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

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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  [1608 journals]
  • Comparative Study of the Biological Activity of Allantoin and Aqueous
           Extract of the Comfrey Root
    • Authors: Vesna Lj. Savić; Vesna D. Nikolić, Ivana A. Arsić, Ljiljana P. Stanojević, Stevo J. Najman, Sanja Stojanović, Ivana I. Mladenović‐Ranisavljević
      Abstract: This study investigates the biological activity of pure allantoin (PA) and aqueous extract of the comfrey (Symphytum officinale L.) root (AECR) standardized to the allantoin content. Cell viability and proliferation of epithelial (MDCK) and fibroblastic (L929) cell line were studied by using MTT test. Anti‐irritant potential was determined by measuring electrical capacitance, erythema index (EI) and transepidermal water loss of artificially irritated skin of young healthy volunteers, 3 and 7 days after application of creams and gels with PA or AECR. Pure allantoin showed mild inhibitory effect on proliferation of both cell lines at concentrations 40 and 100 µg/ml, but more pronounced on MDCK cells. Aqueous extract of the comfrey root effect on cell proliferation in concentrations higher than 40 µg/ml was significantly stimulatory for L929 but inhibitory for MDCK cells. Pharmaceutical preparations that contained AECR showed better anti‐irritant potential compared with PA. Creams showed better effect on hydration and EI compared with the gels that contained the same components. Our results indicate that the biological activity of the comfrey root extract cannot be attributed only to allantoin but is also likely the result of the interaction of different compounds present in AECR. Topical preparations that contain comfrey extract may have a great application in the treatment of skin irritation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:53:15.399453-05:
      DOI: 10.1002/ptr.5356
  • Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate
           the Oral Wound Healing in Rats
    • Authors: Fernanda Hack Coelho; Gabriela Salvadori, Pantelis Varvaki Rados, Alessandra Magnusson, Chris Krebs Danilevicz, Luise Meurer, Manoela Domingues Martins
      Abstract: The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3‐mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re‐epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi‐quantitative analyses, was performed using the Kruskal–Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:22:45.2721-05:00
      DOI: 10.1002/ptr.5352
  • Activation of Caspase‐9/3 and Inhibition of Epithelial Mesenchymal
           Transition are Critically Involved in Antitumor Effect of Phytol in
           Hepatocellular Carcinoma Cells
    • Authors: Chul‐Woo Kim; Hyun Joo Lee, Ji Hoon Jung, Yoon Hyeon Kim, Deok‐Beom Jung, Eun Jung Sohn, Jang Hoon Lee, Hong Jung Woo, Nam‐In Baek, Young Chul Kim, Sung‐Hoon Kim
      Abstract: This study was designed to investigate the antitumor mechanism of Phytol in hepatocellular carcinomas including Huh7 and HepG2 cells in association with caspase dependent apoptosis and epithelial mesenchymal transition (EMT) signaling. Phytol significantly suppressed the viability of Huh7 and HepG2 cells. Also, Phytol significantly increased the sub G1 population and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) positive cells in a concentration dependent manner in Huh7 and HepG2 cells. Consistently, Phytol cleaved poly (adenosine diphosphate‐ribose) polymerase (PARP), activated caspase‐9/3, and Bax attenuated the expression of survival genes such as Bcl‐2, Mcl‐1, and c‐Myc in Huh7 and HepG2 cells. Of note, Phytol also suppressed typical morphology change of EMT such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in HepG2 cells. Furthermore, Phytol also reversed the loss of E‐cadherin and overexpression of p‐smad2/3, alpha‐smooth muscle actin, and Snail induced by EMT promoter transforming growth factor beta1 in HepG2 cells. Overall, our findings suggest that Phytol exerts antitumor activity via apoptosis induction through activation of caspas‐9/3 and inhibition of EMT in hepatocellular carcinoma cells as a potent anticancer candidate for liver cancer treatment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T02:54:00.055236-05:
      DOI: 10.1002/ptr.5342
  • Role of Hydroxytyrosol‐dependent Regulation of HO‐1 Expression
           in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo
           Synthesis and Stabilization
    • Authors: Houda Zrelli; Miki Kusunoki, Hitoshi Miyazaki
      Abstract: Hydroxytyrosol (HT), an olive plant (Olea europaea L.) polyphenol, has proven atheroprotective effects. We previously demonstrated that heme oxygenase‐1 (HO‐1) is involved in the HT dependent prevention of dysfunction induced by oxidative stress in vascular endothelial cells (VECs). Here, we further investigated the signaling pathway of HT‐dependent HO‐1 expression in VECs. HT dose‐ and time‐dependently increased HO‐1 mRNA and protein levels through the PI3K/Akt and ERK1/2 pathways. Cycloheximide and actinomycin D inhibited both increases, suggesting that HT‐triggered HO‐1 induction is transcriptionally regulated and that de novo protein synthesis is necessary for this HT effect. HT stimulated nuclear accumulation of nuclear factor E2‐related factor 2 (Nrf2). This Nrf2 accumulation was blocked by actinomycin D and cycloheximide whereas HT in combination with the 26S proteasome inhibitor MG132 enhanced the accumulation. HT also extended the half‐life of Nrf2 proteins by decelerating its turnover. Moreover, HO‐1 inhibitor, ZnppIX and CO scavenger, hemoglobin impaired HT‐dependent wound healing while CORM‐2, a CO generator, accelerated wound closure. Together, these data demonstrate that HT upregulates HO‐1 expression by stimulating the nuclear accumulation and stabilization of Nrf2, leading to the wound repair of VECs crucial in the prevention of atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:47:03.200679-05:
      DOI: 10.1002/ptr.5339
  • Anti‐Salmonella Activity of Volatile Compounds of Vietnam Coriander
    • Authors: Ken‐ichi Fujita; Warinthorn Chavasiri, Isao Kubo
