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Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 4, SJR: 1.429, h-index: 58)
Pain Medicine     Hybrid Journal   (Followers: 6, SJR: 0.929, h-index: 55)
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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   (Followers: 1, SJR: 0.831, h-index: 53)
Peace & Change     Hybrid Journal   (Followers: 4)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 34, SJR: 1.325, h-index: 62)
Pediatric Anesthesia     Hybrid Journal   (Followers: 5, 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: 17, SJR: 1.027, h-index: 43)
Pediatric Obesity     Hybrid Journal   (Followers: 5, SJR: 1.336, h-index: 33)
Pediatric Pulmonology     Hybrid Journal   (Followers: 5, 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: 2, 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: 4, 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: 25, 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: 4, SJR: 1.566, h-index: 66)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (Followers: 2, SJR: 0.283, h-index: 8)
Pest Management Science     Hybrid Journal   (Followers: 5, SJR: 1.262, h-index: 72)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 10, 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: 20, SJR: 0.852, h-index: 78)
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Philosophical Investigations     Hybrid Journal   (Followers: 3, SJR: 0.162, h-index: 6)
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Philosophical Perspectives     Hybrid Journal   (Followers: 7)
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Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 20, SJR: 1.629, h-index: 11)
Philosophy Compass     Hybrid Journal   (Followers: 9, 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   (Followers: 1)
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 26, SJR: 0.396, h-index: 30)
Phytochemical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.959, h-index: 45)
Phytotherapy Research     Hybrid Journal   (Followers: 1, 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: 7, SJR: 2.463, h-index: 58)
Plant Breeding     Hybrid Journal   (Followers: 15, 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: 11, SJR: 0.415, h-index: 3)
Policy & Internet     Hybrid Journal   (Followers: 8)
Policy Studies J.     Hybrid Journal   (Followers: 4, SJR: 1.362, h-index: 30)
Political Insight     Partially Free   (Followers: 1)
Political Psychology     Hybrid Journal   (Followers: 18, 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)
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Polymer Composites     Hybrid Journal   (Followers: 11, 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: 4, 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: 5, 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: 8)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 3)
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: 28, 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: 6, SJR: 0.387, h-index: 22)
Production and Operations Management     Hybrid Journal   (Followers: 5, SJR: 2.417, h-index: 62)
Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)
Progress in Neurology and Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.124, h-index: 3)
Progress in Photovoltaics: Research & Applications     Hybrid Journal   (Followers: 7, SJR: 4.314, h-index: 74)
Progress in Structural Engineering and Materials     Hybrid Journal   (Followers: 5)
Project Management J.     Hybrid Journal   (Followers: 30, SJR: 0.497, h-index: 8)
Propellants, Explosives, Pyrotechnics     Hybrid Journal   (Followers: 196, SJR: 0.765, h-index: 37)
Protein Science     Hybrid Journal   (Followers: 25, SJR: 2.013, h-index: 132)

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Journal Cover   Phytotherapy Research
  [SJR: 0.82]   [H-I: 76]   [1 followers]  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  [1597 journals]
  • Dammarenediol‐II Prevents VEGF‐Mediated Microvascular
           Permeability in Diabetic Mice
    • Abstract: Diabetic retinopathy is a major diabetic complication predominantly caused by vascular endothelial growth factor (VEGF)‐induced vascular permeability in the retina; however, treatments targeting glycemic control have not been successful. Here, we investigated the protective effect of dammarenediol‐II, a precursor of triterpenoid saponin biosynthesis, on VEGF‐induced vascular leakage using human umbilical vein endothelial cells (HUVECs) and diabetic mice. We overproduced the compound in transgenic tobacco expressing Panax ginseng dammarenediol‐II synthase gene and purified using column chromatography. Analysis of the purified compound using a gas chromatography–mass spectrometry system revealed identical retention time and fragmentation pattern to those of authentic standard dammarenediol‐II. Dammarenediol‐II inhibited VEGF‐induced intracellular reactive oxygen species generation, but it had no effect on the levels of intracellular Ca2+ in HUVECs. We also found that dammarenediol‐II inhibited VEGF‐induced stress fiber formation and vascular endothelial‐cadherin disruption, both of which play critical roles in modulating endothelial permeability. Notably, microvascular leakage in the retina of diabetic mice was successfully inhibited by intravitreal dammarenediol‐II injection. Our results suggest that the natural drug dammarenediol‐II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-24T07:11:46.583813-05:
      DOI: 10.1002/ptr.5480
  • Multiple ABC Transporters Efflux Baicalin
    • Abstract: Baicalein, the aglycone formed by hydrolysis of baicalin in the intestine, is well absorbed by passive diffusion but subjected to extensive intestinal glucuronidation. Efflux of baicalin, the low passive permeability glucuronide of baicalein from enterocytes, likely depends on a carrier‐mediated transport. The present study was designed to explore potential drug–herb interaction by investigating the inhibitory effect of baicalin on the transport of reporter substrates by transporters and to identify the transporters responsible for the efflux of baicalin from enterocytes and hepatocytes. The interaction of baicalin with specific ABC transporters was studied using membranes from cells overexpressing human BCRP, MDR1, MRP2, MRP3 and MRP4. Baicalin was tested for its potential to inhibit vesicular transport by these transporters. The transport of baicalin by the selected transporters was also investigated. Transport by BCRP, MRP3 and MRP4 was inhibited by baicalin with an IC50 of 3.41 ± 1.83 μM, 14.01 ± 2.51 μM and 14.39 ± 5.69 μM respectively. Inhibition of MDR1 (IC50 = 94.84 ± 31.10 μM) and MRP2 (IC50 = 210.13 ± 110.49 μM) was less potent. MRP2 and BCRP are the apical transporters of baicalin that may mediate luminal efflux in enterocytes and biliary efflux in hepatocytes. The basolateral efflux of baicalin is likely mediated by MRP3 and MRP4 both in enterocytes and hepatocytes. Via inhibition of transport by ABC transporters, baicalin could interfere with the absorption and disposition of drugs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-24T06:49:07.346595-05:
      DOI: 10.1002/ptr.5477
  • A Randomized Clinical Trial of Berberine Hydrochloride in Patients with
           Diarrhea‐Predominant Irritable Bowel Syndrome
    • Authors: Chunqiu Chen; Chunhua Tao, Zhongchen Liu, Meiling Lu, Qiuhui Pan, Lijun Zheng, Qing Li, Zhenshun Song, Jakub Fichna
      Abstract: We aimed to evaluate clinical symptoms in diarrhea predominant irritable bowel syndrome (IBS‐D) receiving berberine hydrochloride in a randomized double‐blind placebo‐controlled clinical trial. Overall, 196 patients with IBS‐D were recruited for this study; consequently, 132 patients randomized to receive daily 400 mg of berberine hydrochloride, delivered twice daily or placebo for 8 weeks followed by a 4‐week washout period. After a 2‐week run‐in period, diarrhea, abdominal pain, urgent need for defecation frequency and any adverse events were recorded daily. Prior to administration of the medication and after completing the treatment, assessment of IBS symptom scores, depression and anxiety scale scores and the IBS scale for quality of life (QOL) was carried out. The effects of berberine hydrochloride on IBS‐D, defined by a reduction of diarrhea frequency (P = 0.032), abdominal pain frequency (P 
      PubDate: 2015-09-24T06:42:15.506415-05:
      DOI: 10.1002/ptr.5475
  • The Amoebicidal Effect of Ergosterol Peroxide Isolated from Pleurotus
    • Abstract: Dysentery is an inflammation of the intestine caused by the protozoan parasite Entamoeba histolytica and is a recurrent health problem affecting millions of people worldwide. Because of the magnitude of this disease, finding novel strategies for treatment that does not affect human cells is necessary. Ergosterol peroxide is a sterol particularly known as a major cytotoxic agent with a wide spectrum of biological activities produced by edible and medicinal mushrooms. The aim of this report is to evaluate the amoebicidal activity of ergosterol peroxide (5α, 8α‐epidioxy‐22E‐ergosta‐6,22‐dien‐3β‐ol isolated from 5α, 8α‐epidioxy‐22E‐ergosta‐6,22‐dien‐3β‐ol) (Jacq.) P. Kumm. f. sp. Florida. Our results show that ergosterol peroxide produced a strong cytotoxic effect against amoebic growth. The inhibitory concentration IC50 of ergosterol peroxide was evaluated. The interaction between E. histolytica and ergosterol peroxide in vitro resulted in strong amoebicidal activity (IC50 = 4.23 nM) that may be due to the oxidatory effect on the parasitic membrane. We also tested selective toxicity of ergosterol peroxide using a cell line CCL‐241, a human epithelial cell line isolated from normal human fetal intestinal tissue. To the best of our knowledge, this is the first report on the cytotoxicity of ergosterol peroxide against E. histolytica, which uncovers a new biological property of the lipidic compound isolated from Pleurotus ostreatus (Jacq.) P. Kumm. f. sp. Florida. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-22T01:49:29.38636-05:0
      DOI: 10.1002/ptr.5474
  • Standardized Prunella vulgaris var. lilacina Extract Enhances Cognitive
           Performance in Normal Naive Mice
    • Authors: Se Jin Park; Young Je Ahn, Hyung Eun Lee, Eunyoung Hong, Jong Hoon Ryu
      Abstract: Adult hippocampal neurogenesis is closely associated with neuronal plasticity, cognitive function and the etiology of neurological diseases. We previously reported that the standardized ethanolic extract of Prunella vulgaris var. lilacina (EEPV) can be used for the prevention and treatment of cognitive impairments associated with Alzheimer's disease or schizophrenia. In the present study, we investigated the effects of EEPV on cognitive ability in normal naive mice and the underlying mechanism(s) governing these effects, including adult hippocampal neurogenesis. In the passive avoidance task, sub‐chronic administration of EEPV (25 or 50 mg/kg, p.o.) for 14 days markedly induced the improvement of cognitive function in mice. In addition, sub‐chronic administration of EEPV (25 or 50 mg/kg) for 14 days significantly increased neural cell proliferation and the number of immature neurons, but not newly generated cell survival, in the hippocampal dentate gyrus. Increased ERK, Akt and GSK‐3β phosphorylation levels in the hippocampus were also observed after such administration. Our results indicate that EEPV may enhance cognitive function via the activation of various intracellular signaling molecules and the up‐regulation of adult hippocampal neurogenesis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-17T03:47:38.588031-05:
      DOI: 10.1002/ptr.5449
  • Mechanisms of Vasorelaxation Induced by Hexahydrocurcuminin Isolated Rat
           Thoracic Aorta
    • Authors: Aida Moohammadaree; Chatchawan Changtam, Piyawadee Wicha, Apichart Suksamrarn, Jiraporn Tocharus, Chainarong Tocharus
      Abstract: This study was designed to examine the vasorelaxant effects of hexahydrocurcumin (HHC), one of the major natural metabolites of curcumin from Curcuma longa, on rat isolated aortic rings, and the underlying mechanisms. Isometric tension of the aortic rings was recorded using organ bath system. HHC (1 nM to 1 mM) relaxed the endothelium‐intact aortic rings pre‐contracted with PE and KCl in a concentration‐dependent manner. Removal of the endothelium did not alter the effect of HHC‐induced relaxation. In Ca2+‐free Krebs solution, HHC significantly inhibited the CaCl2‐induced contraction in high K+ depolarized rings and suppressed the transient contraction induced by PE and caffeine in a concentration‐dependent manner. HHC was also observed to relax phobal‐12‐myristate‐13‐acetate (PMA), an activator of protein kinase C (PKC), precontracted aortic rings in a concentration‐dependent manner with EC50 values equivalent to 93.36 ± 1.03 μM. In addition, pre‐incubation with propranolol (a β‐adrenergic receptor blocker) significantly attenuated the HHC‐induced vasorelaxation. These results suggest that the vasorelaxant effect of HHC is mediated by the endothelium‐independent pathway, probably because of the inhibition of extracellular Ca2+ influx through voltage‐operated Ca2+ channels and receptor‐operated Ca2+ channels, the inhibition of Ca2+mobilization from intracellular stores, as well as inhibition of PKC‐mediated Ca2+‐independent contraction. Moreover, HHC produces vasorelaxant effects probably by stimulating the β‐adrenergic receptor. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-11T02:17:43.208581-05:
      DOI: 10.1002/ptr.5448
  • Recent trends in preclinical drug–drug interaction studies of
           flavonoids — Review of case studies, issues and
    • Authors: Nuggehally R. Srinivas
      Abstract: Because of health benefits that are manifested across various disease areas, the consumption of herbal products and/or health supplements containing different kinds of flavonoids has been on the rise. While the drug–drug interaction potential between flavonoids and co‐ingested drugs still remain an issue, opportunities exist for the combination of flavonoids with suitable anti‐cancer drugs to enhance the bioavailability of anti‐cancer drugs and thereby reduce the dose size of the anti‐cancer drugs and improve its therapeutic index. In recent years, scores of flavonoids have undergone preclinical investigation with variety of drugs encompassing therapeutic areas such as oncology (etoposide, doxorubicin, paclitaxel, tamoxifen etc.), immunosuppression (cyclosporine) and hypertension (losartan, felodipine, nitrendipine etc.). The review provides examples of the recent trends in the preclinical investigation of 14 flavonoids (morin, quercetin, silibinin, kaempferol etc.) with various co‐administered drugs. The relevance of combination of flavonoids with anti‐cancer drugs and a framework to help design the in vitro and in vivo preclinical studies to gain better mechanistic insights are discussed. Also, concise discussions on the various physiological factors that contribute for the reduced bioavailability of flavonoids along with the significant challenges in the data interpretation are provided. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-06T22:38:05.672496-05:
      DOI: 10.1002/ptr.5447
  • Effect of Trimeric Myricetin Rhamnoside (TMR) in Carrageenan‐induced
           Inflammation and Caecal Ligation and Puncture‐induced Lung Oxidative
           Stress in Mice
    • Authors: Najeeb Latief; Shikha Anand, Madhu Cholenahalli Lingaraju, Venkanna Balaganur, Nitya Nand Pathak, Jaspreet Kalra, Dinesh Kumar, Brijesh K Bhadoria, Surendra Kumar Tandan
      Abstract: The Eugenia jambolana is used in folklore medicine. Leaves of E. jambolana contain flavonoids as their active constituents which possess in vitro antiinflammatory, antioxidant and the antimicrobial activity. The aim of the present study was to investigate the antiinflammatory and antioxidant effects of a flavonoid glucoside, trimeric myricetin rhamnoside (TMR) isolated from leaves of E. jambolana. TMR was studied for antiinflammatory activity in carrageenan‐induced hind paw oedema and antioxidant activity in lung by caecal ligation and puncture (CLP)‐induced sepsis in mice. Results of the present study indicated that TMR significantly attenuated the oedema, myeloperoxidase (MPO), cytokines and prostaglandin levels in the paw after 5 h of carrageenan injection as compared to vehicle control. It also reduced the lung MPO, lipid peroxides, and serum nitrite plus nitrate levels and increased lung reduced glutathione levels 20 h of CLP as compared to vehicle control. Thus the results of this study concluded that the TMR appears to have potential benefits in diseases that are mediated by both inflammation and oxidative stress and support the pharmacological basis of use of E. jambolana plant as traditional herbal medicine for the treatment of inflammatory diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-06T22:30:59.282409-05:
      DOI: 10.1002/ptr.5446
  • Evaluation of the Wound Healing Properties of Hancornia speciosa Leaves
    • Abstract: The leaves of Hancornia speciosa Gomes (Apocynaceae), a medicinal species found in the Brazilian cerrado biome, are traditionally used to treat wounds and inflammatory disorders. The goal of the present study was to investigate the in vitro wound healing properties of ethanolic extract of H. speciosa leaves and its isolated compounds, using the scratch assay, and to evaluate their effects on the release of the pro‐inflammatory cytokine tumor necrosis factor (TNF‐α) by lipopolysaccharide (LPS)‐stimulated human acute monocytic (THP‐1) cells. H. speciosa ethanolic extract significantly increased (42.8% ± 5.4 at 25 µg/mL) cell migration and proliferation of fibroblasts compared with control cells, as well as the isolated compounds bornesitol (80.8% ± 5.1) and quinic acid (69.1% ± 6.2), both assayed at 50 μM. TNF‐α release by LPS‐stimulated THP‐1 cells was significantly reduced by the ethanolic extract (62.9% ± 8.2, i.e. 1791.1 ± 394.7 pg/mL) at 10 µg/mL, bornesitol (48.9% ± 0.9, i.e. 2461.6 ± 43.1 pg/mL) at 50 μM, and quinic acid (90.2% ± 3.4, i.e. 473.5 ± 164.4 pg/mL) and rutin (82.4% ± 5.6, i.e. 847.0 ± 271.8 pg/mL) at 10 μM. These results provided evidences to support the traditional use of H. speciosa leaves to treat wounds and inflammatory disorders. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-06T21:36:46.738785-05:
      DOI: 10.1002/ptr.5438
  • The Potential of Sub‐Saharan African Plants in the Management of
           Human Immunodeficiency Virus Infections: A Review
    • Authors: Walter Chingwaru; Jerneja Vidmar, Petrina T. Kapewangolo
      Abstract: Acquired immunodeficiency syndrome, caused by human immunodeficiency virus (HIV), is a leading cause of mortality and morbidity in Sub‐Saharan Africa, particularly in Southern Africa. Phytomedicines are an integral part of African health care. The Southern African flora is composed of at least 23 400 taxa. Despite this richness, only a handful of botanical products have been assessed for activities against HIV. This study aimed to summarize the potential of Sub‐Saharan African plants, based on their composition and the established bioactivities, as sources of agents to manage HIV symptoms and as retroviral therapy. At least 109 plant species from 42 families and 94 genera that are found in Southern Africa were shown to have potential or actual activities against HIV. Only 12 of these plant species from 6 families and 10 genera were shown to harbour anti‐HIV properties. Phytochemicals that include β‐sitosterols, terpenoids, glycosides, saponins, flavonoids, triterpenoids, tannins and alkaloids, which harbour anti‐HIV properties, were found to have a near cosmopolitan presence across the plant families in the region. Bioactivities of multiple phytochemicals are comparable to those for standard allopathic antiretroviral drugs. Research to determine the anti‐HIV activities of the identified and other plants, including clinical trials, is long overdue. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-04T03:21:57.190783-05:
      DOI: 10.1002/ptr.5433
  • Anti‐carious Effects of Galla chinensis: A Systematic Review
    • Authors: Tieting Zhang; Jinpu Chu, Xuedong Zhou
      Abstract: As a natural traditional Chinese medicine, Galla chinensis has been widely used since ancient times for its astringency, stypticity, detoxification, and antibacterial activity. Our group has concentrated on the research about its potential of being an applicable anti‐caries agent. The crude extract and some other components purified from it show remarkable efficacy on anticaries, and the most likely mechanism is proposed through specific research. For the fact that crude drugs consist of numerous compounds, and their bioactivity is a result of synergistic effects and/or antagonistic effects of several compounds, it is difficult to clarify the exact mechanism and evaluate the safety and effectiveness of G. chinensis. This review article systematically summarizes previous findings from the following aspects: (1) inhibitory effect on oral bacteria; (2) the demineralization inhibition property; (3) the remineralization‐enhancing property; and (4) stability and toxicity evaluation, and thus indicates the further research direction. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-01T04:49:34.133234-05:
      DOI: 10.1002/ptr.5444
  • The Resveratrol Tetramer r‐Viniferin Induces a Cell Cycle Arrest
           Followed by Apoptosis in the Prostate Cancer Cell Line LNCaP
    • Authors: Michael T. Empl; Malena Albers, Shan Wang, Pablo Steinberg
      Abstract: Polyphenols are secondary plant metabolites that possess potentially health‐promoting properties and which occur in various edible plants and plant products. Especially the stilbenoid resveratrol has been extensively studied regarding its anticarcinogenic and chemopreventive activities. However, research has recently focused on the investigation of other natural or synthetic compounds in order to find substances that show a higher bioactivity and/or bioavailability than resveratrol. In this context, we exemplarily investigated the cytotoxic/growth‐inhibiting properties of the resveratrol tetramer r‐viniferin on the prostate cancer cell line LNCaP and compared them with those of resveratrol. By using the sulforhodamine B assay followed by cell cycle analysis via flow cytometry and commercially available apoptosis/necrosis assay kits, we show that both compounds were able to inhibit the growth of LNCaP cells and to induce a cell cycle arrest in the G1 phase. However, r‐viniferin was significantly more potent in inhibiting cellular growth than resveratrol and the only compound that increased the apoptotic cellular fraction as well as the activity of apoptosis‐associated enzymes. In conclusion, r‐viniferin leads to cytotoxicity in LNCaP cells at fairly low concentrations, and it is therefore conceivable that it might be used as a chemopreventive agent or as an adjuvant in prostate cancer therapy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-01T04:41:01.693716-05:
      DOI: 10.1002/ptr.5443
  • Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a
           High Cholesterol Diet
    • Authors: Ercument Olmez; Kamil Vural, Sule Gok, Zeynep Ozturk, Husniye Kayalar, Semin Ayhan, Ahmet Var
      Abstract: Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low‐density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium‐dependent relaxations in cholesterol‐fed rats. For this purpose, rats were fed by 2% cholesterol‐enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium‐dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL‐cholesterol levels were found to be increased in cholesterol‐fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-29T01:21:15.297089-05:
      DOI: 10.1002/ptr.5445
  • Stilbenoids from Rheum undulatum Protect Hepatocytes Against Oxidative
           Stress Through AMPK Activation
    • Abstract: Oxidative stress promotes several diseases, including liver disease. We have isolated several stilbenoids from Rheum undulatum to investigate their hepatoprotective activities and mechanism. Stilbenoids from R. undulatum protects hepatocytes against arachidonic acid + iron (AA + Fe) induced oxidative stress. Pterostilbene (compound 5) shows stronger activity than the others. Trimethoxystilbenoid (compound 6) shows best activity on protection of HepG2 cells from AA + Fe‐induced oxidative stress, and trans‐stilbenoid (compound 7) shows weak activity. These stilbenoids suppress ROS generation in AA + Fe‐treated HepG2 cells and also suppress AA + Fe‐induced MMP disruption. Their protective effects on AA + Fe‐induced MMP disruption were abrogated by treatment of AMP‐activated protein kinase (AMPK) inhibitor, compound C or transfection of dominant negative form of AMPK. Taken together, stilbenoids from R. undulatum protect hepatocytes against AA + Fe‐induced oxidative stress through AMPK activation. And the methoxy groups in the aryl groups are important for their cytoprotective activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-27T05:51:40.869249-05:
      DOI: 10.1002/ptr.5442
  • Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive
           Oxygen Species‐Mediated Apoptosis in Lung Cancer Cells and Decreases
           Xenograft Tumor Growth
    • Abstract: Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI‐H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl‐2 and Bcl‐xL, and upregulation of Bax, suggesting that caspase‐mediated pathways were involved in MSF‐induced apoptosis. ROS activation of the mitogen‐activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI‐H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd
      PubDate: 2015-08-27T05:30:23.244004-05:
      DOI: 10.1002/ptr.5428
  • Antimicrobial Effects of Blueberry, Raspberry, and Strawberry Aqueous
           Extracts and their Effects on Virulence Gene Expression in Vibrio cholerae
    • Authors: Hazim O. Khalifa; Maki Kamimoto, Toshi Shimamoto, Tadashi Shimamoto
