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Publisher: John Wiley and Sons   (Total: 1607 journals)

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Oxford Bulletin of Economics and Statistics     Hybrid Journal   (Followers: 17, SJR: 1.201, h-index: 45)
Oxford J. of Archaeology     Hybrid Journal   (Followers: 72, SJR: 0.54, h-index: 14)
Oxonomics     Hybrid Journal   (Followers: 1)
Pacific Economic Review     Hybrid Journal   (Followers: 2, SJR: 0.639, h-index: 19)
Pacific Focus     Hybrid Journal   (Followers: 1, SJR: 0.315, h-index: 5)
Pacific Philosophical Quarterly     Hybrid Journal   (Followers: 7, SJR: 0.962, h-index: 14)
Pacing and Clinical Electrophysiology     Hybrid Journal   (Followers: 4, SJR: 0.927, h-index: 77)
Packaging Technology and Science     Hybrid Journal   (Followers: 10, SJR: 0.72, h-index: 27)
Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 3, SJR: 1.429, h-index: 58)
Pain Medicine     Hybrid Journal   (Followers: 5, SJR: 0.929, h-index: 55)
Pain Practice     Hybrid Journal   (Followers: 2, SJR: 0.835, h-index: 30)
Palaeontology     Hybrid Journal   (Followers: 13, SJR: 1.111, h-index: 40)
PAMM : Proceedings in Applied Mathematics and Mechanics     Free  
Papers In Regional Science     Hybrid Journal   (Followers: 6, SJR: 1.332, h-index: 34)
Parasite Immunology     Hybrid Journal   (Followers: 4, SJR: 0.916, h-index: 55)
Parliamentary History     Hybrid Journal   (Followers: 5, SJR: 0.151, h-index: 3)
Particle & Particle Systems Characterization     Hybrid Journal   (SJR: 0.226, h-index: 28)
Pathology Intl.     Hybrid Journal   (SJR: 0.831, h-index: 53)
Peace & Change     Hybrid Journal   (Followers: 5)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 4, SJR: 1.325, h-index: 62)
Pediatric Anesthesia     Hybrid Journal   (Followers: 4, SJR: 0.95, h-index: 53)
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 4, SJR: 1.252, h-index: 67)
Pediatric Dermatology     Hybrid Journal   (Followers: 5, SJR: 0.739, h-index: 50)
Pediatric Diabetes     Hybrid Journal   (Followers: 14, SJR: 1.027, h-index: 43)
Pediatric Obesity     Hybrid Journal   (Followers: 4, SJR: 1.336, h-index: 33)
Pediatric Pulmonology     Hybrid Journal   (Followers: 2, SJR: 1.092, h-index: 77)
Pediatric Transplantation     Hybrid Journal   (SJR: 0.663, h-index: 49)
Pediatrics Intl.     Hybrid Journal   (Followers: 3, SJR: 0.443, h-index: 42)
Performance Improvement     Hybrid Journal   (Followers: 3)
Performance Improvement Quarterly     Hybrid Journal   (Followers: 1, SJR: 0.362, h-index: 7)
Periodontology 2000     Hybrid Journal   (Followers: 4, SJR: 1.467, h-index: 74)
Permafrost and Periglacial Processes     Hybrid Journal   (Followers: 3, SJR: 1.741, h-index: 46)
Personal Relationships     Hybrid Journal   (Followers: 3, SJR: 1.355, h-index: 45)
Personality and Mental Health     Hybrid Journal   (Followers: 12, SJR: 0.39, h-index: 7)
Personnel Psychology     Hybrid Journal   (Followers: 23, SJR: 5.796, h-index: 80)
Perspectives In Psychiatric Care     Hybrid Journal   (Followers: 1, SJR: 0.349, h-index: 20)
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 3, SJR: 1.566, h-index: 66)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (Followers: 1, SJR: 0.283, h-index: 8)
Pest Management Science     Hybrid Journal   (Followers: 5, SJR: 1.262, h-index: 72)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 7, SJR: 0.959, h-index: 20)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 23, SJR: 1.631, h-index: 59)
Pharmacology Research & Perspectives     Open Access  
Pharmacotherapy The J. of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 18, SJR: 0.852, h-index: 78)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 1, SJR: 0.105, h-index: 9)
Philosophical Books     Hybrid Journal   (Followers: 8)
Philosophical Investigations     Hybrid Journal   (Followers: 3, SJR: 0.162, h-index: 6)
Philosophical Issues     Hybrid Journal   (Followers: 8, SJR: 1.009, h-index: 2)
Philosophical Perspectives     Hybrid Journal   (Followers: 6)
Philosophy & Public Affairs     Hybrid Journal   (Followers: 19, SJR: 1.607, h-index: 29)
Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 17, SJR: 1.629, h-index: 11)
Philosophy Compass     Hybrid Journal   (Followers: 8, SJR: 0.282, h-index: 2)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.764, h-index: 96)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 2, SJR: 0.642, h-index: 42)
Phycological Research     Hybrid Journal   (Followers: 2, SJR: 0.405, h-index: 21)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.81, h-index: 72)
physica status solidi (b)     Hybrid Journal   (Followers: 1, SJR: 0.852, h-index: 70)
physica status solidi (c)     Hybrid Journal   (Followers: 1, SJR: 0.471, h-index: 31)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (Followers: 1, SJR: 1.166, h-index: 32)
Physik in unserer Zeit     Hybrid Journal   (Followers: 1)
Physik J.     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (Followers: 1, SJR: 1.442, h-index: 95)
Physiological Entomology     Hybrid Journal   (Followers: 2, SJR: 0.768, h-index: 38)
Physiological Reports     Open Access  
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 27, SJR: 0.396, h-index: 30)
Phytochemical Analysis     Hybrid Journal   (Followers: 1, SJR: 0.959, h-index: 45)
Phytotherapy Research     Hybrid Journal   (SJR: 0.82, h-index: 76)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 3, SJR: 2.572, h-index: 72)
Plant Biotechnology J.     Hybrid Journal   (Followers: 5, SJR: 2.463, h-index: 58)
Plant Breeding     Hybrid Journal   (Followers: 14, SJR: 0.626, h-index: 49)
Plant Pathology     Hybrid Journal   (Followers: 7, SJR: 1.114, h-index: 50)
Plant Species Biology     Hybrid Journal   (Followers: 3, SJR: 0.509, h-index: 26)
Plant, Cell & Environment     Hybrid Journal   (Followers: 5, SJR: 2.821, h-index: 121)
Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.231, h-index: 40)
Poe Studies     Partially Free   (Followers: 5)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 12, SJR: 0.415, h-index: 3)
Policy & Internet     Hybrid Journal   (Followers: 8)
Policy Studies J.     Hybrid Journal   (Followers: 5, SJR: 1.362, h-index: 30)
Political Insight     Partially Free   (Followers: 1)
Political Psychology     Hybrid Journal   (Followers: 17, SJR: 1.885, h-index: 45)
Political Science Quarterly     Hybrid Journal   (Followers: 31, SJR: 0.378, h-index: 26)
Political Studies     Hybrid Journal   (Followers: 24, SJR: 1.107, h-index: 39)
Political Studies Review     Hybrid Journal   (Followers: 15, SJR: 0.488, h-index: 12)
Politics     Hybrid Journal   (Followers: 8, SJR: 0.517, h-index: 12)
Politics & Policy     Hybrid Journal   (Followers: 6, SJR: 0.347, h-index: 8)
Polymer Composites     Hybrid Journal   (Followers: 10, SJR: 0.67, h-index: 53)
Polymer Engineering & Science     Hybrid Journal   (Followers: 13, SJR: 0.572, h-index: 76)
Polymer Intl.     Hybrid Journal   (Followers: 3, SJR: 0.847, h-index: 67)
Polymers for Advanced Technologies     Hybrid Journal   (Followers: 3, SJR: 0.833, h-index: 57)
Population and Development Review     Hybrid Journal   (Followers: 3, SJR: 2.686, h-index: 56)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.836, h-index: 33)
Poverty & Public Policy     Hybrid Journal   (Followers: 13)
Practical Diabetes     Hybrid Journal   (Followers: 6, SJR: 0.175, h-index: 3)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 1.262, h-index: 69)
Prescriber     Hybrid Journal   (Followers: 7)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 4)
Preventive Cardiology     Hybrid Journal   (Followers: 3, SJR: 0.839, h-index: 23)
Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 27, SJR: 0.169, h-index: 21)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (Followers: 3, SJR: 0.381, h-index: 16)
Process Safety Progress     Hybrid Journal   (Followers: 4, SJR: 0.387, h-index: 22)

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Journal Cover   Phytotherapy Research
  [SJR: 0.82]   [H-I: 76]   Follow
   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  [1607 journals]
  • Preclinical Pharmacokinetics and Pharmacodynamics and Content Analysis of
           Gnetol in Foodstuffs
    • Authors: Connie M. Remsberg; Stephanie E. Martinez, Bolanle C. Akinwumi, Hope D. Anderson, Jody K. Takemoto, Casey L. Sayre, Neal M. Davies
      Abstract: Studies were undertaken to evaluate the bioavailability in rats and content analysis of gnetol in Gnetum gnemon products reported to contain gnetol and to examine the pharmacological properties of gnetol in in vitro models including anti‐inflammatory/analgesic, antidiabetic, anti‐adipogenesis, and anticancer activity. Male Sprague–Dawley rats were cannulated and dosed either intravenously with gnetol (10 mg/kg) or orally (100 mg/kg). Various methanolic extractions of G. gnemon products were quantified. Gnetol's effect on cell viability in selected cell lines with or without inflammatory stimulus was assessed. α‐Amylase and α‐glucosidase inhibition was evaluated. Cyclooxygenase (COX)‐1, COX‐2, and histone deacetylase inhibition and adipogenesis inhibition were examined. After oral and intravenous administration, gnetol was detected in both serum and urine as the parent compound and as a glucuronidated metabolite. The bioavailability of gnetol was determined to be 6%. Gnetol is rapidly glucuronidated and is excreted in urine and via nonrenal routes. Gnetol was found to exist as an aglycone and as a glycoside in G. gnemon products. Gnetol showed concentration‐dependent reductions in cell viability in cancer cell lines with greatest activity in colorectal cancer and potent COX‐1, histone deacetylase, and weak COX‐2 activities along with limited reduction in inflammation. Gnetol also possessed concentration‐dependent alpha‐amylase, alpha‐glucosidase, and adipogenesis activities. Pretreatment of mice with gnetol was able to increase the latency period to response in analgesia models. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-04T01:41:59.548364-05:
      DOI: 10.1002/ptr.5363
  • Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with
           Cancer Drugs in Rhabdomyosarcoma Cell Lines
    • Authors: Cheppail Ramachandran; Karl‐W. Quirin, Enrique A. Escalon, Ivonne V. Lollett, Steven J. Melnick
      Abstract: Synergistic effect of supercritical CO2 extracts of Curcuma species with conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger) (CA) extract showed the highest levels of cytotoxicity with inhibitory concentration IC50 values of 7.133 µg/ml and 7.501 µg/ml for SJRH30 and RD cell lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma xanthorrhiza (Javanese turmeric) extracts. CA showed synergistic cytotoxic effects with vinblastine (VBL) and cyclophosphamide (CP) as indicated by the combination index values of
      PubDate: 2015-05-04T00:59:49.030551-05:
      DOI: 10.1002/ptr.5360
  • Pycnogenol® in Metabolic Syndrome and Related Disorders
    • Authors: Om P. Gulati
      Abstract: The present review provides an update of the biological actions of Pycnogenol® in the treatment of metabolic syndrome and related disorders such as obesity, dyslipidaemia, diabetes and hypertension. Pycnogenol® is a French maritime pine bark extract produced from the outer bark of Pinus pinaster Ait. Subsp. atlantica. Its strong antioxidant, antiinflammatory, endothelium‐dependent vasodilator activity, and also its anti‐thrombotic effects make it appropriate for targeting the multifaceted pathophysiology of metabolic syndrome. Clinical studies have shown that it can reduce blood glucose levels in people with diabetes, blood pressure in mild to moderate hypertensive patients, and waist circumference, and improve lipid profile, renal and endothelial functions in metabolic syndrome. This review highlights the pathophysiology of metabolic syndrome and related clinical research findings on the safety and efficacy of Pycnogenol®. The results of clinical research studies performed with Pycnogenol® are discussed using an evidence‐based, target‐oriented approach following the pathophysiology of individual components as well as in metabolic syndrome overall. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-01T03:01:18.157079-05:
      DOI: 10.1002/ptr.5341
  • Antifungal Activity of Ellagic Acid In Vitro and In Vivo
    • Authors: Zhi‐Jian Li; Xin Guo, Gulina Dawuti, Silafu Aibai
      Abstract: Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti‐inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38‐A and M27‐A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC‐based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α‐demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm2) significantly enhanced the cure rate in a guinea‐pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-28T03:16:39.153432-05:
      DOI: 10.1002/ptr.5340
  • Influence of a Specialized Trigonella foenum‐graecum Seed Extract
           (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy
           Menstruating Women, a Randomised Placebo Controlled Study
    • Authors: Amanda Rao; Elizabeth Steels, Gavin Beccaria, Warrick J. Inder, Luis Vitetta
      Abstract: The aim of the study was to evaluate the effect of Trigonella foenum‐graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo‐controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum‐graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self‐administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI‐20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum‐graecum may be a useful treatment for increasing sexual arousal and desire in women. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-24T01:55:12.889074-05:
      DOI: 10.1002/ptr.5355
  • A Review: The Pharmacology of Isoliquiritigenin
    • Authors: Fu Peng; Qiaohui Du, Cheng Peng, Neng Wang, Hailin Tang, Xiaoming Xie, Jiangang Shen, Jianping Chen
      Abstract: Isoliquiritigenin (ISL) is one of the bioactive ingredients isolated from the roots of plants belonging to licorice, including Glycyrrhiza uralensis, Mongolian glycyrrhiza, Glycyrrhiza glabra, and so forth. Liquiritigenin is available in common foods and alternative medicine, and its derivative‐ISL is applied into food additives and disease treatment like cancer therapy, antibiotic therapy, and so on. This review aims at providing a comprehensive summary of the pharmacological activities of ISL. The information published between 1972 and 2014 from a number of reliable sources including PubMed, ScienceDirect, Springer, and Wiley‐Blackwell. The practical application of ISL on the various disease prevention and treatments may stem from its numerous pharmacological properties such as antiinflammatory, anti‐microbial, anti‐oxidative, anticancer activities, immunoregulatory, hepatoprotective, and cardioprotective effects. However, further studies are needed to verify the target‐organ toxicity or side effects investigation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-24T01:21:24.029866-05:
      DOI: 10.1002/ptr.5348
  • In Vitro Assessment of the Anticancer Potential of Evodiamine in Human
           Oral Cancer Cell Lines
    • Authors: Khadka Sachita; Yongsoo Kim, Hyun‐Ju Yu, Sung‐Dae Cho, Jeong‐Sang Lee
      Abstract: Evodiamine, a bioactive alkaloid, has been regarded as having antioxidant, antiinflammatory, and anticancer properties. In the present study, we explored the effects of evodiamine on cell growth and apoptosis in human oral cancer cell lines. Our data revealed that evodiamine significantly inhibited the proliferation of human oral cancer cells and resulted in the cleavages of PARP (poly (ADP‐ribose) polymerase) and caspase‐3, in addition to causing the typical characteristics of apoptosis. Evodiamine also increased Bax protein levels and caused translocation of Bax into mitochondria and Bax oligomerization. In addition, evodiamine decreased expression of myeloid cell leukemia (Mcl‐1) at the transcriptional modification, and knockdown of Mcl‐1 clearly resulted in an increase in expression of Bax and active Bax, resulting in induction of apoptosis. Evodiamine reduced expression of phosphorylated AKT, and LY294002 potentiated evodiamine‐induced apoptosis by regulating Mcl‐1 protein. Our results suggest that evodiamine induces apoptosis in human oral cancer cells through the AKT pathway. These findings provide a rationale for its clinical application in the treatment of oral cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-22T21:33:05.760396-05:
      DOI: 10.1002/ptr.5359
  • The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the
           Senescent Mouse Model Induced by a Combination of d‐gal and AlCl3
    • Authors: Xiao‐Ming Peng; Li Gao, Shi‐Xia Huo, Xin‐Min Liu, Ming Yan
      Abstract: Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d‐galactose and AlCl3, and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step‐down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase‐3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase‐3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T04:30:42.537855-05:
      DOI: 10.1002/ptr.5358
  • Memory Enhancement of Acteoside (Verbascoside) in a Senescent Mice Model
           Induced by a Combination of d‐gal and AlCl3
    • Authors: Li Gao; Xiao‐Ming Peng, Shi‐Xia Huo, Xin‐Ming Liu, Ming Yan
      Abstract: Acteoside, also known as verbascoside or orobanchin, is a common compound found in many important medicinal plants including the Chinese herb Cistanche deserticola Y. C. Ma, which is used for its neuroprotective and memory enhancement properties. We have investigated the effects of acteoside using a senescent mouse model induced by a combination of chronic intraperitoneal administration of d‐gal (60 mg/kg/day) and oral administration AlCl3 (5 mg/kg/day) once daily for 90 days. After 60 days, acteoside (30, 60, and 120 mg/kg/day) was orally administered once daily for 30 days. The memory enhancing effects of acteoside were evaluated using the Morris water maze test. The results showed that 30–120 mg/kg/day of acteoside reduced the escape latency in finding the platform, and increased the number of crossings of the platform. A 30–120 mg/kg/day of acteoside increased significantly the expression of nerve growth factor and tropomycin receptor kinase A mRNA and protein in the hippocampus, measured using real‐time RT‐PCR, immunohistochemical analysis, and western blotting. These results support the use of C. deserticola for memory enhancement and indicate that the effects of acteoside are induced via promotion of nerve growth factor and tropomycin receptor kinase A expression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T04:30:32.826548-05:
      DOI: 10.1002/ptr.5357
  • Effect of Zingiber officinale Supplementation on Obesity Management with
           Respect to the Uncoupling Protein 1 ‐3826A>G and
           ß3‐adrenergic Receptor Trp64Arg Polymorphism
    • Authors: Vahideh Ebrahimzadeh Attari; Mohammad Asghari Jafarabadi, Maryam Zemestani, Alireza Ostadrahimi
      Abstract: The present study aimed to investigate the effect of ginger (Zingiber officinale) supplementation on some obesity‐associated parameters, with nutrigenetics approach. Accordingly, 80 eligible obese women (aged 18–45 years) were randomly assigned to receive either ginger (2‐g ginger rhizomes powder as two 1‐g tablets per day) or placebo supplements (corn starch with the same amount) for 12 weeks. Subjects were tested for changes in body weight, body mass index, waist and hip circumferences, body composition, appetite score, and dietary intake. Moreover, participants were genotyped for the ‐3826A>G and Trp64Arg polymorphisms of uncoupling protein 1 and ß3‐adrenergic receptor genes, respectively. Over 12 weeks, ginger supplementation resulted in a slight but statistically significant decrease in all anthropometric measurements and total appetite score as compared with placebo group, which were more pronounced in subjects with the AA genotype for uncoupling protein 1 and Trp64Trp genotype for ß3‐adrenergic receptor gene. However, there was no significant difference in changes of body composition and total energy and macronutrients intake between groups. In conclusion, our findings suggest that ginger consumption has potential in managing obesity, accompanying with an intervention–genotype interaction effect. However, further clinical trials need to explore ginger's efficacy as an anti‐obesity agent in the form of powder, extract, or its active components. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T03:43:09.350617-05:
      DOI: 10.1002/ptr.5343
  • The Potential for Plant Derivatives against Acrylamide Neurotoxicity
    • Authors: O. O. Adewale; J. M. Brimson, O. A. Odunola, M. A. Gbadegesin, S. E. Owumi, C. Isidoro, T. Tencomnao
      Abstract: Certain industrial chemicals and food contaminants have been demonstrated to possess neurotoxic activity and have been suspected to cause brain‐related disorders in humans. Acrylamide (ACR), a confirmed neurotoxicant, can be found in trace amount in commonly consumed human aliments as a result of food processing or cooking. This discovery aroused a great concern in the public, and increasing efforts are continuously geared towards the resolution of this serious threat. The broad chemical diversity of plants may offer the resources for novel antidotes against neurotoxicants. With the goal of attenuating neurotoxicity of ACR, several plants extracts or derivatives have been employed. This review presents the plants and their derivatives that have been shown most active against ACR‐induced neurotoxicity, with a focus on their origin, pharmacological activity, and antidote effects. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-17T02:50:12.267191-05:
      DOI: 10.1002/ptr.5353
  • Alantolactone from Saussurea lappa Exerts Antiinflammatory Effects by
           Inhibiting Chemokine Production and STAT1 Phosphorylation in
           TNF‐α and IFN‐γ‐induced in HaCaT cells
    • Authors: Hye‐Sun Lim; Sung‐Eun Jin, Ohn‐Soon Kim, Hyeun‐Kyoo Shin, Soo‐Jin Jeong
      Abstract: Skin inflammation is the most common condition seen in dermatology practice and can be caused by various allergic reactions and certain toxins or chemicals. In the present study, we investigated the antiinflammatory effects of Saussurea lappa, a medicinal herb, and its marker compounds alantolactone, caryophyllene, costic acid, costunolide, and dehydrocostuslactone in the HaCaT human keratinocyte cell line. HaCaT cells were stimulated with tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ), and treated with S. lappa or each of five marker compounds. Chemokine production and expression were analyzed by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction, respectively. Phosphorylation of signal transducer and activator of transcription (STAT) 1 was determined by immunoblotting. Stimulation with TNF‐α and IFN‐γ significantly increased the production of the following chemokines: thymus‐regulated and activation‐regulated chemokine (TARC): regulated on activation, normal T‐cell expressed and secreted (RANTES): macrophage‐derived chemokine (MDC): and interleukin‐8 (IL‐8). By contrast, S. lappa and the five marker compounds significantly reduced the production of these chemokines by TNF‐α and IFN‐γ‐treated cells. S. lappa and alantolactone suppressed the TNF‐α and IFN‐γ‐stimulated increase in the phosphorylation of STAT1. Our results demonstrate that alantolactone from S. lappa suppresses TNF‐α and IFN‐γ‐induced production of RANTES and IL‐8 by blocking STAT1 phosphorylation in HaCaT cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-17T02:15:55.129171-05:
      DOI: 10.1002/ptr.5354
  • Comparative Study of the Biological Activity of Allantoin and Aqueous
           Extract of the Comfrey Root
    • Authors: Vesna Lj. Savić; Vesna D. Nikolić, Ivana A. Arsić, Ljiljana P. Stanojević, Stevo J. Najman, Sanja Stojanović, Ivana I. Mladenović‐Ranisavljević
      Abstract: This study investigates the biological activity of pure allantoin (PA) and aqueous extract of the comfrey (Symphytum officinale L.) root (AECR) standardized to the allantoin content. Cell viability and proliferation of epithelial (MDCK) and fibroblastic (L929) cell line were studied by using MTT test. Anti‐irritant potential was determined by measuring electrical capacitance, erythema index (EI) and transepidermal water loss of artificially irritated skin of young healthy volunteers, 3 and 7 days after application of creams and gels with PA or AECR. Pure allantoin showed mild inhibitory effect on proliferation of both cell lines at concentrations 40 and 100 µg/ml, but more pronounced on MDCK cells. Aqueous extract of the comfrey root effect on cell proliferation in concentrations higher than 40 µg/ml was significantly stimulatory for L929 but inhibitory for MDCK cells. Pharmaceutical preparations that contained AECR showed better anti‐irritant potential compared with PA. Creams showed better effect on hydration and EI compared with the gels that contained the same components. Our results indicate that the biological activity of the comfrey root extract cannot be attributed only to allantoin but is also likely the result of the interaction of different compounds present in AECR. Topical preparations that contain comfrey extract may have a great application in the treatment of skin irritation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:53:15.399453-05:
      DOI: 10.1002/ptr.5356
  • Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate
           the Oral Wound Healing in Rats
    • Authors: Fernanda Hack Coelho; Gabriela Salvadori, Pantelis Varvaki Rados, Alessandra Magnusson, Chris Krebs Danilevicz, Luise Meurer, Manoela Domingues Martins
      Abstract: The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3‐mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re‐epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi‐quantitative analyses, was performed using the Kruskal–Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:22:45.2721-05:00
      DOI: 10.1002/ptr.5352
  • Activation of Caspase‐9/3 and Inhibition of Epithelial Mesenchymal
           Transition are Critically Involved in Antitumor Effect of Phytol in
           Hepatocellular Carcinoma Cells
    • Authors: Chul‐Woo Kim; Hyun Joo Lee, Ji Hoon Jung, Yoon Hyeon Kim, Deok‐Beom Jung, Eun Jung Sohn, Jang Hoon Lee, Hong Jung Woo, Nam‐In Baek, Young Chul Kim, Sung‐Hoon Kim
      Abstract: This study was designed to investigate the antitumor mechanism of Phytol in hepatocellular carcinomas including Huh7 and HepG2 cells in association with caspase dependent apoptosis and epithelial mesenchymal transition (EMT) signaling. Phytol significantly suppressed the viability of Huh7 and HepG2 cells. Also, Phytol significantly increased the sub G1 population and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) positive cells in a concentration dependent manner in Huh7 and HepG2 cells. Consistently, Phytol cleaved poly (adenosine diphosphate‐ribose) polymerase (PARP), activated caspase‐9/3, and Bax attenuated the expression of survival genes such as Bcl‐2, Mcl‐1, and c‐Myc in Huh7 and HepG2 cells. Of note, Phytol also suppressed typical morphology change of EMT such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in HepG2 cells. Furthermore, Phytol also reversed the loss of E‐cadherin and overexpression of p‐smad2/3, alpha‐smooth muscle actin, and Snail induced by EMT promoter transforming growth factor beta1 in HepG2 cells. Overall, our findings suggest that Phytol exerts antitumor activity via apoptosis induction through activation of caspas‐9/3 and inhibition of EMT in hepatocellular carcinoma cells as a potent anticancer candidate for liver cancer treatment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T02:54:00.055236-05:
      DOI: 10.1002/ptr.5342
  • Role of Hydroxytyrosol‐dependent Regulation of HO‐1 Expression
           in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo
           Synthesis and Stabilization
    • Authors: Houda Zrelli; Miki Kusunoki, Hitoshi Miyazaki
      Abstract: Hydroxytyrosol (HT), an olive plant (Olea europaea L.) polyphenol, has proven atheroprotective effects. We previously demonstrated that heme oxygenase‐1 (HO‐1) is involved in the HT dependent prevention of dysfunction induced by oxidative stress in vascular endothelial cells (VECs). Here, we further investigated the signaling pathway of HT‐dependent HO‐1 expression in VECs. HT dose‐ and time‐dependently increased HO‐1 mRNA and protein levels through the PI3K/Akt and ERK1/2 pathways. Cycloheximide and actinomycin D inhibited both increases, suggesting that HT‐triggered HO‐1 induction is transcriptionally regulated and that de novo protein synthesis is necessary for this HT effect. HT stimulated nuclear accumulation of nuclear factor E2‐related factor 2 (Nrf2). This Nrf2 accumulation was blocked by actinomycin D and cycloheximide whereas HT in combination with the 26S proteasome inhibitor MG132 enhanced the accumulation. HT also extended the half‐life of Nrf2 proteins by decelerating its turnover. Moreover, HO‐1 inhibitor, ZnppIX and CO scavenger, hemoglobin impaired HT‐dependent wound healing while CORM‐2, a CO generator, accelerated wound closure. Together, these data demonstrate that HT upregulates HO‐1 expression by stimulating the nuclear accumulation and stabilization of Nrf2, leading to the wound repair of VECs crucial in the prevention of atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:47:03.200679-05:
      DOI: 10.1002/ptr.5339
  • Anti‐Salmonella Activity of Volatile Compounds of Vietnam Coriander
    • Authors: Ken‐ichi Fujita; Warinthorn Chavasiri, Isao Kubo
      Abstract: Essential oil derived from the fresh leaves of Polygonum odoratum Lour was tested for their effects on a foodborne bacterium Salmonella choleraesuis subsp. choleraesuis ATCC 35640 using a broth dilution method. This essential oil showed a significant antibacterial activity against S. choleraesuis at the concentration of 200 µg/mL. Twenty‐five volatile compounds were characterized from this essential oil by GC‐MS, and aldehyde compounds were found abundant and accounted for more than three‐fourths of the essential oil. Among the compounds characterized, dodecanal (C12) was the most abundant (55.5%), followed by decanal (C10) (11.6%). Both alkanals were effective against S. choleraesuis with the minimum growth inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 100 µg/mL. The most potent antibacterial activity against this bacterium was found with two minor compounds, dodecanol (lauryl alcohol) and 2E‐dodecenal, both with each MBC of 6.25 µg/mL. Their primary antibacterial action against S. choleraesuis provably comes from their ability to function as nonionic surface‐active agents (surfactants), disrupting the native function of integral membrane proteins nonspecifically. Thus, the antibacterial activity is mediated by biophysical processes. In the case of 2E‐alkenals, a biochemical mechanism is also somewhat involved, depending on their alkyl chain length. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:21:30.240534-05:
      DOI: 10.1002/ptr.5351
  • In vitro and in vivo Bone‐Forming Activity of Saururus chinensis
    • Authors: Seong‐Hee Moon; Sik‐Won Choi, Sang‐Joon Park, Shi‐Yong Ryu, Kyu‐Seok Hwang, Cheol‐Hee Kim, Seong Hwan Kim
      Abstract: Bone is maintained by osteoclast‐mediated resorption and osteoblast‐mediated formation. Recently, anti‐osteoporotic activity of Saururus chinensis extract (SCE) and anti‐osteoclastogenic activity of its components have been reported, but the effect of SCE on bone formation has not been studied well. Therefore, in this study, we investigated whether Saururus chinensis SCE exhibits in vitro osteogenic and in vivo bone‐forming activity. extract strongly enhanced the bone morphogenetic protein (BMP)‐2‐stimulated induction of alkaline phosphatase, an early phase biomarker of osteoblast differentiation, in bi‐potential mesenchymal progenitor C2C12 cells. In vitro osteogenic activity of SCE was accompanied by enhanced expression of BMP‐2, BMP‐4, BMP‐7 and BMP‐9 mRNA. In addition, a pharmacological inhibition study suggested the involvement of p38 activation in the osteogenic action of SCE. Moreover, the BMP dependency and the involvement of p38 activation in the osteogenic action of SCE were confirmed by the treatment of noggin, an antagonist of BMP. Saururus chinensis extract also exhibited to induce runt‐related transcription factor 2 activation at the high concentration. Furthermore, the in vivo osteogenic activity of SCE was confirmed in zebrafish and mouse calvarial bone formation models, suggesting the possibility of its use for bone formation. In conclusion, we suggested that in vivo anti‐osteoporotic activity of SCE could be because of its dual action in bone, anti‐osteoclastogenic and anabolic activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:06:19.190115-05:
      DOI: 10.1002/ptr.5349
  • Hypericum perforatum Reduces Paracetamol‐Induced Hepatotoxicity and
           Lethality in Mice by Modulating Inflammation and Oxidative Stress
    • Authors: Miriam S. N. Hohmann; Renato D. R. Cardoso, Victor Fattori, Nilton S. Arakawa, José C. Tomaz, Norberto P. Lopes, Rubia Casagrande, Waldiceu A. Verri
      Abstract: Hypericum perforatum is a medicinal plant with anti‐inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)‐induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15–3.0 g/kg, p.o.) induced dose‐dependent mortality. The sub‐maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30–300 mg/kg, i.p.) dose‐dependently reduced paracetamol‐induced lethality. Paracetamol‐induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL‐1β, TNF‐α, and IFN‐γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonate radical cation; ABTS˙+) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol‐induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol‐induced cytokine production, neutrophil recruitment, and oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T04:21:33.002971-05:
      DOI: 10.1002/ptr.5350
  • Korean Red Ginseng Extract Enhances the Anticancer Effects of Imatinib
    • Authors: Sang Yoon Jung; Chulwon Kim, Wan‐Seok Kim, Seok‐Geun Lee, Jun‐Hee Lee, Bum Sang Shim, Sung‐Hoon Kim, Kyoo Seok Ahn, Kwang Seok Ahn
      Abstract: Although imatinib mesylate (IM) in the treatment of chronic myelogenous leukemia (CML) remains the best example of successful targeted therapy, majority of patients with CML suffer its toxicity profile and develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of CML. Here, we investigated whether Korean red ginseng extract (KRGE) could suppress the proliferation and induce chemosensitization in human CML cells. Also, we used a human phospho‐antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after treatment. Korean red ginseng extract broadly suppressed the proliferation of five different cell lines, but KRGE was found to be the most potent inducer of apoptosis against KBM‐5 cells. It also abrogated the expression of Bcl‐2 (B‐cell lymphoma 2), Bcl‐xL (B‐cell lymphoma‐extra large), survivin, inhibitors of apoptosis protein 1/2, COX‐2 (Cyclooxygenase‐2), cyclin D1, matrix metalloproteinase‐9, and VEGF (Vascular endothelial growth factor), as well as upregulated the expression of pro‐apoptotic gene products. Interestingly, KRGE also enhanced the cytotoxic and apoptotic effect of IM in KBM‐5 cells. The combination treatment of KRGE and IM caused pronounced suppression of p38 and signal transducer and activator of transcription 5 phosphorylation and induced phosphorylation of p53 compared with the individual treatment. Our results demonstrate that KRGE can enhance the anticancer activity of IM and may have a substantial potential in the treatment of CML. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T02:27:14.326739-05:
      DOI: 10.1002/ptr.5347
  • Some South African Rubiaceae Tree Leaf Extracts Have Antimycobacterial
           Activity Against Pathogenic and Non‐pathogenic Mycobacterium Species
    • Authors: Abimbola O. Aro; Jean P. Dzoyem, Tiny M. Hlokwe, Evelyn Madoroba, Jacobus N. Eloff, Lyndy J. McGaw
      Abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Many plant species contain antimycobacterial compounds, which may serve as template molecules for new anti‐TB drugs. The Rubiaceae family is the largest family of trees in southern Africa, and preliminary evidence revealed antimycobacterial activity in several species of the genus, motivating further studies. Leaf extracts of 15 tree species from the Rubiaceae family were screened for antimycobacterial activity against pathogenic M. tuberculosis and non‐pathogenic Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium bovis BCG (Bacillus Calmette‐Guérin) using a twofold serial microdilution assay. Cytotoxicity was determined using a tetrazolium‐based colorimetric assay against C3A liver cells and Vero kidney cells. Minimum inhibitory concentration values as low as 0.04 mg/mL against M. smegmatis and M. tuberculosis were recorded. Activity against M. aurum was the best predictor of activity against pathogenic M. tuberculosis (correlation coefficient = 0.9). Bioautography indicated at least 40 different antimycobacterial compounds in the extracts. Cytotoxicity of the extracts varied, and Oxyanthus speciosus had the most promising selectivity index values. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T01:56:19.724173-05:
      DOI: 10.1002/ptr.5338
  • Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by
           Ischemia in H9c2 Cells Via Antioxidant Potential
    • Authors: P. L. Reshma; V. S. Lekshmi, Vandana Sankar, K. G. Raghu
      Abstract: Tribulus terrestris L. was evaluated for its cardioprotective property against myocardial ischemia in a cell line model. Initially, methanolic extract was prepared and subjected to sequential extraction with various solvents. The extract with high phenolic content (T. terrestris L. ethyl acetate extract–TTME) was further characterized for its chemical constituents and taken forward for evaluation against cardiac ischemia. HPLC analysis revealed the presence of phenolic compounds like caffeic acid (12.41 ± 0.22 mg g−1), chlorogenic acid (0.52 ± 0.06 mg g−1) and 4‐hydroxybenzoic acid (0.60 ± 0.08 mg g−1). H9c2 cells were pretreated with TTME (10, 25, 50 and 100 µg/ml) for 24 h before the induction of ischemia. Then ischemia was induced by exposing cells to ischemia buffer, in a hypoxic chamber, maintained at 0.1% O2, 95% N2 and 5% CO2, for 1 h. A significant (p ≤ 0.05) increase in reactive oxygen species generation (56%), superoxide production (18%), loss of plasma membrane integrity, dissipation of transmembrane potential, permeability transition pore opening and apoptosis had been observed during ischemia. However, pretreatment with TTME was found to significantly (p ≤ 0.05) attenuate the alterations caused by ischemia. The overall results of this study partially reveal the scientific basis of the use of T. terrestris L. in the traditional system of medicine for heart diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T01:30:58.838259-05:
      DOI: 10.1002/ptr.5336
  • Cytoprotective and Anti‐secretory Effects of Azadiradione Isolated
           from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat
    • Authors: Rohit Singh; Vaibhav Mishra, Sukanya Pandeti, Gautam Palit, Manoj K. Barthwal, Haushila Prasad Pandey, Tadigoppula Narender
      Abstract: Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in‐vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+‐ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T00:57:41.815633-05:
      DOI: 10.1002/ptr.5332
  • Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report
           from A Pilot, Randomized, Double‐Blinded, Placebo‐Controlled
           Clinical Trial
    • Authors: Foroud Shahbazi; Sanambar Sadighi, Simin Dashti‐Khavidaki, Farhad Shahi, Mehrzad Mirzania, Alireza Abdollahi, Mohammad‐Hossein Ghahremani
      Abstract: Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity 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 24–48 h before the initiation of cisplatin infusion and continuing to the end of three 21‐day cisplatin‐containing chemotherapy courses on cisplatin‐induced renal electrolytes wasting and kidney function were assessed. Cisplatin‐associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase‐associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin‐induced urine electrolyte wasting or renal function impairment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-07T06:02:29.261814-05:
      DOI: 10.1002/ptr.5345
  • Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus
           tatarinowii on mice and rats
    • Authors: Hao Liu; Zhi Song, Da‐Guang Liao, Tian‐Yi Zhang, Feng Liu, Kai Zhuang, Kui Luo, Liang Yang, Jing He, Jian‐Ping Lei
