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Publisher: John Wiley and Sons   (Total: 1610 journals)

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Oral Surgery     Hybrid Journal   (Followers: 1, SJR: 0.185, h-index: 5)
Orbis Litterarum     Hybrid Journal   (Followers: 6, SJR: 0.1, h-index: 4)
Orthodontics & Craniofacial Research     Hybrid Journal   (SJR: 1.192, h-index: 31)
Orthopaedic Surgery     Hybrid Journal   (Followers: 2, SJR: 0.28, h-index: 4)
Oxford Bulletin of Economics and Statistics     Hybrid Journal   (Followers: 17, SJR: 1.201, h-index: 45)
Oxford J. of Archaeology     Hybrid Journal   (Followers: 73, SJR: 0.54, h-index: 14)
Oxonomics     Hybrid Journal   (Followers: 1)
Pacific Economic Review     Hybrid Journal   (Followers: 2, SJR: 0.639, h-index: 19)
Pacific Focus     Hybrid Journal   (Followers: 2, SJR: 0.315, h-index: 5)
Pacific Philosophical Quarterly     Hybrid Journal   (Followers: 7, SJR: 0.962, h-index: 14)
Pacing and Clinical Electrophysiology     Hybrid Journal   (Followers: 4, SJR: 0.927, h-index: 77)
Packaging Technology and Science     Hybrid Journal   (Followers: 10, SJR: 0.72, h-index: 27)
Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 3, SJR: 1.429, h-index: 58)
Pain Medicine     Hybrid Journal   (Followers: 5, SJR: 0.929, h-index: 55)
Pain Practice     Hybrid Journal   (Followers: 3, SJR: 0.835, h-index: 30)
Palaeontology     Hybrid Journal   (Followers: 13, SJR: 1.111, h-index: 40)
PAMM : Proceedings in Applied Mathematics and Mechanics     Free  
Papers In Regional Science     Hybrid Journal   (Followers: 6, SJR: 1.332, h-index: 34)
Parasite Immunology     Hybrid Journal   (Followers: 4, SJR: 0.916, h-index: 55)
Parliamentary History     Hybrid Journal   (Followers: 5, SJR: 0.151, h-index: 3)
Particle & Particle Systems Characterization     Hybrid Journal   (SJR: 0.226, h-index: 28)
Pathology Intl.     Hybrid Journal   (Followers: 1, SJR: 0.831, h-index: 53)
Peace & Change     Hybrid Journal   (Followers: 4)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 33, 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: 15, SJR: 1.027, h-index: 43)
Pediatric Obesity     Hybrid Journal   (Followers: 5, SJR: 1.336, h-index: 33)
Pediatric Pulmonology     Hybrid Journal   (Followers: 3, SJR: 1.092, h-index: 77)
Pediatric Transplantation     Hybrid Journal   (SJR: 0.663, h-index: 49)
Pediatrics Intl.     Hybrid Journal   (Followers: 3, SJR: 0.443, h-index: 42)
Performance Improvement     Hybrid Journal   (Followers: 3)
Performance Improvement Quarterly     Hybrid Journal   (Followers: 1, SJR: 0.362, h-index: 7)
Periodontology 2000     Hybrid Journal   (Followers: 4, SJR: 1.467, h-index: 74)
Permafrost and Periglacial Processes     Hybrid Journal   (Followers: 3, SJR: 1.741, h-index: 46)
Personal Relationships     Hybrid Journal   (Followers: 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: 24, SJR: 5.796, h-index: 80)
Perspectives In Psychiatric Care     Hybrid Journal   (Followers: 1, SJR: 0.349, h-index: 20)
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 3, SJR: 1.566, h-index: 66)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (Followers: 1, SJR: 0.283, h-index: 8)
Pest Management Science     Hybrid Journal   (Followers: 5, SJR: 1.262, h-index: 72)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 7, SJR: 0.959, h-index: 20)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 23, SJR: 1.631, h-index: 59)
Pharmacology Research & Perspectives     Open Access  
Pharmacotherapy The J. of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 19, SJR: 0.852, h-index: 78)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 1, SJR: 0.105, h-index: 9)
Philosophical Books     Hybrid Journal   (Followers: 8)
Philosophical Investigations     Hybrid Journal   (Followers: 3, SJR: 0.162, h-index: 6)
Philosophical Issues     Hybrid Journal   (Followers: 8, SJR: 1.009, h-index: 2)
Philosophical Perspectives     Hybrid Journal   (Followers: 6)
Philosophy & Public Affairs     Hybrid Journal   (Followers: 19, SJR: 1.607, h-index: 29)
Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 17, SJR: 1.629, h-index: 11)
Philosophy Compass     Hybrid Journal   (Followers: 8, SJR: 0.282, h-index: 2)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.764, h-index: 96)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 2, SJR: 0.642, h-index: 42)
Phycological Research     Hybrid Journal   (Followers: 2, SJR: 0.405, h-index: 21)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.81, h-index: 72)
physica status solidi (b)     Hybrid Journal   (Followers: 1, SJR: 0.852, h-index: 70)
physica status solidi (c)     Hybrid Journal   (Followers: 1, SJR: 0.471, h-index: 31)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (Followers: 1, SJR: 1.166, h-index: 32)
Physik in unserer Zeit     Hybrid Journal   (Followers: 1)
Physik J.     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (Followers: 1, SJR: 1.442, h-index: 95)
Physiological Entomology     Hybrid Journal   (Followers: 2, SJR: 0.768, h-index: 38)
Physiological Reports     Open Access  
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 27, SJR: 0.396, h-index: 30)
Phytochemical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.959, h-index: 45)
Phytotherapy Research     Hybrid Journal   (SJR: 0.82, h-index: 76)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 3, SJR: 2.572, h-index: 72)
Plant Biotechnology J.     Hybrid Journal   (Followers: 6, SJR: 2.463, h-index: 58)
Plant Breeding     Hybrid Journal   (Followers: 14, SJR: 0.626, h-index: 49)
Plant Pathology     Hybrid Journal   (Followers: 7, SJR: 1.114, h-index: 50)
Plant Species Biology     Hybrid Journal   (Followers: 3, SJR: 0.509, h-index: 26)
Plant, Cell & Environment     Hybrid Journal   (Followers: 5, SJR: 2.821, h-index: 121)
Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.231, h-index: 40)
Poe Studies     Partially Free   (Followers: 5)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 12, SJR: 0.415, h-index: 3)
Policy & Internet     Hybrid Journal   (Followers: 8)
Policy Studies J.     Hybrid Journal   (Followers: 5, SJR: 1.362, h-index: 30)
Political Insight     Partially Free   (Followers: 1)
Political Psychology     Hybrid Journal   (Followers: 17, SJR: 1.885, h-index: 45)
Political Science Quarterly     Hybrid Journal   (Followers: 31, SJR: 0.378, h-index: 26)
Political Studies     Hybrid Journal   (Followers: 24, SJR: 1.107, h-index: 39)
Political Studies Review     Hybrid Journal   (Followers: 16, SJR: 0.488, h-index: 12)
Politics     Hybrid Journal   (Followers: 8, SJR: 0.517, h-index: 12)
Politics & Policy     Hybrid Journal   (Followers: 6, SJR: 0.347, h-index: 8)
Polymer Composites     Hybrid Journal   (Followers: 10, SJR: 0.67, h-index: 53)
Polymer Engineering & Science     Hybrid Journal   (Followers: 13, SJR: 0.572, h-index: 76)
Polymer Intl.     Hybrid Journal   (Followers: 3, SJR: 0.847, h-index: 67)
Polymers for Advanced Technologies     Hybrid Journal   (Followers: 3, SJR: 0.833, h-index: 57)
Population and Development Review     Hybrid Journal   (Followers: 3, SJR: 2.686, h-index: 56)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.836, h-index: 33)
Poverty & Public Policy     Hybrid Journal   (Followers: 13)
Practical Diabetes     Hybrid Journal   (Followers: 6, SJR: 0.175, h-index: 3)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 1.262, h-index: 69)
Prescriber     Hybrid Journal   (Followers: 8)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 4)

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Journal Cover   Phytotherapy Research
  [SJR: 0.82]   [H-I: 76]   Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
   Published by John Wiley and Sons Homepage  [1610 journals]
  • 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
    • Authors: Juventino III Colado‐Velázquez; Patrick Mailloux‐Salinas, JML Medina‐Contreras, David Cruz‐Robles, Guadalupe Bravo
      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
    • Authors: C. Vlachojannis; S. Chrubasik‐Hausmann, E. Hellwig, A. Al‐Ahmad
      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
    • Authors: Priscilla R. V. Campana; Daniel S. Mansur, Grasielle S. Gusman, Daneel Ferreira, Mauro M. Teixeira, Fernão C. Braga
      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
    • Authors: Jin‐Ju Jeong; Dong‐Hyun Kim
      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
    • Authors: Ute Wölfle; Birgit Haarhaus, Astrid Kersten, Bernd Fiebich, Martin J. Hug, Christoph M. Schempp
      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
  • Obituary
    • PubDate: 2015-06-18T05:30:09.325235-05:
      DOI: 10.1002/ptr.5403
  • 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
    • Authors: Jin‐Hui Song; Li Cui, Li‐Bin An, Wen‐Tao Li, Zhong‐Ze Fang, Yan‐Yan Zhang, Pei‐Pei Dong, Xue Wu, Li‐Xuan Wang, Frank J. Gonzalez, Xiao‐Yu Sun, De‐Wei Zhao
      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
    • Authors: Xin‐Li Liang; Jing Zhang, Zheng‐Gen Liao, Guo‐Wei Zhao, Yun Luo, Zhe Li, Andrew Satterlee
      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
    • Authors: Amani S. Awaad; Asmaa A. Al‐Rifai, Reham M. El‐Meligy, Ahmed M. Alafeefy, Mohamed E. Zain
      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
    • Authors: Ji‐Hye Ahn; Tae‐won Lee, Ki‐Hee Kim, Hoyong Byun, Byeol Ryu, Kyung‐Tae Lee, Dae Sik Jang, Jung‐Hye Choi
      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
    • Authors: Arif‐ullah Khan; Anwarul‐Hassan Gilani
      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
    • Authors: Maja Šikić Pogačar; Anja Klančnik, Franz Bucar, Tomaž Langerholc, Sonja Smole Možina
      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
  • 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
      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
  • 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
    • Authors: Muhammad Hanif Siddiqi; Muhammad Zubair Siddiqi, Sera Kang, Hae Yong Noh, Sungeun Ahn, Shakina Yesmin Simu, Mohamed Antar Aziz, Natarajan Sathishkumar, Zuly Elizabeth Jiménez Pérez, Deok‐Chun Yang
      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
  • Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia
           HL‐60 Cells
    • Authors: Ignacio Bejarano; Belén Godoy‐Cancho, Lourdes Franco, Manuel A. Martínez‐Cañas, María A. Tormo
      Abstract: Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro‐apoptotic events in cancerous cells. However, the literature related to the anti‐cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase‐3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time‐dependent and dose‐dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase‐3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti‐cancer properties. Moreover, it opens new possibilities of application of cork by‐products, being more efficient in the sector of cork‐based agriculture. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-05T03:49:02.754766-05:
      DOI: 10.1002/ptr.5364
  • Studies on Bronchodilator Activity of Salvia officinalis (Sage): Possible
           Involvement of K+ Channel Activation and Phosphodiesterase Inhibition
    • Authors: Anwarul‐Hassan Gilani; Najeeb‐ur Rehman, Aslam Khan, Khalid M. Alkharfy
      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
  • Anti‐diabetic and Anti‐hyperlipidemic Effects and Safety of
           Salacia reticulata and Related Species
    • Authors: Sidney J. Stohs; Sidhartha Ray
      Abstract: Extracts of Salacia reticulata Wight (Hypocrataceae) roots, stems, and leaves have been used in Asia for hundreds of years for the folkloric treatment of diabetes and other health problems. Constituents that have been identified as exhibiting anti‐diabetic effects include salacinol, kotalanol, ponkorinol, salaprinol, and their corresponding de‐0‐sulfonated compounds. Mangiferin, kotalagenin 16‐acetate and various proanthocyanidin oligomers have also been isolated. Studies indicate that Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α‐glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator‐activated receptor‐α, glucose transporter‐4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities. In human studies, Salacia extracts have been shown to decrease plasma glucose and insulin levels, decrease HbA1c, and modulate serum lipid levels with no adverse effects being reported. Similar results have been demonstrated in rat and mouse models as well as in vitro systems. Safety of S. reticulata and other Salacia species as S. oblonga and S. chinensis in rats and mice indicate that extracts are exceedingly safe. No clinical studies have examined the effects of Salacia extracts on human weight loss, although weight loss and decreases in weight gain have been demonstrated in animal models. Because of the large number of pharmacologically active compounds, it is difficult to establish standards for extracts. © 2015 The
      Authors . Phytotheraphy Research published by John Wiley & Sons Ltd.
      PubDate: 2015-05-31T22:51:50.782165-05:
      DOI: 10.1002/ptr.5382
  • The Antioxidant Effect of Fermented Papaya Preparation in the Oral Cavity
    • Authors: E. Fibach; I. Ginsburg
      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
  • 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
      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
  • Inhibition of Myeloid Cell Leukemia 1 and Activation of Caspases Are
           Critically Involved in Gallotannin‐induced Apoptosis in Prostate
           Cancer Cells
    • Authors: Eunkyung Park; Hee Young Kwon, Ji Hoon Jung, Deok‐Beom Jung, Arong Jeong, Jinhong Cheon, Bonglee Kim, Sung‐Hoon Kim
      Abstract: Although gallotannin contained in several medicinal plants was known to have multi‐biological activities, such as antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and antitumor effects, the underlying apoptotic mechanism of gallotannin is not fully understood so far. Thus, in the present study, the apoptotic mechanism of gallotannin was elucidated in DU145, PC‐3, and M2182 prostate cancer cells in association with myeloid cell leukemia 1 (Mcl‐1) signaling. Gallotannin exerted dose‐dependent cytotoxicity in DU145, PC‐3, and M2182 prostate cancer cells. Also, gallotannin showed apoptotic morphological features and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and sub‐G1 accumulation in three prostate cancer cell lines. Consistently, gallotannin cleaved poly (ADP‐ribose) polymerase (PARP) and attenuated the expression of procaspases 9 and 3 in three prostate cancer cell lines. Furthermore, gallotannin attenuated the expression of survival genes such as Mcl‐1, B‐cell lymphoma 2, and B‐cell lymphoma 2 extra large in three prostate cancer cell lines. Interestingly, overexpression of Mcl‐1 reversed the ability of gallotannin to cleave PARP and increase sub‐G1 population in three prostate cancer cell lines. Conversely, silencing of Mcl‐1 enhanced apoptosis by gallotannin in three prostate cancer cell lines by FACSCalibur (Becton Dickinson, Franklin Lakes, NJ, USA). Taken together, our findings demonstrate that inhibition of Mcl‐1 and activation of caspases are critically involved in gallotannin‐induced apoptosis in prostate cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-27T03:15:08.394691-05:
      DOI: 10.1002/ptr.5371
  • Involvement of Renin–Angiotensin System Inhibition, the Potential
           Risk of Danshen in the Treatment of Pregnancy‐Induced Hypertension
    • Authors: Baofang Liang; Jianwei Su
      PubDate: 2015-05-25T03:05:56.54065-05:0
      DOI: 10.1002/ptr.5383
  • Transcriptomic Analysis Reveals Wound Healing of Morus alba Root Extract
           by Up‐Regulating Keratin Filament and CXCL12/CXCR4 Signaling
    • Authors: Kang‐Hoon Kim; Won‐Seok Chung, Yoomi Kim, Ki‐Suk Kim, In‐Seung Lee, Ji Young Park, Hyeon‐Soo Jeong, Yun‐Cheol Na, Chang‐Hun Lee, Hyeung‐Jin Jang
      Abstract: Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA‐mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real‐time cell analysis and real‐time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose‐dependent manner on Kera‐308 cell line, and up‐regulated keratin expression including wound‐induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up‐regulated mRNA associated keratin filaments and toward a more up‐regulated mRNA level of C‐X‐C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-25T02:55:36.84349-05:0
      DOI: 10.1002/ptr.5375
  • Modulation of Cytochrome P450 Activity by 18β‐Glycyrrhetic Acid
           and its Consequence on Buspirone Pharmacokinetics in Rats
    • Authors: Sang‐Bum Kim; Hyun‐Jong Cho, Yeong Shik Kim, Dae‐Duk Kim, In‐Soo Yoon
      Abstract: The aim of this study was to elucidate the inhibition mechanism of 18β‐glycyrrhetic acid (GLY) on cytochrome P450 (CYP) activity and in vivo pharmacokinetic consequences of single GLY dose in rats. An in vitro CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous and oral buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral GLY in rats. In the in vitro CYP inhibition study, CYP3A was involved in the metabolism of GLY. Moreover, GLY inhibited CYP3A activity with an IC50 of 20.1 ± 10.7 μM via a mixed inhibition mechanism. In the in vivo rat pharmacokinetic study, single oral GLY dose enhanced the area under plasma concentration–time curve (AUC) of intravenous and oral BUS, but the extent of increase in AUC was only minimal (1.12–1.45 fold). These results indicate that GLY can inhibit the in vitro CYP3A‐mediated drug metabolism in RLM via a mixed inhibition mechanism. However, the impact of single oral GLY dose on the pharmacokinetics of BUS in rats was limited, showing that GLY could function as merely a weak inhibitor for CYP3A‐mediated drug metabolism in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-23T09:05:50.670082-05:
      DOI: 10.1002/ptr.5365
  • Efficacy and Safety of White Willow Bark (Salix alba) Extracts
    • Authors: Mohd Shara; Sidney J. Stohs
      Abstract: Willow bark extract has been used for thousands of years as an anti‐inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti‐inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti‐inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor‐α and nuclear factor‐kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non‐steroidal anti‐inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate‐sensitive individuals. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-22T04:31:20.539222-05:
      DOI: 10.1002/ptr.5377
  • 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
      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
  • Relationship Between Emotional Behavior in Mice and the Concentration of
           (+)‐α‐Santalol in the Brain
    • Authors: Tadaaki Satou; Yuko Ogawa, Kazuo Koike
      Abstract: We previously reported finding anxiolytic‐like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)‐α‐santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)‐α‐santalol by inhalation or intraperitoneal injection, we assessed anxiolytic‐like and locomotor activities using elevated‐plus maze tests. We also examined the relationship between the emotional behavior and the (+)‐α‐santalol brain concentration. Anxiolytic‐like activity was not observed immediately after administration or after water‐immersion stress for 24 h for either the (+)‐α‐santalol 2 μL/L air inhalation or the (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)‐α‐santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water‐immersion stress for 24 h. The brain (+)‐α‐santalol concentration was 2.6 µg/g tissue after (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)‐α‐santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic‐like activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-19T00:45:35.582483-05:
      DOI: 10.1002/ptr.5372
  • An Effect of Oak‐Wood Extract (Robuvit®) on Energy State of
           Healthy Adults—A Pilot Study
    • Authors: Zuzana Országhová; Iveta Waczulíková, Carolina Burki, Peter Rohdewald, Zdeňka Ďuračková
      Abstract: The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) – polyphenolic extract obtained from the wood of oak Quercus robur – on the healthy elderly individuals using energy subscale scores of the Activation – Deactivation Adjective Check List. Analysis was focused on the comparison of pre‐post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre‐treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