      Abstract: The antimicrobial effects of aqueous extracts of blueberry, raspberry, and strawberry on 13 pathogenic bacteria were evaluated. The minimum inhibitory concentrations and minimum bactericidal concentrations of the extracts were determined before and after neutralization to pH 7.03 ± 0.15. Both Gram‐positive and Gram‐negative pathogenic bacteria were selectively inhibited by the non‐neutralized berries. Blueberry was the best inhibitor, and Vibrio and Listeria were the most sensitive bacteria. After neutralization, blueberry affected only Vibrio and Listeria, whereas the antimicrobial activities of raspberry and strawberry were abolished. The total contents of phenolics, flavonoids, and proanthocyanidins in the extracts were measured with colorimetric methods and were highest in strawberry, followed by raspberry, and then blueberry. We also studied the effects of sub‐bactericidal concentrations of the three berry extracts on virulence gene expression in Vibrio cholerae. Real‐time quantitative reverse transcription–polymerase chain reaction revealed that the three berry extracts effectively repressed the transcription of the tcpA gene. Raspberry also repressed the transcription of the ctxA gene, whereas blueberry and strawberry did not. However, the three berry extracts did not affect the transcription of toxT. These results suggest that the three berry extracts exert potent antimicrobial effects and inhibit the expression of the virulence factors of V. cholerae. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-21T03:05:29.627726-05:
      DOI: 10.1002/ptr.5436
  • The Protective Effect of α‐Hederin, the Active Constituent of
           Nigella sativa, on Lung Inflammation and Blood Cytokines in Ovalbumin
           Sensitized Guinea Pigs
    • Abstract: In the present study, the preventive effect of two different concentrations of α‐hederin, the active constituent of Nigella sativa, on lung inflammation and blood cytokines in ovalbumin sensitized guinea pigs was examined. Forty eight male adult guinea pigs were divided into control (C), sensitized (S) and sensitized pretreated groups; with thymoquinone (S+TQ), low dose (S+LAH) and high dose of α‐hederin (S+HAH) and inhaled fluticasone propionate (S+FP). The lung histopathology and blood levels of IL‐4, IFN‐γ and IL‐17 were assessed. Compared to sensitized animals, all pathological changes improved significantly in pretreated groups (p 
      PubDate: 2015-08-21T02:19:21.605391-05:
      DOI: 10.1002/ptr.5429
  • Distinct Responses of Cytotoxic Ganoderma lucidum Triterpenoids in Human
           Carcinoma Cells
    • Authors: Weimei Ruan; Ying Wei, David G. Popovich
      Abstract: The medicinal mushroom Ganoderma lucidum is well recognized for its effective cancer‐preventative and therapeutic properties, while specific components responsible for these anticancer effects are not well studied. Six triterpenoids that are ganolucidic acid E, lucidumol A, ganodermanontriol, 7‐oxo‐ganoderic acid Z, 15‐hydroxy‐ganoderic acid S, and ganoderic acid DM were isolated and identified from an extract of the mushroom. All compounds reduced cell growth in three human carcinoma cells (Caco‐2, HepG2, and HeLa cells) dose dependently with LC50s from 20.87 to 84.36 μM. Moreover, the six compounds induced apoptosis in HeLa cells with a maximum increase (22%) of sub‐G1 accumulations and 43.03% apoptotic cells in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (15‐hydroxy‐ganoderic acid S treatment). Apoptosis was further confirmed by annexin‐V staining. Four of the compounds also caused apoptosis in Caco‐2 cells with maximum 9.5% increase of sub‐G1 accumulations (7‐oxo‐ganoderic acid Z treatment) and maximum 29.84% apoptotic cells in TUNEL assay (ganoderic acid DM treatment). Contrarily, none of the compounds induced apoptosis in HepG2 cells. The different responses of the three cell lines following these treatments indicated that the bioactive properties of these compounds may vary from cells of different sites of origin and are likely acting under diverse regulatory mechanisms. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-21T02:08:56.7812-05:00
      DOI: 10.1002/ptr.5426
  • Zingerone activates VMAT2 during MPP+‐induced Cell Death
    • Abstract: Parkinson's disease (PD) is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatum. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is used to produce an animal model for PD, and it is converted to 1‐methyl‐4‐phenylpyridine (MPP+) in animals. MPP+ accumulation leads to neuronal cell death. Vesicular monoamine transporter 2 (VMAT2) regulates the accumulation of monoamine neurotransmitters into synaptic vesicles and is involved in neuroprotection against neurotoxin‐induced cell death. Recently, zingerone has been reported to reduce oxidative stress and inhibit inflammation. Therefore, we examined the effect of zingerone on neuronal cell death in a PD model. In an MPP+ and MPTP‐mediated PD model, neuronal cell survival was increased by zingerone without modifying neuroinflammation or reactive oxygen species generation. Zingerone also induced ERK activation and VMAT2 expression, leading to the attenuation of MPP+‐induced neuronal cell death. Our current results suggest that zingerone has a neuroprotective effect in a PD model. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-17T22:51:47.82582-05:0
      DOI: 10.1002/ptr.5435
  • Corrigendum: An Acute, Double‐Blind, Placebo‐Controlled
           Cross‐over Study of 320 mg and 640 mg Doses of Bacopa
           monnieri (CDRI 08) on Multitasking Stress Reactivity and Mood
    • Authors: Sarah Benson; Luke A. Downey, Con Stough, Mark Wetherell, Andrea Zangara, Andrew Scholey
      PubDate: 2015-08-16T22:22:21.301799-05:
      DOI: 10.1002/ptr.5439
  • Corrigendum: Examining the Nootropic Effects of a Special Extract of
           Bacopa monniera on Human Cognitive Functioning: 90 day
           Double‐Blind Placebo‐Controlled Randomized Trial
    • Authors: Con Stough; Luke A. Downey, Jenny Lloyd, Beata Silber, Stephanie Redman, Chris Hutchison, Keith Wesnes, Pradeep J. Nathan
      PubDate: 2015-08-16T22:21:11.405809-05:
      DOI: 10.1002/ptr.5441
  • Antifolate Activity of Plant Polyphenols against Mycobacterium
    • Authors: Archana Raju; Mariam S. Degani, Mihir P. Khambete, M. K. Ray, M. G. R. Rajan
      Abstract: With the view of exploring phytochemicals as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors, known plant polyphenols from various classes were subjected to detailed docking studies. From this in‐silico screening, seven polyphenols were selected and tested against Mtb H37Rv in whole cell assays. The phytochemicals exhibited potential activity ranging from 3 to 183 µm. These molecules were then tested against the pathogenic and human enzymes in a high‐throughput microtitre assay. Epigallocatechin gallate showed the best activity and selectivity. The in‐silico analysis was in agreement with the assay results. Of these 7 polyphenols, 5 exhibiting minimum inhibitory concentration values of ≤15 µm were tested for synergistic activity with first line drug Ethambutol and second line folate inhibitor para‐amino salicylic acid. Epigallocatechin gallate, Magnolol and Bakuchiol exhibited moderate synergistic association by lowering the minimum inhibitory concentration of these drugs. These simple phytochemicals could hence be considered as leads for further studies, or for preparation of semi‐synthetic derivatives to be used in combination therapy, for increased anti‐tuberculosis activity after validation in‐vivo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-15T01:08:13.944382-05:
      DOI: 10.1002/ptr.5437
  • Corrigendum: An Acute, Double‐Blind, Placebo‐Controlled
           Crossover Study of 320 mg and 640 mg Doses of a Special
           Extract of Bacopa monnieri (CDRI 08) on Sustained Cognitive Performance
    • Authors: Luke A. Downey; James Kean, Fiona Nemeh, Angela Lau, Alex Poll, Rebecca Gregory, Margaret Murray, Johanna Rourke, Brigit Patak, Matthew P. Pase, Andrea Zangara, Justine Lomas, Andrew Scholey, Con Stough
      PubDate: 2015-08-14T04:21:13.831329-05:
      DOI: 10.1002/ptr.5440
  • Phytochemical and Botanical Therapies for Rosacea: A Systematic Review
    • Abstract: Botanical and cosmeceutical therapies are commonly used to treat symptoms of rosacea such as facial erythema, papules/pustule counts, and telangiectasia. These products may contain plant extracts, phytochemicals, and herbal formulations. The objective of this study was to review clinical studies evaluating the use of botanical agents for the treatment of rosacea. MEDLINE and Embase databases were searched for clinical studies evaluating botanical therapies for rosacea. Major results were summarized, and study methodology was analyzed. Several botanical therapies may be promising for rosacea symptoms, but few studies are methodologically rigorous. Several plant extract and phytochemicals effectively improved facial erythema and papule/pustule counts caused by rosacea. Many studies are not methodologically rigorous. Further research is critical, as many botanicals have been evaluated in only one study. Botanical agents may reduce facial erythema and effectively improve papule/pustule counts associated with rosacea. Although promising, further research in the area is imperative. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-14T04:07:01.277721-05:
      DOI: 10.1002/ptr.5432
  • Anti‐lung Cancer Effects of Polyphyllin VI and VII Potentially
           Correlate with Apoptosis In Vitro and In Vivo
    • Authors: Zhufen Lin; Yuting Liu, Fangyuan Li, Jinjun Wu, Guiyu Zhang, Ying Wang, Linlin Lu, Zhongqiu Liu
      Abstract: Polyphyllin VI (PVI) and polyphyllin VII (PVII) derived from Paris polyphylla possess anti‐cancer activities. However, the mechanisms for the anti‐lung cancer effects of PVI and PVII remain poorly understood. In this study, PVI and PVII exhibited inhibitory effects on the proliferation of A549 and NCI‐H1299 cells. PVI and PVII induced G2/M cell cycle arrest and triggered apoptosis. PVI and PVII upregulated the tumor suppressor protein p53 and downregulated cyclin B1. The two treatments significantly increased the expression levels of death receptor 3, death receptor 5, Fas, cleaved PARP, and cleaved caspase‐3. Furthermore, PVI and PVII significantly inhibited the growth of A549 cells in vivo. The tumor inhibitory rates of PVI were 25.74%, 34.62%, and 40.43% at 2, 3, and 4 mg/kg, respectively, and those of PVII were 25.63%, 41.71%, and 40.41% at 1, 2, and 3 mg/kg, respectively. Finally, PVI and PVII regulated the expression of proteins related to the apoptotic pathway in A549 xenografts. In summary, PVI and PVII exhibited strong inhibitory effects on lung cancer cell growth in vitro and in vivo by inducing G2/M cell cycle arrest and triggering apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T22:33:57.164392-05:
      DOI: 10.1002/ptr.5430
  • Paeoniflorin ameliorates ANIT‐induced cholestasis by activating Nrf2
           through an PI3K/Akt‐dependent pathway in rats
    • Authors: Zhe Chen; Xiao Ma, Yun Zhu, Yanling Zhao, Jiabo Wang, Ruisheng Li, Chang Chen, Shizhang Wei, Wenjuan Jiao, Yaming Zhang, Jianyu Li, Lifu Wang, Ruilin Wang, Honghong Liu, Honghui Shen, Xiaohe Xiao
      Abstract: Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha‐naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT‐induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma‐glutamyl transpeptidase (γ‐GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT‐administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate‐cysteine ligase catalytic subunit (GCLc) and glutamate‐cysteine ligase modifier subunit (GCLm) in ANIT‐treated group. In addition, the RNA and protein expression of Akt and nuclear factor‐E2‐related factor‐2 (Nrf2) were also activated by paeoniflorin in ANIT‐induced rats. These findings indicated that paeoniflorin protected ANIT‐induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt‐dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T02:09:39.806322-05:
      DOI: 10.1002/ptr.5431
  • Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of
           Recurrent Urinary Tract Infection'
    • Authors: Jitka Vostalova; Ales Vidlar, Vilim Simanek, Adela Galandakova, Pavel Kosina, Jan Vacek, Jana Vrbkova, Benno F. Zimmermann, Jitka Ulrichova, Vladimir Student
      Abstract: Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent‐to‐treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age‐standardized 12‐month UTI history (p = 0.01)]. The Kaplan–Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T01:20:41.21443-05:0
      DOI: 10.1002/ptr.5427
  • Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian
    • Authors: Mohammad A. Khanfar; Sanaa K. Bardaweel, Mohamed R. Akl, Khalid A. El Sayed
      Abstract: The established anticancer and neuroprotective properties of oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimer's disease development encouraged us to examine the possibility that oleocanthal inhibits mTOR. To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K‐γ. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3‐γ/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose‐dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA‐MB‐231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-07T03:46:17.655965-05:
      DOI: 10.1002/ptr.5434
  • Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic
           Activity: From a Bioactivity‐guided Approach to Comprehensive
           Metabolite Profiling
    • Abstract: Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n‐butanol, and the remaining water fractions was evaluated in streptozotocin‐induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large‐scale untargeted metabolite profiling of methanol extract was performed via UPLC‐PDA and qTOF‐MS (ultra‐performance liquid chromatography photodiode array detection and quadrupole time‐of‐flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O‐caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-03T01:00:28.451313-05:
      DOI: 10.1002/ptr.5424
  • In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida
           spp. and Probiotic Vaginal Microbiota
    • Authors: Maura Di Vito; Paola Mattarelli, Monica Modesto, Antonietta Girolamo, Milva Ballardini, Annunziata Tamburro, Marcello Meledandri, Francesca Mondello
      Abstract: The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO‐VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R‐215 and Lactobacillus acidophilus R‐52) was tested. Both TTO‐VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo‐VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations 
      PubDate: 2015-08-03T00:43:01.936183-05:
      DOI: 10.1002/ptr.5422
  • 3,4,5‐Tricaffeoylquinic Acid Attenuates TRAIL‐induced
           Apoptosis in Human Keratinocytes by Suppressing Apoptosis‐related
           Protein Activation
    • Authors: Da Hee Lee; Yoon Jeong Nam, Min Sung Lee, Dong Suep Sohn, Yong Kyoo Shin, Chung Soo Lee
      Abstract: Caffeoyl derivatives exhibit antiinflammatory and antioxidant effects. However, the effect of 3,4,5‐tricaffeoylquinic acid on the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of 3,4,5‐tricaffeoylquinic acid on TRAIL‐induced apoptosis in human keratinocytes. 3,4,5‐Tricaffeoylquinic acid and oxidant scavengers attenuated the decrease in the cytosolic levels of Bid, Bcl‐2, and survivin proteins; the increase in the levels of cytosolic Bax, p53, and phosphorylated p53; the increase in the levels of phosphorylated p38; the increase in the mitochondrial levels of the voltage‐dependent anion channel; loss of the mitochondrial transmembrane potential; the release of cytochrome c; activation of caspases (8, 9, and 3); cleavage of poly [ADP‐ribose] polymerase‐1; production of reactive oxygen species; the depletion of glutathione (GSH); nuclear damage; and cell death in keratinocytes treated with TRAIL. These results suggest that 3,4,5‐tricaffeoylquinic acid may reduce TRAIL‐induced apoptosis in human keratinocytes by suppressing the activation of the caspase‐8 and Bid pathways and the mitochondria‐mediated cell death pathway. The effect appears to be associated with the inhibitory effect on the production of reactive oxygen species and depletion of GSH. 3,4,5‐Tricaffeoylquinic acid appears to be effective in the prevention of TRAIL‐induced apoptosis‐mediated skin diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-30T00:51:09.126653-05:
      DOI: 10.1002/ptr.5425
  • Therapeutic and Prophylactic Potential of Morama (Tylosema esculentum): A
    • Authors: Walter Chingwaru; Jerneja Vidmar, Petrina T. Kapewangolo, Ofentse Mazimba, Jose Jackson
      Abstract: Tylosema esculentum (morama) is a highly valued traditional food and source of medicine for the San and other indigenous populations that inhabit the arid to semi‐arid parts of Southern Africa. Morama beans are a rich source of phenolic acids, flavonoids, certain fatty acids, non‐essential amino acids, certain phytosterols, tannins and minerals. The plant's tuber contains griffonilide, behenic acid and starch. Concoctions of extracts from morama bean, tuber and other local plants are frequently used to treat diarrhoea and digestive disorders by the San and other indigenous populations. Information on composition and bioactivity of phytochemical components of T. esculentum suggests that the polyphenol‐rich extracts of the bean testae and cotyledons have great potential as sources of chemicals that inhibit infectious microorganisms (viral, bacterial and fungal, including drug‐resistant strains), offer protection against certain non‐communicable diseases and promote wound healing and gut health. The potential antinutritional properties of a few morama components are also highlighted. More research is necessary to reveal the full prophylactic and therapeutic potential of the plant against diseases of the current century. Research on domestication and conservation of the plant offers new hope for sustainable utilisation of the plant. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-21T04:07:19.530086-05:
      DOI: 10.1002/ptr.5419
  • Extract from Ceratonia siliqua Exhibits Depigmentation Properties
    • Authors: Namrita Lall; Navneet Kishore, Saeideh Momtaz, Ahmed Hussein, Sanushka Naidoo, Mabatho Nqephe, Bridget Crampton
      Abstract: Skin hyper‐pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L‐tyrosine as a substrate and showed diphenolase activity. The extract further significantly lowered tyrosinase mRNA levels in B16‐F10 mouse melanocytes. Bioassay‐guided fractionation led to the isolation of six compounds. Compounds (−)‐epicatechin‐3‐O‐gallate, 1,2,3,6‐tetra‐O‐galloyl‐ß‐D‐glucose and gallocatechin‐3‐O‐gallate showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30 µg/mL, respectively. These compounds also exhibited L‐DOPA activities with IC50 values of >200, 150 and 200 µg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non‐irritant with irritancy potential of −34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-20T04:33:50.189768-05:
      DOI: 10.1002/ptr.5420
  • Antiamoebic and Antigiardial Activity of Clerodane Diterpenes from Mexican
           Salvia Species Used for the Treatment of Diarrhea
    • Abstract: Terpenoids from Salvia species have been identified to possess biological properties as antiprotozoal agents. Here, we evaluated the antiamoebic and antigiardial activities of 14 known clerodane and modified clerodane‐type diterpenes isolated from five Mexican Salvia species against Entamoeba histolytica and Giardia lamblia, and analyzed the effects of the functionalities in decalin ring or in the whole clerodane framework to visualize the structural requirements necessary to produce an antiprotozoal activity. Among these, linearolactone was the most active clerodane diterpene against both protozoa with IC50 values of 22.9 μM for E. histolytica and of 28.2 μM in the case of G. lamblia. In this context it may be a lead compound for the development of novel therapeutic agent for the treatment of diarrhea and dysentery. The remaining diterpenes assayed showed moderate to weak activity against both protozoa. These findings give support to the use of Salvia species in the traditional medicine from México for the treatment of diarrhea. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-16T22:55:30.11824-05:0
      DOI: 10.1002/ptr.5421
  • Lupeol Protects Against Cerulein‐Induced Acute Pancreatitis in Mice
    • Abstract: Lupeol is a triterpenoid commonly found in fruits and vegetables and is known to exhibit a wide range of biological activities, including antiinflammatory and anti‐cancer effects. However, the effects of lupeol on acute pancreatitis specifically have not been well characterized. Here, we investigated the effects of lupeol on cerulein‐induced acute pancreatitis in mice. Acute pancreatitis was induced via an intraperitoneal injection of cerulein (50 µg/kg). In the lupeol treatment group, lupeol was administered intraperitoneally (10, 25, or 50 mg/kg) 1 h before the first cerulein injection. Blood samples were taken to determine serum cytokine and amylase levels. The pancreas was rapidly removed for morphological examination and used in the myeloperoxidase assay, trypsin activity assay, and real‐time reverse transcription polymerase chain reaction. In addition, we isolated pancreatic acinar cells using a collagenase method to examine the acinar cell viability. Lupeol administration significantly attenuated the severity of pancreatitis, as was shown by reduced pancreatic edema, and neutrophil infiltration. In addition, lupeol inhibited elevation of digestive enzymes and cytokine levels, such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1, and interleukin (IL)‐6. Furthermore, lupeol inhibited the cerulein‐induced acinar cell death. In conclusion, these results suggest that lupeol exhibits protective effects on cerulein‐induced acute pancreatitis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-16T04:33:20.435491-05:
      DOI: 10.1002/ptr.5423
  • Oxidative Stress Responses to Nigella sativa Oil Concurrent with a
           Low‐Calorie Diet in Obese Women: A Randomized, Double‐Blind
           Controlled Clinical Trial
    • Authors: Nazli Namazi; Reza Mahdavi, Mohammad Alizadeh, Safar Farajnia
      Abstract: The aim of the present study was to determine the effects of Nigella sativa (NS) oil concurrent with a low‐calorie diet on lipid peroxidation and oxidative status in obese women. In this double‐blind placebo‐controlled randomized clinical trial, 50 volunteer obese (body mass index = 30–35 kg/m2) women aged 25–50 years old were recruited. Participants were randomly divided into intervention (n = 25) and placebo (n = 25) groups. They received a low‐calorie diet with 3 g/day NS oil or low‐calorie diet with 3 g/day placebo for 8 weeks. Forty‐nine women (intervention group = 25; placebo group = 24) completed the trial. NS oil concurrent with a low‐calorie diet decreased weight in the NS group compared to the placebo group (−4.80 ± 1.50 vs. −1.40 ± 1.90 kg; p 
      PubDate: 2015-07-14T22:56:08.570371-05:
      DOI: 10.1002/ptr.5417
  • A polymethoxy flavonoids‐rich Citrus aurantium extract ameliorates
           ethanol‐induced liver injury through modulation of AMPK and
           Nrf2‐related signals in a binge drinking mouse model
    • Abstract: Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor‐α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP‐activated protein kinase (AMPK) and nuclear factor E2‐related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase‐1, NAD(P)H quinone oxidoreductase 1, and γ‐glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti‐inflammatory, and antiapoptotic activity against ethanol‐induced liver injury. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T09:59:09.764987-05:
      DOI: 10.1002/ptr.5415
  • Effects of Lonicera japonica Thunb. on Type 2 Diabetes via
           PPAR‐γ Activation in Rats
    • Authors: Jae Min Han; Mi Hye Kim, You Yeon Choi, Haesu Lee, Jongki Hong, Woong Mo Yang
      Abstract: Lonicera japonica Thunb. (Caprifoliaceae) is a traditional herbal medicine and has been used to treat diabetic symptoms. Notwithstanding its use, the scientific basis on anti‐diabetic properties of L. japonica is not yet established. This study is designed to investigate anti‐diabetic effects of L. japonica in type 2 diabetic rats. L. japonica was orally administered at the dose of 100 mg/kg in high‐fat diet‐fed and low‐dose streptozotocin‐induced rats. After the treatment of 4 weeks, L. japonica reduced high blood glucose level and homeostatic model assessment of insulin resistance in diabetic rats. In addition, body weight and food intake were restored by the L. japonica treatment. In the histopathologic examination, the amelioration of damaged β‐islet in pancreas was observed in L. japonica‐treated diabetic rats. The administration of L. japonica elevated peroxisome proliferator‐activated receptor gamma and insulin receptor subunit‐1 protein expressions. The results demonstrated that L. japonica had anti‐diabetic effects in type 2 diabetic rats via the peroxisome proliferator‐activated receptor gamma regulatory action of L. japonica as a potential mechanism. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T09:55:35.538741-05:
      DOI: 10.1002/ptr.5413
  • Potent Insulin Secretagogue from Scoparia dulcis Linn of Nepalese Origin
    • Abstract: Ethno‐botanical inspired isolation from plant Scoparia dulcis Linn. (Sweet Broomweed) yielded six compounds, coixol (1), glutinol (2), glutinone (3), friedelin (4), betulinic acid (5), and tetratriacontan‐1‐ol (6). There structures were identified using mass and 1D‐ and 2D‐NMR spectroscopy techniques. Compounds 1–6 were evaluated for their insulin secretory activity on isolated mice islets and MIN‐6 pancreatic β‐cell line, and compounds 1 and 2 were found to be potent and mildly active, respectively. Compound 1 was further evaluated for insulin secretory activity on MIN‐6 cells. Compound 1 was subjected to in vitro cytotoxicity assay against MIN‐6, 3T3 cell lines, and islet cells, and in vivo acute toxicity test in mice that was found to be non‐toxic. The insulin secretory activity of compounds 1 and 2 supported the ethno‐botanic uses of S. dulcis as an anti‐diabetic agent. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T09:50:41.514169-05:
      DOI: 10.1002/ptr.5412
  • Differential Inhibition of T Lymphocyte Proliferation and Cytokine
           Synthesis by [6]‐Gingerol, [8]‐Gingerol, and
    • Authors: Megan Bernard; Suzanne J. Furlong, Melanie R. Power Coombs, David W. Hoskin