      Abstract: This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)‐induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium‐induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma‐aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA, Bcl‐2, and caspase‐3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl‐2 were up‐regulated by treating with eudesmin, whereas the caspase‐3 obviously was down‐regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up‐regulation of GABAA and GAD65 expressions, and anti‐apoptosis of neuron the in brain. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-07T05:46:32.29086-05:0
      DOI: 10.1002/ptr.5337
  • Enhanced Estrogenic Activity of Soybean Isoflavones by Coadministration of
           Liuwei Dihuang Pills in Ovariectomized Rats
    • Authors: Baogang Xie; Shuohua Zhang, Jie Liu, Xuejun Zhan, Daze Xie, Zhirong Zhang
      Abstract: Soybean isoflavones are beneficial for treating hormone‐related diseases. Simultaneous consumption of soybean isoflavones and Liuwei Dihuang pills (LWPs) is effective for treating perimenopausal period syndrome. However, why the combination of isoflavones and LWPs is more effective than ingestion of each component alone remains unknown. Here, we show that enhanced estrogenic activities would appear when the ovariectomized rats were fed with a soybean diet in combination of LWPs treatment. Our further studies explored enhancements of Lactobacillus (19‐fold) and Bifidobacterium (12‐fold) contents in the intestine of rat and 1.84‐fold higher intestinal β‐glucosidase activity in LWPs treatment group compared with the control group. As a result, steady‐state concentrations of genistein (1.20‐fold), daidzein (1.36‐fold), and equol (1.43‐fold) in serum were significantly elevated in the combination group compared with the soybean alone group. The results present the first evidence of the mechanism of enhanced estrogenic activity of dietary soybean isoflavones in combination with LWPs. Our study indicates that alterations of gut bacteria after LWPs treatment play a key role in the enhanced estrogenic effect of dietary soybean, suggesting a direct relationship between dietary soybean, LWPs, and gut flora. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:28:56.975643-05:
      DOI: 10.1002/ptr.5346
  • Inhibitory Effects of
           on Mushroom Tyrosinase and Melanogenesis in B16‐F10 Melanoma Cells
    • Authors: Jing‐jie Zhu; Gui‐rui Yan, Zhi‐jian Xu, Xiao Hu, Gai‐hong Wang, Ting Wang, Wei‐liang Zhu, Ai‐jun Hou, He‐yao Wang
      Abstract: (2′R)‐2′,3′‐Dihydro‐2′‐(1‐hydroxy‐1‐methylethyl)‐2,6′‐bibenzofuran‐6,4′‐diol (DHMB) is a natural compound extracted from Morus notabilis. It was found that DHMB acts as a competitive inhibitor against mushroom tyrosinase with a Ki value of 14.77 μM. Docking results further indicated that it could form strong interactions with one copper ion with a distance of 2.7 Å, suggesting the mechanism of inhibition might be due to chelating copper ions in the active site. Furthermore, melanin production in B16‐F10 murine melanoma cells was significantly inhibited by DHMB in a concentration‐dependent manner without cytotoxicity. The results of western blotting also showed that DHMB decreased 3‐isobuty‐1‐methxlzanthine‐induced mature tyrosinase expression. Taken together, these findings indicated that DHMB may be a new promising pigmentation‐altering agent for agriculture, cosmetic, and therapeutic applications. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:12:57.080312-05:
      DOI: 10.1002/ptr.5344
  • The Lignan Pinoresinol Induces Nuclear Translocation of DAF‐16 in
           Caenorhabditis elegans but has No Effect on Life Span
    • Authors: Karoline Koch; Christian Büchter, Susannah Havermann, Wim Wätjen
      Abstract: The lignan pinoresinol is a constituent of flaxseed, sesame seeds and olive oil. Because of different molecular effects reported for this compound, e.g. antioxidative activity, pinoresinol is suggested to cause positive effects on humans. Because experimental data are limited, we have analysed the effects of the lignan on the nematode Caenorhabditis elegans: in spite of a strong antioxidative capacity detected in an in vitro assay, no antioxidative effects were detectable in vivo. In analogy to this result, no modulation of the sensitivity against thermal stress was detectable. However, incubation with pinoresinol caused an enhanced nuclear accumulation of the transcription factor DAF‐16 (insulin/IGF‐like signalling pathway). Using a strain with an enhanced oxidative stress level (mev‐1 mutant), we clearly see an increase in stress resistance caused by this lignan, but no change in reactive oxygen species. Furthermore, we investigated the effects of pinoresinol on the life span of the nematode, but no modulation was found, neither in wild‐type nor in mev‐1 mutant nematodes. These results suggest that pinoresinol may exert pharmacologically interesting effects via modulation of the insulin‐like signalling pathway in C. elegans as well as in other species like mammals due to the evolutionary conservation of this signalling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:06:03.508341-05:
      DOI: 10.1002/ptr.5330
  • Castalagin Exerts Inhibitory Effects on Osteoclastogenesis Through
           Blocking a Broad Range of Signaling Pathways with Low Cytotoxicity
    • Authors: Mayumi Iwatake; Kuniaki Okamoto, Takashi Tanaka, Takayuki Tsukuba
      Abstract: Castalagin is a rare plant polyphenol that is classified as a hydrolyzable tannin. Although it has antioxidant, antitumorigenic, and leishmanicidal effects, the utility of castalagin against bone diseases remain to be elucidated. Here, we investigated the effects of castalagin on the differentiation of osteoclasts (OCLs), multinucleated bone‐resorbing cells. After stimulation with receptor activator of nuclear factor kappa‐B ligand (RANKL), the formation of OCLs from bone marrow‐derived macrophages was significantly inhibited by castalagin even at 1 μM. However, castalagin displayed little cytotoxicity at a higher concentration of 50 μM. The effects of castalagin on intracellular signaling during OCL differentiation showed that castalagin suppresses RANKL‐stimulated phosphorylation of major signaling pathways including protein kinase B (Akt), extracellular signal‐regulated kinase, Jun N‐terminal kinase, p38 mitogen‐activated protein kinases, and inhibitor of nuclear factor kappa B alpha. Moreover, following castalagin treatment, the protein levels of nuclear factor of activated T‐cells, cytoplasmic 1, a master regulator for OCL differentiation, and NF‐κB were decreased. Thus, castalagin exerts inhibitory effects on osteoclastogenesis through blockage of a broad range of signaling pathways, but has low cytotoxicity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T02:35:46.223762-05:
      DOI: 10.1002/ptr.5333
  • Effects of Glucosinolates from Turnip (Brassica rapa L.) Root on Bone
           Formation by Human Osteoblast‐Like MG‐63 Cells and in Normal
           Young Rats
    • Authors: Jaehoon Jeong; Heajin Park, Hanbit Hyun, Jihye Kim, Haesung Kim, Hyun Il Oh, Hye Seong Hwang, Dae Kyong Kim, Ha Hyung Kim
      Abstract: Turnip (Brassica rapa L.) root ethanol extract (TRE) was prepared, and its chemical constituents were characterized by ultra‐performance liquid chromatography and mass spectrometry. Thirteen glucosinolates (GSLs) were identified, comprising eight aliphatic, four indolic, and one aromatic compounds. The effects of these GSLs on bone formation were investigated in vitro by incubating human osteoblast‐like MG‐63 cells with TRE and then analyzing their viability, alkaline phosphatase (ALP) activity, collagen content, and mineralization and in vivo by administering TRE orally to normal young rats (500 mg/kg/day) and assessing subsequent changes in serum osteocalcin and bone microstructure in these animals. No TRE‐related toxicity was found, and the levels of cell viability, ALP activity, collagen synthesis, and mineralization were significantly increased relative to the negative control. In particular, stimulatory effects on the differentiation of MG‐63 cells were strongly enhanced as compared with a positive control (daidzein). Serum osteocalcin was also significantly increased, and some important bone microstructural parameters were improved in TRE‐administered rats compared with their saline‐administered counterparts. GSLs therefore appear to have a stimulatory effect on bone formation in both MG‐63 cells and normal young rats. This is the first report on the usefulness of turnip root and its GSL compounds for bone formation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T02:10:27.977479-05:
      DOI: 10.1002/ptr.5331
  • Review of the Safety and Efficacy of Moringa oleifera
    • Authors: Sidney J. Stohs; Michael J. Hartman
      Abstract: Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti‐hyperglycemic (antidiabetic) and anti‐dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
      PubDate: 2015-03-24T01:44:35.928976-05:
      DOI: 10.1002/ptr.5325
  • The Androgenic Alopecia Protective Effects of Forsythiaside‐A and
           the Molecular Regulation in a Mouse Model
    • Authors: Heon‐Sub Shin; Sang‐Yong Park, Hyun‐Geun Song, Eunson Hwang, Don‐Gil Lee, Tae‐Hoo Yi
      Abstract: This study examined the inhibitory effect of forsythiaside‐A, a natural substance derived from Forsythia suspensa (F. suspensa), on entry into catagen induced by dihydrotestosterone (DHT) in an androgenic alopecia mouse model. In vitro experiment comparing finasteride with forsythiaside‐A showed that forsythiaside‐A treatment resulted in a 30% greater inhibition of DHT‐induced apoptosis in human hair dermal papilla cell (HHDPCs) and human keratinocytes (HaCaTs). In vivo experiment showed that mouse hair density and thickness were increased by 50% and 30%, respectively, in the forsythiaside‐A‐treated group when compared to a DHT group. Tissue histological results revealed that the forsythiaside‐A‐treated group had an increase in size and shape of the hair follicles and a 1.5 times increase in the follicle anagen/telogen ratio when compared to the finasteride group. Western blot examination of TGF‐β2 expression related to apoptosis signaling in mouse skin verified that forsythiaside‐A reduced the expression of TGF‐β2 by 75% and suppressed apoptosis by reducing the expression of caspase‐9 by 40%, and caspase‐3 by 53%, which play an roles up‐regulator in the apoptosis signal. The forsythiaside‐A group also showed a 60% increase in the Bcl‐2/Bax ratio, which is a factor related to mitochondrial apoptosis. Our results indicated that forsythiaside‐A prevents apoptosis by similar mechanism with finasteride, but forsythiaside‐A is more effective than finasteride. In summary, forsythiaside‐A controlled the apoptosis of hair cells and retarded the entry into the catagen phase and therefore represents a natural product with much potential for use as a treatment for androgenic alopecia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T01:27:46.476074-05:
      DOI: 10.1002/ptr.5324
  • The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene
           Expression, Production, and Secretion via Regulation of NF‐κB,
           STAT6, and HDAC2
    • Authors: Changda Liu; David Weir, Paula Busse, Nan Yang, Zhenwen Zhou, Charles Emala, Xiu‐Min Li
      Abstract: Mucus overproduction is a significant component of the pathophysiology of obstructive lung diseases. Currently, there are only a few medications available that inhibit mucus production. Previous studies showed that glycyrrhizin, a triterpenoid in Glycyrrhiza uralensis inhibits mucin 5AC (MUC5AC) mRNA and protein expression. Other potential mucus production inhibitory compounds contained within in G. uralensis have not been fully investigated. The aim of the present study was to determine if the G. uralensis flavonoid 7,4′‐dihydroxyflavone (7,4′‐DHF) inhibits MUC5AC gene expression, mucus production, and secretion, and if so, to elucidate the mechanism of this inhibition. 7,4′‐Dihydroxyflavone significantly decreased phorbol 12‐myristate 13‐acetate‐stimulated NCI‐H292 human airway epithelial cell MUC5AC gene expression and mucus production, at a 28‐fold lower concentration than glycyrrhizin (The half maximal inhibitory concentration IC50 value of 1.4 μM vs 38 μM, respectively); 7,4′‐DHF also inhibited MUC5AC mucus secretion. Inhibition was associated with the suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), signal transducer and activator of transcription 6 (STAT6) activation, and enhanced histone deacetylase 2 (HDAC2) expression. In a murine model of asthma, 7,4′‐DHF‐treated mice exhibited a marked reduction in MUC5AC secretion in the bronchoalveolar lavage fluid compared with control mice. These findings, together with previous findings linking NF‐κB, STAT6, and HDAC2 modulation to the control of MUC5AC expression, demonstrate that 7,4′‐DHF is a newly identified component of G. uralensis that regulates MUC5AC expression and secretion via regulation of NF‐κB, STAT6, and HDAC2. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-23T02:33:11.505342-05:
      DOI: 10.1002/ptr.5334
  • Antioxidant, Anti‐inflammatory, and Chemoprotective Properties of
           Acacia catechu Heartwood Extracts
    • Authors: Sidney J. Stohs; Debasis Bagchi
