐β‐boswellic acid (AKBA) is an active triterpenoid compound from B. serrate. In the current study, the neuroprotective effects of aqueous and ethanolic extracts of B. serrata (named ABS and EBS, respectively) and AKBA were investigated against middle cerebral artery occlusion‐induced cerebral I‐R injury in rats. ABS and EBS with doses of 125, 250 and 500 and AKBA with a dose of 50 mg/kg were administered (intraperitoneally) just after middle cerebral artery occlusion induction for 30 min and reperfusion for 24 h. HPLC analysis suggested that ABS and EBS had AKBA of 8.8% and 9.5% (w/w), respectively. B. serrata and AKBA significantly improved neurological deficit and reduced brain infarction, neuronal cell loss and apoptosis and also attenuated lipid peroxidation while increasing glutathione content and superoxide dismutase activity in the cerebral cortex following a stroke. Apoptosis suppression was found to be mediated through regulating caspase‐3 and bax/bcl‐2 expressions. In conclusion, our results demonstrated that B. serrata and AKBA attenuate oxidative damage and inhibit cell apoptosis, subsequently protecting cerebral I‐R injury in rats. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-12T00:46:07.239712-05:
      DOI: 10.1002/ptr.5701
  • Silibinin Inhibits Neutrophilic Inflammation and Mucus Secretion Induced
           by Cigarette Smoke via Suppression of ERK‐SP1 Pathway
    • Authors: Ji-Won Park; Na-Rae Shin, In-Sik Shin, Ok-Kyoung Kwon, Joong-Sun Kim, Sei-Ryang Oh, Jae-hong Kim, Kyung-Seop Ahn
      Abstract: Silibinin, the main ingredient of silymarin, has been used as a traditional drug for over 2000 years to treat a range of liver diseases. Recent studies have also demonstrated that silibinin possesses antiinflammatory and anticancer properties. In the study, we researched the efficacy of silibinin on the development of COPD using a cigarette smoke (CS)‐induced and lipopolysaccharide (LPS)‐induced COPD model mice and stimulation of NCI‐H292 cells with CS condensate. Silibinin was administered to mice by oral gavage 1 h before CS exposure for 10 days. In in vitro experiment, we evaluated the effect of silibinin on the expression of MUC5AC in H292 cells stimulated with CS condensate. Furthermore, silibinin suppressed the CS and LPS treatment‐induced extracellular signal‐regulated kinase (ERK) phosphorylation and SP‐1 expression. Silibinin also decreased airway inflammation and reduced the expression of MUC5AC and myeloperoxidase. Furthermore, co‐treatment with silibinin and ERK inhibitors considerably decreased the levels of pro‐inflammatory mediators, ERK phosphorylation, and SP‐1 expression. Taken together, the results indicate that silibinin effectively suppressed the neutrophilic airway inflammation provoked by treatment with LPS and CS, which was closely associated with downregulation of ERK phosphorylation. Therefore, our searching offers that silibinin has a remedical probable for COPD disease. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-29T00:00:45.843294-05:
      DOI: 10.1002/ptr.5686
  • Effects of Ginkgo Biloba Extract EGb‐761 on Neuropathic Pain in Mice:
           Involvement of Opioid System
    • Authors: Chao Zhu; Wei Li, Fan Xu, Mo Li, Liu Yang, Xue‐Yu Hu, Zheng‐Xu Ye, Zhe Wang, Zhuo‐Jing Luo
      Abstract: Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb‐761 is extracted from leaves of Ginkgo biloba and has analgesia and anti‐inflammatory properties. This study aimed to examine the effect of EGb‐761 on chronic constriction injury (CCI)‐induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb‐761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu‐opioid receptor expression were measured. Results showed that EGb‐761 attenuated thermal hyperalgesia and mechanical allodynia dose‐dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb‐761 treatment significantly decreased pro‐inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb‐761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb‐761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb‐761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb‐761‐induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-25T04:21:40.643989-05:
      DOI: 10.1002/ptr.5685
  • Issue Information - TOC
    • First page: 1721
      Abstract: No abstract is available for this article.
      PubDate: 2016-11-04T05:09:02.52725-05:0
      DOI: 10.1002/ptr.5470
  • Issue Information - Info Page
    • First page: 1722
      Abstract: No abstract is available for this article.