      Abstract: [6]‐Gingerol, [8]‐gingerol, and [10]‐gingerol are pungent components of fresh ginger, extracts of which inhibit various components of the inflammatory response. Because little is known regarding the effect of gingerols with different unbranched alkyl side chain lengths on the activation and effector function of T lymphocytes, we compared the effects of [6]‐gingerol, [8]‐gingerol, and [10]‐gingerol on murine T lymphocyte proliferation, expression of CD25 and CD69 activation markers, cytokine synthesis, and interleukin (IL)‐2 receptor signaling. All three gingerols inhibited DNA synthesis by T lymphocytes, as well as interferon‐γ synthesis. In contrast, only [8]‐gingerol and [10]‐gingerol inhibited CD25 and CD69 expression, and IL‐2 synthesis. None of the gingerols affected IL‐4 synthesis. Exogenous IL‐2 enhanced T lymphocyte proliferation in the presence of [6]‐gingerol but did not significantly increase T lymphocyte proliferation in the presence of [8]‐gingerol or [10]‐gingerol. In line with this finding, [8]‐gingerol and [10]‐gingerol impaired IL‐2‐induced proliferation of CTLL‐2 cells, but constitutive CD25 expression was unaffected, indicating inhibition of IL‐2 receptor signaling. In general, [10]‐gingerol and [8]‐gingerol were more potent inhibitors of T lymphocytes than [6]‐gingerol. Suppression of T lymphocyte responses by gingerols suggests that these phytochemicals may be beneficial in chronic inflammatory conditions associated with excessive or inappropriate T lymphocyte activation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:51:04.302563-05:
      DOI: 10.1002/ptr.5414
  • Constipation and Botanical Medicines: An Overview
    • Authors: Carla Cirillo; Raffaele Capasso
      Abstract: Constipation affects 14% of the adult population globally, mainly women, and significantly impacts on health‐related quality of life. The causes of constipation are mainly three: lifestyle related (functional constipation), disease related, and drug induced. Constipation can generate considerable suffering, including abdominal pain and distension, anorexia, and nausea. The value of some therapeutic measures such as increased fluid intake, physical activity, diet rich in fiber, and nutritional supplements recommended for the relief of constipation is still questionable. The treatment of constipation can be carried out not only with traditional drugs but also with herbal medicines or with nutraceuticals, which are used to prevent or treat the disorder. We have reviewed the most common botanical laxatives such as senna, cascara, frangula, aloe, and rhubarb and their use in the treatment of constipation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:48:22.078572-05:
      DOI: 10.1002/ptr.5410
  • Cytotoxic Impact of Costunolide Isolated from Costus speciosus on Breast
           Cancer via Differential Regulation of Cell Cycle—An In‐vitro
           and In‐silico Approach
    • Authors: Anita Roy; Rajalakshmi Manikkam
      Abstract: Costunolide, a sesquiterpene lactone, is a biologically active molecule found in most of the medicinally valuable plants. The present study aims to evaluate the anticancer property of costunolide isolated from Costus speciosus against breast cancer cell lines (MCF‐7 and MDA‐MB‐231). Costunolide effectively reduced the viability of both MCF‐7 and MDA‐MB‐231 cell lines at an IC50 value of 40 μM. Flow cytometric analysis revealed costunolide mediated cell cycle arrest at G2/M phase in both the cell types. Western blotting results confirmed the alterations in the expression of cell cycle regulators (cyclin D1, D3, CDK‐4, CDK‐6, p18 INK4c, p21 CIP1/Waf‐1 and p27 KIP1) and apoptosis inducers (caspase‐3 and caspase‐9) upon costunolide treatment in comparison with their expressions in normal breast cell line (MCF‐10A). Costunolide mediated downregulation of positive cell cycle regulators and upregulation of negative cell cycle regulators were related to the induction of apoptosis in cancer cells. The above results were validated with in‐silico results that predicted stable interactions between costunolide and cancer targets. Thus costunolide effectively induced breast cancer cell apoptosis targeting cell cycle regulation, and the compound can be used as an effective herbal therapeutic molecule to treat breast cancer with further explorations. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:48:17.124578-05:
      DOI: 10.1002/ptr.5408

  •        3,6‐Dimethoxy‐6″,6″‐Dimethyl‐(7,8,2″,3″)‐Chromeneflavone,
           a Flavonoid Isolated from Lonchocarpus Araripensis Benth. (Fabaceae),
           Reduces Nociceptive Behaviour in Mice
    • Abstract: Lonchocarpus araripensis Benth. is largely distributed in the northeast region of Brazil. It is popularly known as ‘sucupira’. Recent studies have shown that some species of Lonchocarpus have interesting pharmacological activities. In this study, we evaluated the antinociceptive effect of a flavone isolated from L. araripensis. The chemical examination resulted in the isolation of 3,6‐dimethoxy‐6″,6″‐dimethyl‐(7,8,2″,3″)‐chromeneflavone (DDF). The structure of the compound was established by spectral analysis. Antinociceptive activity of DDF was evaluated by measuring nociception by acetic acid, formalin and hot plate tests. The rota rod test was used to evaluate motor coordination. The results demonstrated that DDF was able to prevent acetic‐acid‐writhing‐induced nociception (p 
      PubDate: 2015-07-14T08:47:08.141689-05:
      DOI: 10.1002/ptr.5418
  • Dual Effects of Liquiritigenin on the Proliferation of Bone Cells:
           Promotion of Osteoblast Differentiation and Inhibition of Osteoclast
    • Authors: Kaho Uchino; Kuniaki Okamoto, Eiko Sakai, Erika Yoneshima, Mayumi Iwatake, Yutaka Fukuma, Kazuhisa Nishishita, Takayuki Tsukuba
      Abstract: Bone is constantly controlled by a balance between osteoblastic bone formation and osteoclastic bone resorption. Liquiritigenin is a plant‐derived flavonoid and has various pharmacological effects, such as antioxidative, antitumor, and antiinflammatory effects. Here, we show that liquiritigenin has dual effects on the proliferation of bone cells, regarding the promotion of osteoblast differentiation and the inhibition of osteoclast differentiation. Liquiritigenin‐treated murine osteoblastic MC3T3‐E1 cells showed an increased alkaline phosphatase activity and enhanced phosphorylation of Smad1/5 compared with untreated cells. Moreover, liquiritigenin inhibited osteoclast differentiation, its bone‐resorption activity through slightly decreased the phosphorylation of extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase, and inhibitor of nuclear factor kappa Bα; however, the phosphorylation of Akt and p38 slightly increased in bone marrow‐derived osteoclasts. The expression levels of the osteoclast marker proteins nuclear factor of activated T‐cell cytoplasmic‐1, Src, and cathepsin K diminished. These results suggest that liquiritigenin may be useful as a therapeutic and/or preventive agent for osteoporosis or inflammatory bone diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:46:57.664656-05:
      DOI: 10.1002/ptr.5416
  • Asiaticoside Inhibits TNF‐α‐Induced Endothelial
           Hyperpermeability of Human Aortic Endothelial Cells
    • Authors: Lai Yen Fong; Chin Theng Ng, Zainul Amiruddin Zakaria, Mohamad Taufik Hidayat Baharuldin, Abdul Kadir Arifah, Muhammad Nazrul Hakim, Ahmad Zuraini
      Abstract: The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor‐alpha (TNF‐α), a pro‐atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF‐α in human aortic endothelial cells (HAEC). TNF‐α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)‐dextran. Asiaticoside pretreatment significantly suppressed TNF‐α‐induced increased permeability. Asiaticoside also prevented TNF‐α‐induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF‐α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti‐hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D‐induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF‐α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F‐actin organization. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:37:57.735185-05:
      DOI: 10.1002/ptr.5404
  • Thymoquinone Inhibition of Acquisition and Expression of
           Alcohol‐Induced Behavioral Sensitization
    • Authors: Muhammad Sona Khan; Aneela Gohar, Ghulam Abbas, Wajahat Mahmood, Khalid Rauf, Robert D. E. Sewell
      Abstract: Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol‐induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose‐dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T07:28:48.996394-05:
      DOI: 10.1002/ptr.5409
  • Chemical Constituents of Euonymus alatus (Thunb.) Sieb. and Their PTP1B
           and α‐Glucosidase Inhibitory Activities
    • Abstract: Phytochemical study on the corks of Euonymus alatus resulted in the isolation of a novel 3‐hydroxycoumarinflavanol (23), along with ten triterpenoids (1–10), ten phenolic derivatives (11–20), and two flavonoid glycosides (21 and 22). Their structures were determined by extensive 1D and 2D‐nuclear magnetic resonance spectroscopic and mass spectrometry data analysis. Furthermore, their inhibitory effects against the protein tyrosine phosphatases 1B (PTP1B) and α‐glucosidase enzyme activity were evaluated. Compounds 6, 7, 9, 15, 19, and 23 were non‐competitive inhibitors, exhibiting most potency with IC50 values ranging from 5.6 ± 0.9 to 18.4 ± 0.3 µm, against PTP1B. Compound 3 (competitive), compounds 5 and 15 (mixed‐competitive) displayed potent inhibition with IC50 values of 15.1 ± 0.7, 23.6 ± 0.6 and 14.8 ± 0.9 µm, respectively. Moreover, compounds 15, 20, and 23 exhibited potent inhibition on α‐glucosidase with IC50 values of 10.5 ± 0.8, 9.5 ± 0.6, and 9.1 ± 0.5 µm, respectively. Thus, these active ingredients may have value as new lead compounds for the development of new antidiabetic agents. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T07:28:18.988798-05:
      DOI: 10.1002/ptr.5411
  • Phloroglucinol Protects INS‐1 Pancreatic β‐cells Against
           Glucotoxicity‐Induced Apoptosis
    • Authors: Mi Hwa Park; Ji Sook Han
      Abstract: Decreasing numbers, and impaired function, of pancreatic β‐cells are key factors in the development of type 2 diabetes. This study was designed to investigate whether phloroglucinol protected pancreatic β‐cells against glucotoxicity‐induced apoptosis using a rat insulinoma cell line (INS‐1). High glucose treatment (30 mM) induced INS‐1 cell death; however, the level of glucose‐induced apoptosis was significantly reduced in cells treated with 100‐μM phloroglucinol. Treatment with 10–100‐μM phloroglucinol increased cell viability and decreased intracellular levels of reactive oxygen species, nitric oxide, and lipid peroxidation dose‐dependently in INS‐1 cells pretreated with high glucose. Furthermore, phloroglucinol treatment markedly reduced the protein expression of Bax, cytochrome c, and caspase 9, while increasing anti‐apoptotic Bcl‐2 protein expression. Cell death type was examined using annexin V/propidium iodide staining, revealing that phloroglucinol markedly reduced high glucose‐induced apoptosis. These results demonstrated that phloroglucinol could be useful as a potential therapeutic agent for the protection of pancreatic β‐cells against glucose‐induced apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-07T03:30:50.137997-05:
      DOI: 10.1002/ptr.5407
  • Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5
           Up‐Regulation, ROS Generation, Modulation of Bcl‐2 and IAP
           Family Members
    • Abstract: Pachymic acid (PA) is a lanostane‐type triterpenoid derived from Poria cocos mushroom that possess various biological effects such as anti‐cancer, antiinflammatory and anti‐metastasis effects. In this study, we investigated the anti‐cancer effects of PA in EJ bladder cancer cells. The results showed that PA significantly inhibited proliferation of EJ cells in a dose‐dependent manner. PA induced accumulation of sub‐G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in EJ cells in a dose‐dependent manner. PA also induces activation of caspase‐3, ‐8 and ‐9, and subsequent cleavage of poly (ADP‐ribose) polymerase, and significantly suppressed the inhibitor of apoptosis protein family proteins in a dose‐dependent manner. Furthermore, PA activates Bid and induced the loss of mitochondrial membrane potential (ΔΨm) with up‐regulated pro‐apoptotic proteins (Bax and Bad), down‐regulated anti‐apoptotic proteins (Bcl‐2 and Bcl‐xL) and cytochrome c release. In turn, PA increased the generation of reactive oxygen species (ROS); also, the ROS production was blocked by N‐acetyl‐L‐cysteine. The expressions of TNF‐related apoptosis inducing ligand and death receptor 5 were up‐regulated by PA in a dose‐dependent manner, suggesting extrinsic pathway also involved in PA‐induced apoptosis. This study provides evidence that PA might be useful in the treatment of human bladder cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-07T03:28:19.687546-05:
      DOI: 10.1002/ptr.5402
  • Becatamide Found in Houttuynia cordata Suppresses P‐selectin