      Abstract: Essential oil derived from the fresh leaves of Polygonum odoratum Lour was tested for their effects on a foodborne bacterium Salmonella choleraesuis subsp. choleraesuis ATCC 35640 using a broth dilution method. This essential oil showed a significant antibacterial activity against S. choleraesuis at the concentration of 200 µg/mL. Twenty‐five volatile compounds were characterized from this essential oil by GC‐MS, and aldehyde compounds were found abundant and accounted for more than three‐fourths of the essential oil. Among the compounds characterized, dodecanal (C12) was the most abundant (55.5%), followed by decanal (C10) (11.6%). Both alkanals were effective against S. choleraesuis with the minimum growth inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 100 µg/mL. The most potent antibacterial activity against this bacterium was found with two minor compounds, dodecanol (lauryl alcohol) and 2E‐dodecenal, both with each MBC of 6.25 µg/mL. Their primary antibacterial action against S. choleraesuis provably comes from their ability to function as nonionic surface‐active agents (surfactants), disrupting the native function of integral membrane proteins nonspecifically. Thus, the antibacterial activity is mediated by biophysical processes. In the case of 2E‐alkenals, a biochemical mechanism is also somewhat involved, depending on their alkyl chain length. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:21:30.240534-05:
      DOI: 10.1002/ptr.5351
  • In vitro and in vivo Bone‐Forming Activity of Saururus chinensis
    • Authors: Seong‐Hee Moon; Sik‐Won Choi, Sang‐Joon Park, Shi‐Yong Ryu, Kyu‐Seok Hwang, Cheol‐Hee Kim, Seong Hwan Kim
      Abstract: Bone is maintained by osteoclast‐mediated resorption and osteoblast‐mediated formation. Recently, anti‐osteoporotic activity of Saururus chinensis extract (SCE) and anti‐osteoclastogenic activity of its components have been reported, but the effect of SCE on bone formation has not been studied well. Therefore, in this study, we investigated whether Saururus chinensis SCE exhibits in vitro osteogenic and in vivo bone‐forming activity. extract strongly enhanced the bone morphogenetic protein (BMP)‐2‐stimulated induction of alkaline phosphatase, an early phase biomarker of osteoblast differentiation, in bi‐potential mesenchymal progenitor C2C12 cells. In vitro osteogenic activity of SCE was accompanied by enhanced expression of BMP‐2, BMP‐4, BMP‐7 and BMP‐9 mRNA. In addition, a pharmacological inhibition study suggested the involvement of p38 activation in the osteogenic action of SCE. Moreover, the BMP dependency and the involvement of p38 activation in the osteogenic action of SCE were confirmed by the treatment of noggin, an antagonist of BMP. Saururus chinensis extract also exhibited to induce runt‐related transcription factor 2 activation at the high concentration. Furthermore, the in vivo osteogenic activity of SCE was confirmed in zebrafish and mouse calvarial bone formation models, suggesting the possibility of its use for bone formation. In conclusion, we suggested that in vivo anti‐osteoporotic activity of SCE could be because of its dual action in bone, anti‐osteoclastogenic and anabolic activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-14T01:06:19.190115-05:
      DOI: 10.1002/ptr.5349
  • Hypericum perforatum Reduces Paracetamol‐Induced Hepatotoxicity and
           Lethality in Mice by Modulating Inflammation and Oxidative Stress
    • Authors: Miriam S. N. Hohmann; Renato D. R. Cardoso, Victor Fattori, Nilton S. Arakawa, José C. Tomaz, Norberto P. Lopes, Rubia Casagrande, Waldiceu A. Verri
      Abstract: Hypericum perforatum is a medicinal plant with anti‐inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)‐induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15–3.0 g/kg, p.o.) induced dose‐dependent mortality. The sub‐maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30–300 mg/kg, i.p.) dose‐dependently reduced paracetamol‐induced lethality. Paracetamol‐induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL‐1β, TNF‐α, and IFN‐γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonate radical cation; ABTS˙+) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol‐induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol‐induced cytokine production, neutrophil recruitment, and oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T04:21:33.002971-05:
      DOI: 10.1002/ptr.5350
  • Korean Red Ginseng Extract Enhances the Anticancer Effects of Imatinib
    • Authors: Sang Yoon Jung; Chulwon Kim, Wan‐Seok Kim, Seok‐Geun Lee, Jun‐Hee Lee, Bum Sang Shim, Sung‐Hoon Kim, Kyoo Seok Ahn, Kwang Seok Ahn
      Abstract: Although imatinib mesylate (IM) in the treatment of chronic myelogenous leukemia (CML) remains the best example of successful targeted therapy, majority of patients with CML suffer its toxicity profile and develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of CML. Here, we investigated whether Korean red ginseng extract (KRGE) could suppress the proliferation and induce chemosensitization in human CML cells. Also, we used a human phospho‐antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after treatment. Korean red ginseng extract broadly suppressed the proliferation of five different cell lines, but KRGE was found to be the most potent inducer of apoptosis against KBM‐5 cells. It also abrogated the expression of Bcl‐2 (B‐cell lymphoma 2), Bcl‐xL (B‐cell lymphoma‐extra large), survivin, inhibitors of apoptosis protein 1/2, COX‐2 (Cyclooxygenase‐2), cyclin D1, matrix metalloproteinase‐9, and VEGF (Vascular endothelial growth factor), as well as upregulated the expression of pro‐apoptotic gene products. Interestingly, KRGE also enhanced the cytotoxic and apoptotic effect of IM in KBM‐5 cells. The combination treatment of KRGE and IM caused pronounced suppression of p38 and signal transducer and activator of transcription 5 phosphorylation and induced phosphorylation of p53 compared with the individual treatment. Our results demonstrate that KRGE can enhance the anticancer activity of IM and may have a substantial potential in the treatment of CML. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T02:27:14.326739-05:
      DOI: 10.1002/ptr.5347
  • Some South African Rubiaceae Tree Leaf Extracts Have Antimycobacterial
           Activity Against Pathogenic and Non‐pathogenic Mycobacterium Species
    • Authors: Abimbola O. Aro; Jean P. Dzoyem, Tiny M. Hlokwe, Evelyn Madoroba, Jacobus N. Eloff, Lyndy J. McGaw
      Abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Many plant species contain antimycobacterial compounds, which may serve as template molecules for new anti‐TB drugs. The Rubiaceae family is the largest family of trees in southern Africa, and preliminary evidence revealed antimycobacterial activity in several species of the genus, motivating further studies. Leaf extracts of 15 tree species from the Rubiaceae family were screened for antimycobacterial activity against pathogenic M. tuberculosis and non‐pathogenic Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium bovis BCG (Bacillus Calmette‐Guérin) using a twofold serial microdilution assay. Cytotoxicity was determined using a tetrazolium‐based colorimetric assay against C3A liver cells and Vero kidney cells. Minimum inhibitory concentration values as low as 0.04 mg/mL against M. smegmatis and M. tuberculosis were recorded. Activity against M. aurum was the best predictor of activity against pathogenic M. tuberculosis (correlation coefficient = 0.9). Bioautography indicated at least 40 different antimycobacterial compounds in the extracts. Cytotoxicity of the extracts varied, and Oxyanthus speciosus had the most promising selectivity index values. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T01:56:19.724173-05:
      DOI: 10.1002/ptr.5338
  • Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by
           Ischemia in H9c2 Cells Via Antioxidant Potential
    • Authors: P. L. Reshma; V. S. Lekshmi, Vandana Sankar, K. G. Raghu
      Abstract: Tribulus terrestris L. was evaluated for its cardioprotective property against myocardial ischemia in a cell line model. Initially, methanolic extract was prepared and subjected to sequential extraction with various solvents. The extract with high phenolic content (T. terrestris L. ethyl acetate extract–TTME) was further characterized for its chemical constituents and taken forward for evaluation against cardiac ischemia. HPLC analysis revealed the presence of phenolic compounds like caffeic acid (12.41 ± 0.22 mg g−1), chlorogenic acid (0.52 ± 0.06 mg g−1) and 4‐hydroxybenzoic acid (0.60 ± 0.08 mg g−1). H9c2 cells were pretreated with TTME (10, 25, 50 and 100 µg/ml) for 24 h before the induction of ischemia. Then ischemia was induced by exposing cells to ischemia buffer, in a hypoxic chamber, maintained at 0.1% O2, 95% N2 and 5% CO2, for 1 h. A significant (p ≤ 0.05) increase in reactive oxygen species generation (56%), superoxide production (18%), loss of plasma membrane integrity, dissipation of transmembrane potential, permeability transition pore opening and apoptosis had been observed during ischemia. However, pretreatment with TTME was found to significantly (p ≤ 0.05) attenuate the alterations caused by ischemia. The overall results of this study partially reveal the scientific basis of the use of T. terrestris L. in the traditional system of medicine for heart diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T01:30:58.838259-05:
      DOI: 10.1002/ptr.5336
  • Cytoprotective and Anti‐secretory Effects of Azadiradione Isolated
           from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat
    • Authors: Rohit Singh; Vaibhav Mishra, Sukanya Pandeti, Gautam Palit, Manoj K. Barthwal, Haushila Prasad Pandey, Tadigoppula Narender
      Abstract: Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in‐vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+‐ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-08T00:57:41.815633-05:
      DOI: 10.1002/ptr.5332
  • Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report
           from A Pilot, Randomized, Double‐Blinded, Placebo‐Controlled
           Clinical Trial
    • Authors: Foroud Shahbazi; Sanambar Sadighi, Simin Dashti‐Khavidaki, Farhad Shahi, Mehrzad Mirzania, Alireza Abdollahi, Mohammad‐Hossein Ghahremani
      Abstract: Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24–48 h before the initiation of cisplatin infusion and continuing to the end of three 21‐day cisplatin‐containing chemotherapy courses on cisplatin‐induced renal electrolytes wasting and kidney function were assessed. Cisplatin‐associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase‐associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin‐induced urine electrolyte wasting or renal function impairment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-07T06:02:29.261814-05:
      DOI: 10.1002/ptr.5345
  • Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus
           tatarinowii on mice and rats
    • Authors: Hao Liu; Zhi Song, Da‐Guang Liao, Tian‐Yi Zhang, Feng Liu, Kai Zhuang, Kui Luo, Liang Yang, Jing He, Jian‐Ping Lei
      Abstract: This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)‐induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium‐induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma‐aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA, Bcl‐2, and caspase‐3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl‐2 were up‐regulated by treating with eudesmin, whereas the caspase‐3 obviously was down‐regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up‐regulation of GABAA and GAD65 expressions, and anti‐apoptosis of neuron the in brain. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-07T05:46:32.29086-05:0
      DOI: 10.1002/ptr.5337
  • Enhanced Estrogenic Activity of Soybean Isoflavones by Coadministration of
           Liuwei Dihuang Pills in Ovariectomized Rats
    • Authors: Baogang Xie; Shuohua Zhang, Jie Liu, Xuejun Zhan, Daze Xie, Zhirong Zhang
      Abstract: Soybean isoflavones are beneficial for treating hormone‐related diseases. Simultaneous consumption of soybean isoflavones and Liuwei Dihuang pills (LWPs) is effective for treating perimenopausal period syndrome. However, why the combination of isoflavones and LWPs is more effective than ingestion of each component alone remains unknown. Here, we show that enhanced estrogenic activities would appear when the ovariectomized rats were fed with a soybean diet in combination of LWPs treatment. Our further studies explored enhancements of Lactobacillus (19‐fold) and Bifidobacterium (12‐fold) contents in the intestine of rat and 1.84‐fold higher intestinal β‐glucosidase activity in LWPs treatment group compared with the control group. As a result, steady‐state concentrations of genistein (1.20‐fold), daidzein (1.36‐fold), and equol (1.43‐fold) in serum were significantly elevated in the combination group compared with the soybean alone group. The results present the first evidence of the mechanism of enhanced estrogenic activity of dietary soybean isoflavones in combination with LWPs. Our study indicates that alterations of gut bacteria after LWPs treatment play a key role in the enhanced estrogenic effect of dietary soybean, suggesting a direct relationship between dietary soybean, LWPs, and gut flora. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:28:56.975643-05:
      DOI: 10.1002/ptr.5346
  • Inhibitory Effects of
           on Mushroom Tyrosinase and Melanogenesis in B16‐F10 Melanoma Cells
    • Authors: Jing‐jie Zhu; Gui‐rui Yan, Zhi‐jian Xu, Xiao Hu, Gai‐hong Wang, Ting Wang, Wei‐liang Zhu, Ai‐jun Hou, He‐yao Wang
      Abstract: (2′R)‐2′,3′‐Dihydro‐2′‐(1‐hydroxy‐1‐methylethyl)‐2,6′‐bibenzofuran‐6,4′‐diol (DHMB) is a natural compound extracted from Morus notabilis. It was found that DHMB acts as a competitive inhibitor against mushroom tyrosinase with a Ki value of 14.77 μM. Docking results further indicated that it could form strong interactions with one copper ion with a distance of 2.7 Å, suggesting the mechanism of inhibition might be due to chelating copper ions in the active site. Furthermore, melanin production in B16‐F10 murine melanoma cells was significantly inhibited by DHMB in a concentration‐dependent manner without cytotoxicity. The results of western blotting also showed that DHMB decreased 3‐isobuty‐1‐methxlzanthine‐induced mature tyrosinase expression. Taken together, these findings indicated that DHMB may be a new promising pigmentation‐altering agent for agriculture, cosmetic, and therapeutic applications. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:12:57.080312-05:
      DOI: 10.1002/ptr.5344
  • The Lignan Pinoresinol Induces Nuclear Translocation of DAF‐16 in
           Caenorhabditis elegans but has No Effect on Life Span
    • Authors: Karoline Koch; Christian Büchter, Susannah Havermann, Wim Wätjen
      Abstract: The lignan pinoresinol is a constituent of flaxseed, sesame seeds and olive oil. Because of different molecular effects reported for this compound, e.g. antioxidative activity, pinoresinol is suggested to cause positive effects on humans. Because experimental data are limited, we have analysed the effects of the lignan on the nematode Caenorhabditis elegans: in spite of a strong antioxidative capacity detected in an in vitro assay, no antioxidative effects were detectable in vivo. In analogy to this result, no modulation of the sensitivity against thermal stress was detectable. However, incubation with pinoresinol caused an enhanced nuclear accumulation of the transcription factor DAF‐16 (insulin/IGF‐like signalling pathway). Using a strain with an enhanced oxidative stress level (mev‐1 mutant), we clearly see an increase in stress resistance caused by this lignan, but no change in reactive oxygen species. Furthermore, we investigated the effects of pinoresinol on the life span of the nematode, but no modulation was found, neither in wild‐type nor in mev‐1 mutant nematodes. These results suggest that pinoresinol may exert pharmacologically interesting effects via modulation of the insulin‐like signalling pathway in C. elegans as well as in other species like mammals due to the evolutionary conservation of this signalling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-31T06:06:03.508341-05:
      DOI: 10.1002/ptr.5330
  • Castalagin Exerts Inhibitory Effects on Osteoclastogenesis Through
           Blocking a Broad Range of Signaling Pathways with Low Cytotoxicity
    • Authors: Mayumi Iwatake; Kuniaki Okamoto, Takashi Tanaka, Takayuki Tsukuba
      Abstract: Castalagin is a rare plant polyphenol that is classified as a hydrolyzable tannin. Although it has antioxidant, antitumorigenic, and leishmanicidal effects, the utility of castalagin against bone diseases remain to be elucidated. Here, we investigated the effects of castalagin on the differentiation of osteoclasts (OCLs), multinucleated bone‐resorbing cells. After stimulation with receptor activator of nuclear factor kappa‐B ligand (RANKL), the formation of OCLs from bone marrow‐derived macrophages was significantly inhibited by castalagin even at 1 μM. However, castalagin displayed little cytotoxicity at a higher concentration of 50 μM. The effects of castalagin on intracellular signaling during OCL differentiation showed that castalagin suppresses RANKL‐stimulated phosphorylation of major signaling pathways including protein kinase B (Akt), extracellular signal‐regulated kinase, Jun N‐terminal kinase, p38 mitogen‐activated protein kinases, and inhibitor of nuclear factor kappa B alpha. Moreover, following castalagin treatment, the protein levels of nuclear factor of activated T‐cells, cytoplasmic 1, a master regulator for OCL differentiation, and NF‐κB were decreased. Thus, castalagin exerts inhibitory effects on osteoclastogenesis through blockage of a broad range of signaling pathways, but has low cytotoxicity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T02:35:46.223762-05:
      DOI: 10.1002/ptr.5333
  • Effects of Glucosinolates from Turnip (Brassica rapa L.) Root on Bone
           Formation by Human Osteoblast‐Like MG‐63 Cells and in Normal
           Young Rats
    • Authors: Jaehoon Jeong; Heajin Park, Hanbit Hyun, Jihye Kim, Haesung Kim, Hyun Il Oh, Hye Seong Hwang, Dae Kyong Kim, Ha Hyung Kim
      Abstract: Turnip (Brassica rapa L.) root ethanol extract (TRE) was prepared, and its chemical constituents were characterized by ultra‐performance liquid chromatography and mass spectrometry. Thirteen glucosinolates (GSLs) were identified, comprising eight aliphatic, four indolic, and one aromatic compounds. The effects of these GSLs on bone formation were investigated in vitro by incubating human osteoblast‐like MG‐63 cells with TRE and then analyzing their viability, alkaline phosphatase (ALP) activity, collagen content, and mineralization and in vivo by administering TRE orally to normal young rats (500 mg/kg/day) and assessing subsequent changes in serum osteocalcin and bone microstructure in these animals. No TRE‐related toxicity was found, and the levels of cell viability, ALP activity, collagen synthesis, and mineralization were significantly increased relative to the negative control. In particular, stimulatory effects on the differentiation of MG‐63 cells were strongly enhanced as compared with a positive control (daidzein). Serum osteocalcin was also significantly increased, and some important bone microstructural parameters were improved in TRE‐administered rats compared with their saline‐administered counterparts. GSLs therefore appear to have a stimulatory effect on bone formation in both MG‐63 cells and normal young rats. This is the first report on the usefulness of turnip root and its GSL compounds for bone formation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T02:10:27.977479-05:
      DOI: 10.1002/ptr.5331
  • Review of the Safety and Efficacy of Moringa oleifera
    • Authors: Sidney J. Stohs; Michael J. Hartman
      Abstract: Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti‐hyperglycemic (antidiabetic) and anti‐dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
      PubDate: 2015-03-24T01:44:35.928976-05:
      DOI: 10.1002/ptr.5325
  • The Androgenic Alopecia Protective Effects of Forsythiaside‐A and
           the Molecular Regulation in a Mouse Model
    • Authors: Heon‐Sub Shin; Sang‐Yong Park, Hyun‐Geun Song, Eunson Hwang, Don‐Gil Lee, Tae‐Hoo Yi
      Abstract: This study examined the inhibitory effect of forsythiaside‐A, a natural substance derived from Forsythia suspensa (F. suspensa), on entry into catagen induced by dihydrotestosterone (DHT) in an androgenic alopecia mouse model. In vitro experiment comparing finasteride with forsythiaside‐A showed that forsythiaside‐A treatment resulted in a 30% greater inhibition of DHT‐induced apoptosis in human hair dermal papilla cell (HHDPCs) and human keratinocytes (HaCaTs). In vivo experiment showed that mouse hair density and thickness were increased by 50% and 30%, respectively, in the forsythiaside‐A‐treated group when compared to a DHT group. Tissue histological results revealed that the forsythiaside‐A‐treated group had an increase in size and shape of the hair follicles and a 1.5 times increase in the follicle anagen/telogen ratio when compared to the finasteride group. Western blot examination of TGF‐β2 expression related to apoptosis signaling in mouse skin verified that forsythiaside‐A reduced the expression of TGF‐β2 by 75% and suppressed apoptosis by reducing the expression of caspase‐9 by 40%, and caspase‐3 by 53%, which play an roles up‐regulator in the apoptosis signal. The forsythiaside‐A group also showed a 60% increase in the Bcl‐2/Bax ratio, which is a factor related to mitochondrial apoptosis. Our results indicated that forsythiaside‐A prevents apoptosis by similar mechanism with finasteride, but forsythiaside‐A is more effective than finasteride. In summary, forsythiaside‐A controlled the apoptosis of hair cells and retarded the entry into the catagen phase and therefore represents a natural product with much potential for use as a treatment for androgenic alopecia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-24T01:27:46.476074-05:
      DOI: 10.1002/ptr.5324
  • The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene
           Expression, Production, and Secretion via Regulation of NF‐κB,
           STAT6, and HDAC2
    • Authors: Changda Liu; David Weir, Paula Busse, Nan Yang, Zhenwen Zhou, Charles Emala, Xiu‐Min Li
      Abstract: Mucus overproduction is a significant component of the pathophysiology of obstructive lung diseases. Currently, there are only a few medications available that inhibit mucus production. Previous studies showed that glycyrrhizin, a triterpenoid in Glycyrrhiza uralensis inhibits mucin 5AC (MUC5AC) mRNA and protein expression. Other potential mucus production inhibitory compounds contained within in G. uralensis have not been fully investigated. The aim of the present study was to determine if the G. uralensis flavonoid 7,4′‐dihydroxyflavone (7,4′‐DHF) inhibits MUC5AC gene expression, mucus production, and secretion, and if so, to elucidate the mechanism of this inhibition. 7,4′‐Dihydroxyflavone significantly decreased phorbol 12‐myristate 13‐acetate‐stimulated NCI‐H292 human airway epithelial cell MUC5AC gene expression and mucus production, at a 28‐fold lower concentration than glycyrrhizin (The half maximal inhibitory concentration IC50 value of 1.4 μM vs 38 μM, respectively); 7,4′‐DHF also inhibited MUC5AC mucus secretion. Inhibition was associated with the suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), signal transducer and activator of transcription 6 (STAT6) activation, and enhanced histone deacetylase 2 (HDAC2) expression. In a murine model of asthma, 7,4′‐DHF‐treated mice exhibited a marked reduction in MUC5AC secretion in the bronchoalveolar lavage fluid compared with control mice. These findings, together with previous findings linking NF‐κB, STAT6, and HDAC2 modulation to the control of MUC5AC expression, demonstrate that 7,4′‐DHF is a newly identified component of G. uralensis that regulates MUC5AC expression and secretion via regulation of NF‐κB, STAT6, and HDAC2. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-23T02:33:11.505342-05:
      DOI: 10.1002/ptr.5334
  • Antioxidant, Anti‐inflammatory, and Chemoprotective Properties of
           Acacia catechu Heartwood Extracts
    • Authors: Sidney J. Stohs; Debasis Bagchi
      Abstract: Aqueous extracts of Acacia catechu heartwood are rich source of catechin and epicatechin (gallic acid derivatives), with smaller amounts of flavonoids. Extracts have also been prepared with ethyl acetate, ethanol, and methanol, and the properties of these extracts have been studied and are reviewed. Potent antioxidant activity has been well established in both in vitro and in vivo studies. This antioxidant activity is believed to be responsible for the anti‐inflammatory, tissue protectant, antineoplastic, and analgesic activities that have been demonstrated and clearly established in animal and cell culture systems. Furthermore, antihyperglycemic, antidiarrheal, antinociceptive, and antipyretic activities have been demonstrated in animal studies. No adverse effects have been observed in animal or human studies or in cell culture systems. In spite of the fact that Acacia products have been used for many years and the general safety of catechins and epicatechins is well documented, few human studies have ever been conducted on the efficacy or safety of A. catechu heartwood extracts. Several studies have shown that a two‐ingredient combination product containing A. catechu extract exhibited no adverse effects when administered daily for up to 12 weeks while exhibiting significant anti‐inflammatory activity in subjects with osteoarthritis of the knee. There is a need for additional human clinical studies with regard to efficacy and safety. © 2015 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2015-03-20T07:43:27.697385-05:
      DOI: 10.1002/ptr.5335
  • The Effects of Pre‐Exercise Ginger Supplementation on Muscle Damage
           and Delayed Onset Muscle Soreness
    • Authors: Melissa D. Matsumura; Gerald S. Zavorsky, James M. Smoliga
      Abstract: Ginger possesses analgesic and pharmacological properties mimicking non‐steroidal antiinflammatory drugs. We aimed to determine if ginger supplementation is efficacious for attenuating muscle damage and delayed onset muscle soreness (DOMS) following high‐intensity resistance exercise. Following a 5‐day supplementation period of placebo or 4 g ginger (randomized groups), 20 non‐weight trained participants performed a high‐intensity elbow flexor eccentric exercise protocol to induce muscle damage. Markers associated with muscle damage and DOMS were repeatedly measured before supplementation and for 4 days following the exercise protocol. Repeated measures analysis of variance revealed one repetition maximum lift decreased significantly 24 h post‐exercise in both groups (p 
      PubDate: 2015-03-18T05:34:13.795414-05:
      DOI: 10.1002/ptr.5328
  • A Review: Phytochemicals Targeting JAK/STAT Signaling and IDO Expression
           in Cancer
    • Authors: Niroshaathevi Arumuggam; Neil A. Bhowmick, H. P. Vasantha Rupasinghe
      Abstract: Cancer remains a major health problem worldwide. Among many other factors, two regulatory defects that are present in most cancer cells are constitutive activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and the induction of indoleamine 2, 3‐dioxygenase (IDO), an enzyme that catalyzes tryptophan degradation, through JAK/STAT signaling. Cytokine signaling activates STAT proteins in regulating cell proliferation, differentiation, and survival through modulation of target genes. Many phytochemicals can inhibit both JAK/STAT signaling and IDO expression in antigen‐presenting cells by targeting different pathways. Some of the promising phytochemicals that are discussed in this review include resveratrol, cucurbitacin, curcumin, (−)‐epigallocatechin gallate, and others. It is now evident that phytochemicals play key roles in inhibition of tumor proliferation and development and provide novel means for therapeutic targeting of cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-18T03:15:55.781213-05:
      DOI: 10.1002/ptr.5327
  • Multiple Biological Effects of Olive Oil By‐products such as Leaves,
           Stems, Flowers, Olive Milled Waste, Fruit Pulp, and Seeds of the Olive
           Plant on Skin
    • Authors: Asuka Kishikawa; Ahmed Ashour, Qinchang Zhu, Midori Yasuda, Hiroya Ishikawa, Kuniyoshi Shimizu
      Abstract: As olive oil production increases, so does the amount of olive oil by‐products, which can cause environmental problems. Thus, new ways to utilize the by‐products are needed. In the present study, five bioactive characteristics of olive oil by‐products were assessed, namely their antioxidant, anti‐bacterial, anti‐melanogenesis, anti‐allergic, and collagen‐production‐promoting activities. First, the extracts of leaves (May and October), stems (May and October), flowers, olive milled waste, fruit pulp and seeds were prepared using two safe solvents, ethanol and water. According to HPLC and LC/MS analysis and Folin–Ciocalteu assay, the ethanol extracts of the leaves (May and October), stems (May and October) and flowers contained oleuropein, and the ethanol extract of the stems showed the highest total phenol content. Oleuropein may contribute to the antioxidant and anti‐melanogenesis activities of the leaves, stems, and flowers. However, other active compounds or synergistic effects present in the ethanol extracts are also likely to contribute to the anti‐bacterial activity of the leaves and flowers, the anti‐melanogenesis activity of some parts, the anti‐allergic activity of olive milled waste, and the collagen‐production‐promoting activity of the leaves, stems, olive milled waste and fruit pulp. This study provides evidence that the by‐products of olive oil have the potential to be further developed and used in the skin care industry. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-16T04:52:23.460242-05:
      DOI: 10.1002/ptr.5326
  • Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different
           Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung
           Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells
    • Authors: Norazah Basar; Olayinka Ayotunde Oridupa, Kenneth J. Ritchie, Lutfun Nahar, Nashwa Mostafa M. Osman, Angela Stafford, Habibjon Kushiev, Asuman Kan, Satyajit D. Sarker
      Abstract: Glycyrrhiza glabra L. (Fabaceae), commonly known as ‘liquorice’, is a well‐known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet‐tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-16T04:30:00.739637-05:
      DOI: 10.1002/ptr.5329
  • A Clinical Trial with Brazilian Arnica (Solidago chilensis Meyen) Glycolic
           Extract in the Treatment of Tendonitis of Flexor and Extensor Tendons of
           Wrist and Hand
    • Authors: Ary Gomes Silva; Elbe Rodrigues Machado, Leonardo Mendes Almeida, Ricardo Marcelo Menezes Nunes, Patrícia Caldeira Pena Giesbrecht, Regina Mamed Costa, Helber B. Costa, Wanderson Romão, Ricardo Machado Kuster
      Abstract: One of the Brazilian arnicas, Solidago chilensis Meyen, is a species of the Asteraceae family. This plant is known by this common name because it shares remarkably similar organoleptic properties with the genus Arnica L., also within the family Asteraceae. We examined the effectiveness of the S. chilensis fluid extract used externally for treating tendinitis of flexor and extensor tendons of wrist and hand in placebo‐controlled double‐blind clinical pharmacological studies. This study was approved by the Ethical Committee for Scientific Research in Human Beings at University Vila Velha‐UVV. Two daily skin applications on the arm skin of a gel cream containing a 5% glycolic plant extract were administered to eight volunteers for 21 days. Among the volunteers, one of their arms was used as the placebo group, and the other one was used as a test group. Statistical data analyses demonstrated a significant reduction in the perception of pain in the arms in the test group, when it was compared to those receiving only the placebo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T06:17:17.000478-05:
      DOI: 10.1002/ptr.5323
  • Antiinflammatory and Wound Healing Effects of Caesalpinia sappan L.