      PubDate: 2016-11-04T05:09:01.793199-05:
      DOI: 10.1002/ptr.5471
  • Natural Products as Mechanism‐based Anticancer Agents: Sp
           Transcription Factors as Targets
    • Authors: Stephen Safe; Ravi Kasiappan
      First page: 1723
      Abstract: Naturally occurring anticancer agents and their derivatives act on multiple pathways to inhibit carcinogenesis and their inhibition of migration, invasion, growth, survival, and metastasis is associated with downregulation of genes associated with these responses. Several phytochemical‐derived anticancer drugs including curcumin, betulinic acid, phenethylisothiocyanate and celastrol, and many others induce reactive oxygen species, and their effects on gene regulation show some overlap in various cancer cell lines. We hypothesize that reactive oxygen species‐inducing anticancer agents and many other natural products target a common pathway in cancer cells, which initially involves downregulation of specificity protein 1 (Sp1), Sp3, and Sp4, which are highly expressed in tumors/cell lines derived from solid tumors. This hypothesis is supported by several published reports showing that a large number of phytochemical‐derived anticancer agents downregulate Sp1, Sp3, Sp4, and pro‐oncogenic Sp‐regulated genes involved in cell growth (cyclin D1 and growth factor receptors), survival (bcl‐2 and survivin), angiogenesis and migration (MMP‐9, vascular endothelial growth factor and its receptors), and inflammation (NF‐kB). The contribution of this pathway to the anticancer activity of drugs such as curcumin, celastrol, betulinic acid, and phenethylisothiocyanate must be determined in order to optimize clinical applications of drug combinations containing these compounds. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-07T00:00:32.706912-05:
      DOI: 10.1002/ptr.5669
  • Pharmacological Effects of Capparis spinosa L.
    • Authors: Seyed Fazel Nabavi; Filippo Maggi, Maria Daglia, Solomon Habtemariam, Luca Rastrelli, Seyed Mohammad Nabavi
      First page: 1733
      Abstract: Medicinal plants have been known as one of the most important therapeutic agents since ancient times. During the last two decades, much attention has been paid to the health‐promoting effects of edible medicinal plants, because of multiple beneficial effects and negligible adverse effects. Capparis spinosa L. is one of the most common medicinal plants, used widely in different parts of the world to treat numerous human diseases. This paper aims to critically review the available scientific literature regarding the health‐promoting effects of C. spinosa, its traditional uses, cultivation protocols and phytochemical constituents. Recently, a wide range of evidence has shown that this plant possesses different biological effects, including antioxidant, anticancer and antibacterial effects. Phytochemical analysis shows that C. spinosa has high quantities of bioactive constituents, including polyphenolic compounds, which are responsible for its health‐promoting effects, although many of these substances are present in low concentrations and significant changes in their content occur during processing. In addition, there is negligible scientific evidence regarding any adverse effects. Different health promotion activities, as well as tremendous diversity of active constituents, make C. spinosa a good candidate for discovering new drugs. However these findings are still in its infancy and future experimental and clinical studies are needed. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-13T02:41:06.524886-05:
      DOI: 10.1002/ptr.5684
  • Berberis Vulgaris and Berberine: An Update Review
    • Authors: Mohsen Imenshahidi; Hossein Hosseinzadeh
      First page: 1745
      Abstract: Berberine is an isoquinoline alkaloid present in several plants, including Coptis sp. and Berberis sp. Berberine is a customary component in Chinese medicine, and is characterized by a diversity of pharmacological effects. An extensive search in electronic databases (PubMed, Scopus, Ovid, Wiley, ProQuest, ISI, and Science Direct) were used to identify the pharmacological and clinical studies on Berberis vulgaris and berberine, during 2008 to 2015, using ‘berberine’ and ‘Berberis vulgaris’ as search words. We found more than 1200 new article studying the properties and clinical uses of berberine and B. vulgaris, for treating tumor, diabetes, cardiovascular disease, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. In this article, we have updated the pharmacological effects of B. vulgaris and its active constituent, berberine. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-16T01:16:14.844591-05:
      DOI: 10.1002/ptr.5693
  • Overview of Oroxylin A: A Promising Flavonoid Compound
    • Authors: Lu Lu; Qinglong Guo, Li Zhao
      First page: 1765