      Abstract: Aqueous extracts of Acacia catechu heartwood are rich source of catechin and epicatechin (gallic acid derivatives), with smaller amounts of flavonoids. Extracts have also been prepared with ethyl acetate, ethanol, and methanol, and the properties of these extracts have been studied and are reviewed. Potent antioxidant activity has been well established in both in vitro and in vivo studies. This antioxidant activity is believed to be responsible for the anti‐inflammatory, tissue protectant, antineoplastic, and analgesic activities that have been demonstrated and clearly established in animal and cell culture systems. Furthermore, antihyperglycemic, antidiarrheal, antinociceptive, and antipyretic activities have been demonstrated in animal studies. No adverse effects have been observed in animal or human studies or in cell culture systems. In spite of the fact that Acacia products have been used for many years and the general safety of catechins and epicatechins is well documented, few human studies have ever been conducted on the efficacy or safety of A. catechu heartwood extracts. Several studies have shown that a two‐ingredient combination product containing A. catechu extract exhibited no adverse effects when administered daily for up to 12 weeks while exhibiting significant anti‐inflammatory activity in subjects with osteoarthritis of the knee. There is a need for additional human clinical studies with regard to efficacy and safety. © 2015 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2015-03-20T07:43:27.697385-05:
      DOI: 10.1002/ptr.5335
  • The Effects of Pre‐Exercise Ginger Supplementation on Muscle Damage
           and Delayed Onset Muscle Soreness
    • Authors: Melissa D. Matsumura; Gerald S. Zavorsky, James M. Smoliga
      Abstract: Ginger possesses analgesic and pharmacological properties mimicking non‐steroidal antiinflammatory drugs. We aimed to determine if ginger supplementation is efficacious for attenuating muscle damage and delayed onset muscle soreness (DOMS) following high‐intensity resistance exercise. Following a 5‐day supplementation period of placebo or 4 g ginger (randomized groups), 20 non‐weight trained participants performed a high‐intensity elbow flexor eccentric exercise protocol to induce muscle damage. Markers associated with muscle damage and DOMS were repeatedly measured before supplementation and for 4 days following the exercise protocol. Repeated measures analysis of variance revealed one repetition maximum lift decreased significantly 24 h post‐exercise in both groups (p 
      PubDate: 2015-03-18T05:34:13.795414-05:
      DOI: 10.1002/ptr.5328
  • A Review: Phytochemicals Targeting JAK/STAT Signaling and IDO Expression
           in Cancer
    • Authors: Niroshaathevi Arumuggam; Neil A. Bhowmick, H. P. Vasantha Rupasinghe
      Abstract: Cancer remains a major health problem worldwide. Among many other factors, two regulatory defects that are present in most cancer cells are constitutive activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and the induction of indoleamine 2, 3‐dioxygenase (IDO), an enzyme that catalyzes tryptophan degradation, through JAK/STAT signaling. Cytokine signaling activates STAT proteins in regulating cell proliferation, differentiation, and survival through modulation of target genes. Many phytochemicals can inhibit both JAK/STAT signaling and IDO expression in antigen‐presenting cells by targeting different pathways. Some of the promising phytochemicals that are discussed in this review include resveratrol, cucurbitacin, curcumin, (−)‐epigallocatechin gallate, and others. It is now evident that phytochemicals play key roles in inhibition of tumor proliferation and development and provide novel means for therapeutic targeting of cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-18T03:15:55.781213-05:
      DOI: 10.1002/ptr.5327
  • Multiple Biological Effects of Olive Oil By‐products such as Leaves,
           Stems, Flowers, Olive Milled Waste, Fruit Pulp, and Seeds of the Olive
           Plant on Skin
    • Authors: Asuka Kishikawa; Ahmed Ashour, Qinchang Zhu, Midori Yasuda, Hiroya Ishikawa, Kuniyoshi Shimizu
      Abstract: As olive oil production increases, so does the amount of olive oil by‐products, which can cause environmental problems. Thus, new ways to utilize the by‐products are needed. In the present study, five bioactive characteristics of olive oil by‐products were assessed, namely their antioxidant, anti‐bacterial, anti‐melanogenesis, anti‐allergic, and collagen‐production‐promoting activities. First, the extracts of leaves (May and October), stems (May and October), flowers, olive milled waste, fruit pulp and seeds were prepared using two safe solvents, ethanol and water. According to HPLC and LC/MS analysis and Folin–Ciocalteu assay, the ethanol extracts of the leaves (May and October), stems (May and October) and flowers contained oleuropein, and the ethanol extract of the stems showed the highest total phenol content. Oleuropein may contribute to the antioxidant and anti‐melanogenesis activities of the leaves, stems, and flowers. However, other active compounds or synergistic effects present in the ethanol extracts are also likely to contribute to the anti‐bacterial activity of the leaves and flowers, the anti‐melanogenesis activity of some parts, the anti‐allergic activity of olive milled waste, and the collagen‐production‐promoting activity of the leaves, stems, olive milled waste and fruit pulp. This study provides evidence that the by‐products of olive oil have the potential to be further developed and used in the skin care industry. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-16T04:52:23.460242-05:
      DOI: 10.1002/ptr.5326
  • Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different
           Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung
           Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells
    • Authors: Norazah Basar; Olayinka Ayotunde Oridupa, Kenneth J. Ritchie, Lutfun Nahar, Nashwa Mostafa M. Osman, Angela Stafford, Habibjon Kushiev, Asuman Kan, Satyajit D. Sarker
      Abstract: Glycyrrhiza glabra L. (Fabaceae), commonly known as ‘liquorice’, is a well‐known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet‐tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-16T04:30:00.739637-05:
      DOI: 10.1002/ptr.5329
  • A Clinical Trial with Brazilian Arnica (Solidago chilensis Meyen) Glycolic
           Extract in the Treatment of Tendonitis of Flexor and Extensor Tendons of
           Wrist and Hand
    • Authors: Ary Gomes Silva; Elbe Rodrigues Machado, Leonardo Mendes Almeida, Ricardo Marcelo Menezes Nunes, Patrícia Caldeira Pena Giesbrecht, Regina Mamed Costa, Helber B. Costa, Wanderson Romão, Ricardo Machado Kuster
      Abstract: One of the Brazilian arnicas, Solidago chilensis Meyen, is a species of the Asteraceae family. This plant is known by this common name because it shares remarkably similar organoleptic properties with the genus Arnica L., also within the family Asteraceae. We examined the effectiveness of the S. chilensis fluid extract used externally for treating tendinitis of flexor and extensor tendons of wrist and hand in placebo‐controlled double‐blind clinical pharmacological studies. This study was approved by the Ethical Committee for Scientific Research in Human Beings at University Vila Velha‐UVV. Two daily skin applications on the arm skin of a gel cream containing a 5% glycolic plant extract were administered to eight volunteers for 21 days. Among the volunteers, one of their arms was used as the placebo group, and the other one was used as a test group. Statistical data analyses demonstrated a significant reduction in the perception of pain in the arms in the test group, when it was compared to those receiving only the placebo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T06:17:17.000478-05:
      DOI: 10.1002/ptr.5323
  • Antiinflammatory and Wound Healing Effects of Caesalpinia sappan L.
    • Authors: Supinya Tewtrakul; Pattreeya Tungcharoen, Teeratad Sudsai, Chatchanok Karalai, Chanita Ponglimanont, Orapun Yodsaoue
      Abstract: Extracted compounds from Caesalpinia sappan L. were examined for the inhibitory activity against NO, PGE2, and TNF‐α productions and on associated transcription levels using RAW264.7 cells. They were also tested for their effects on wound healing using fibroblast L929 cells. Among the compounds tested, brazilin (8) was the most effective against lipopolysaccharide (LPS)‐induced NO production in RAW264.7 cells with an IC50 value of 10.3 μM, followed by sappanchalcone (2, 31.0 μM). Brazilin (8) also inhibited PGE2 and TNF‐α production with IC50 values of 12.6 and 87.2 μM, respectively. The antiinflammatory mechanism of brazilin involved down regulation of the mRNA expressions of the iNOS, COX‐2, and TNF‐α genes in a dose‐dependent manner. An ethanol (EtOH) extract of C. sappan significantly increased fibroblast proliferation, fibroblast migration, and collagen production, whereas brazilin (8) only stimulated fibroblast migration. In addition, the EtOH extract showed no acute toxicity in mice, and it was therefore safe to make use of its potent antiinflammatory and wound healing activities. Brazilin was mainly responsible for its antiinflammatory effect through its ability to inhibit the production of NO, PGE2, and TNF‐α. This study supports the traditional use of C. sappan for treatment of inflammatory‐related diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T05:48:03.497675-05:
      DOI: 10.1002/ptr.5321
  • Soy Isoflavone Glycitin
           Promotes Human Dermal Fibroblast Cell Proliferation and Migration via
           TGF‐β Signaling
    • Authors: Young Mee Kim; Jung Sik Huh, Yoongho Lim, Moonjae Cho
      Abstract: Glycitin is a soy isoflavone that exhibits antioxidant, antiallergic, and anti‐osteoporosis activities. We investigated the effects of glycitin on dermal fibroblast proliferation and migration. Treatment of primary dermal fibroblasts with glycitin increased cell proliferation and migration. In addition, treatment with 20 μM glycitin for 24 h induced the synthesis of collagen type I and type III at both the mRNA and protein levels. Fibronectin was also increased by 20% after treatment. Matrix metalloproteinase‐1 collagenase was decreased in the media after 24‐h incubation with glycitin, and the synthesis of transforming growth factor‐beta (TGF‐β) mRNA increased approximately twofold in cells following glycitin treatment. Phosphorylation of Smad2 and Smad3 increased after 1 h of glycitin treatment, and phosphorylation continued for 24 h. Furthermore, the phosphorylated form of AKT was increased in glycitin‐treated cells after 3 h and remained higher for 24 h. Thus, glycitin treatment produces anti‐aging effects including increased total collagen in the culture media, decreased elastase, and decreased β‐galactosidase. Together, these results indicate that glycitin stimulates TGF‐β secretion, and the subsequent autocrine actions of TGF‐β induce proliferation of fibroblasts, ultimately protecting skin cells from aging and wrinkling. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T03:33:12.586432-05:
      DOI: 10.1002/ptr.5313
  • Review of Clinical Pharmacology of Aloe vera L. in the Treatment of
    • Authors: Marco Miroddi; Michele Navarra, Fabrizio Calapai, Ferdinando Mancari, Salvatore Vincenzo Giofrè, Sebastiano Gangemi, Gioacchino Calapai
      Abstract: Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune‐mediated chronic inflammatory disease, involving mainly the skin, affects about the 2–3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-10T05:19:04.976434-05:
      DOI: 10.1002/ptr.5316
  • Toxicity of Anthraquinones: Differential Effects of Rumex Seed Extracts on
           Rat Organ Weights and Biochemical and Haematological Parameters
    • Authors: Rabigul Islam; Yultuz Mamat, Ilyar Ismayil, Ming Yan, Mahsutjan Kadir, Abdujilil Abdugheny, Haximjan Rapkat, Mardan Niyaz, Yusupjan Ali, Sirapil Abay
      Abstract: The genus Rumex and related species such as Rheum and Polygonum are widely used as medicinal herbs and foods. They contain anthraquinones (AQ) such as emodin and chrysophanol as active ingredients, and there is concern about the toxicity of these compounds. This study evaluated the chronic effects of Rumex patientia seed aqueous and ethanolic extracts, in male and female rats separately, on organ weights and over 30 haematological, biochemical and histological parameters, immediately after 14‐week administration and after a further period of 15 days without drug treatment. Adverse changes were associated with long‐term AQ administration, and these focussed on the liver, lung and kidney, but after 15‐day convalescence, most had reverted to normal. In general, male rats appeared to be more susceptible than female rats at similar doses. The water extract produced no irreversible changes, which may reflect the lower dose of the AQ constituents or the presence of different ancillary compounds, and supports the traditional method of extracting Rumex seeds with water. In conclusion, ethanolic extracts of R. patientia caused irreversible pathological changes at very high doses (4000mg/kg), but lower doses and aqueous extracts produced either non‐significant or reversible changes. Long‐term administration of high doses of AQ extracts over a long period of time should be avoided until further assurances can be given, and given other existing reports of reproductive toxicity, should be avoided altogether during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-09T03:53:34.884696-05:
      DOI: 10.1002/ptr.5317
  • Inhibition of Cancer Cell Proliferation and Antiradical Effects of
           Decoction, Hydroalcoholic Extract, and Principal Constituents of
           Hemidesmus indicus R. Br.