      PubDate: 2015-05-18T01:05:15.525509-05:
      DOI: 10.1002/ptr.5368
  • Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing
           DNA Methylation
    • Authors: Apei Jiang; Xuemin Wang, Xiaoyun Shan, Yuan Li, Pengqi Wang, Pan Jiang, Qing Feng
      Abstract: Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor β (RARβ), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RARβ has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RARβ is a major mechanism for its silencing in tumors. Recently, curcumin has been considered as a potential DNA methyltransferase inhibitor. Herein, we demonstrated that curcumin significantly elevate RARβ expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RARβ promoter methylation in lung cancer A549 and H460 cells. Mechanistic study demonstrated that curcumin was able to downregulate the mRNA levels of DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective effect against weight loss because of tumor burden. Tumor growth was strongly repressed by curcumin treatment. As the results from in vitro, RARβ mRNA were increased and DNMT3b mRNA were decreased by curcumin treatment compared with the mice in control group. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo‐preventive agent for lung cancer through reactivation of RARβ. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-15T08:45:41.8658-05:00
      DOI: 10.1002/ptr.5373
  • Incidence and Causes of Aconitum Alkaloid Poisoning in Hong Kong from 1989
           to 2010
    • Authors: Thomas Y. K. Chan
      Abstract: Aconite roots contain Aconitum alkaloids, which are highly toxic cardiotoxins and neurotoxins. In this review, the main objective was to determine the incidence and causes of Aconitum alkaloid poisoning in Hong Kong between 1989 and 2010, based on six published reports from the territory‐wide poison control units. In the New Territories East of Hong Kong, the incidence of aconite poisoning showed a sudden and sustained decrease from 0.60 (1989–1991) to 0.16 (1992–1993) and 0.17 (1996–1998) per 100 000 population, after publicity measures in late 1991 to promote awareness of the toxicity of aconite roots. In the whole of Hong Kong, the incidence of aconite poisoning was even lower in January 2000–June 2004 (0.03 per 100 000 population). However, aconite poisoning became more common again in April 2004–July 2009 and 2008–2010 (0.15 and 0.28 per 100 000 population). Overdoses and use of inadequately processed aconite roots were important causes. As from 2004 to 2009, ‘hidden’ aconite poisoning (toxicity caused by contaminants in other dispensed herbs) emerged as an important cause. It is important to continue the safety monitoring of potent herbs and the networking of poison control units. Further systematic studies would be required to identify the likely sources of contamination of herbs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-14T03:52:59.231857-05:
      DOI: 10.1002/ptr.5370
  • Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are
           Mediated Through Dual Inhibition of Ca++ Influx and Phosphodiesterase
    • Authors: Najeeb‐ur Rehman; Anwarul‐Hassan Gilani, Aslam Khan, Maryam Nazneen, Ali A. El Gamal, Ghada A. Fawzy, Hanan Y. Al‐Ati, Maged S. Abdel‐kader
      Abstract: This study describes the antidiarrheal and antispasmodic activities of the hydro‐alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action explored along with activity‐directed fractionation. Bp.Cr and its aqueous (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in‐vivo and in‐vitro assays. The crude extract (100–300 mg/kg) showed 20 and 60% protection of castor oil‐induced diarrhea in mice. In isolated rabbit jejunum, Bp.Cr like papaverine inhibited spontaneous and high K+ (80 mM)‐induced contractions equi‐potently. In guinea‐pig ileum, Bp.Cr showed a moderate spasmogenic effect. The activity‐directed fractionation revealed that the spasmolytic activity was concentrated in the organic fractions and spasmogenic component in the aqueous fraction. Amongst the organic fractions, BP.DCM and Bp.Pet inhibited spontaneous and high K+‐induced contractions equi‐potently, while Bp.But, like verapamil was more potent against high K+. The crude extract and its organic fractions caused rightward shift in the Ca++‐concentration response curves (CRCs), similar to verapamil, and all except Bp.But potentiated the isoprenaline‐inhibitory CRCs to the left, similar to papaverine. The results of this study indicate that the crude extract of B. polystachya possesses antidiarrheal and antispasmodic activities, mediated possibly through dual inhibition of Ca++ influx and phospodiesterase enzyme. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-14T03:19:27.2465-05:00
      DOI: 10.1002/ptr.5367
  • Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin
           (Corilagin) Rich Extracts of Phyllanthus amarus in
           Carrageenan‐induced Thermal and Mechanical Chronic Muscle
    • Authors: Atul R. Chopade; F. J. Sayyad
      Abstract: The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-14T01:10:50.434932-05:
      DOI: 10.1002/ptr.5366
  • The Influence of Aconitum carmichaelii Debx. on the Pharmacokinetic
           Characteristics of Main Components in Rheum palmatum L.
    • Authors: Yun‐xia Li; Xiao‐hong Gong, Yan Li, Ruo‐qi Zhang, An Yuan, Meng‐jie Zhao, Dai‐wen Zeng, Cheng Peng
      Abstract: Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines, and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata was the basic herb pair applied in many Chinese traditional prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb anthraquinones as the main marker constituents were investigated. In the present study, pharmacokinetic differences of rhubarb anthraquinones were detected after oral administration of extract of Rheum palmatum L. and compatibility with Aconitum carmichaelii Debx. After oral administration, no difference of peak time can be found for anthraquinones between rhubarb group and compatibility group. But Cmax and area under the curve of aloe‐emodin, emodin and chrysophanol in compatibility group were significantly higher than that in rhubarb group. Although the Cmax of rhein in compatibility group was much lower than that in rhubarb group, the area under the curve value was similar in two groups. The clearance and t1/2 of rhubarb anthraquinone were also changed after compatibility. The change of pharmacokinetics characteristics of rhubarb anthraquinone after compatibility may be caused by the drug–drug interaction medicated by chemical reaction and cytochromes P450. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-12T01:43:38.817337-05:
      DOI: 10.1002/ptr.5369
  • Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe
           Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of
           Neutrophil Activation
    • Authors: Tao Wen; Wenjun Xu, Lianchun Liang, Junhong Li, Xiaorong Ding, Xiao Chen, Jianhua Hu, Aiping Lv, Xiuhui Li
      Abstract: Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post‐medication, the MPO, S100A8/A9, histone, and interleukin‐6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide‐stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-09T02:51:59.35239-05:0
      DOI: 10.1002/ptr.5361
  • In vivo Antimalarial Activity of α‐Mangostin and the New
           Xanthone δ‐Mangostin
    • Authors: Yulieth Upegui; Sara M. Robledo, Juan Fernando Gil Romero, Winston Quiñones, Rosendo Archbold, Fernando Torres, Gustavo Escobar, Bibiana Nariño, Fernando Echeverri
      Abstract: Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α‐mangostin and a new compound, δ‐mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α‐Mangostin was more active against the resistant Plasmodium falciparum chloroquine‐resistant (FCR3) strain (IC50 = 0.2 ± 0.01 μM) than δ‐mangostin (IC50 = 121.2 ± 1.0 μM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-05T08:58:22.257848-05:
      DOI: 10.1002/ptr.5362
  • Preclinical Pharmacokinetics and Pharmacodynamics and Content Analysis of
           Gnetol in Foodstuffs
    • Authors: Connie M. Remsberg; Stephanie E. Martinez, Bolanle C. Akinwumi, Hope D. Anderson, Jody K. Takemoto, Casey L. Sayre, Neal M. Davies
      Abstract: Studies were undertaken to evaluate the bioavailability in rats and content analysis of gnetol in Gnetum gnemon products reported to contain gnetol and to examine the pharmacological properties of gnetol in in vitro models including anti‐inflammatory/analgesic, antidiabetic, anti‐adipogenesis, and anticancer activity. Male Sprague–Dawley rats were cannulated and dosed either intravenously with gnetol (10 mg/kg) or orally (100 mg/kg). Various methanolic extractions of G. gnemon products were quantified. Gnetol's effect on cell viability in selected cell lines with or without inflammatory stimulus was assessed. α‐Amylase and α‐glucosidase inhibition was evaluated. Cyclooxygenase (COX)‐1, COX‐2, and histone deacetylase inhibition and adipogenesis inhibition were examined. After oral and intravenous administration, gnetol was detected in both serum and urine as the parent compound and as a glucuronidated metabolite. The bioavailability of gnetol was determined to be 6%. Gnetol is rapidly glucuronidated and is excreted in urine and via nonrenal routes. Gnetol was found to exist as an aglycone and as a glycoside in G. gnemon products. Gnetol showed concentration‐dependent reductions in cell viability in cancer cell lines with greatest activity in colorectal cancer and potent COX‐1, histone deacetylase, and weak COX‐2 activities along with limited reduction in inflammation. Gnetol also possessed concentration‐dependent alpha‐amylase, alpha‐glucosidase, and adipogenesis activities. Pretreatment of mice with gnetol was able to increase the latency period to response in analgesia models. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-04T01:41:59.548364-05:
      DOI: 10.1002/ptr.5363
  • Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with
           Cancer Drugs in Rhabdomyosarcoma Cell Lines
    • Authors: Cheppail Ramachandran; Karl‐W. Quirin, Enrique A. Escalon, Ivonne V. Lollett, Steven J. Melnick