      Abstract: Oroxylin A is one of the main active components extracted from Scutellariae radix. It has been proved that oroxylin A possesses a broad spectrum of pharmacological functions, including anti‐cancer, antiinflammation, neuroprotective, anti‐coagulation and so on. The pharmacological activity of oroxylin A has been studied in vitro and on animal models, which reflected its promising potency in disease treatment. This review aims to recapitulate the pharmacological function and the molecular mechanisms of oroxylin A, as well as its sources, extraction, synthesis and toxicity study. These data confirmed the therapeutic potential of oroxylin A and provided reference for further development. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-19T02:35:38.012663-05:
      DOI: 10.1002/ptr.5694
  • A Novel Extract of Fenugreek Husk (FenuSMART™) Alleviates Postmenopausal
           Symptoms and Helps to Establish the Hormonal Balance: A Randomized,
           Double‐Blind, Placebo‐Controlled Study
    • Authors: S. Shamshad Begum; H. K. Jayalakshmi, H. G. Vidyavathi, G. Gopakumar, Issac Abin, Maliakel Balu, K. Geetha, S. V. Suresha, M. Vasundhara, I. M. Krishnakumar
      First page: 1775
      Abstract: Despite the widespread use of hormone replacement therapy, various reports on its side effects have generated an increasing interest in the development of safe natural agents for the management of postmenopausal discomforts. The present randomized, double‐blinded, placebo‐controlled study investigated the effect of 90‐day supplementation of a standardized extract of fenugreek (Trigonella foenum‐graecum) (FenuSMART™), at a dose of 1000 mg/day, on plasma estrogens and postmenopausal discomforts. Eighty‐eight women having moderate to severe postmenopausal discomforts and poor quality of life (as evidenced from the scores of Greene Climacteric Scale, short form SF‐36® and structured medical interview) were randomized either to extract‐treated (n = 44) or placebo (n = 44) groups. There was a significant (p 
      PubDate: 2016-07-13T01:20:33.41771-05:0
      DOI: 10.1002/ptr.5680
  • In Vitro Assessment of Plants Growing in Cuba Belonging to Solanaceae
           Family Against Leishmania amazonensis
    • Authors: Lianet Monzote; Jenny Jiménez, Osmany Cuesta-Rubio, Ingrid Márquez, Yamile Gutiérrez, Cláudia Quintino Rocha, Mary Marchi, William N. Setzer, Wagner Vilegas
      First page: 1785
      Abstract: In this study, an in vitro antileishmanial assessment of plant extracts from 12 genera and 46 species growing in Cuba belonging to Solanaceae family was performed. A total of 226 extracts were screened against promastigotes of Leishmania amazonensis, and cytotoxicity of active extracts [median inhibitory concentration (IC50) promastigotes 5 were then assayed against intracellular amastigote. Metabolomics analysis of promissory extracts was performed using chemical profile obtained by ultra performance liquid chromatography. Only 11 extracts (4.9%) from nine plants were selected as potentially actives: Brunfelsia cestroides A. Rich, Capsicum annuum L., Capsicum chinense Jacq., Cestrum nocturnum L., Nicotiana plumbaginifolia Viv., Solanum havanense Jacq., Solanum myriacanthum Dunal, Solanum nudum Dunal and Solanum seaforthianum And., with IC50 5. Metabolomics analysis demonstrated significant differences in the chemical profiles with an average of 42.8 (range 31–88) compounds from m/z 104 to 1477, which demonstrated the complex mixture of compounds. In addition, no common markers among active extracts were identified. The results demonstrate the importance of the Solanaceae family to search new antileishmanial agents, particularly in unexplored species of this family. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-02T00:01:04.069015-05:
      DOI: 10.1002/ptr.5681
  • Bacopa monnieri‐Induced Protective Autophagy Inhibits
           Benzo[a]pyrene‐Mediated Apoptosis
    • Authors: Durgesh Nandini Das; Prajna Paramita Naik, Aditi Nayak, Prashanta Kumar Panda, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
      First page: 1794
      Abstract: Benzo[a]pyrene (B[a]P) is capable of inducing oxidative stress and cellular injuries leading to cell death and associates with a significant risk of cancer development. Prevention of B[a]P‐induced cellular toxicity with herbal compound through regulation of mitochondrial oxidative stress might protect cell death and have therapeutic benefit to human health. In this study, we demonstrated the cytoprotective role of Bacopa monnieri (BM) against B[a]P‐induced apoptosis through autophagy induction. Pretreatment with BM rescued the reduction in cell viability in B[a]P‐treated human keratinocytes (HaCaT) cells indicating the cytoprotective potential of BM against B[a]P. Moreover, BM was found to inhibit B[a]P‐mediated reactive oxygen species (ROS)‐induced apoptosis activation in HaCaT cells. Furthermore, BM was found to preserve mitochondrial membrane potential and inhibited release of cytochrome c in B[a]P‐treated HaCaT cells. Bacopa monnieri induced protective autophagy; we knocked down Beclin‐1, and data showed that BM was unable to protect from B[a]P‐induced mitochondrial ROS‐mediated apoptosis in Beclin‐1‐deficient HaCaT cells. Moreover, we established that B[a]P‐induced damaged mitochondria were found to colocalize and degraded within autolysosomes in order to protect HaCaT cells from mitochondrial injury. In conclusion, B[a]P‐induced apoptosis was rescued by BM treatment and provided cytoprotection through Beclin‐1‐dependent autophagy activation. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-19T03:05:30.026777-05:
      DOI: 10.1002/ptr.5682
  • Fucoxanthin Suppresses Lipid Accumulation and ROS Production During
           Differentiation in 3T3‐L1 Adipocytes
    • Authors: Min‐Jung Seo; Young‐Jin Seo, Cheol‐Ho Pan, Ok‐Hwan Lee, Kui‐Jin Kim, Boo‐Yong Lee
      First page: 1802
      Abstract: Fucoxanthin, a pigment from the chloroplasts of marine brown algae, has a number of effects against obesity, diabetes, inflammation and cancer and provides cerebrovascular protection. In this study, we investigated the inhibitory effects of fucoxanthin on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis. Treatment with fucoxanthin suppresses protein levels of the adipogenic transcription factors CCAAT/enhancer‐binding protein alpha C/EBPα and peroxisome proliferator‐activated receptor‐γ and of their target protein, fatty acid binding protein 4. Lipogenesis‐related enzymes, such as diglyceride acyltransferase 1 and lysophosphatidic acid acyltransferase‐θ, were downregulated by fucoxanthin. The ROS‐producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and the NADPH‐generating enzyme glucose‐6‐phosphate dehydrogenase also decreased following fucoxanthin treatment. The adipokine adiponectin and the ROS‐scavenging enzymes superoxide dismutase 2, glutathione reductase and catalase were dose‐dependently increased by fucoxanthin. Furthermore, lipolysis‐related enzymes and superoxide dismutase 1 were slightly decreased, because of the suppression of lipid‐generating factors and the cytosolic enzyme NOX4. To confirm these results, we investigated lipid accumulation and ROS production in zebrafish, where fucoxanthin suppressed lipid and triglyceride accumulation, as well as ROS production. Our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic and lipogenic factors and ROS‐regulating enzymes.We provide evidence that fucoxanthin suppresses protein levels of the adipogenic transcription factors and lipogenesis‐associated enzymes in 3T3‐L1. The reactive oxygen species (ROS) producing enzyme NOX4 and the nicotinamide adenine dinucleotide phosphate‐generating enzyme glucose‐6‐phosphate dehydrogenase is also decreased in 3T3‐L1 treated with fucoxanthin. Moreover, fucoxanthin inhibits the accumulation of intracellular lipid and the production of ROS in high‐fat diet‐induced obese zebrafish model. Therefore, our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic factors and ROS‐regulating enzymes in vitro and in vivo.
      PubDate: 2016-07-13T01:40:42.111458-05:
      DOI: 10.1002/ptr.5683
  • Synergistic Effect of SH003 and Doxorubicin in Triple‐negative
           Breast Cancer
    • Authors: Sang-Mi Woo; Ah Jeong Kim, Youn Kyung Choi, Young Cheol Shin, Sung-Gook Cho, Seong-Gyu Ko
      First page: 1817
      Abstract: Triple‐negative breast cancer (TNBC) is highly aggressive, resulting in poor prognosis. Chemotherapy of TNBC relies on anti‐cancer agents with strong cytotoxicity, but it causes several side effects with recurrence. While combinational approaches of chemotherapeutics have been highlighted as a new treatment strategy for TNBC to reduce side effects, combinations of anti‐cancer agents with herbal medicines have not been reported. We recently reported that newly modified traditional Chinese medicine named SH003 inhibited TNBC growth. Considering a combinational strategy for TNBC treatment, we further studied synergistic effects of SH003 with various anti‐cancer drugs in TNBC treatment. Here, we demonstrate that SH003 shows a synergistic effect with doxorubicin on TNBC treatment. Our in vitro cell viability assays revealed that SH003 and doxorubicin showed a synergistic effect in the well‐defined TNBC cell line, MDA‐MB‐231. Moreover, we found that the combinational treatment caused Caspase‐dependent apoptotic cell death. Our in vivo mouse xenograft tumor growth assays confirmed that combinational treatment of SH003 with doxorubicin repressed MDA‐MB‐231 tumor growth with no weight loss. Therefore, we conclude that the combinational treatment of SH003 with doxorubicin shows the synergism in TNBC treatment, and suggest that SH003 can be used together with conventional anti‐cancer drugs in chemotherapeutic approaches. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-01T06:10:33.902122-05:
      DOI: 10.1002/ptr.5687
  • Flavonoids Isolated from Flowers of Lonicera japonica Thunb. Inhibit
           Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF‐α and
           IL‐β Through PI3K/Akt/NF‐kb Signaling Pathways
    • Authors: Min Ho Han; Won Sup Lee, Arulkumar Nagappan, Su Hyun Hong, Ji Hyun Jung, Cheol Park, Hye Jung Kim, Gi-Young Kim, GonSup Kim, Jin-Myung Jung, Chung Ho Ryu, Sung Chul Shin, Soon Chan Hong, Yung Hyun Choi
      First page: 1824