    • Authors: Giancarlo Statti; Mariangela Marrelli, Filomena Conforti, Antonella Spagnoletti, Massimo Tacchini, Carmela Fimognari, Eleonora Brognara, Roberto Gambari, Gianni Sacchetti, Alessandra Guerrini
      Abstract: Indian Sarsaparilla (Hemidesmus indicus R. Br.) is widely used in Indian traditional medicine. In the present work, we explored the effects of decoction, traditional Ayurvedic preparation, and hydroalcoholic extract, a phytocomplex more traditionally studied and commercialized as food supplement in western medicine, from the roots as possible source of chemicals with new functional potential linked to their nutritional uses. The antiproliferative and antioxidant properties were assayed. To test antiproliferative affects, different cancer cell lines, growing both as monolayers (CaCo2, MCF‐7, A549, K562, MDA‐MB‐231, Jurkat, HepG2, and LoVo) and in suspension (K562 and Jurkat) were used. The decoction showed strong activity on HepG2 cells, while the hydroalcoholic extracts were active on HepG2, LoVo, MCF‐7, K562, and Jurkat cell lines. Weak inhibition of cancer cell proliferation was observed for the principal constituents of the preparations: 2‐hydroxy‐4‐methoxybenzaldehyde, 2‐hydroxy‐4‐methoxybenzoic acid, and 3‐hydroxy‐4‐methoxybenzaldehyde that were tested alone. The antiradical activity was tested with 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid)diammonium salt tests and inhibition of nitric oxide production in lipopolysaccharide‐stimulated RAW 264.7 macrophages. Interesting result has also been obtained for hydroalcoholic extract regarding genoprotective potential (58.79% of inhibition at 37.5 µg/mL). Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-06T08:14:13.939725-05:
      DOI: 10.1002/ptr.5322
  • Enhanced HIV‐1 Reverse Transcriptase Inhibitory and Antibacterial
           Properties in Callus of Catha edulis Forsk.
    • Authors: Aloka Kumari; Ponnusamy Baskaran, Johannes Van Staden
      Abstract: Developing tissue culture systems for medicinal plants is important in that they may offer an alternative to protect wild populations. However, analysis of bioactivity for tissue culture developed plant tissues is required to offer support and allow acceptance in traditional medicine. The use of propagated callus could provide potential material for therapeutic purposes. This study was aimed at evaluating the anti‐HIV and antibacterial properties of a three‐month‐old tissue culture‐derived calli and leaves of cultivated mother plants of Catha edulis Forsk. The calli were derived from leaf explants using different plant growth regulators. The calli obtained from callus cultured on 9.8 μM indole‐3‐butyric acid plus 2.7 μM naphthalene acetic acid exhibited the highest HIV‐1 reverse transcriptase inhibitory effects when compared with other treatments and the mother plants. Different extracts of callus exhibited high antibacterial activity (
      PubDate: 2015-03-06T07:47:20.630215-05:
      DOI: 10.1002/ptr.5318
  • Apoptotic Effect of Galbanic Acid via Activation of Caspases and
           Inhibition of Mcl‐1 in H460 Non‐Small Lung Carcinoma Cells
    • Authors: Bum‐Seok Oh; Eun Ah Shin, Ji Hoon Jung, Deok‐Beom Jung, Bonglee Kim, Bum Sang Shim, Mahsa Chitsazian Yazdi, Mehrdad Iranshahi, Sung‐Hoon Kim
      Abstract: Galbanic acid (GBA), a major compound of Ferula assafoetida, was known to have cytotoxic, anti‐angiogenic and apoptotic effects in prostate cancer and murine Lewis lung cancer cells; the underling apoptotic mechanism of GBA still remains unclear so far. Thus, in the present study, the apoptotic mechanism of GBA was investigated mainly in H460 non‐small cell lung carcinoma (NSCLC) cells because H460 cells were most susceptible to GBA than A549, PC‐9 and HCC827 NSCLC cells. Galbanic acid showed cytotoxicity in wild EGFR type H460 and A549 cells better than other mutant type PC‐9 and HCC827 NSCLC cells. Also, GBA significantly increased the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and sub G1 population in H460 cells. Western blotting revealed that GBA cleaved poly (ADP‐ribose) polymerase (PARP), activated Bax and caspase 9, attenuated the expression of Bcl‐2, Bcl‐xL, and Myeloid cell leukemia 1 (Mcl‐1) in H460 cells. However, interestingly, overexpression of Mcl‐1 blocked the ability of GBA to exert cytotoxicity, activate caspase9 and Bax, cleave PARP, and increase sub G1 accumulation in H460 cells. Overall, these findings suggest that GBA induces apoptosis in H460 cells via caspase activation and Mcl‐1 inhibition in H460 cells as a potent anticancer agent for NSCLC treatment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-06T06:57:33.9375-05:00
      DOI: 10.1002/ptr.5320
  • The Antiinflammatory Properties of Humic Substances: A Mini Review
    • Authors: Constance E. J. Rensburg
      Abstract: Humic substances are effective in the suppression of delayed type hypersensitivity, rat paw oedema, a graft‐versus‐host reaction and contact hypersensitivity in rats. They reduce the C‐reactive protein levels of patients suffering from osteoarthritis of the knee and the wheel and flare reaction of patients suffering from hay fever. They have also been described as cardioprotective and pro‐angiogenic. Toxicity studies have indicated that potassium humate is safe in humans up to a daily dosage of 1 g/kg, whereas fulvic acid is safe in humans up to a daily dosage of 1.8 g per adult. The antiinflammatory action of potassium humate can be contributed to the inhibition of the release of inflammatory‐related cytokines, an adhesion molecule, oxidants and components of the complement system. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-03T02:27:47.336031-05:
      DOI: 10.1002/ptr.5319
  • The Involvement of Serotonin in the Hypoglycemic Effects Produced by
           Administration of the Aqueous Extract of Xylaria nigripes with
           Steroid‐Induced Insulin‐Resistant Rats
    • Authors: Ying‐I Chen; Chung‐Yuh Tzeng, Yu‐Wen Cheng, Tai‐Hao Hsu, Wai Jane Ho, Zeng‐Chin Liang, Chang‐Wei Hsieh, Jason T. C. Tzen, Shih‐Liang Chang
      Abstract: Xylaria nigripes (XN) is a medicinal fungus with a high‐economic value. The aim of this study was to explore the hypoglycemic effects and mechanisms of the XN aqueous extract in steroid‐induced insulin‐resistant (SIIR) rats. Significant hypoglycemic effects were observed 60 min after administration of XN aqueous extract. In normal Wistar, hypoglycemic effects were 21% (the plasma glucose level decreased from 128.6 ± 12.5 to 100.9 ± 10.7 mg/dL). In SIIR, hypoglycemic effects were 26% (the plasma glucose level decreased from 177.6 ± 12.5 to 133.3 ± 29.7 mg/dL) rats refer to their baseline. The signaling proteins for insulin‐receptor substrate‐1 and glucose transporter‐4 increased 0.51‐fold and 1.12‐fold, respectively, as determined by Western blotting; the increase in the proteins was 13% and 9%, respectively, as determined by immunohistochemistry. The serotonin antagonist, α‐p‐chlorophenylalanine, effectively blocked the hypoglycemic effects and increased the signaling protein levels. After XN administration, none of the animals showed significant changes in plasma‐free fatty acids in 60 min. In summary, the XN extract may have hypoglycemic effects in normal Wistar and SIIR rats that may have a serotonin‐related hypoglycemic effect and enhance insulin sensitivity in the SIIR rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-25T02:05:38.513317-05:
      DOI: 10.1002/ptr.5314
  • Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and
           Centella asiatica in Human Liver Microsomes
    • Authors: Jay Savai; Alice Varghese, Nancy Pandita, Meena Chintamaneni
      Abstract: Withania somnifera is commonly used as a rejuvenator, whereas Centella asiatica is well known for its anxiolytic and nootropic effects. The present study aims at investigating the effect of crude extracts and principal phytoconstituents of both the medicinal plants with CYP3A4 and CYP2D6 enzyme activity in human liver microsomes (HLM). Phytoconstituents were quantified in the crude extracts of both the medicinal plants using reverse phase HPLC. Crude extracts and phytoconstituents of W. somnifera showed no significant interaction with both CYP3A4 and CYP2D6 enzymes in HLM. Of the crude extracts of C. asiatica screened in vitro, methanolic extract showed potent noncompetitive inhibition of only CYP3A4 enzyme (Ki—64.36 ± 1.82 µg/mL), whereas ethanol solution extract showed potent noncompetitive inhibition of only CYP2D6 enzyme (Ki—36.3 ± 0.44 µg/mL). The flavonoids, quercetin, and kaempferol showed potent (IC50 values less than 100 μM) inhibition of CYP3A4 activity, whereas quercetin alone showed potent inhibition of CYP2D6 activity in HLM. Because methanolic extract of C. asiatica showed a relatively high percentage content of quercetin and kaempferol than ethanol solution extract, the inhibitory effect of methanolic extract on CYP3A4 enzyme activity could be attributed to the flavonoids. Thus, co‐administration of the alcoholic extracts of C. asiatica with drugs that are substrates of CYP3A4 and CYP2D6 enzymes may lead to undesirable herb‐drug interactions in humans. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-13T04:01:24.010829-05:
      DOI: 10.1002/ptr.5308
  • Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl
           Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells
    • Authors: Yoon Jung Jeon; Seung‐Nam Jung, Hyeyoun Chang, Jieun Yun, Chang Woo Lee, Joonku Lee, Sangho Choi, Oyekanmi Nash, Dong Cho Han, Byoung‐Mog Kwon
      Abstract: Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose‐dependent manner. To identify the active components, a bioassay‐guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down‐regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase‐3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3‐related diseases, including cancer and inflammation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-13T03:41:26.933955-05:
      DOI: 10.1002/ptr.5311
  • The Effect of Zataria multiflora and its Constituent, Carvacrol, on
           Tracheal Responsiveness and Lung Pathology in Guinea Pig Model of COPD
    • Authors: L. Gholami Mahtaj; M.H. Boskabady, N. Mohamadian Roshan
      Abstract: The effects of Zataria multiflora (Z. multiflora) and its constituent, carvacrol, in guinea pigs model of chronic obstructive pulmonary disease (COPD) were examined. Animals were divided into control, COPD, COPD + drinking water containing three concentrations of extract of Z. multiflora (0.4, 0.8 and 1.6 mg/ml), COPD + drinking water containing three concentrations of carvacrol (60, 120 and 240 µg/ml) and COPD + dexamethasone (50 µg/ml). COPD was induced by exposing animals to cigarette smoke for 3 months. Emphysema as a pathological change of the lung and tracheal responsiveness were measured (n = 5 for control and COPD groups and n = 6 for another groups). Tracheal responsiveness (p 
      PubDate: 2015-02-13T03:32:07.203715-05:
      DOI: 10.1002/ptr.5309
  • Protective Effects of Turbinaria ornata and Padina pavonia against
           Azoxymethane‐Induced Colon Carcinogenesis through Modulation of PPAR
           Gamma, NF‐κB and Oxidative Stress
    • Authors: Ayman M. Mahmoud; Ehab M. Abdella, Azza M. El‐Derby, Eman M. Abdella
      Abstract: The aim of this study was to investigate the antiproliferative and protective effects of the brown seaweeds, Turbinaria ornata and Padina pavonia, against azoxymethane (AOM)‐induced colon carcinogenesis in mice. Both algal extracts showed anti‐proliferative effects on the human carcinoma cell line HCT‐116 in vitro, with T. ornata demonstrating a more potent effect. Male albino Swiss mice received intraperitoneal injections of AOM (10 mg/kg) once a week for two consecutive weeks and 100 mg/kg of either T. ornata or P. pavonia extracts. AOM‐induced mice exhibited alterations in the histological structure of the colon, elevated lipid peroxidation and nitric oxide, declined glutathione content and reduced activity of superoxide dismutase and glutathione peroxidase. In addition, AOM induced downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and p53 mRNA expression, with concomitant upregulation of nuclear factor‐kappa B (NF‐κB) in colon tissue. Administration of either algal extract markedly alleviated the recorded alterations. In conclusion, the current study suggests that T. ornata and P. pavonia, through their antioxidant and anti‐inflammatory effects, are able to attenuate colon inflammation by downregulating NF‐κB expression. Furthermore, the protective effects of both algae against AOM‐initiated carcinogenesis were attributed, at least in part, to their ability to upregulate colonic PPARγ and p53 expression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-12T00:17:22.01702-05:0
      DOI: 10.1002/ptr.5310
  • Anti‐HIV‐1 Integrase Activity and Molecular Docking Study of
           Compounds from Caesalpinia  sappan L.