           Expression Via Inhibiting COX Enzyme, Not Increasing cAMP in Platelets
    • Authors: Jae B. Park
      Abstract: Atherosclerosis is a well‐known inflammatory cardiovascular disease. Recent studies suggested potential anti‐atherosclerosis effects of becatamide found in Houttuynia cordata. Therefore, in this study, we investigated potential effect of becatamide (1) and its analogues (enferamide (2), veskamide (3), oretamide (4) and amkamide (5)) on cyclooxygenase (COX)‐1 and ‐2 and the production of cyclic adenosine monophosphate (cAMP), which are critically involved in platelet activation. Among them, becatamide was the most potent compound able to inhibit COX‐1 (IC50 = 0.27 µm) and ‐2 (IC50 = 0.78 µm) (p  veskamide > enferamide > oretamide > amkamide. As a result of the inhibition, the production of thromboxane B2 and P‐selectin expression were suppressed by 35% (p 
      PubDate: 2015-06-26T00:47:17.842447-05:
      DOI: 10.1002/ptr.5391
  • Effect of Serenoa Repens on Oxidative Stress, Inflammatory and Growth
           Factors in Obese Wistar Rats with Benign Prostatic Hyperplasia
    • Abstract: Serenoa repens has been widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms; however, most of the studies have been conducted in individuals with normal weight and not obese. In this study, the effects of a lipidic extract of S. repens, in markers of oxidative stress, inflammation, and growth factors, in obese rats with testosterone‐induced prostatic hyperplasia, were investigated. Total nitrites, malondialdehyde, total glutathione, superoxide dismutase (SOD), and catalase activity were measured; in addition, assays for inflammatory cytokines TNF‐α, IL‐1β, IL‐6 and the growth factors basic fibroblast growth factor (FGFb) and vascular endothelial growth factor (VEGF) were performed. The obese rats had a higher prostate weight compared with controls. S. repens significantly decreased prostate weight, total nitrites, and malondialdehyde; improved total glutathione, SOD, and catalase activity; and significantly reduced inflammatory (TNF‐α, IL‐1β and IL‐6) and growth factors (VEGF and FGFb). S. repens showed high antioxidant and antiinflammatory activity in obese rats, suggesting that their use could be beneficial in the treatment of benign prostatic hyperplasia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-24T03:21:32.753432-05:
      DOI: 10.1002/ptr.5406
  • A Preliminary Investigation on the Antimicrobial Activity of
           Listerine®, Its Components, and of Mixtures Thereof
    • Abstract: Listerine® is one of the most popular mouthwashes worldwide and claims to combat harmful bacteria. In the past century, its recipe was changed from an essential oil mouthwash to a five‐component mixture (thymol, menthol, eucalyptol, and methyl salicylate dissolved in 27% ethanol). The aim of this study was to get preliminary information about the antimicrobial activities of individual Listerine® components and their mixtures. We tested the bacterial strains Streptococcus mutans, Enterococcus faecalis, and Eikenella corrodens and the yeast Candida albicans. The established minimum inhibitory concentration (MIC) assay and the minimum bactericidal/fungicidal concentration (MBC/MFC) assay were applied. None of the combinations of two phenols at the concentrations contained within Listerine® were associated with either an additive or synergistic effect. Thymol had lower MIC and MBC/MFC values than the other Listerine® components and Listerine® against E. corrodens and C. albicans. The mixtures consisting of eucalyptol, methyl salicylate, and thymol were the most effective against S. mutans and E. faecalis and more effective than Listerine®. Our results demonstrate that the phenols and their concentrations as contained within Listerine® could be further optimized in terms of selecting those which increase their general effectiveness, at concentrations that do not induce harm. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-24T02:29:48.86281-05:0
      DOI: 10.1002/ptr.5399
  • Paris Saponin VII Inhibits the Migration and Invasion in Human A549 Lung
           Cancer Cells
    • Authors: Lei Fan; Yuhua Li, Yang Sun, Jing Han, Zhenggang Yue, Jin Meng, Xutao Zhang, Feng Zhang, Qibing Mei
      Abstract: Metastasis is the main cause of death in lung cancer. Targeting the process of metastasis is a strategy to lung cancer treatment. Trillium tschonoskii Maxim., a traditional Chinese medicine, has been used for treatment of many diseases, including cancer. This study aims to determine the anti‐metastatic effect of paris saponin VII (PS VII) which was extracted from T. tschonoskii Maxim. by using human lung cancer cell line A549 cells. Our results showed that PS VII could significantly suppress the viability as well as cell migration and invasion abilities of A549 cells in a concentration‐dependent manner. PS VII reduced the activity of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 by elevating the expression of TIMP1/2. These data indicated that PS VII could reduce the metastatic capability of A549 cells, probably through up‐regulating the expression of TIMP1/2. These findings demonstrated a new therapeutic potential for PS VII in anti‐metastatic therapy of lung cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-24T02:21:11.697583-05:
      DOI: 10.1002/ptr.5389
  • Consumption of Argan Oil Improves Anti‐Oxidant and Lipid Status in
           Hemodialysis Patients
    • Authors: Rachid Eljaoudi; Driss Elkabbaj, Abdelali Bahadi, Azeddine Ibrahimi, Mohammed Benyahia, Mourad Errasfa
      Abstract: Objective: Virgin Argan oil (VAO) is of interest in oxidative stress and lipid profile because of its fat composition and antioxidant compounds. We investigated the effect of VAO consumption on lipid profile and antioxidant status in hemodialysis patients after a 4‐week period of consumption. Methods: In a crossover, controlled trial, 37 patients (18 men, 19 women) with end‐stage renal disease on maintenance hemodialysis, were randomly assigned to a 4‐week VAO diet. Fasting plasma lipids, vitamin E and oxidized LDL (ox‐LDL) were analyzed. Malondialdehyde (MDA) was determined before and after hemodialysis session. Results: There was no significant change in serum total cholesterol and ox‐LDL. However, VAO consumption decreased the levels of triglyceride (p = 0.03), total cholesterol (p = 0.02) and low‐density lipoprotein (p = 0.03) and increased the levels of high‐density lipoprotein (p = 0.01). Plasma vitamin E contents significantly increased from baseline only in VAO‐group (p 
      PubDate: 2015-06-23T00:35:26.51914-05:0
      DOI: 10.1002/ptr.5405
  • Anti‐TNF‐α Activity of Brazilian Medicinal Plants and
           Compounds from Ouratea semiserrata
    • Abstract: Several plant species are used in Brazil to treat inflammatory diseases and associated conditions. TNF‐α plays a pivotal role on inflammation, and several plant extracts have been assayed against this target, both in vitro and in vivo. The effect of 11 Brazilian medicinal plants on TNF‐α release by LPS‐activated THP‐1 cells was evaluated. The plant materials were percolated with different solvents to afford 15 crude extracts, whose effect on TNF‐α release was determined by ELISA. Among the evaluated extracts, only Jacaranda caroba (Bignoniaceae) presented strong toxicity to THP‐1 cells. Considering the 14 non‐toxic extracts, TNF‐α release was significantly reduced by seven of them (inhibition > 80%), originating from six plants, namely Cuphea carthagenensis (Lythraceae), Echinodorus grandiflorus (Alismataceae), Mansoa hirsuta (Bignoniaceae), Ouratea semiserrata (Ochnaceae), Ouratea spectabilis and Remijia ferruginea (Rubiaceae). The ethanol extract from O. semiserrata leaves was fractionated over Sephadex LH‐20 and RP‐HPLC to give three compounds previously reported for the species, along with agathisflavone and epicatechin, here described for the first time in the plant. Epicatechin and lanceoloside A elicited significant inhibition of TNF‐α release, indicating that they may account for the effect produced by O. semiserrata crude extract. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-22T03:23:45.058363-05:
      DOI: 10.1002/ptr.5401
  • Blood Glucose‐lowering Effect of T. procumbens L.: A Pilot
           Clinical Study in Individuals with Type 2 Diabetes
    • Authors: Gauri S. Desai; Shirish V. Desai, Rajendra S. Gavaskar, Vanisree Mulabagal, Yonnie Wu, Suresh T. Mathews
      Abstract: Traditional knowledge, in vitro studies, and studies using animal models suggest that Tridax procumbens L. exhibits blood glucose‐lowering properties and antiinflammatory effects. In this study, we evaluated the blood glucose‐lowering effect of T. procumbens supplementation in individuals with type 2 diabetes. An extract (asava) of T. procumbens L. was prepared following Ayurveda guidelines. Chemical and microbial analyses indicated presence of phenolics, flavonoids, and carotenoids, and absence of microbial contamination, aflatoxins, heavy metals, and pesticide residues. A chemical fingerprint of T. procumbens L. asava, developed using Ultra high pressure liquid chromatography/electron spray ionization‐mass spectrometry (UPLC/ESI‐MS) in negative mode, suggest the presence of several compounds including polyphenols. T. procumbens asava demonstrated strong total antioxidant capacity, Fe3+ reducing potential, Fe2+ chelation, H2O2 scavenging activity, and inhibition of lipid peroxidation. We recruited 20 type 2 diabetic individuals from Kolhapur, India. Participants received 15 mL of T. procumbens asava, twice daily, for 4 weeks, while continuing their prescribed antidiabetic medications. Fasting blood glucose decreased by 11% in men (p 
      PubDate: 2015-06-22T03:03:28.038241-05:
      DOI: 10.1002/ptr.5394
  • 5,7‐Dihydroxy‐6‐Methoxy‐Flavonoids Eliminate
           HIV‐1 D3‐transfected Cytoprotective Macrophages by Inhibiting
           the PI3K/Akt Signaling Pathway
    • Abstract: Flavonoids, well‐documented secondary metabolites in many vegetables and plants, exhibit antiinflammatory, anti‐oxidant, anti‐microbial, and anticancer activities. However, their cytotoxic effects against human immunodeficiency virus type 1 (HIV‐1)‐infected cytoprotective macrophages have not been studied. In the present study, we investigated their effects and their molecular mechanisms. Treatment with flavonoids in the presence of lipopolysaccharide (LPS)/cycloheximide (CHX) potently eliminated HIV‐1 Tat‐transduced cytoprotective human microglial CHME5 cells; the 5,7‐dihydroxy‐6‐methoxy‐flavonoids oroxylin A and tectorigenin, at a concentration of 10 μM, most potently eliminated the cytoprotective phenotype. These flavonoids eliminated Tat‐transduced CHME5 cells, D3‐transfected CHME5 cells, and HIV‐1 D3‐infected human primary macrophages, in a dose‐dependent manner. Furthermore, oroxylin A and tectorigenin potently inhibited LPS/CHX‐induced phosphorylation of phosphoinositide 3‐kinase (PI3K), pyruvate dehydrogenase lipoamide kinase isozyme 1, Akt, and glycogen synthase kinase‐3β in the Tat‐transduced cells, D3‐transfected CHME5 cells, and D3‐infected human primary macrophages. Based on these findings, 5,7‐dihydroxy‐6‐methoxy‐flavonoids may eliminate HIV‐1 infected cytoprotective macrophages by inhibiting the PI3K/Akt signaling pathway and deliver anti‐HIV‐1 effects in vivo by shortening the lifespan of infected macrophages. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-22T02:28:06.953132-05:
      DOI: 10.1002/ptr.5388
  • Salicin from Willow Bark can Modulate Neurite Outgrowth in Human
           Neuroblastoma SH‐SY5Y Cells
    • Abstract: Salicin from willow bark has been used throughout centuries in China and Europe for the treatment of pain, headache, and inflammatory conditions. Recently, it could be demonstrated that salicin binds and activates the bitter taste receptor TAS2R16. Studies on rodent tissues showed the general expression of bitter taste receptors (TAS2Rs) in rodent brain. Here, we demonstrate the expression of hTAS2R16 in human neuronal tissues and the neuroblastoma cell line SH‐SY5Y. The functionality was analyzed in the neuroblastoma cell line SH‐SY5Y after stimulation with salicin, a known TAS2R16 agonist. In this setting salicin induced in SH‐SY5Y cells phosphorylation of ERK and CREB, the key transcription factor of neuronal differentiation. PD98059, an inhibitor of the ERK pathway, as well as probenecid, a TAS2R16 antagonist, inhibited receptor phosphorylation as well as neurite outgrowth. These data show that salicin might modulate neurite outgrowth by bitter taste receptor activation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-19T05:19:44.438953-05:
      DOI: 10.1002/ptr.5400
  • Dietary Doses of Sulforaphane Affect Hepatic Drug Metabolizing Enzymes in
           Spontaneously Hypertensive Rats
    • Authors: Anik Amin; Margarita CanGongora, Fawzy Elbarbry