      Abstract: Decoctions of the dried flowers of Lonicera japonica Thunb. (Indongcho) have been utilized in folk remedies against various inflammatory diseases, and it is reported neuroprotective effects. The cytokines release from microglia is closely linked to various chronic neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. It is still unknown whether the neuroprotective effects are associated with the antiinflammatory effects. Here, we determined whether polyphenols extracted from lyophilized Lonicera japonica Thunb. (PELJ) would inhibit inflammatory cytokines and mediators. We stimulated microglia with lipopolysaccharide (LPS) to produce inflammatory cytokines, and then assessed the effects of PELJ on these cytokines. PELJ significantly inhibited LPS‐induced interleukin‐1β and tumor necrosis factor‐α expressions and LPS‐induced nitric oxide (NO) and prostaglandin E2 expressions by down‐regulating inducible enzyme NO synthase and cyclooxygenase‐2 at the protein and mRNA levels. All the suppression of these mediators did not cause any significant cytotoxicity. PELJ also inhibited the nuclear translocation of nuclear factor‐kappa B and phosphorylated Akt. These findings suggest that PELJ may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases by inhibiting pro‐inflammatory cytokines through inhibiting phosphoinositol 3‐kinase /Akt/nuclear factor‐kappa B signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-18T02:10:53.47435-05:0
      DOI: 10.1002/ptr.5688
  • Apigenin Inhibits Cancer Stem Cell‐Like Phenotypes in Human Glioblastoma
           Cells via Suppression of c‐Met Signaling
    • Authors: Boram Kim; Narae Jung, Sanghun Lee, Jae Kyung Sohng, Hye Jin Jung
      First page: 1833
      Abstract: Glioblastoma (GBM) is a highly malignant human brain tumor with limited treatment choices. The extremely aggressive characteristics of GBM result from GBM stem cells (GSCs), a subpopulation in tumor having self‐renewal potential and resistance to chemotherapy and radiotherapy. Therefore, eliminating GSCs is an effective strategy to treat this fatal disease. In this study, we investigated the therapeutic effects of dietary flavonoids, including apigenin, quercetin, and naringenin, against cancer stem cell‐like phenotypes of human GBM cell lines U87MG and U373MG. Among flavonoids studied, apigenin and quercetin significantly suppressed not only the self‐renewal capacity such as cell growth and clonogenicity, but also the invasiveness of GBM stem‐like cells. Notably, apigenin blocked the phosphorylation of c‐Met and its downstream effectors, transducer and activator of transcription 3, AKT (Protein kinase B), and mitogen‐activated protein kinase in the GSCs, thereby reducing the expression levels of GSC markers such as CD133, Nanog, and Sox2. These results suggest that the GSC inhibition effect of apigenin may be caused by downregulation of c‐Met signaling pathway.
      PubDate: 2016-07-29T02:15:53.862272-05:
      DOI: 10.1002/ptr.5689
  • Obovatol Induces Apoptosis in Non‐small Cell Lung Cancer Cells via C/EBP
           Homologous Protein Activation
    • Authors: Heejeong Kim; Eun Ah Shin, Chang Geun Kim, Dae Young Lee, Bonglee Kim, Nam-In Baek, Sung-Hoon Kim
      First page: 1841
      Abstract: Although obovatol, a phenolic compound from the bark of Magnolia obovata, was known to have antioxidant, neuroprotective, antiinflammatory, antithrombotic and antitumour effects, its underlying antitumour mechanism is poorly understood so far. Thus, in the present study, the antitumour molecular mechanism of obovatol was investigated in non‐small cell lung cancer cells (NSCLCs). Obovatol exerted cytotoxicity in A549 and H460 NSCLCs, but not in BEAS‐2B cells. Also, obovatol increased sub‐G1 accumulation and early and late apoptotic portion in A549 and H460 NSCLCs. Consistently, obovatol cleaved PARP, activated caspase 9/3 and Bax and attenuated the expression of cyclin D1 in A549 and H460 NSCLCs. Interestingly, obovatol upregulated the expression of endoplasmic reticulum stress proteins such as C/EBP homologous protein (CHOP), IRE1α, ATF4 and p‐elF2 in A549 and H460 NSCLCs. Conversely, depletion of CHOP blocked the apoptotic activity of obovatol to increase sub‐G1 accumulation in A549 and H460 NSCLCs. Overall, our findings support scientific evidences that obovatol induces apoptosis via CHOP activation in A549 and H460 NSCLCs. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-04T02:08:40.218167-05:
      DOI: 10.1002/ptr.5690
  • Effect of the Capsicoside G‐rich Fraction from Pepper (Capsicum annuum
           L.) Seeds on High‐fat Diet‐induced Obesity in Mice
    • Authors: Jeehye Sung; Heon Sang Jeong, Junsoo Lee
      First page: 1848
      Abstract: Obesity is one of the most common metabolic syndromes and is a major threat to human health worldwide. Given the size of this problem, there is growing interest in natural agents that may decrease obesity. In this study, we investigated the anti‐obesity effect of a capsicoside G‐rich fraction (CRF; 13.35% capsicoside G) isolated from pepper seeds in diet‐induced obese mice. C57BL/6J mice were fed either a normal diet or a high‐fat diet (HFD), with or without CRF (HFD + CRF; 10 and 100 mg/kg body weight). The body weight and food efficiency ratio of mice fed HFD + CRF were lower in comparison to that of mice fed only an HFD. Epididymal adipose tissue weight and adipocyte hypertrophy were significantly lower in HFD + CRF mice than in HFD mice. The fat deposition in the liver of mice fed HFD + CRF was lower compared to that of mice fed only an HFD. CRF significantly reversed the HFD‐induced elevation of the expression of key adipocyte differentiation regulators, including peroxisome proliferator‐activated receptor γ, CCAAT/enhancer‐binding protein α, sterol regulatory element binding protein 1c, and their target genes. These results suggest that CRF could be used as dietary therapy for the prevention of obesity and obesity‐related metabolic diseases. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-19T02:15:32.808712-05:
      DOI: 10.1002/ptr.5692
  • Magnolol Enhances Hippocampal Neurogenesis and Exerts
           Antidepressant‐Like Effects in Olfactory Bulbectomized Mice
    • Authors: Nobuaki Matsui; Haruka Akae, Nana Hirashima, Yuki Kido, Satoshi Tanabe, Mayumi Koseki, Yoshiyasu Fukuyama, Masaaki Akagi
      First page: 1856
      Abstract: Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain‐derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin‐related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5‐bromo‐2′‐deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX‐induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein after 3 h. The present data indicate that magnolol exerts antidepressant‐like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin‐related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-11T04:45:26.62144-05:0
      DOI: 10.1002/ptr.5695
  • Cytotoxic activity of Secondary Metabolites from Marine‐derived Fungus
           Neosartorya siamensis in Human Cancer Cells
    • Authors: M. Prata-Sena; A.A. Ramos, S. Buttachon, B. Castro-Carvalho, P. Marques, T. Dethoup, A. Kijjoa, E. Rocha
      First page: 1862
      Abstract: Compounds isolated from the marine sea fan‐derived fungus Neosartorya siamensis (KUFA 0017), namely, 2,4‐dihydroxy‐3‐methylacetophenon (1), chevalone C (2), nortryptoquivaline (4), tryptoquivaline H (6), tryptoquivaline F (7), fiscalin A (8), epi‐fiscalin A (9), epi‐neofiscalin A (11) and epi‐fiscalin C (13) were tested for anti‐proliferative activity by MTT assay, DNA damage induction by comet assay, and induction of cell death by nuclear condensation assay on colon HCT116, liver HepG2 and melanoma A375 cancer cell lines. Compounds 2, 4, 8, 9, 11 and 13 presented IC50 values ranging from 24 to 153 μM in the selected cell lines. Cell death was induced in HCT116 by compounds 2, 4 and 8. In HepG2, compounds 4, 8, 9 and 11 were able to induce significant cell death. This induction of cell death is possibly not related to genotoxicity because none of the compounds induced significant DNA damage. These results suggest that selected compounds present an interesting anti‐proliferative activity and cell death induction, consequently showing potential (specifically epi‐fiscalin C) as future leads for chemotherapeutic agents. Further studies on mechanisms of action should ensue. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-17T00:35:32.17262-05:0
      DOI: 10.1002/ptr.5696
  • The Inhibition of UDP‐Glucuronosyltransferase (UGT) Isoforms by
           Praeruptorin A and B
    • Authors: Xin Liu; Da-Wei Chen, Xue Wu, Zhenying Zhao, Zhi-Wei Fu, Chun-Ting Huang, Li-Xin Ye, Zuo Du, Yang Yu, Zhong-Ze Fang, Hong-Zhi Sun
      First page: 1872
      Abstract: Praeruptorin A (PA) and B (PB) are two important compounds isolated from Bai‐hua Qian‐hu and have been reported to exert multiple biochemical and pharmacological activities. The present study aims to determine the inhibition of PA and PB on the activity of important phase II drug‐metabolizing enzymes uridine 5'‐diphospho‐glucuronosyltransferase (UGTs) isoforms. In vitro UGT incubation system was used to determine the inhibition potential of PA and PB on the activity of various UGT isoforms. In silico docking was performed to explain the inhibition difference between PA and PB towards the activity of UGT1A6. Inhibition behaviour was determined, and in vitro–in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (Ki) and in vivo exposure level of PA. Praeruptorin A (100 μM) exhibited the strongest inhibition on the activity of UGT1A6 and UGT2B7, with 97.8% and 90.1% activity inhibited by 100 μM of PA, respectively. In silico docking study indicates the significant contribution of hydrogen bond interaction towards the stronger inhibition of PA than PB towards UGT1A6. Praeruptorin A noncompetitively inhibited the activity of UGT1A6 and competitively inhibited the activity of UGT2B7. The inhibition kinetic parameter (Ki) of PA towards UGT1A6 and UGT2B7 was calculated to be 1.2 and 3.3 μM, respectively. The [I]/Ki value was calculated to be 15.8 and 5.8 for the inhibition of PA on UGT1A6 and UGT2B7, indicating high inhibition potential of PA towards these two UGT isoforms in vivo. Therefore, closely monitoring the interaction between PA and drugs mainly undergoing UGT1A6 or UGT2B7‐catalyzed metabolism is very necessary. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-18T01:25:28.179214-05:
      DOI: 10.1002/ptr.5697
  • Effect of Oral Silymarin Administration on Prevention of Radiotherapy
           Induced Mucositis: A Randomized, Double‐Blinded, Placebo‐Controlled