      Abstract: Synergistic effect of supercritical CO2 extracts of Curcuma species with conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger) (CA) extract showed the highest levels of cytotoxicity with inhibitory concentration IC50 values of 7.133 µg/ml and 7.501 µg/ml for SJRH30 and RD cell lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma xanthorrhiza (Javanese turmeric) extracts. CA showed synergistic cytotoxic effects with vinblastine (VBL) and cyclophosphamide (CP) as indicated by the combination index values of
      PubDate: 2015-05-04T00:59:49.030551-05:
      DOI: 10.1002/ptr.5360
  • Pycnogenol® in Metabolic Syndrome and Related Disorders
    • Authors: Om P. Gulati
      Abstract: The present review provides an update of the biological actions of Pycnogenol® in the treatment of metabolic syndrome and related disorders such as obesity, dyslipidaemia, diabetes and hypertension. Pycnogenol® is a French maritime pine bark extract produced from the outer bark of Pinus pinaster Ait. Subsp. atlantica. Its strong antioxidant, antiinflammatory, endothelium‐dependent vasodilator activity, and also its anti‐thrombotic effects make it appropriate for targeting the multifaceted pathophysiology of metabolic syndrome. Clinical studies have shown that it can reduce blood glucose levels in people with diabetes, blood pressure in mild to moderate hypertensive patients, and waist circumference, and improve lipid profile, renal and endothelial functions in metabolic syndrome. This review highlights the pathophysiology of metabolic syndrome and related clinical research findings on the safety and efficacy of Pycnogenol®. The results of clinical research studies performed with Pycnogenol® are discussed using an evidence‐based, target‐oriented approach following the pathophysiology of individual components as well as in metabolic syndrome overall. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-01T03:01:18.157079-05:
      DOI: 10.1002/ptr.5341
  • Antifungal Activity of Ellagic Acid In Vitro and In Vivo
    • Authors: Zhi‐Jian Li; Xin Guo, Gulina Dawuti, Silafu Aibai
      Abstract: Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti‐inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38‐A and M27‐A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC‐based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α‐demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm2) significantly enhanced the cure rate in a guinea‐pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-28T03:16:39.153432-05:
      DOI: 10.1002/ptr.5340
  • Influence of a Specialized Trigonella foenum‐graecum Seed Extract
           (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy
           Menstruating Women, a Randomised Placebo Controlled Study
    • Authors: Amanda Rao; Elizabeth Steels, Gavin Beccaria, Warrick J. Inder, Luis Vitetta
      Abstract: The aim of the study was to evaluate the effect of Trigonella foenum‐graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo‐controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum‐graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self‐administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI‐20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum‐graecum may be a useful treatment for increasing sexual arousal and desire in women. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-24T01:55:12.889074-05:
      DOI: 10.1002/ptr.5355
  • A Review: The Pharmacology of Isoliquiritigenin
    • Authors: Fu Peng; Qiaohui Du, Cheng Peng, Neng Wang, Hailin Tang, Xiaoming Xie, Jiangang Shen, Jianping Chen
      Abstract: Isoliquiritigenin (ISL) is one of the bioactive ingredients isolated from the roots of plants belonging to licorice, including Glycyrrhiza uralensis, Mongolian glycyrrhiza, Glycyrrhiza glabra, and so forth. Liquiritigenin is available in common foods and alternative medicine, and its derivative‐ISL is applied into food additives and disease treatment like cancer therapy, antibiotic therapy, and so on. This review aims at providing a comprehensive summary of the pharmacological activities of ISL. The information published between 1972 and 2014 from a number of reliable sources including PubMed, ScienceDirect, Springer, and Wiley‐Blackwell. The practical application of ISL on the various disease prevention and treatments may stem from its numerous pharmacological properties such as antiinflammatory, anti‐microbial, anti‐oxidative, anticancer activities, immunoregulatory, hepatoprotective, and cardioprotective effects. However, further studies are needed to verify the target‐organ toxicity or side effects investigation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-24T01:21:24.029866-05:
      DOI: 10.1002/ptr.5348
  • In Vitro Assessment of the Anticancer Potential of Evodiamine in Human
           Oral Cancer Cell Lines
    • Authors: Khadka Sachita; Yongsoo Kim, Hyun‐Ju Yu, Sung‐Dae Cho, Jeong‐Sang Lee
      Abstract: Evodiamine, a bioactive alkaloid, has been regarded as having antioxidant, antiinflammatory, and anticancer properties. In the present study, we explored the effects of evodiamine on cell growth and apoptosis in human oral cancer cell lines. Our data revealed that evodiamine significantly inhibited the proliferation of human oral cancer cells and resulted in the cleavages of PARP (poly (ADP‐ribose) polymerase) and caspase‐3, in addition to causing the typical characteristics of apoptosis. Evodiamine also increased Bax protein levels and caused translocation of Bax into mitochondria and Bax oligomerization. In addition, evodiamine decreased expression of myeloid cell leukemia (Mcl‐1) at the transcriptional modification, and knockdown of Mcl‐1 clearly resulted in an increase in expression of Bax and active Bax, resulting in induction of apoptosis. Evodiamine reduced expression of phosphorylated AKT, and LY294002 potentiated evodiamine‐induced apoptosis by regulating Mcl‐1 protein. Our results suggest that evodiamine induces apoptosis in human oral cancer cells through the AKT pathway. These findings provide a rationale for its clinical application in the treatment of oral cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-22T21:33:05.760396-05:
      DOI: 10.1002/ptr.5359
  • The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the
           Senescent Mouse Model Induced by a Combination of d‐gal and AlCl3
    • Authors: Xiao‐Ming Peng; Li Gao, Shi‐Xia Huo, Xin‐Min Liu, Ming Yan
      Abstract: Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d‐galactose and AlCl3, and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step‐down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase‐3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase‐3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T04:30:42.537855-05:
      DOI: 10.1002/ptr.5358
  • Memory Enhancement of Acteoside (Verbascoside) in a Senescent Mice Model
           Induced by a Combination of d‐gal and AlCl3
    • Authors: Li Gao; Xiao‐Ming Peng, Shi‐Xia Huo, Xin‐Ming Liu, Ming Yan
      Abstract: Acteoside, also known as verbascoside or orobanchin, is a common compound found in many important medicinal plants including the Chinese herb Cistanche deserticola Y. C. Ma, which is used for its neuroprotective and memory enhancement properties. We have investigated the effects of acteoside using a senescent mouse model induced by a combination of chronic intraperitoneal administration of d‐gal (60 mg/kg/day) and oral administration AlCl3 (5 mg/kg/day) once daily for 90 days. After 60 days, acteoside (30, 60, and 120 mg/kg/day) was orally administered once daily for 30 days. The memory enhancing effects of acteoside were evaluated using the Morris water maze test. The results showed that 30–120 mg/kg/day of acteoside reduced the escape latency in finding the platform, and increased the number of crossings of the platform. A 30–120 mg/kg/day of acteoside increased significantly the expression of nerve growth factor and tropomycin receptor kinase A mRNA and protein in the hippocampus, measured using real‐time RT‐PCR, immunohistochemical analysis, and western blotting. These results support the use of C. deserticola for memory enhancement and indicate that the effects of acteoside are induced via promotion of nerve growth factor and tropomycin receptor kinase A expression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T04:30:32.826548-05:
      DOI: 10.1002/ptr.5357
  • Effect of Zingiber officinale Supplementation on Obesity Management with
           Respect to the Uncoupling Protein 1 ‐3826A>G and
           ß3‐adrenergic Receptor Trp64Arg Polymorphism
    • Authors: Vahideh Ebrahimzadeh Attari; Mohammad Asghari Jafarabadi, Maryam Zemestani, Alireza Ostadrahimi
      Abstract: The present study aimed to investigate the effect of ginger (Zingiber officinale) supplementation on some obesity‐associated parameters, with nutrigenetics approach. Accordingly, 80 eligible obese women (aged 18–45 years) were randomly assigned to receive either ginger (2‐g ginger rhizomes powder as two 1‐g tablets per day) or placebo supplements (corn starch with the same amount) for 12 weeks. Subjects were tested for changes in body weight, body mass index, waist and hip circumferences, body composition, appetite score, and dietary intake. Moreover, participants were genotyped for the ‐3826A>G and Trp64Arg polymorphisms of uncoupling protein 1 and ß3‐adrenergic receptor genes, respectively. Over 12 weeks, ginger supplementation resulted in a slight but statistically significant decrease in all anthropometric measurements and total appetite score as compared with placebo group, which were more pronounced in subjects with the AA genotype for uncoupling protein 1 and Trp64Trp genotype for ß3‐adrenergic receptor gene. However, there was no significant difference in changes of body composition and total energy and macronutrients intake between groups. In conclusion, our findings suggest that ginger consumption has potential in managing obesity, accompanying with an intervention–genotype interaction effect. However, further clinical trials need to explore ginger's efficacy as an anti‐obesity agent in the form of powder, extract, or its active components. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T03:43:09.350617-05:
      DOI: 10.1002/ptr.5343
  • The Potential for Plant Derivatives against Acrylamide Neurotoxicity
    • Authors: O. O. Adewale; J. M. Brimson, O. A. Odunola, M. A. Gbadegesin, S. E. Owumi, C. Isidoro, T. Tencomnao
      Abstract: Certain industrial chemicals and food contaminants have been demonstrated to possess neurotoxic activity and have been suspected to cause brain‐related disorders in humans. Acrylamide (ACR), a confirmed neurotoxicant, can be found in trace amount in commonly consumed human aliments as a result of food processing or cooking. This discovery aroused a great concern in the public, and increasing efforts are continuously geared towards the resolution of this serious threat. The broad chemical diversity of plants may offer the resources for novel antidotes against neurotoxicants. With the goal of attenuating neurotoxicity of ACR, several plants extracts or derivatives have been employed. This review presents the plants and their derivatives that have been shown most active against ACR‐induced neurotoxicity, with a focus on their origin, pharmacological activity, and antidote effects. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-17T02:50:12.267191-05:
      DOI: 10.1002/ptr.5353
  • Alantolactone from Saussurea lappa Exerts Antiinflammatory Effects by
           Inhibiting Chemokine Production and STAT1 Phosphorylation in
           TNF‐α and IFN‐γ‐induced in HaCaT cells
    • Authors: Hye‐Sun Lim; Sung‐Eun Jin, Ohn‐Soon Kim, Hyeun‐Kyoo Shin, Soo‐Jin Jeong
      Abstract: Skin inflammation is the most common condition seen in dermatology practice and can be caused by various allergic reactions and certain toxins or chemicals. In the present study, we investigated the antiinflammatory effects of Saussurea lappa, a medicinal herb, and its marker compounds alantolactone, caryophyllene, costic acid, costunolide, and dehydrocostuslactone in the HaCaT human keratinocyte cell line. HaCaT cells were stimulated with tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ), and treated with S. lappa or each of five marker compounds. Chemokine production and expression were analyzed by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction, respectively. Phosphorylation of signal transducer and activator of transcription (STAT) 1 was determined by immunoblotting. Stimulation with TNF‐α and IFN‐γ significantly increased the production of the following chemokines: thymus‐regulated and activation‐regulated chemokine (TARC): regulated on activation, normal T‐cell expressed and secreted (RANTES): macrophage‐derived chemokine (MDC): and interleukin‐8 (IL‐8). By contrast, S. lappa and the five marker compounds significantly reduced the production of these chemokines by TNF‐α and IFN‐γ‐treated cells. S. lappa and alantolactone suppressed the TNF‐α and IFN‐γ‐stimulated increase in the phosphorylation of STAT1. Our results demonstrate that alantolactone from S. lappa suppresses TNF‐α and IFN‐γ‐induced production of RANTES and IL‐8 by blocking STAT1 phosphorylation in HaCaT cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-17T02:15:55.129171-05:
      DOI: 10.1002/ptr.5354
  • Comparative Study of the Biological Activity of Allantoin and Aqueous
           Extract of the Comfrey Root
    • Authors: Vesna Lj. Savić; Vesna D. Nikolić, Ivana A. Arsić, Ljiljana P. Stanojević, Stevo J. Najman, Sanja Stojanović, Ivana I. Mladenović‐Ranisavljević
      Abstract: This study investigates the biological activity of pure allantoin (PA) and aqueous extract of the comfrey (Symphytum officinale L.) root (AECR) standardized to the allantoin content. Cell viability and proliferation of epithelial (MDCK) and fibroblastic (L929) cell line were studied by using MTT test. Anti‐irritant potential was determined by measuring electrical capacitance, erythema index (EI) and transepidermal water loss of artificially irritated skin of young healthy volunteers, 3 and 7 days after application of creams and gels with PA or AECR. Pure allantoin showed mild inhibitory effect on proliferation of both cell lines at concentrations 40 and 100 µg/ml, but more pronounced on MDCK cells. Aqueous extract of the comfrey root effect on cell proliferation in concentrations higher than 40 µg/ml was significantly stimulatory for L929 but inhibitory for MDCK cells. Pharmaceutical preparations that contained AECR showed better anti‐irritant potential compared with PA. Creams showed better effect on hydration and EI compared with the gels that contained the same components. Our results indicate that the biological activity of the comfrey root extract cannot be attributed only to allantoin but is also likely the result of the interaction of different compounds present in AECR. Topical preparations that contain comfrey extract may have a great application in the treatment of skin irritation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:53:15.399453-05:
      DOI: 10.1002/ptr.5356
  • Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate
           the Oral Wound Healing in Rats
    • Authors: Fernanda Hack Coelho; Gabriela Salvadori, Pantelis Varvaki Rados, Alessandra Magnusson, Chris Krebs Danilevicz, Luise Meurer, Manoela Domingues Martins
      Abstract: The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3‐mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re‐epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi‐quantitative analyses, was performed using the Kruskal–Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:22:45.2721-05:00
      DOI: 10.1002/ptr.5352
  • Activation of Caspase‐9/3 and Inhibition of Epithelial Mesenchymal
           Transition are Critically Involved in Antitumor Effect of Phytol in
           Hepatocellular Carcinoma Cells
    • Authors: Chul‐Woo Kim; Hyun Joo Lee, Ji Hoon Jung, Yoon Hyeon Kim, Deok‐Beom Jung, Eun Jung Sohn, Jang Hoon Lee, Hong Jung Woo, Nam‐In Baek, Young Chul Kim, Sung‐Hoon Kim
      Abstract: This study was designed to investigate the antitumor mechanism of Phytol in hepatocellular carcinomas including Huh7 and HepG2 cells in association with caspase dependent apoptosis and epithelial mesenchymal transition (EMT) signaling. Phytol significantly suppressed the viability of Huh7 and HepG2 cells. Also, Phytol significantly increased the sub G1 population and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) positive cells in a concentration dependent manner in Huh7 and HepG2 cells. Consistently, Phytol cleaved poly (adenosine diphosphate‐ribose) polymerase (PARP), activated caspase‐9/3, and Bax attenuated the expression of survival genes such as Bcl‐2, Mcl‐1, and c‐Myc in Huh7 and HepG2 cells. Of note, Phytol also suppressed typical morphology change of EMT such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in HepG2 cells. Furthermore, Phytol also reversed the loss of E‐cadherin and overexpression of p‐smad2/3, alpha‐smooth muscle actin, and Snail induced by EMT promoter transforming growth factor beta1 in HepG2 cells. Overall, our findings suggest that Phytol exerts antitumor activity via apoptosis induction through activation of caspas‐9/3 and inhibition of EMT in hepatocellular carcinoma cells as a potent anticancer candidate for liver cancer treatment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T02:54:00.055236-05:
      DOI: 10.1002/ptr.5342
  • Role of Hydroxytyrosol‐dependent Regulation of HO‐1 Expression
           in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo
           Synthesis and Stabilization
    • Authors: Houda Zrelli; Miki Kusunoki, Hitoshi Miyazaki
      Abstract: Hydroxytyrosol (HT), an olive plant (Olea europaea L.) polyphenol, has proven atheroprotective effects. We previously demonstrated that heme oxygenase‐1 (HO‐1) is involved in the HT dependent prevention of dysfunction induced by oxidative stress in vascular endothelial cells (VECs). Here, we further investigated the signaling pathway of HT‐dependent HO‐1 expression in VECs. HT dose‐ and time‐dependently increased HO‐1 mRNA and protein levels through the PI3K/Akt and ERK1/2 pathways. Cycloheximide and actinomycin D inhibited both increases, suggesting that HT‐triggered HO‐1 induction is transcriptionally regulated and that de novo protein synthesis is necessary for this HT effect. HT stimulated nuclear accumulation of nuclear factor E2‐related factor 2 (Nrf2). This Nrf2 accumulation was blocked by actinomycin D and cycloheximide whereas HT in combination with the 26S proteasome inhibitor MG132 enhanced the accumulation. HT also extended the half‐life of Nrf2 proteins by decelerating its turnover. Moreover, HO‐1 inhibitor, ZnppIX and CO scavenger, hemoglobin impaired HT‐dependent wound healing while CORM‐2, a CO generator, accelerated wound closure. Together, these data demonstrate that HT upregulates HO‐1 expression by stimulating the nuclear accumulation and stabilization of Nrf2, leading to the wound repair of VECs crucial in the prevention of atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:47:03.200679-05:
      DOI: 10.1002/ptr.5339
  • Anti‐Salmonella Activity of Volatile Compounds of Vietnam Coriander
    • Authors: Ken‐ichi Fujita; Warinthorn Chavasiri, Isao Kubo
      Abstract: Essential oil derived from the fresh leaves of Polygonum odoratum Lour was tested for their effects on a foodborne bacterium Salmonella choleraesuis subsp. choleraesuis ATCC 35640 using a broth dilution method. This essential oil showed a significant antibacterial activity against S. choleraesuis at the concentration of 200 µg/mL. Twenty‐five volatile compounds were characterized from this essential oil by GC‐MS, and aldehyde compounds were found abundant and accounted for more than three‐fourths of the essential oil. Among the compounds characterized, dodecanal (C12) was the most abundant (55.5%), followed by decanal (C10) (11.6%). Both alkanals were effective against S. choleraesuis with the minimum growth inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 100 µg/mL. The most potent antibacterial activity against this bacterium was found with two minor compounds, dodecanol (lauryl alcohol) and 2E‐dodecenal, both with each MBC of 6.25 µg/mL. Their primary antibacterial action against S. choleraesuis provably comes from their ability to function as nonionic surface‐active agents (surfactants), disrupting the native function of integral membrane proteins nonspecifically. Thus, the antibacterial activity is mediated by biophysical processes. In the case of 2E‐alkenals, a biochemical mechanism is also somewhat involved, depending on their alkyl chain length. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:21:30.240534-05:
      DOI: 10.1002/ptr.5351
  • The Antiinflammatory Properties of Humic Substances: A Mini Review
    • Authors: Constance E. J. Rensburg
      Pages: 791 - 795
      Abstract: Humic substances are effective in the suppression of delayed type hypersensitivity, rat paw oedema, a graft‐versus‐host reaction and contact hypersensitivity in rats. They reduce the C‐reactive protein levels of patients suffering from osteoarthritis of the knee and the wheel and flare reaction of patients suffering from hay fever. They have also been described as cardioprotective and pro‐angiogenic. Toxicity studies have indicated that potassium humate is safe in humans up to a daily dosage of 1 g/kg, whereas fulvic acid is safe in humans up to a daily dosage of 1.8 g per adult. The antiinflammatory action of potassium humate can be contributed to the inhibition of the release of inflammatory‐related cytokines, an adhesion molecule, oxidants and components of the complement system. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-03T02:27:47.336031-05:
      DOI: 10.1002/ptr.5319
  • Review of the Safety and Efficacy of Moringa oleifera
    • Authors: Sidney J. Stohs; Michael J. Hartman
      First page: 796
      Abstract: Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti‐hyperglycemic (antidiabetic) and anti‐dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
      PubDate: 2015-03-24T01:44:35.928976-05:
      DOI: 10.1002/ptr.5325
  • A Review: Phytochemicals Targeting JAK/STAT Signaling and IDO Expression
           in Cancer
    • Authors: Niroshaathevi Arumuggam; Neil A. Bhowmick, H. P. Vasantha Rupasinghe
      First page: 805
      Abstract: Cancer remains a major health problem worldwide. Among many other factors, two regulatory defects that are present in most cancer cells are constitutive activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and the induction of indoleamine 2, 3‐dioxygenase (IDO), an enzyme that catalyzes tryptophan degradation, through JAK/STAT signaling. Cytokine signaling activates STAT proteins in regulating cell proliferation, differentiation, and survival through modulation of target genes. Many phytochemicals can inhibit both JAK/STAT signaling and IDO expression in antigen‐presenting cells by targeting different pathways. Some of the promising phytochemicals that are discussed in this review include resveratrol, cucurbitacin, curcumin, (−)‐epigallocatechin gallate, and others. It is now evident that phytochemicals play key roles in inhibition of tumor proliferation and development and provide novel means for therapeutic targeting of cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-18T03:15:55.781213-05:
      DOI: 10.1002/ptr.5327
  • Antioxidant, Anti‐inflammatory, and Chemoprotective Properties of
           Acacia catechu Heartwood Extracts
    • Authors: Sidney J. Stohs; Debasis Bagchi
      First page: 818
      Abstract: Aqueous extracts of Acacia catechu heartwood are rich source of catechin and epicatechin (gallic acid derivatives), with smaller amounts of flavonoids. Extracts have also been prepared with ethyl acetate, ethanol, and methanol, and the properties of these extracts have been studied and are reviewed. Potent antioxidant activity has been well established in both in vitro and in vivo studies. This antioxidant activity is believed to be responsible for the anti‐inflammatory, tissue protectant, antineoplastic, and analgesic activities that have been demonstrated and clearly established in animal and cell culture systems. Furthermore, antihyperglycemic, antidiarrheal, antinociceptive, and antipyretic activities have been demonstrated in animal studies. No adverse effects have been observed in animal or human studies or in cell culture systems. In spite of the fact that Acacia products have been used for many years and the general safety of catechins and epicatechins is well documented, few human studies have ever been conducted on the efficacy or safety of A. catechu heartwood extracts. Several studies have shown that a two‐ingredient combination product containing A. catechu extract exhibited no adverse effects when administered daily for up to 12 weeks while exhibiting significant anti‐inflammatory activity in subjects with osteoarthritis of the knee. There is a need for additional human clinical studies with regard to efficacy and safety. © 2015 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2015-03-20T07:43:27.697385-05:
      DOI: 10.1002/ptr.5335
  • Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from
           Traditional Chinese Herbs
    • Authors: Yong Zhao; Bent Håvard Hellum, Aihua Liang, Odd Georg Nilsen
      Pages: 825 - 834
      Abstract: The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed by time‐dependent and nicotinamide adenine dinucleotide phosphate‐dependent and reversible inhibition by Lineweaver–Burk plot assessments. Inhibition mechanisms were also assessed by computerized interaction prediction by using the Discovery Studio CDOCKER software (Accelrys, San Diego, CA, USA). Tetrahydropalmatine showed a mechanism‐based inhibition of both CYP1A2 and CYP2D6, and Ber of CYP2D6. Neferine and Ber both showed a nonmechanistic inhibition of CYP1A2. All compounds showed a similar and significant mechanism‐based inhibition of CYP3A4. Tetrahydropalmatine and Ber demonstrated both reversible and irreversible inhibition of CYP2D6 and CYP3A4. Tetrahydropalmatine and Ber displayed H‐bond and several Pi‐bond connections with specific amino acid residues of CYP1A2, CYP2D6 and CYP3A4, giving further knowledge to the identified reversible and irreversible herb–drug interactions. Tetrahydropalmatine and Ber should be considered for herb–drug interactions in clinical therapy until relevant clinical studies are available. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T03:03:13.149626-05:
      DOI: 10.1002/ptr.5285
  • Therapeutic Potential of Resveratrol in Type I Gaucher Disease
    • Authors: Cheong Hoon Seo; June‐Bum Kim
      Pages: 835 - 839
      Abstract: Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti‐inflammatory, anti‐oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis‐inducing factor (AIF), Bax, cleaved caspase‐3, acetyl‐coenzyme A acetyltransferase 1 (ACAT1), E3‐binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol‐treated patient cells were determined by thin‐layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase‐3 dose‐dependently decreased, while those of ACAT1, E3BP, and CS dose‐dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:54:46.076223-05:
      DOI: 10.1002/ptr.5304
  • Enhanced HIV‐1 Reverse Transcriptase Inhibitory and Antibacterial
           Properties in Callus of Catha edulis Forsk.
    • Authors: Aloka Kumari; Ponnusamy Baskaran, Johannes Van Staden
      Pages: 840 - 843
      Abstract: Developing tissue culture systems for medicinal plants is important in that they may offer an alternative to protect wild populations. However, analysis of bioactivity for tissue culture developed plant tissues is required to offer support and allow acceptance in traditional medicine. The use of propagated callus could provide potential material for therapeutic purposes. This study was aimed at evaluating the anti‐HIV and antibacterial properties of a three‐month‐old tissue culture‐derived calli and leaves of cultivated mother plants of Catha edulis Forsk. The calli were derived from leaf explants using different plant growth regulators. The calli obtained from callus cultured on 9.8 μM indole‐3‐butyric acid plus 2.7 μM naphthalene acetic acid exhibited the highest HIV‐1 reverse transcriptase inhibitory effects when compared with other treatments and the mother plants. Different extracts of callus exhibited high antibacterial activity (
      PubDate: 2015-03-06T07:47:20.630215-05:
      DOI: 10.1002/ptr.5318
  • Apoptotic Effect of Galbanic Acid via Activation of Caspases and
           Inhibition of Mcl‐1 in H460 Non‐Small Lung Carcinoma Cells
    • Authors: Bum‐Seok Oh; Eun Ah Shin, Ji Hoon Jung, Deok‐Beom Jung, Bonglee Kim, Bum Sang Shim, Mahsa Chitsazian Yazdi, Mehrdad Iranshahi, Sung‐Hoon Kim
      Pages: 844 - 849
      Abstract: Galbanic acid (GBA), a major compound of Ferula assafoetida, was known to have cytotoxic, anti‐angiogenic and apoptotic effects in prostate cancer and murine Lewis lung cancer cells; the underling apoptotic mechanism of GBA still remains unclear so far. Thus, in the present study, the apoptotic mechanism of GBA was investigated mainly in H460 non‐small cell lung carcinoma (NSCLC) cells because H460 cells were most susceptible to GBA than A549, PC‐9 and HCC827 NSCLC cells. Galbanic acid showed cytotoxicity in wild EGFR type H460 and A549 cells better than other mutant type PC‐9 and HCC827 NSCLC cells. Also, GBA significantly increased the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and sub G1 population in H460 cells. Western blotting revealed that GBA cleaved poly (ADP‐ribose) polymerase (PARP), activated Bax and caspase 9, attenuated the expression of Bcl‐2, Bcl‐xL, and Myeloid cell leukemia 1 (Mcl‐1) in H460 cells. However, interestingly, overexpression of Mcl‐1 blocked the ability of GBA to exert cytotoxicity, activate caspase9 and Bax, cleave PARP, and increase sub G1 accumulation in H460 cells. Overall, these findings suggest that GBA induces apoptosis in H460 cells via caspase activation and Mcl‐1 inhibition in H460 cells as a potent anticancer agent for NSCLC treatment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-06T06:57:33.9375-05:00
      DOI: 10.1002/ptr.5320
  • Antiinflammatory and Wound Healing Effects of Caesalpinia sappan L.