      Abstract: We previously demonstrated that exposure of spontaneously hypertensive rats (SHR) to dietary doses of sulforaphane (SF) results in resisting the progressive rise in blood pressure that is normally seen in these rats. This study investigates the potential effect of SF on hepatic drug metabolizing enzymes (DME) in SHR. The activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase (mEH) were measured in hepatic microsomes using specific probe substrates and/or polyclonal antibodies. Cytosolic fraction was utilized to measure protein level and activity of major antioxidant systems. The high dose SF resulted in a significant reduction of activity and apoproteins level of CYP1A2 and CYP2C9 and activities of CYP2B1/2 and mEH. No effect of SF was observed on the rest of the studied CYP enzymes. Both doses of SF resulted in a significant induction of both hepatic glutathione level and activities of superoxide dismutase and catalase. Activities of hepatic glutathione‐S‐transferases, glutathione reductase, and glutathione peroxidase were significantly induced only with the high dose. This study demonstrates that dietary doses of SF modulate the activity or protein expression of DME. Additionally, induction of the impaired antioxidant system in SHR may explain the blood pressure lowering effect of SF in this rat model. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-18T01:29:50.905812-05:
      DOI: 10.1002/ptr.5397
  • Inhibition of UDP‐Glucuronosyltransferases (UGTs) Activity by
           constituents of Schisandra chinensis
    • Abstract: Structure–activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine‐Diphosphate) UDP‐glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb–drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9‐mediated metabolism. In conclusion, in silico‐in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-18T01:27:36.354289-05:
      DOI: 10.1002/ptr.5395
  • Quantitative Evaluation of the Mechanism Underlying the Biotransportation
           of the Active Ingredients in Puerariae lobatae Radix and
           Chuanxiong rhizoma
    • Abstract: The objective of this study was to establish a quantitative method to evaluate the biotransportation of a drug across the cell membrane. Through the application of the law of mass conservation, the drug transportation rate was calculated based on Fick's law of passive diffusion and the Michaelis–Menten equation. The overall membrane‐transportation rate was the sum of the passive diffusion rate and the carrier‐mediated diffusion rate, which were calculated as the transportation mass divided by the respective rate. The active ingredients of Puerariae lobatae Radix and Chuanxiong rhizoma, namely, puerarin and ferulic acid, respectively, were used as two model drugs. The transportation rates of puerarin and ferulic acid were obtained by fitting a model that includes both Fick's law of diffusion and the Michaelis–Menten equation. Compared with the overall transportation, the carrier‐mediated transport and passive diffusion of 1.59 mmol/L puerarin were −35.07% and 64.93%, respectively, whereas the respective transportation modes of 0.1 mmol/L ferulic acid were −35.40% and 64.60%, respectively. Verapamil and MK‐571 increased the overall transport rate and ratio, and MK‐571 treatment changed the carrier‐mediated transport from negative to positive. However, the transport rate and ratio of ferulic acid did not change significantly. The cell transportation mechanisms of puerarin and ferulic acid primarily involve simple passive diffusion and carrier‐mediated transportation. Moreover, P‐glycoprotein and multidrug resistance‐associated protein efflux proteins, and other transportation proteins were found to be involved in the transportation of puerarin. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-15T02:17:03.601756-05:
      DOI: 10.1002/ptr.5393
  • Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke‐induced
           Gastric Epithelial–Mesenchymal Transition in Mice
    • Authors: Zhaofeng Liang; Rui Wu, Wei Xie, Hao Geng, Li Zhao, Chunfeng Xie, Jieshu Wu, Shanshan Geng, Xiaoting Li, Mingming Zhu, Weiwei Zhu, Jianyun Zhu, Cong Huang, Xiao Ma, Caiyun Zhong, Hongyu Han
      Abstract: Tobacco smoke (TS) has been shown to cause gastric cancer. Epithelial–mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. Mitogen‐activated protein kinase (MAPK) pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study, we investigated the effects of TS on MAPK pathway activation and EMT alterations in the stomach of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12 weeks resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2), the Jun N‐terminal kinase (JNK), p38, and ERK5 MAPK pathways as well as activator protein 1 (AP‐1) proteins in stomach. TS reduced the mRNA and protein expression levels of the epithelial markers E‐cadherin and ZO‐1, while the mRNA and protein expression levels of the mesenchymal markers vimentin and N‐cadherin were increased. Treatment of curcumin effectively abrogated TS‐triggered gastric activation of ERK1/2 and JNK MAPK pathways, AP‐1 proteins, and EMT alterations. These results suggest for the first time the protective effects of curcumin in long‐term TS exposure‐induced gastric MAPK activation and EMT, thus providing new insights into the pathogenesis and chemoprevention of TS‐associated gastric cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-14T23:07:44.565783-05:
      DOI: 10.1002/ptr.5398
  • Schisandrin C Ameliorates Learning and Memory Deficits by
           Aβ1–42‐induced Oxidative Stress and Neurotoxicity in Mice
    • Authors: Xin Mao; Zhengzheng Liao, Lin Guo, Xuan Xu, Bo Wu, Mengjie Xu, Xu Zhao, Kaishun Bi, Ying Jia
      Abstract: Schisandrin C (SCH‐C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH‐C on memory impairment and further research on pathological changes in Aβ1–42‐induced Alzheimer's disease mice. Mice were administration with SCH‐C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y‐maze test, active avoidance test and Morris water maze test in all groups, and the level of Aβ1–42 and neuronal injury induced by Aβ1–42 were reversed remarkably following SCH‐C treatment compared with sham group; meanwhile the impairment of short‐term or working memory was dramatically improved. In addition, SCH‐C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH‐C offers protection against Aβ1–42‐induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-14T22:49:48.362028-05:
      DOI: 10.1002/ptr.5390
  • Equol, a Metabolite of Daidzein, Is More Efficient than Daidzein for Bone
           Formation in Growing Female Rats
    • Authors: Yuko Tousen; Hajimu Ishiwata, Yoshiko Ishimi, Sachie Ikegami
      Abstract: Few studies have examined the effects of isoflavones and particularly equol, a metabolite of the isoflavone daidzein, on bone formation during the growth period in animals. The present study investigated the effects of orally administered daidzein or equol on bone formation and bone mineral density in growing female rats. Female Sprague‐Dawley rats, aged 3 weeks, were divided into four groups (n = 8 per group) as follows: rats were orally administered a corn oil, 8 mg/day of daidzein, 4 mg/day of equol or 8 mg/day of equol in corn oil for 4 weeks. Daidzein and equol increased the bone mineral density of growing female rats by stimulating bone formation without exhibiting a substantial effect on the weight of their reproductive organs. Bone growth caused by increased bone mineralizing surface and bone formation rate in rats administered with equol was approximately twice that of rats administered with daidzein. These results suggest that equol might be more efficient than daidzein for bone formation in growing female rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-11T01:17:43.78504-05:0
      DOI: 10.1002/ptr.5387
  • New Activities for Isolated Compounds from Convolvulus
           austro‐aegyptiacus as Anti‐ulcerogenic,
           Anti‐Helicobacter pylori and Their Mimic Synthesis Using
           Bio‐guided Fractionation
    • Abstract: Bio‐guided fractionation of the total alcoholic extract of Convolvulus austro‐aegyptiacus was screened for its anti‐ulcerogenic activity, using an absolute‐ethanol‐induced ulcer model at 500 and 1000 mg/kg doses. Two compounds were isolated from the butanol extract of C. austro‐aegyptiacus and identified by 1H and 13C nuclear magnetic resonance as scopoletin and scopolin. The isolated compounds (50 mg/kg) showed a remarkable anti‐ulcerogenic activity because they exhibited control‐ulcer protection by 16.7% and 90.8%, respectively. The acute toxicity study showed that the extract is highly safe; the median lethal dose (LD50) was more than 4000 mg/kg. Moreover, the obtained results were confirmed by the sub‐chronic toxicity because the rats that have been administered 1000 mg/kg of the extract for 15 consecutive days showed no alteration in the liver and kidney functions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-10T23:09:08.660853-05:
      DOI: 10.1002/ptr.5379
  • 6‐Acetoxy Cyperene, a Patchoulane‐type Sesquiterpene Isolated
           from Cyperus rotundus Rhizomes Induces Caspase‐dependent Apoptosis
           in Human Ovarian Cancer Cells
    • Abstract: Cyperus rotundus (Cyperaceae) has been widely used in traditional medicine for the treatment of various diseases, including cancer. Although an anti‐tumour effect has been suggested for C. rotundus, the anti‐tumour effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The n‐hexane fraction of an ethanol extract of C. rotundus rhizomes was found to inhibit cell growth in ovarian cancer (A2780, SKOV3 and OVCAR3) and endometrial cancer (Hec1A and Ishikawa) cells. Among the thirteen sesquiterpenes isolated from the n‐hexane fraction, some patchoulane‐type compounds, but not eudesmane‐type compounds, showed moderate cytotoxic activity in human ovarian cancer cells. In particular, the patchoulane sesquiterpene 6‐acetoxy cyperene had the most potent cytotoxicity. In this regard, propidium iodide/Annexin V staining and terminal deoxynucleotidyl transferase dUTP (deoxynucleotide triphosphate) nick end labeling assay were performed to study cell cycle progression and apoptosis. 6‐acetoxy cyperene induced apoptosis, as shown by the accumulation of sub‐G1 and apoptotic cells. Furthermore, treatment with 6‐acetoxy cyperene stimulated the activation of caspase‐3, caspase‐8 and caspase‐9 and poly(ADP‐ribose)polymerase in a dose‐dependent manner. Pretreatment with caspase inhibitors neutralized the pro‐apoptotic activity of 6‐acetoxy cyperene. Taken together, these data suggest that 6‐acetoxy cyperene, a patchoulane‐type sesquiterpene isolated from C. rotundus rhizomes, is an anti‐tumour compound that causes caspase‐dependent apoptosis in ovarian cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-10T01:53:55.222237-05:
      DOI: 10.1002/ptr.5385
  • Natural Products Useful in Respiratory Disorders: Focus on
           Side‐Effect Neutralizing Combinations
    • Abstract: This review summarizes literature related to medicinal plants reputed in traditional medical systems for treatment of asthma and coughs. The plants that are pharmacologically investigated for their effectiveness in such conditions, along with respective experimental protocol details, are also discussed. Some of plant origin compounds, which are considered useful as antitussive and antiasthmatic agents, are described as well. Chrysoeriol, a constituent of Aspalathus linearis (Fabaceae) was observed to be selective for relaxant effect in airways (through K+ channel activation), compared with other smooth muscles. We reported that Hypericum perforatum (Hyperieaceae), Andropogon muricatus (Poaceae), Juniper excelsa (Coniferae) and Nepeta cataria (Lamiaceae) exhibit bronchodilatory action, mediated through combination of Ca++ antagonist and phospohodiesrase inhibitory mechanisms, which scientifically explains their medicinal use in asthma. Hyocyamus niger (Solanaceae), Artemisia vulgaris (Compositae), Fumaria parviflora (Fumariaceae) and Terminalia bellerica (Combretaceae) caused bronchodilation via dual blockade of muscarinic receptors and Ca++ influx. Acorus calamus (Araceae), Carum roxburghianum (Apiaceae), Lens culinaris (Fabaceae) and Lepidium sativum (Cruciferae) mediate bronchodilatation through multiple pathways: anticholinergic and inhibition of Ca++ channels and PDE enzyme(s). In conclusion, this review presents an analysis of different novel combinations of pharmacological activities in medicinal plants with side effect‐neutralizing/synergistic potential, setting new trends in the therapeutic options for hyperactive respiratory disorders such as asthma and cough. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-10T01:53:24.012638-05:
      DOI: 10.1002/ptr.5380
  • Tyrosinase and Cholinesterase Inhibitory Potential and Flavonoid
           Characterization of Viola odorata L. (Sweet Violet)
    • Authors: Ilkay Erdogan Orhan; Fatma Sezer Senol, Sinem Aslan Erdem, I. Irem Tatli, Murat Kartal, Sevket Alp