           Clinical Trial
    • Authors: Sepideh Elyasi; Sare Hosseini, Mohammad Reza Niazi Moghadam, Seyed Amir Aledavood, Gholamreza Karimi
      First page: 1879
      Abstract: Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty‐seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute–Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p 
      PubDate: 2016-08-23T21:45:25.202697-05:
      DOI: 10.1002/ptr.5704
  • Effect of Ginkgo Biloba Extract on the Pharmacokinetics and Metabolism of
           Clopidogrel in Rats
    • Authors: Ying Deng; Yu-fei Mo, Xin-meng Chen, Lv-zhao Zhang, Chao-feng Liao, Yu Song, Chenshu Xu
      First page: 1886
      Abstract: Ginkgo biloba extract (GBE), a traditional herbal product used worldwide as both medicine and supplement, is often supplied with clopidogrel for the treatment of cerebrovascular diseases. The aim of the current study was to explore the effect of GBE on the metabolism and pharmacokinetics of clopidogrel. The in vitro study using rat liver microsomes revealed that GBE significantly induced the conversion of clopidogrel into its active metabolite. The effect of GBE on the pharmacokinetics of clopidogrel was also investigated in vivo. Compared to rats without GBE pretreatment, administration of 4 mg/kg, 20 mg/kg, and 100 mg/kg of GBE significantly decreased the Cmax and the AUC0–∞ of clopidogrel in a dose‐dependent manner. As expected, pretreatment of high dose GBE significantly increased the Cmax and AUC0–∞ of the clopidogrel active metabolite. However, no marked change was observed following medium and low dose of GBE, suggesting that the biotransformation of clopidogrel was altered differently by high dose of GBE. Our study suggested that the awareness of the potential herb–drug interactions between GBE and clopidogrel should be increased in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-08-04T03:36:58.433627-05:
      DOI: 10.1002/ptr.5691
  • (-)-Epigallocatechin-3-Gallate Antihyperalgesic Effect Associates With
           Reduced CX3CL1 Chemokine Expression in Spinal Cord
    • Abstract: (-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the neuropathic pain alleviation in animal models. Because chemokine fractalkine (CX3CL1) has been suggested as an important signal during neuropathic pain development, this study aimed to investigate whether CX3CL1 expression may be modulated by EGCG treatment reducing hyperalgesia in chronic constriction injured mice. To this end, Balb/c mice were subjected to a chronic constriction injury of sciatic nerve (CCI) and treated with EGCG or vehicle once a day during the first week following surgery. Thermal hyperalgesia was tested at 7 and 14 days post-surgery, and the expression of CX3CL1 and its mRNA were analyzed in spinal cord at the end of the experimental period. Results revealed that EGCG treatment significantly reduced thermal hyperalgesia in CCI-injured mice at short time, and this antihyperalgesic effect was associated with a down-regulation of CX3CL1 protein expression in the spinal cord. On the other hand, EGCG treatment did not affect the CX3CL1 transcription. Overall, our results suggest a new role of EGCG-treatment in an experimental model of neuropathic pain as a mediator of nociceptive signaling cross talk between neurons and glial cells in the dorsal horn of the spinal cord. Copyright © 2016 John Wiley & Sons, Ltd.
  • Flavonoids of Herba Epimedii Enhances Bone Repair in a Rabbit Model of
           Chronic Osteomyelitis During Post-infection Treatment and Stimulates
           Osteoblast Proliferation in Vitro
    • Abstract: Flavonoids are the active component of the Herba Epimedii (H. Epimedii), which is commonly used in Asia. This study is to investigate the effect of H. Epimedii on bone repair after anti-infection treatment in vivo. The bioactive-composition group of H. Epimedii (BCGE) contained four flavonoids with the total content of 43.34%. Rabbits with chronic osteomyelitis in response to injection with Staphylococcus aureus were treated with BCGE of 242.70 mg/kg/day intragastrically after vancomycin-calcium sulphate treatment. Micro-computerd tomography (CT), morphology, blood biochemistry and osteocalcin levels were assessed for effect evaluation. In addition, the rat calvarial osteoblasts infected with S. aureus were treated with vancomycin and BCGE. Cell viability, alkaline phosphatase activity, bone morphogenetic protein 2, Runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor-κB ligand mRNA levels and protein expression were assessed. Our results indicated that BCGE promoted bone repair via increasing the bone mass, the volume of bone, promoting osteocalcin secretion after vancomycin-calcium sulfate treatment. BCGE enhanced the cell proliferation, by regulating bone morphogenetic protein 2, runt-related transcription factor 2, and osteoprotegerin/receptor activator of nuclear factor κ-B ligand mRNA and protein expression to maintain the balance between bone formation and bone resorption. Therefore, BCGE is a potential adjuvant herbal remedy for the post-infection treatment of chronic osteomyelitis. Copyright © 2016 John Wiley & Sons, Ltd.