    • Authors: Supinya Tewtrakul; Pattreeya Tungcharoen, Teeratad Sudsai, Chatchanok Karalai, Chanita Ponglimanont, Orapun Yodsaoue
      First page: 850
      Abstract: Extracted compounds from Caesalpinia sappan L. were examined for the inhibitory activity against NO, PGE2, and TNF‐α productions and on associated transcription levels using RAW264.7 cells. They were also tested for their effects on wound healing using fibroblast L929 cells. Among the compounds tested, brazilin (8) was the most effective against lipopolysaccharide (LPS)‐induced NO production in RAW264.7 cells with an IC50 value of 10.3 μM, followed by sappanchalcone (2, 31.0 μM). Brazilin (8) also inhibited PGE2 and TNF‐α production with IC50 values of 12.6 and 87.2 μM, respectively. The antiinflammatory mechanism of brazilin involved down regulation of the mRNA expressions of the iNOS, COX‐2, and TNF‐α genes in a dose‐dependent manner. An ethanol (EtOH) extract of C. sappan significantly increased fibroblast proliferation, fibroblast migration, and collagen production, whereas brazilin (8) only stimulated fibroblast migration. In addition, the EtOH extract showed no acute toxicity in mice, and it was therefore safe to make use of its potent antiinflammatory and wound healing activities. Brazilin was mainly responsible for its antiinflammatory effect through its ability to inhibit the production of NO, PGE2, and TNF‐α. This study supports the traditional use of C. sappan for treatment of inflammatory‐related diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T05:48:03.497675-05:
      DOI: 10.1002/ptr.5321
  • Inhibition of Cancer Cell Proliferation and Antiradical Effects of
           Decoction, Hydroalcoholic Extract, and Principal Constituents of
           Hemidesmus indicus R. Br.
    • Authors: Giancarlo Statti; Mariangela Marrelli, Filomena Conforti, Antonella Spagnoletti, Massimo Tacchini, Carmela Fimognari, Eleonora Brognara, Roberto Gambari, Gianni Sacchetti, Alessandra Guerrini
      First page: 857
      Abstract: Indian Sarsaparilla (Hemidesmus indicus R. Br.) is widely used in Indian traditional medicine. In the present work, we explored the effects of decoction, traditional Ayurvedic preparation, and hydroalcoholic extract, a phytocomplex more traditionally studied and commercialized as food supplement in western medicine, from the roots as possible source of chemicals with new functional potential linked to their nutritional uses. The antiproliferative and antioxidant properties were assayed. To test antiproliferative affects, different cancer cell lines, growing both as monolayers (CaCo2, MCF‐7, A549, K562, MDA‐MB‐231, Jurkat, HepG2, and LoVo) and in suspension (K562 and Jurkat) were used. The decoction showed strong activity on HepG2 cells, while the hydroalcoholic extracts were active on HepG2, LoVo, MCF‐7, K562, and Jurkat cell lines. Weak inhibition of cancer cell proliferation was observed for the principal constituents of the preparations: 2‐hydroxy‐4‐methoxybenzaldehyde, 2‐hydroxy‐4‐methoxybenzoic acid, and 3‐hydroxy‐4‐methoxybenzaldehyde that were tested alone. The antiradical activity was tested with 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid)diammonium salt tests and inhibition of nitric oxide production in lipopolysaccharide‐stimulated RAW 264.7 macrophages. Interesting result has also been obtained for hydroalcoholic extract regarding genoprotective potential (58.79% of inhibition at 37.5 µg/mL). Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-06T08:14:13.939725-05:
      DOI: 10.1002/ptr.5322
  • A Clinical Trial with Brazilian Arnica (Solidago chilensis Meyen) Glycolic
           Extract in the Treatment of Tendonitis of Flexor and Extensor Tendons of
           Wrist and Hand
    • Authors: Ary Gomes Silva; Elbe Rodrigues Machado, Leonardo Mendes Almeida, Ricardo Marcelo Menezes Nunes, Patrícia Caldeira Pena Giesbrecht, Regina Mamed Costa, Helber B. Costa, Wanderson Romão, Ricardo Machado Kuster
      First page: 864
      Abstract: One of the Brazilian arnicas, Solidago chilensis Meyen, is a species of the Asteraceae family. This plant is known by this common name because it shares remarkably similar organoleptic properties with the genus Arnica L., also within the family Asteraceae. We examined the effectiveness of the S. chilensis fluid extract used externally for treating tendinitis of flexor and extensor tendons of wrist and hand in placebo‐controlled double‐blind clinical pharmacological studies. This study was approved by the Ethical Committee for Scientific Research in Human Beings at University Vila Velha‐UVV. Two daily skin applications on the arm skin of a gel cream containing a 5% glycolic plant extract were administered to eight volunteers for 21 days. Among the volunteers, one of their arms was used as the placebo group, and the other one was used as a test group. Statistical data analyses demonstrated a significant reduction in the perception of pain in the arms in the test group, when it was compared to those receiving only the placebo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T06:17:17.000478-05:
      DOI: 10.1002/ptr.5323
  • The Androgenic Alopecia Protective Effects of Forsythiaside‐A and
           the Molecular Regulation in a Mouse Model
    • Authors: Heon‐Sub Shin; Sang‐Yong Park, Hyun‐Geun Song, Eunson Hwang, Don‐Gil Lee, Tae‐Hoo Yi
      First page: 870
      Abstract: This study examined the inhibitory effect of forsythiaside‐A, a natural substance derived from Forsythia suspensa (F. suspensa), on entry into catagen induced by dihydrotestosterone (DHT) in an androgenic alopecia mouse model. In vitro experiment comparing finasteride with forsythiaside‐A showed that forsythiaside‐A treatment resulted in a 30% greater inhibition of DHT‐induced apoptosis in human hair dermal papilla cell (HHDPCs) and human keratinocytes (HaCaTs). In vivo experiment showed that mouse hair density and thickness were increased by 50% and 30%, respectively, in the forsythiaside‐A‐treated group when compared to a DHT group. Tissue histological results revealed that the forsythiaside‐A‐treated group had an increase in size and shape of the hair follicles and a 1.5 times increase in the follicle anagen/telogen ratio when compared to the finasteride group. Western blot examination of TGF‐β2 expression related to apoptosis signaling in mouse skin verified that forsythiaside‐A reduced the expression of TGF‐β2 by 75% and suppressed apoptosis by reducing the expression of caspase‐9 by 40%, and caspase‐3 by 53%, which play an roles up‐regulator in the apoptosis signal. The forsythiaside‐A group also showed a 60% increase in the Bcl‐2/Bax ratio, which is a factor related to mitochondrial apoptosis. Our results indicated that forsythiaside‐A prevents apoptosis by similar mechanism with finasteride, but forsythiaside‐A is more effective than finasteride. In summary, forsythiaside‐A controlled the apoptosis of hair cells and retarded the entry into the catagen phase and therefore represents a natural product with much potential for use as a treatment for androgenic alopecia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T01:27:46.476074-05:
      DOI: 10.1002/ptr.5324
  • Multiple Biological Effects of Olive Oil By‐products such as Leaves,
           Stems, Flowers, Olive Milled Waste, Fruit Pulp, and Seeds of the Olive
           Plant on Skin
    • Authors: Asuka Kishikawa; Ahmed Ashour, Qinchang Zhu, Midori Yasuda, Hiroya Ishikawa, Kuniyoshi Shimizu
      First page: 877
      Abstract: As olive oil production increases, so does the amount of olive oil by‐products, which can cause environmental problems. Thus, new ways to utilize the by‐products are needed. In the present study, five bioactive characteristics of olive oil by‐products were assessed, namely their antioxidant, anti‐bacterial, anti‐melanogenesis, anti‐allergic, and collagen‐production‐promoting activities. First, the extracts of leaves (May and October), stems (May and October), flowers, olive milled waste, fruit pulp and seeds were prepared using two safe solvents, ethanol and water. According to HPLC and LC/MS analysis and Folin–Ciocalteu assay, the ethanol extracts of the leaves (May and October), stems (May and October) and flowers contained oleuropein, and the ethanol extract of the stems showed the highest total phenol content. Oleuropein may contribute to the antioxidant and anti‐melanogenesis activities of the leaves, stems, and flowers. However, other active compounds or synergistic effects present in the ethanol extracts are also likely to contribute to the anti‐bacterial activity of the leaves and flowers, the anti‐melanogenesis activity of some parts, the anti‐allergic activity of olive milled waste, and the collagen‐production‐promoting activity of the leaves, stems, olive milled waste and fruit pulp. This study provides evidence that the by‐products of olive oil have the potential to be further developed and used in the skin care industry. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-16T04:52:23.460242-05:
      DOI: 10.1002/ptr.5326
  • The Effects of Pre‐Exercise Ginger Supplementation on Muscle Damage
           and Delayed Onset Muscle Soreness
    • Authors: Melissa D. Matsumura; Gerald S. Zavorsky, James M. Smoliga
      First page: 887
      Abstract: Ginger possesses analgesic and pharmacological properties mimicking non‐steroidal antiinflammatory drugs. We aimed to determine if ginger supplementation is efficacious for attenuating muscle damage and delayed onset muscle soreness (DOMS) following high‐intensity resistance exercise. Following a 5‐day supplementation period of placebo or 4 g ginger (randomized groups), 20 non‐weight trained participants performed a high‐intensity elbow flexor eccentric exercise protocol to induce muscle damage. Markers associated with muscle damage and DOMS were repeatedly measured before supplementation and for 4 days following the exercise protocol. Repeated measures analysis of variance revealed one repetition maximum lift decreased significantly 24 h post‐exercise in both groups (p 
      PubDate: 2015-03-18T05:34:13.795414-05:
      DOI: 10.1002/ptr.5328
  • The Lignan Pinoresinol Induces Nuclear Translocation of DAF‐16 in