    • Authors: Supinya Tewtrakul; Prapaporn Chaniad, Somsak Pianwanit, Chatchanok Karalai, Chanita Ponglimanont, Orapun Yodsaoue
      Abstract: Caesalpinia sappan L. (Caesalpiniaceae) has been traditionally used as blood tonic, expectorant, and astringent by boiling with water. Searching for HIV‐1 integrase (IN) inhibitors from this plant is a promising approach. The EtOH extract of C. sappan and its isolated compounds were tested for their anti‐HIV‐1 IN effect using the multiplate integration assay, and the active compounds were determined for their mechanisms by molecular docking technique. Extraction from the heartwoods and roots of C. sappan led to the isolation of nine compounds. Among the compounds tested, sappanchalcone (2) displayed the strongest effect against HIV‐1 IN with an IC50 value of 2.3 μM followed by protosappanin A (9, IC50 = 12.6 μM). Structure‐activity relationships of compounds from C. sappan were found, in which the vicinal hydroxyl moiety were essential for anti‐HIV‐1 IN effect of compounds 2 and 9 by binding with the amino acid residues Gln148 and Thr66 in the core domain of the HIV‐ 1 IN enzyme, respectively. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-11T06:41:26.45842-05:0
      DOI: 10.1002/ptr.5307
  • Corosolic Acid Exhibits Anti‐angiogenic and
           Anti‐lymphangiogenic Effects on In Vitro Endothelial Cells and on an
           In Vivo CT‐26 Colon Carcinoma Animal Model
    • Authors: Ki Hyun Yoo; Jong‐Hwa Park, Dae Young Lee, Jeon Hwang‐Bo, Nam In Baek, In Sik Chung
      Abstract: We describe the anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid, a pentacyclic triterpenoid isolated from Cornus kousa Burg. A mouse colon carcinoma CT‐26 animal model was employed to determine the in vivo anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid. Corosolic acid induced apoptosis in CT‐26 cells, mediated by the activation of caspase‐3. In addition, it reduced the final tumor volume and the blood and lymphatic vessel densities of tumors, indicating that it suppresses in vivo angiogenesis and lymphangiogenesis. Corosolic acid inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells. In addition, corosolic acid decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin‐1. Pretreatment with corosolic acid decreased the phosphorylation of focal adhesion kinase (FAK) and ERK1/2, suggesting that corosolic acid contains anti‐angiogenic activity that can suppress FAK signaling induced by angiopoietin‐1. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-02T21:48:33.330524-05:
      DOI: 10.1002/ptr.5306
  • Apoptotic Effects of the Extracts of Cordyceps militaris via Erk
           Phosphorylation in a Renal Cell Carcinoma Cell Line
    • Authors: Kazuhiro Yamamoto; Hiroaki Shichiri, Atsushi Uda, Kazuhiko Yamashita, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai
      Abstract: Cordyceps militaris (CM) is gaining attention as a traditional medicinal food, but its molecular biological mechanisms for anti‐cancer activity are not identified or clarified. We aimed to elucidate the synthesizing apoptotic effects of CM extracts and to determine the biological effects of CM extract against cordycepin alone in a renal cell carcinoma (RCC) cell line. CM extract showed higher effects of growth inhibition, apoptotic effect, and cell cycle arrest than cordycepin alone. Moreover, CM extract activated extracellular signal‐regulated kinase (Erk) highly more than cordycepin alone. We suggest that cordycepin and CM extract induced apoptosis via the activation of Erk dominantly and AMP‐activated protein kinase slightly; CM extract has more potent effects on apoptotic effects associated with Erk activation than cordycepin alone. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-02T21:31:40.659915-05:
      DOI: 10.1002/ptr.5305
  • Natural Sesquiterpene Lactones Enhance Oxacillin and Gentamicin
           Effectiveness Against Pathogenic Bacteria Without Antibacterial Effects on
           Beneficial Lactobacilli
    • Authors: Elena Cartagena; Mariana Alva, Susana Montanaro, Alicia Bardón
      Abstract: This is a report on the synergistic interactions (SIs) between melampolide‐type sesquiterpene lactones 1–8 from Acanthospermum hispidum DC., and oxacillin or gentamicin, against four pathogenic strains of Staphylococcus aureus and Enterococcus faecalis; two of them were multi‐resistant strains obtained from chronic infectious processes. Our results showed that all associations of 1–8 with antibiotics (ATBs) are more effective than pure ATBs to control pathogenic strains of S. aureus and E. faecalis. The most relevant SIs were observed when the major lactone of A. hispidum, acanthospermal B [5], was combined with gentamicin (protein synthesis inhibitor) against an ex vivo culture of methicillin‐resistant S. aureus SAR 1, displaying a significant MIC reduction in 5 (312.5 to 78.1 µg/mL), and gentamicin (120 µg/mL to 3 µg/mL). Compound 4 improved the antibiotic potency of oxacillin (cell wall synthesis inhibitor) against ampicillin‐resistant E. faecalis (60 µg/mL to 1.5 µg/mL). It is important to remark that three beneficial lactobacilli were resistant to 1–8 and their mixtures with gentamicin or oxacillin in effective concentrations against pathogenic bacteria. Synergism between ATBs and phytochemicals is a therapeutically helpful concept to improve ATB efficacy and prevent resistance. The present results show that selective SIs occur between melampolides and gentamicin or oxacillin, and open a new field of research. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-02T01:23:35.949148-05:
      DOI: 10.1002/ptr.5301
  • Phytochemical and Pharmacological Profile of Vitex negundo
    • Authors: Cheng‐Jian Zheng; Hua‐Qiang Li, Shan‐Cheng Ren, Chuan‐Liang Xu, Khalid Rahman, Lu‐Ping Qin, Ying‐Hao Sun
      Abstract: The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti‐nociceptive, antiinflammatory, anti‐tumor, anti‐oxidant, insecticidal, antimicrobial, anti‐androgenic, anti‐osteoporotic, anti‐cataract, hepatoprotective and anti‐hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure–activity relationship and their molecular mechanisms of action. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T04:47:58.268409-05:
      DOI: 10.1002/ptr.5303
  • Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from
           Traditional Chinese Herbs
    • Authors: Yong Zhao; Bent Håvard Hellum, Aihua Liang, Odd Georg Nilsen
      Abstract: The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed by time‐dependent and nicotinamide adenine dinucleotide phosphate‐dependent and reversible inhibition by Lineweaver–Burk plot assessments. Inhibition mechanisms were also assessed by computerized interaction prediction by using the Discovery Studio CDOCKER software (Accelrys, San Diego, CA, USA). Tetrahydropalmatine showed a mechanism‐based inhibition of both CYP1A2 and CYP2D6, and Ber of CYP2D6. Neferine and Ber both showed a nonmechanistic inhibition of CYP1A2. All compounds showed a similar and significant mechanism‐based inhibition of CYP3A4. Tetrahydropalmatine and Ber demonstrated both reversible and irreversible inhibition of CYP2D6 and CYP3A4. Tetrahydropalmatine and Ber displayed H‐bond and several Pi‐bond connections with specific amino acid residues of CYP1A2, CYP2D6 and CYP3A4, giving further knowledge to the identified reversible and irreversible herb–drug interactions. Tetrahydropalmatine and Ber should be considered for herb–drug interactions in clinical therapy until relevant clinical studies are available. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T03:03:13.149626-05:
      DOI: 10.1002/ptr.5285
  • Therapeutic Potential of Resveratrol in Type I Gaucher Disease
    • Authors: Cheong Hoon Seo; June‐Bum Kim
      Abstract: Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti‐inflammatory, anti‐oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis‐inducing factor (AIF), Bax, cleaved caspase‐3, acetyl‐coenzyme A acetyltransferase 1 (ACAT1), E3‐binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol‐treated patient cells were determined by thin‐layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase‐3 dose‐dependently decreased, while those of ACAT1, E3BP, and CS dose‐dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:54:46.076223-05:
      DOI: 10.1002/ptr.5304
  • Effects of Jitai Tablet, A Traditional Chinese Medicine, on Spontaneous
           Withdrawal Symptoms and Modulation of Dopaminergic Functions in
           Morphine‐Dependent Rats
    • Authors: Shaoang Tu; Jinlong Gao, Jia Liu, Jinming Zhang, Yiyun Huang, Shasha Xu, Mei Han, Jianhui Liang
      Abstract: Chronic opioid abuse can cause damage to dopamine neurons. However, there are currently no effective pharmacotherapies to reverse this damage, even though progress has been made in the development of therapeutic strategies for opioid dependence. The Jitai tablet (JTT) is a traditional Chinese medicine formulation most commonly used for opioid addiction treatment in China. In a morphine spontaneous withdrawal rat model we investigated the effects of JTT, either given before (pre‐treatment) or after (post‐treatment) morphine administration, on the dopamine system. Our study has shown the following: (1) pre‐ and post‐treatment with JTT were effective at alleviating the wet dog shakes and episodes of writhing; (2) pre‐treatment with JTT inhibited the morphine‐induced decreases in dopamine transporter (DAT), dopamine D2 receptor (D2R) and tyrosine hydroxylase (TH) levels in the striatum (p 
      PubDate: 2015-01-27T04:50:18.412115-05:
      DOI: 10.1002/ptr.5300
  • An Effect of Oak‐Wood Extract (Robuvit®) on Energy State of
           Healthy Adults—A Pilot Study
    • Abstract: The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) – polyphenolic extract obtained from the wood of oak Quercus robur – on the healthy elderly individuals using energy subscale scores of the Activation – Deactivation Adjective Check List. Analysis was focused on the comparison of pre‐post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre‐treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
  • Relationship Between Emotional Behavior in Mice and the Concentration of
           (+)‐α‐Santalol in the Brain
    • Abstract: We previously reported finding anxiolytic‐like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)‐α‐santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)‐α‐santalol by inhalation or intraperitoneal injection, we assessed anxiolytic‐like and locomotor activities using elevated‐plus maze tests. We also examined the relationship between the emotional behavior and the (+)‐α‐santalol brain concentration. Anxiolytic‐like activity was not observed immediately after administration or after water‐immersion stress for 24 h for either the (+)‐α‐santalol 2 μL/L air inhalation or the (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)‐α‐santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water‐immersion stress for 24 h. The brain (+)‐α‐santalol concentration was 2.6 µg/g tissue after (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)‐α‐santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic‐like activity. Copyright © 2015 John Wiley & Sons, Ltd.