  • Diterpenes as lead molecules against neglected tropical diseases
    • Abstract: Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd.
  • Mulberrofuran G Protects Ischemic Injury-induced Cell Death via Inhibition
           of NOX4-mediated ROS Generation and ER Stress
    • Abstract: The aim of this study was to investigate the neuroprotective effect of mulberrofuran G (MG) in in vitro and in vivo models of cerebral ischemia. MG was isolated from the root bark of Morus bombycis. MG inhibited nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme activity and oxygen–glucose deprivation/reoxygenation (OGD/R)-induced NOX4 protein expression in SH-SY5Y cells. MG inhibited the expression of activated caspase-3 and caspase-9 and cleaved poly adenine dinucleotide phosphate-ribose polymerase in OGD/R-induced SH-SY5Y cells. In addition, MG protected OGD/R-induced neuronal cell death and inhibited OGD/R-induced reactive oxygen species generation in SH-SY5Y cells. In in vivo model, MG-treated groups (0.2, 1, and 5 mg/kg) reduced the infarct volume in middle cerebral artery occlusion/reperfusion-induced ischemic rats. The MG-treated groups also reduced NOX4 protein expression in middle cerebral artery occlusion/reperfusion-induced ischemic rats. Furthermore, protein expression of 78-kDa glucose-regulated protein/binding immunoglobulin protein, phosphorylated IRE1α, X-box-binding protein 1, and cytosine enhancer binding protein homologous protein, mediators of endoplasmic reticulum stress, were inhibited in MG-treated groups. Taken together, MG showed protective effect in in vitro and in vivo models of cerebral ischemia through inhibition of NOX4-mediated reactive oxygen species generation and endoplasmic reticulum stress. This finding will give an insight that inhibition of NOX enzyme activity and NOX4 protein expression could be a new potential therapeutic strategy for cerebral ischemia. Copyright © 2016 John Wiley & Sons, Ltd.
  • Side-Effects of Irinotecan (CPT-11), the Clinically Used Drug for Colon
           Cancer Therapy, Are Eliminated in Experimental Animals Treated with Latex
           Proteins from Calotropis procera (Apocynaceae)
    • Abstract: Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1β, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
  • Metabolomics Reveals that Momordica charantia Attenuates Metabolic Changes
           in Experimental Obesity
    • Abstract: Momordica charantia L., also known as bitter melon, has been shown to ameliorate obesity and insulin resistance. However, metabolic changes regulated by M. charantia in obesity are not clearly understood. In this study, serums obtained from obese and M. charantia-treated mice were analyzed by using gas and liquid chromatography-mass spectrometry, and multivariate statistical analysis was performed by Orthogonal partial least squares discriminant analysis. The results from this study indicated that body weight fat and insulin levels of obese mice are dramatically suppressed by 8 weeks of dietary supplementation of M. charantia. Metabolomic data revealed that overproductions of energy and nutrient metabolism in obese mice were restored by M. charantia treatment. The antiinflammatory and inhibition of insulin resistance effect of M. charantia in obesity was illustrated with the restoration of free fatty acids and eicosanoids. The findings achieved in this study further strengthen the therapeutic value of using M. charantia to treat obesity. Copyright © 2016 John Wiley & Sons, Ltd.
  • Withanolides against TLR4-Activated Innate Inflammatory Signalling
           Pathways: A Comparative Computational and Experimental Study
    • Abstract: Innate inflammations are dominant causes of poor health and high mortality. The pathogen-associated molecular pattern and lipopolysaccharide (LPS) are sensed by immune cells through activation of toll-like receptor 4 leading to mitogen-activated protein kinases (MAPKs) and NF-κB activations. Controlled MAPK and Nf-κB inhibitors have been proposed as potential antiinflammatory drugs. Withania somnifera is an important medicinal herb with known antiinflammatory activity. In this study, the selected Withania somnifera extracts and withanolides were analysed on LPS-induced macrophages comparatively. Molecular docking analysis revealed withaferin A, withanone and withanolide A as effective withanolides against inflammatory target molecules. In experiments, withaferin A and withanone treatment had prominent suppressions on LPS-induced expression of pro-inflammatory cytokines in bone marrow-derived macrophages. Withaferin A regulated all the major four pathways (MAPKs and NF-κB) involved in innate inflammations. Similarly among the Withania extracts analysed, the in vitro propagated leaf and field grown root extracts containing high withaferin A content suppressed the inflammatory molecules through NF-κB and MAPK pathways. Withaferin A was found to be best in suppressing the activated inflammatory pathways among all the analysed withanolides. Therefore, withaferin A and extracts with high withaferin A content can be used as promising drug candidates against innate inflammations. Copyright © 2016 John Wiley & Sons, Ltd.
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