    • Authors: Supinya Tewtrakul; Pattreeya Tungcharoen, Teeratad Sudsai, Chatchanok Karalai, Chanita Ponglimanont, Orapun Yodsaoue
      Abstract: Extracted compounds from Caesalpinia sappan L. were examined for the inhibitory activity against NO, PGE2, and TNF‐α productions and on associated transcription levels using RAW264.7 cells. They were also tested for their effects on wound healing using fibroblast L929 cells. Among the compounds tested, brazilin (8) was the most effective against lipopolysaccharide (LPS)‐induced NO production in RAW264.7 cells with an IC50 value of 10.3 μM, followed by sappanchalcone (2, 31.0 μM). Brazilin (8) also inhibited PGE2 and TNF‐α production with IC50 values of 12.6 and 87.2 μM, respectively. The antiinflammatory mechanism of brazilin involved down regulation of the mRNA expressions of the iNOS, COX‐2, and TNF‐α genes in a dose‐dependent manner. An ethanol (EtOH) extract of C. sappan significantly increased fibroblast proliferation, fibroblast migration, and collagen production, whereas brazilin (8) only stimulated fibroblast migration. In addition, the EtOH extract showed no acute toxicity in mice, and it was therefore safe to make use of its potent antiinflammatory and wound healing activities. Brazilin was mainly responsible for its antiinflammatory effect through its ability to inhibit the production of NO, PGE2, and TNF‐α. This study supports the traditional use of C. sappan for treatment of inflammatory‐related diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T05:48:03.497675-05:
      DOI: 10.1002/ptr.5321
  • Soy Isoflavone Glycitin
           Promotes Human Dermal Fibroblast Cell Proliferation and Migration via
           TGF‐β Signaling
    • Authors: Young Mee Kim; Jung Sik Huh, Yoongho Lim, Moonjae Cho
      Abstract: Glycitin is a soy isoflavone that exhibits antioxidant, antiallergic, and anti‐osteoporosis activities. We investigated the effects of glycitin on dermal fibroblast proliferation and migration. Treatment of primary dermal fibroblasts with glycitin increased cell proliferation and migration. In addition, treatment with 20 μM glycitin for 24 h induced the synthesis of collagen type I and type III at both the mRNA and protein levels. Fibronectin was also increased by 20% after treatment. Matrix metalloproteinase‐1 collagenase was decreased in the media after 24‐h incubation with glycitin, and the synthesis of transforming growth factor‐beta (TGF‐β) mRNA increased approximately twofold in cells following glycitin treatment. Phosphorylation of Smad2 and Smad3 increased after 1 h of glycitin treatment, and phosphorylation continued for 24 h. Furthermore, the phosphorylated form of AKT was increased in glycitin‐treated cells after 3 h and remained higher for 24 h. Thus, glycitin treatment produces anti‐aging effects including increased total collagen in the culture media, decreased elastase, and decreased β‐galactosidase. Together, these results indicate that glycitin stimulates TGF‐β secretion, and the subsequent autocrine actions of TGF‐β induce proliferation of fibroblasts, ultimately protecting skin cells from aging and wrinkling. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-11T03:33:12.586432-05:
      DOI: 10.1002/ptr.5313
  • Review of Clinical Pharmacology of Aloe vera L. in the Treatment of
    • Authors: Marco Miroddi; Michele Navarra, Fabrizio Calapai, Ferdinando Mancari, Salvatore Vincenzo Giofrè, Sebastiano Gangemi, Gioacchino Calapai
      Abstract: Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune‐mediated chronic inflammatory disease, involving mainly the skin, affects about the 2–3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-10T05:19:04.976434-05:
      DOI: 10.1002/ptr.5316
  • Toxicity of Anthraquinones: Differential Effects of Rumex Seed Extracts on
           Rat Organ Weights and Biochemical and Haematological Parameters
    • Authors: Rabigul Islam; Yultuz Mamat, Ilyar Ismayil, Ming Yan, Mahsutjan Kadir, Abdujilil Abdugheny, Haximjan Rapkat, Mardan Niyaz, Yusupjan Ali, Sirapil Abay
      Abstract: The genus Rumex and related species such as Rheum and Polygonum are widely used as medicinal herbs and foods. They contain anthraquinones (AQ) such as emodin and chrysophanol as active ingredients, and there is concern about the toxicity of these compounds. This study evaluated the chronic effects of Rumex patientia seed aqueous and ethanolic extracts, in male and female rats separately, on organ weights and over 30 haematological, biochemical and histological parameters, immediately after 14‐week administration and after a further period of 15 days without drug treatment. Adverse changes were associated with long‐term AQ administration, and these focussed on the liver, lung and kidney, but after 15‐day convalescence, most had reverted to normal. In general, male rats appeared to be more susceptible than female rats at similar doses. The water extract produced no irreversible changes, which may reflect the lower dose of the AQ constituents or the presence of different ancillary compounds, and supports the traditional method of extracting Rumex seeds with water. In conclusion, ethanolic extracts of R. patientia caused irreversible pathological changes at very high doses (4000mg/kg), but lower doses and aqueous extracts produced either non‐significant or reversible changes. Long‐term administration of high doses of AQ extracts over a long period of time should be avoided until further assurances can be given, and given other existing reports of reproductive toxicity, should be avoided altogether during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-09T03:53:34.884696-05:
      DOI: 10.1002/ptr.5317
  • Inhibition of Cancer Cell Proliferation and Antiradical Effects of
           Decoction, Hydroalcoholic Extract, and Principal Constituents of
           Hemidesmus indicus R. Br.