  • Cardioprotective Effects of Tannic Acid on Isoproterenol‐Induced
           Myocardial Injury in Rats: Further Insight into ‘French
    • Abstract: Tannic acid (TA) is a polyphenolic compound, which has shown diverse pharmacological effects with antimutagenic, anticarcinogenic and antibactericidal properties. However, cardioprotective effects of TA have not been reported. To investigate the protective effects of TA, rats were administered TA for 7 days and then intoxicated with isoproterenol (ISO). Myocardial ischemia injury was indicated by changes in electrocardiographic (ECG) patterns, morphology and cardiac marker enzymes. Furthermore, protein expression levels of c‐fos, c‐jun, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), cleaved‐caspase‐3 and ‐9 were analyzed by immunohistochemistry, and activities of apoptosis‐related proteins Bax, Bcl‐2, caspase‐3 and nuclear factor kappa B (NF‐κB) were detected by Western blot. Pretreatment with TA ameliorated changes in morphology and ECG, reduced activities of marker enzymes, suppressed overexpression of apoptosis‐related proteins, upregulated expression of antioxidants. Moreover, TA pretreatment contributed to the decrease in ratio of Bax/Bcl‐2, as well as reduced expression of TNF‐α, IL‐1β, caspase‐3, cleaved‐caspase‐3 and ‐9. TA displayed cardioprotective effects, which may be attributed to lowering of Bax/Bcl‐2 ratio, c‐fos and c‐jun expression and inhibition of NF‐κB activation, as well as oxidative stress, inflammation and apoptosis. These findings provide further insight into the ‘French paradox’ and the mechanisms underlying the beneficial effects of TA. Copyright © 2015 John Wiley & Sons, Ltd.
  • Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are
           Mediated Through Dual Inhibition of Ca++ Influx and Phosphodiesterase
    • Abstract: This study describes the antidiarrheal and antispasmodic activities of the hydro‐alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action explored along with activity‐directed fractionation. Bp.Cr and its aqueous (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in‐vivo and in‐vitro assays. The crude extract (100–300 mg/kg) showed 20 and 60% protection of castor oil‐induced diarrhea in mice. In isolated rabbit jejunum, Bp.Cr like papaverine inhibited spontaneous and high K+ (80 mM)‐induced contractions equi‐potently. In guinea‐pig ileum, Bp.Cr showed a moderate spasmogenic effect. The activity‐directed fractionation revealed that the spasmolytic activity was concentrated in the organic fractions and spasmogenic component in the aqueous fraction. Amongst the organic fractions, BP.DCM and Bp.Pet inhibited spontaneous and high K+‐induced contractions equi‐potently, while Bp.But, like verapamil was more potent against high K+. The crude extract and its organic fractions caused rightward shift in the Ca++‐concentration response curves (CRCs), similar to verapamil, and all except Bp.But potentiated the isoprenaline‐inhibitory CRCs to the left, similar to papaverine. The results of this study indicate that the crude extract of B. polystachya possesses antidiarrheal and antispasmodic activities, mediated possibly through dual inhibition of Ca++ influx and phospodiesterase enzyme. Copyright © 2015 John Wiley & Sons, Ltd.
  • Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin
           (Corilagin) Rich Extracts of Phyllanthus amarus in
           Carrageenan‐induced Thermal and Mechanical Chronic Muscle
    • Abstract: The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. Copyright © 2015 John Wiley & Sons, Ltd.
  • Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing
           DNA Methylation
    • Abstract: Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor β (RARβ), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RARβ has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RARβ is a major mechanism for its silencing in tumors. Recently, curcumin has been considered as a potential DNA methyltransferase inhibitor. Herein, we demonstrated that curcumin significantly elevate RARβ expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RARβ promoter methylation in lung cancer A549 and H460 cells. Mechanistic study demonstrated that curcumin was able to downregulate the mRNA levels of DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective effect against weight loss because of tumor burden. Tumor growth was strongly repressed by curcumin treatment. As the results from in vitro, RARβ mRNA were increased and DNMT3b mRNA were decreased by curcumin treatment compared with the mice in control group. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo‐preventive agent for lung cancer through reactivation of RARβ. Copyright © 2015 John Wiley & Sons, Ltd.
  • Incidence and Causes of Aconitum Alkaloid Poisoning in Hong Kong from 1989
           to 2010
    • Abstract: Aconite roots contain Aconitum alkaloids, which are highly toxic cardiotoxins and neurotoxins. In this review, the main objective was to determine the incidence and causes of Aconitum alkaloid poisoning in Hong Kong between 1989 and 2010, based on six published reports from the territory‐wide poison control units. In the New Territories East of Hong Kong, the incidence of aconite poisoning showed a sudden and sustained decrease from 0.60 (1989–1991) to 0.16 (1992–1993) and 0.17 (1996–1998) per 100 000 population, after publicity measures in late 1991 to promote awareness of the toxicity of aconite roots. In the whole of Hong Kong, the incidence of aconite poisoning was even lower in January 2000–June 2004 (0.03 per 100 000 population). However, aconite poisoning became more common again in April 2004–July 2009 and 2008–2010 (0.15 and 0.28 per 100 000 population). Overdoses and use of inadequately processed aconite roots were important causes. As from 2004 to 2009, ‘hidden’ aconite poisoning (toxicity caused by contaminants in other dispensed herbs) emerged as an important cause. It is important to continue the safety monitoring of potent herbs and the networking of poison control units. Further systematic studies would be required to identify the likely sources of contamination of herbs. Copyright © 2015 John Wiley & Sons, Ltd.
  • The Influence of Aconitum carmichaelii Debx. on the Pharmacokinetic
           Characteristics of Main Components in Rheum palmatum L.
    • Abstract: Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines, and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata was the basic herb pair applied in many Chinese traditional prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb anthraquinones as the main marker constituents were investigated. In the present study, pharmacokinetic differences of rhubarb anthraquinones were detected after oral administration of extract of Rheum palmatum L. and compatibility with Aconitum carmichaelii Debx. After oral administration, no difference of peak time can be found for anthraquinones between rhubarb group and compatibility group. But Cmax and area under the curve of aloe‐emodin, emodin and chrysophanol in compatibility group were significantly higher than that in rhubarb group. Although the Cmax of rhein in compatibility group was much lower than that in rhubarb group, the area under the curve value was similar in two groups. The clearance and t1/2 of rhubarb anthraquinone were also changed after compatibility. The change of pharmacokinetics characteristics of rhubarb anthraquinone after compatibility may be caused by the drug–drug interaction medicated by chemical reaction and cytochromes P450. Copyright © 2015 John Wiley & Sons, Ltd.
  • Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe
           Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of
           Neutrophil Activation
    • Abstract: Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post‐medication, the MPO, S100A8/A9, histone, and interleukin‐6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide‐stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.
  • Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in
           Hamsters Fed High‐Fat diet
    • Abstract: Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high‐fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up‐regulated low‐density lipoprotein receptor (LDLR) and cholesterol 7α‐hydroxylase (CYP7A1) mRNA and protein expression and down‐regulated apical sodium‐dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up‐regulating LDLR and CYP7A1 mRNA and protein expression, down‐regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia. Copyright © 2015 John Wiley & Sons, Ltd.
  • Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian
           Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells
    • Abstract: Baicalein (BA), isolated from the Chinese medicinal herb Scutellariae radix (Huangqin in Chinese), is a flavonoid with various pharmacological effects. Herein, we found that BA only slightly reduced the cell viability on HepG2 cells after 24‐h treatment as determined by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay. However, BA (50 μM) effectively blocked the colony formation. Meanwhile, BA remarkably induced the formation of autophagosomes after 24‐h treatment as determined by immunofluorescence with monodansylcadaverine staining as well as transmission electron microscopy, respectively. Moreover, BA obviously up‐regulated the expression of microtubule‐associated protein 1A/1B‐light chain 3‐II in concentration‐dependent and time‐dependent manners in HepG2 cells. When combined with the autophagy inhibitor chloroquine and BA, the cell viability and colony formation were significantly decreased, indicating that BA triggered protective autophagy, which prevented cell death. Further study showed that BA concentration‐dependently and time‐dependently decreased the expression of p‐AKT (S473), p‐ULK1 (S757) and p‐4EBP1 (T37 and S65), suggesting the involvement of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) in BA‐triggered autophagy. Copyright © 2015 John Wiley & Sons, Ltd.
  • Inhibition of Wnt/β‐Catenin Pathway by Dehydrocostus Lactone
           and Costunolide in Colon Cancer Cells
    • Abstract: Abnormal activation of β‐catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β‐catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti‐colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β‐catenin. They also suppressed the nuclear translocation of galectin‐3 that is one of the coactivators of β‐catenin in SW‐480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW‐480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti‐colorectal cancer activities through inhibiting Wnt/β‐catenin pathway. Copyright © 2015 John Wiley & Sons, Ltd.
  • Effect of Resveratrol on the Pharmacokinetics of Carbamazepine in Healthy
           Human Volunteers
    • Abstract: The purpose of the present study was to assess the effect of resveratrol (RSV) pretreatment on CYP3A4 enzyme activity and pharmacokinetics of carbamazepine (CBZ) in healthy human volunteers. The open‐label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC‐MS/MS. In comparison with the control, RSV pretreatment significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC), and half life (t1/2) and significantly decreased apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F), while there was no significant change observed in time to reach maximum concentration (tmax) and elimination rate constant (kel) of CBZ. Furthermore, RSV pretreatment significantly decreased metabolite to parent (CBZE/CBZ) ratios of Cmax and AUC and significantly increased CBZE/CBZ ratios of CL/F and Vd/F, indicating the reduced formation of CBZE to CBZ. The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to RSV‐mediated inhibition of CYP3A4 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CBZ including other CYP3A4 substrates. Copyright © 2015 John Wiley & Sons, Ltd.
  • The Potential Drug–Drug Interactions of Ginkgolide B Mediated by
           Renal Transporters
    • Abstract: Ginkgolide B (GB) is a selective and strong antagonist of platelet‐activating factor with great benefits in CNS diseases treatment. The renal excretion constitutes the predominant secretory pathway of GB. Here, we investigated the potential role of renal drug transporters in GB urinary excretion. The intravenous administration of GB was conducted at 10 min post‐administration of probenecid (potential inhibitor of organic anion transporters/organic anion transporting polypeptides) or bromosulfophthalein (traditional inhibitor of multi‐drug resistance proteins) in rats. Pretreated with probenecid, the systemic exposure of GB was significantly elevated from 8.319 ± 1.646 to 14.75 ± 1.328 µg · mL−1∙h but with reduced total clearance from 1.17 ± 0.331 to 0.596 ± 0.0573 L · h−1∙kg−1 accompanying no changes in plasma elimination half‐lives compared with control group. With no pronounced effect on metabolic elimination, the decreased total clearance was closely pertained to the reduced renal excretion, indicating the potential effect of organic anion transporters and/or organic anion transporting polypeptides in renal secretory of GB from blood to urine. However, the possible effect of bromosulfophthalein was restricted within a minor extent, suggesting the mild role of multi‐drug resistance protein in GB renal excretion. Copyright © 2015 John Wiley & Sons, Ltd.
  • Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Induces Gene
           Expression of Anti‐viral Proteins and Inhibits Neuraminidase
    • Abstract: Yu Ping Feng San (YPFS), a Chinese herbal decoction comprised of Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu) and Saposhnikoviae Radix (Fangfeng), has been used clinically for colds and flus; however, the action mechanism of which is not known. Previously, we had demonstrated that YPFS could modulate inflammatory response and phagocytosis in exerting anti‐viral and anti‐bacterial effects. Here, we further evaluated the bioactivities of YPFS in gene expression regulated by interferon (IFN) signaling and neuraminidase activity of influenza virus A. Application of YPFS onto cultured murine macrophages, the expressions of mRNAs encoding ribonuclease L (RNaseL), myxovirus (influenza virus) resistance 2 (Mx2), protein kinase R (PKR) and IFN‐stimulated gene 15 (ISG15) were induced from 2 to 30 folds in dose‐dependent manners. In parallel, the transcriptional activity of IFN‐stimulated response element (ISRE), an up stream regulator of the above anti‐viral proteins, was also triggered by YPFS treatment. Conversely, YPFS was found to suppress the neuraminidase activity of influenza virus A in cultured epithelial cells, thereby preventing the viral release and spreading. Taken together, YPFS exerted anti‐bacterial and anti‐viral effects in innate immunity. Copyright © 2015 John Wiley & Sons, Ltd.
  • In vivo Antimalarial Activity of α‐Mangostin and the New
           Xanthone δ‐Mangostin
    • Abstract: Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α‐mangostin and a new compound, δ‐mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α‐Mangostin was more active against the resistant Plasmodium falciparum chloroquine‐resistant (FCR3) strain (IC50 = 0.2 ± 0.01 μM) than δ‐mangostin (IC50 = 121.2 ± 1.0 μM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances. Copyright © 2015 John Wiley & Sons, Ltd.
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