      Abstract: Inhibitory potential of the dichloromethane, ethyl acetate, ethanol, and aqueous extracts of Viola odorata L. (VO) was investigated against tyrosinase (TYR) and cholinesterases by microplate assays. The antioxidant activity was tested using six in vitro assays. Only the ethanol extract inhibited TYR (80.23 ± 0.87% at 100 µg mL−1), whereas none of them were able to inhibit cholinesterases. The extracts were more able to scavenge NO radical (31.98 ± 0.53–56.68 ± 1.10%) than other radicals tested, and displayed low to moderate activity in the rest of the assays. HPLC analysis revealed that the aqueous extract of VO contained a substantial amount of vitexin (18.81 ± 0.047 mg g−1 extract), while the ethanol extract also possessed rutin (1.31 ± 0.013 mg g−1 extract) and vitexin (4.65 ± 0.103 mg g−1 extract). Furthermore, three flavonoids (rutin, isovitexin, and kaempferol‐6‐glucoside) were isolated from the ethanol extract. This is the first report on TYR inhibitory activity of VO as well as presence of vitexin and isovitexin in this species. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-09T04:02:59.19184-05:0
      DOI: 10.1002/ptr.5378
  • Alpinia katsumadai Extracts Inhibit Adhesion and Invasion of Campylobacter
           jejuni in Animal and Human Foetal Small Intestine Cell Lines
    • Abstract: Alpinia katsumadai is used in traditional Chinese medicine for abdominal distention, pain, and diarrhoea. Campylobacter jejuni is the most common cause of bacterial food‐borne diarrhoeal illnesses worldwide. Adhesion to gut epithelium is a prerequisite in its pathogenesis. The antimicrobial, cytotoxic, and anti‐adhesive activities of a chemically characterised extract (SEE) and its residual material of hydrodistillation (hdSEE‐R) from A. katsumadai seeds were evaluated against C. jejuni. Minimal inhibitory concentrations for SEE and hdSEE‐R were 0.5 mg/mL and 0.25 mg/mL, respectively, and there was no cytotoxic influence in the anti‐adhesion tests, as these were performed at much lower concentrations of these tested plant extracts. Adhesion of C. jejuni to pig (PSI) and human foetal (H4) small‐intestine cell lines was significantly decreased at lower concentrations (0.2 to 50 µg/mL). In the same concentration range, the invasiveness of C. jejuni in PSI cells was reduced by 45% to 65% when they were treated with SEE or hdSEE‐R. The hdSEE‐R represents a bioactive waste with a high phenolic content and an anti‐adhesive activity against C. jejuni and thus has the potential for use in pharmaceutical and food products. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-09T03:07:56.259338-05:
      DOI: 10.1002/ptr.5396
  • Inhibition of Osteoclast Differentiation by Ginsenoside Rg3 in RAW264.7
           Cells via RANKL, JNK and p38 MAPK Pathways Through a Modulation of
           Cathepsin K: An In Silico and In Vitro Study
    • Pages: 1286 - 1294
      Abstract: Various studies have demonstrated that overexpression of cathepsin K (Cat‐K) causes excessive bone loss, which ultimately leads to a variety of bone diseases including osteoporosis. Therefore, inhibition of Cat‐K signifies a potential therapeutic target in osteoporosis treatment. Ginsenoside Rg3 is one of the most promising compound of Panax ginseng Meyer (P. ginseng) with numerous biological activities. Thus, in recent study the inhibitory effect of Rg3 isolated from P. ginseng was investigated in order to impede the osteoclast activity by an in silico approach followed by in vitro study validation using RAW264.7 cells through the investigation of different biological activity prediction such as absorption distribution metabolism and excretion (ADMET) properties against Cat‐K protein. The docking results of our study showed that Rg3 is a non‐toxic compound and may act as a drug‐like molecule. Additionally, the molecular interaction of Rg3 with the active residues of Cat‐K markedly describes its inhibitory effects on osteoclastogenesis. Findings of the present study exhibited that Rg3 significantly reduced receptor activator of nuclear factor kappa B ligand (RANKL)‐induced tartrate‐resistant acid phosphatase (TRAP) activity, pit formation (actin rings), and TRAP‐positive multinucleated cells development in RAW264.7 cells. Furthermore, Rg3 dose‐dependently reduced the mRNA expression levels of osteoclast‐specific markers such as RANK, TRAP, and Cat‐K induced by RANKL through the down regulation of p38, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase (JNK) pathways. In conclusion, in silico docking study and in vitro validation together suggested that Rg3 inhibits osteoclastogenesis and reduces bone resorption through the inhibition of Cat‐K. Therefore, Rg3 might be a useful therapeutic agent for the treatment of osteoporosis and proper bone formation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-08T05:40:30.283349-05:
      DOI: 10.1002/ptr.5374
  • Cardioprotective Effects of Tannic Acid on Isoproterenol‐Induced
           Myocardial Injury in Rats: Further Insight into ‘French
    • Authors: Xitian Hu; Hua Wang, Xinhu Lv, Li Chu, Zhenyi Liu, Xiaogang Wei, Qincong Chen, Lei Zhu, Wei Cui
      Pages: 1295 - 1303
      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.
      PubDate: 2015-05-20T03:43:58.755784-05:
      DOI: 10.1002/ptr.5376
  • The Antioxidant Effect of Fermented Papaya Preparation in the Oral Cavity
    • Authors: E. Fibach; I. Ginsburg
      Pages: 1317 - 1322
      Abstract: Oxidative stress has been recognized to play important roles in various diseases, including of the oral cavity. However, nutritional supplementation of antioxidants to ameliorate the consequences of oxidative stress is debatable. One caveat is that oxidative status is often measured under non‐physiological conditions. Here, we investigated the antioxidant potential of fermented papaya preparation (FPP), a product of yeast fermentation of Carica papaya Linn, under conditions that prevail in the oral cavity. Employing highly sensitive luminol‐dependent chemiluminescence assays, we show that its antioxidant capacity was augmented by saliva (up to 20‐fold, p 
      PubDate: 2015-05-31T22:04:58.066505-05:
      DOI: 10.1002/ptr.5381
  • Studies on Bronchodilator Activity of Salvia officinalis (Sage): Possible
           Involvement of K+ Channel Activation and Phosphodiesterase Inhibition
    • Pages: 1323 - 1329
      Abstract: The aqueous methanolic extract of the aerial parts of Salvia officinalis (So.Cr) was studied to provide possible underlying mechanism(s) for its medicinal use in asthma using the in vivo bronchodilatory assay and isolated tracheal preparations. S. officinalis (1–10 mg/kg) dose‐dependently inhibited carbachol (CCh)‐induced bronchospasm in anesthetized rats with three‐fold greater potency than the positive control, aminophylline. In tracheal preparations, So.Cr inhibited the low K+ (25 mM)‐induced contractions. Pretreatment of the tissues with 4‐aminopyridine reversed the inhibitory effect of the plant extract against low K+, whereas glibenclamide did not show any effect, thus showing the involvement of voltage‐sensitive K+ channels. When tested against the CCh‐induced pre‐contractions for the involvement of any additional mechanism, interestingly, the extract showed a dose‐dependent (0.03–0.1 mg/mL) inhibitory effect and shifted the inhibitory concentration response curves of isoprenaline to the left, thus showing phosphodiesterase enzyme inhibitory‐like action, similar to that of papaverine. These results indicate that the crude extract of S. officinalis possesses bronchodilatory activity mediated predominantly via activation of voltage‐dependent K+ channels and inhibition of phosphodiesterase enzyme; thus, this study provides sound pharmacological basis for its medicinal use in hyperactive airways disorders such as asthma and cough. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-01T00:52:07.358341-05:
      DOI: 10.1002/ptr.5384
  • Effects of Artemetin on Nitric Oxide Release and Protection against
           Peroxidative Injuries in Porcine Coronary Artery Endothelial Cells
    • Authors: Elena Grossini; Patrizia Marotta, Serena Farruggio, Lorenzo Sigaudo, Fatima Qoqaiche, Giulia Raina, Veronica Giuli, David Mary, Giovanni Vacca, Federica Pollastro
      Pages: 1339 - 1348
      Abstract: Artemetin is one of the main components of Achillea millefolium L. and Artemisia absinthium, which have long been used for the treatment of various diseases. To date, however, available information about protective effects of their extracts on the cardiovascular system is scarce. Therefore, we planned to analyze the effects of artemetin on nitric oxide (NO) release and the protection exerted against oxidation in porcine aortic endothelial (PAE) cells. In PAE, we examined the modulation of NO release caused by artemetin and the involvement of muscarinic receptors, β2‐adrenoreceptors, estrogenic receptors (ER), protein‐kinase A, phospholipase‐C, endothelial‐NO‐synthase (eNOS), Akt, extracellular‐signal‐regulated kinases 1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK). Moreover, in cells treated with hydrogen peroxide, the effects of artemetin were examined on cell survival, glutathione (GSH) levels, apoptosis, mitochondrial membrane potential and transition pore opening. Artemetin increased eNOS‐dependent NO production by the involvement of muscarinic receptors, β2‐adrenoreceptors, ER and all the aforementioned kinases. Furthermore, artemetin improved cell viability in PAE that were subjected to peroxidation by counteracting GSH depletion and apoptosis and through the modulation of mitochondrial function. In conclusion, artemetin protected endothelial function by acting as antioxidant and antiapoptotic agent and through the activation of ERK1/2 and Akt. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-29T12:09:48.720655-05:
      DOI: 10.1002/ptr.5386
  • Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in
           High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetic Rats
    • Authors: Jarinyaporn Naowaboot; Nuntiya Somparn, Suphaket Saentaweesuk, Patchareewan Pannangpetch
      Pages: 1388 - 1395
      Abstract: Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-08T05:53:44.538507-05:
      DOI: 10.1002/ptr.5392
  • Involvement of Renin–Angiotensin System Inhibition, the Potential
           Risk of Danshen in the Treatment of Pregnancy‐Induced Hypertension
    • Authors: Baofang Liang; Jianwei Su
      Pages: 1421 - 1422
      PubDate: 2015-05-25T03:05:56.54065-05:0
      DOI: 10.1002/ptr.5383
  • Effects of Cyanidin‐3‐O‐glucoside on Synthetic and
           Metabolic Activity of Ethanol Stimulated Human Pancreatic Stellate Cells
    • Abstract: Activated pancreatic stellate cells (PSC) play a major role in the development of chronic pancreatitis. Flavonoids (C‐3‐O‐G) theoretically may have potential to suppress activated PSC. The aim of our study was to determine the ability of C‐3‐O‐G to invert synthetic and metabolic activity of alcohol stimulated human pancreatic stellate cells (hPSC). In the present study we demonstrate that treatment with C‐3‐O‐G decreased proliferation rate of ethanol activated hPSC by 51%. Synthesis of extracellular matrix proteins in activated hPSC was markedly inhibited, as shown by reduced levels of collagen I and fibronectin expression. The decrease of secretion of fibronectin by 33% and in collagen I‐25% in ethanol activated and C‐3‐O‐G treated hPSC was observed. Moreover, treatment of ethanol activated hPSC with C‐3‐O‐G resulted in the decrease of oxygen consumption rate by 44% and reduced levels of ATP synthesis (i.e. energy production) by 41%. Hence, the effects of C‐3‐O‐G on ethanol activated hPSC may provide new insights for the use of anthocyanins as anti‐fibrogenic agents in treatment and/or prevention of pancreatic fibrosis. Copyright © 2015 John Wiley & Sons, Ltd.
  • Brassinin Combined with Capsaicin Enhances Apoptotic and
           Anti‐metastatic Effects in PC‐3 Human Prostate Cancer Cells
    • Abstract: Brassinin (BSN), a type of indole compound derived from cruciferous vegetables, has shown anti‐cancer effects in cells and animals. Capsaicin (CAP), an alkaloid derived from the chilli pepper, is also of interest in for its reported efficacy against various malignancies. The objective of our study was to analyze the potential synergistic anti‐tumor effects of BSN combined with CAP on prostate cancer PC‐3 cells. After treatment with BSN and CAP at various concentrations, the synergistic cytotoxic effect of PC‐3 cells was analyzed by MTT method, proliferation, apoptosis, mitochondrial membrane potential, colony formation, and Western blotting. Moreover, the inhibitory effects of BSN and CAP on the constitutive expressions of MMP‐9/2, their enzymatic activities, cellular migration, and cell invasion were also investigated. The cytotoxicity was synergistically increased in combination compared with the single drug used; moreover, proliferation, apoptosis, mitochondrial membrane potential, and colony formation were significantly suppressed and anti‐apoptotic‐, proliferative‐, and metastatic‐related proteins were clearly abolished in the combination group. Besides, constitutive MMP‐9/2 expression, their enzymatic activities, cell migration, and tumor cell invasion were inhibited, and TIMP‐1 was up‐regulated in the combination group in PC‐3 cells. Our results indicate, for the first time, that BSN and CAP in combination exert synergistic anticancer effects in prostate carcinoma. Copyright © 2015 John Wiley & Sons, Ltd.
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