           Caenorhabditis elegans but has No Effect on Life Span
    • Authors: Karoline Koch; Christian Büchter, Susannah Havermann, Wim Wätjen
      First page: 894
      Abstract: The lignan pinoresinol is a constituent of flaxseed, sesame seeds and olive oil. Because of different molecular effects reported for this compound, e.g. antioxidative activity, pinoresinol is suggested to cause positive effects on humans. Because experimental data are limited, we have analysed the effects of the lignan on the nematode Caenorhabditis elegans: in spite of a strong antioxidative capacity detected in an in vitro assay, no antioxidative effects were detectable in vivo. In analogy to this result, no modulation of the sensitivity against thermal stress was detectable. However, incubation with pinoresinol caused an enhanced nuclear accumulation of the transcription factor DAF‐16 (insulin/IGF‐like signalling pathway). Using a strain with an enhanced oxidative stress level (mev‐1 mutant), we clearly see an increase in stress resistance caused by this lignan, but no change in reactive oxygen species. Furthermore, we investigated the effects of pinoresinol on the life span of the nematode, but no modulation was found, neither in wild‐type nor in mev‐1 mutant nematodes. These results suggest that pinoresinol may exert pharmacologically interesting effects via modulation of the insulin‐like signalling pathway in C. elegans as well as in other species like mammals due to the evolutionary conservation of this signalling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:06:03.508341-05:
      DOI: 10.1002/ptr.5330
  • Effects of Glucosinolates from Turnip (Brassica rapa L.) Root on Bone
           Formation by Human Osteoblast‐Like MG‐63 Cells and in Normal
           Young Rats
    • Authors: Jaehoon Jeong; Heajin Park, Hanbit Hyun, Jihye Kim, Haesung Kim, Hyun Il Oh, Hye Seong Hwang, Dae Kyong Kim, Ha Hyung Kim
      First page: 902
      Abstract: Turnip (Brassica rapa L.) root ethanol extract (TRE) was prepared, and its chemical constituents were characterized by ultra‐performance liquid chromatography and mass spectrometry. Thirteen glucosinolates (GSLs) were identified, comprising eight aliphatic, four indolic, and one aromatic compounds. The effects of these GSLs on bone formation were investigated in vitro by incubating human osteoblast‐like MG‐63 cells with TRE and then analyzing their viability, alkaline phosphatase (ALP) activity, collagen content, and mineralization and in vivo by administering TRE orally to normal young rats (500 mg/kg/day) and assessing subsequent changes in serum osteocalcin and bone microstructure in these animals. No TRE‐related toxicity was found, and the levels of cell viability, ALP activity, collagen synthesis, and mineralization were significantly increased relative to the negative control. In particular, stimulatory effects on the differentiation of MG‐63 cells were strongly enhanced as compared with a positive control (daidzein). Serum osteocalcin was also significantly increased, and some important bone microstructural parameters were improved in TRE‐administered rats compared with their saline‐administered counterparts. GSLs therefore appear to have a stimulatory effect on bone formation in both MG‐63 cells and normal young rats. This is the first report on the usefulness of turnip root and its GSL compounds for bone formation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T02:10:27.977479-05:
      DOI: 10.1002/ptr.5331
  • Cytoprotective and Anti‐secretory Effects of Azadiradione Isolated
           from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat
    • Authors: Rohit Singh; Vaibhav Mishra, Sukanya Pandeti, Gautam Palit, Manoj K. Barthwal, Haushila Prasad Pandey, Tadigoppula Narender
      First page: 910
      Abstract: Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in‐vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+‐ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T00:57:41.815633-05:
      DOI: 10.1002/ptr.5332
  • Castalagin Exerts Inhibitory Effects on Osteoclastogenesis Through
           Blocking a Broad Range of Signaling Pathways with Low Cytotoxicity
    • Authors: Mayumi Iwatake; Kuniaki Okamoto, Takashi Tanaka, Takayuki Tsukuba
      First page: 917
      Abstract: Castalagin is a rare plant polyphenol that is classified as a hydrolyzable tannin. Although it has antioxidant, antitumorigenic, and leishmanicidal effects, the utility of castalagin against bone diseases remain to be elucidated. Here, we investigated the effects of castalagin on the differentiation of osteoclasts (OCLs), multinucleated bone‐resorbing cells. After stimulation with receptor activator of nuclear factor kappa‐B ligand (RANKL), the formation of OCLs from bone marrow‐derived macrophages was significantly inhibited by castalagin even at 1 μM. However, castalagin displayed little cytotoxicity at a higher concentration of 50 μM. The effects of castalagin on intracellular signaling during OCL differentiation showed that castalagin suppresses RANKL‐stimulated phosphorylation of major signaling pathways including protein kinase B (Akt), extracellular signal‐regulated kinase, Jun N‐terminal kinase, p38 mitogen‐activated protein kinases, and inhibitor of nuclear factor kappa B alpha. Moreover, following castalagin treatment, the protein levels of nuclear factor of activated T‐cells, cytoplasmic 1, a master regulator for OCL differentiation, and NF‐κB were decreased. Thus, castalagin exerts inhibitory effects on osteoclastogenesis through blockage of a broad range of signaling pathways, but has low cytotoxicity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T02:35:46.223762-05:
      DOI: 10.1002/ptr.5333
  • The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene
           Expression, Production, and Secretion via Regulation of NF‐κB,
           STAT6, and HDAC2
    • Authors: Changda Liu; David Weir, Paula Busse, Nan Yang, Zhenwen Zhou, Charles Emala, Xiu‐Min Li
      First page: 925
      Abstract: Mucus overproduction is a significant component of the pathophysiology of obstructive lung diseases. Currently, there are only a few medications available that inhibit mucus production. Previous studies showed that glycyrrhizin, a triterpenoid in Glycyrrhiza uralensis inhibits mucin 5AC (MUC5AC) mRNA and protein expression. Other potential mucus production inhibitory compounds contained within in G. uralensis have not been fully investigated. The aim of the present study was to determine if the G. uralensis flavonoid 7,4′‐dihydroxyflavone (7,4′‐DHF) inhibits MUC5AC gene expression, mucus production, and secretion, and if so, to elucidate the mechanism of this inhibition. 7,4′‐Dihydroxyflavone significantly decreased phorbol 12‐myristate 13‐acetate‐stimulated NCI‐H292 human airway epithelial cell MUC5AC gene expression and mucus production, at a 28‐fold lower concentration than glycyrrhizin (The half maximal inhibitory concentration IC50 value of 1.4 μM vs 38 μM, respectively); 7,4′‐DHF also inhibited MUC5AC mucus secretion. Inhibition was associated with the suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), signal transducer and activator of transcription 6 (STAT6) activation, and enhanced histone deacetylase 2 (HDAC2) expression. In a murine model of asthma, 7,4′‐DHF‐treated mice exhibited a marked reduction in MUC5AC secretion in the bronchoalveolar lavage fluid compared with control mice. These findings, together with previous findings linking NF‐κB, STAT6, and HDAC2 modulation to the control of MUC5AC expression, demonstrate that 7,4′‐DHF is a newly identified component of G. uralensis that regulates MUC5AC expression and secretion via regulation of NF‐κB, STAT6, and HDAC2. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-23T02:33:11.505342-05:
      DOI: 10.1002/ptr.5334
  • Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by
           Ischemia in H9c2 Cells Via Antioxidant Potential
    • Authors: P. L. Reshma; V. S. Lekshmi, Vandana Sankar, K. G. Raghu
      First page: 933
      Abstract: Tribulus terrestris L. was evaluated for its cardioprotective property against myocardial ischemia in a cell line model. Initially, methanolic extract was prepared and subjected to sequential extraction with various solvents. The extract with high phenolic content (T. terrestris L. ethyl acetate extract–TTME) was further characterized for its chemical constituents and taken forward for evaluation against cardiac ischemia. HPLC analysis revealed the presence of phenolic compounds like caffeic acid (12.41 ± 0.22 mg g−1), chlorogenic acid (0.52 ± 0.06 mg g−1) and 4‐hydroxybenzoic acid (0.60 ± 0.08 mg g−1). H9c2 cells were pretreated with TTME (10, 25, 50 and 100 µg/ml) for 24 h before the induction of ischemia. Then ischemia was induced by exposing cells to ischemia buffer, in a hypoxic chamber, maintained at 0.1% O2, 95% N2 and 5% CO2, for 1 h. A significant (p ≤ 0.05) increase in reactive oxygen species generation (56%), superoxide production (18%), loss of plasma membrane integrity, dissipation of transmembrane potential, permeability transition pore opening and apoptosis had been observed during ischemia. However, pretreatment with TTME was found to significantly (p ≤ 0.05) attenuate the alterations caused by ischemia. The overall results of this study partially reveal the scientific basis of the use of T. terrestris L. in the traditional system of medicine for heart diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T01:30:58.838259-05:
      DOI: 10.1002/ptr.5336
  • Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different
           Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung
           Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells
    • Authors: Norazah Basar; Olayinka Ayotunde Oridupa, Kenneth J. Ritchie, Lutfun Nahar, Nashwa Mostafa M. Osman, Angela Stafford, Habibjon Kushiev, Asuman Kan, Satyajit D. Sarker
      First page: 944
      Abstract: Glycyrrhiza glabra L. (Fabaceae), commonly known as ‘liquorice’, is a well‐known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet‐tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-16T04:30:00.739637-05:
      DOI: 10.1002/ptr.5329
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