    • Authors: Giancarlo Statti; Mariangela Marrelli, Filomena Conforti, Antonella Spagnoletti, Massimo Tacchini, Carmela Fimognari, Eleonora Brognara, Roberto Gambari, Gianni Sacchetti, Alessandra Guerrini
      Abstract: Indian Sarsaparilla (Hemidesmus indicus R. Br.) is widely used in Indian traditional medicine. In the present work, we explored the effects of decoction, traditional Ayurvedic preparation, and hydroalcoholic extract, a phytocomplex more traditionally studied and commercialized as food supplement in western medicine, from the roots as possible source of chemicals with new functional potential linked to their nutritional uses. The antiproliferative and antioxidant properties were assayed. To test antiproliferative affects, different cancer cell lines, growing both as monolayers (CaCo2, MCF‐7, A549, K562, MDA‐MB‐231, Jurkat, HepG2, and LoVo) and in suspension (K562 and Jurkat) were used. The decoction showed strong activity on HepG2 cells, while the hydroalcoholic extracts were active on HepG2, LoVo, MCF‐7, K562, and Jurkat cell lines. Weak inhibition of cancer cell proliferation was observed for the principal constituents of the preparations: 2‐hydroxy‐4‐methoxybenzaldehyde, 2‐hydroxy‐4‐methoxybenzoic acid, and 3‐hydroxy‐4‐methoxybenzaldehyde that were tested alone. The antiradical activity was tested with 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid)diammonium salt tests and inhibition of nitric oxide production in lipopolysaccharide‐stimulated RAW 264.7 macrophages. Interesting result has also been obtained for hydroalcoholic extract regarding genoprotective potential (58.79% of inhibition at 37.5 µg/mL). Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-06T08:14:13.939725-05:
      DOI: 10.1002/ptr.5322
  • Enhanced HIV‐1 Reverse Transcriptase Inhibitory and Antibacterial
           Properties in Callus of Catha edulis Forsk.
    • Authors: Aloka Kumari; Ponnusamy Baskaran, Johannes Van Staden
      Abstract: Developing tissue culture systems for medicinal plants is important in that they may offer an alternative to protect wild populations. However, analysis of bioactivity for tissue culture developed plant tissues is required to offer support and allow acceptance in traditional medicine. The use of propagated callus could provide potential material for therapeutic purposes. This study was aimed at evaluating the anti‐HIV and antibacterial properties of a three‐month‐old tissue culture‐derived calli and leaves of cultivated mother plants of Catha edulis Forsk. The calli were derived from leaf explants using different plant growth regulators. The calli obtained from callus cultured on 9.8 μM indole‐3‐butyric acid plus 2.7 μM naphthalene acetic acid exhibited the highest HIV‐1 reverse transcriptase inhibitory effects when compared with other treatments and the mother plants. Different extracts of callus exhibited high antibacterial activity (
      PubDate: 2015-03-06T07:47:20.630215-05:
      DOI: 10.1002/ptr.5318
  • Apoptotic Effect of Galbanic Acid via Activation of Caspases and
           Inhibition of Mcl‐1 in H460 Non‐Small Lung Carcinoma Cells
    • Authors: Bum‐Seok Oh; Eun Ah Shin, Ji Hoon Jung, Deok‐Beom Jung, Bonglee Kim, Bum Sang Shim, Mahsa Chitsazian Yazdi, Mehrdad Iranshahi, Sung‐Hoon Kim
      Abstract: Galbanic acid (GBA), a major compound of Ferula assafoetida, was known to have cytotoxic, anti‐angiogenic and apoptotic effects in prostate cancer and murine Lewis lung cancer cells; the underling apoptotic mechanism of GBA still remains unclear so far. Thus, in the present study, the apoptotic mechanism of GBA was investigated mainly in H460 non‐small cell lung carcinoma (NSCLC) cells because H460 cells were most susceptible to GBA than A549, PC‐9 and HCC827 NSCLC cells. Galbanic acid showed cytotoxicity in wild EGFR type H460 and A549 cells better than other mutant type PC‐9 and HCC827 NSCLC cells. Also, GBA significantly increased the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and sub G1 population in H460 cells. Western blotting revealed that GBA cleaved poly (ADP‐ribose) polymerase (PARP), activated Bax and caspase 9, attenuated the expression of Bcl‐2, Bcl‐xL, and Myeloid cell leukemia 1 (Mcl‐1) in H460 cells. However, interestingly, overexpression of Mcl‐1 blocked the ability of GBA to exert cytotoxicity, activate caspase9 and Bax, cleave PARP, and increase sub G1 accumulation in H460 cells. Overall, these findings suggest that GBA induces apoptosis in H460 cells via caspase activation and Mcl‐1 inhibition in H460 cells as a potent anticancer agent for NSCLC treatment. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-06T06:57:33.9375-05:00
      DOI: 10.1002/ptr.5320
  • The Antiinflammatory Properties of Humic Substances: A Mini Review
    • Authors: Constance E. J. Rensburg
      Abstract: Humic substances are effective in the suppression of delayed type hypersensitivity, rat paw oedema, a graft‐versus‐host reaction and contact hypersensitivity in rats. They reduce the C‐reactive protein levels of patients suffering from osteoarthritis of the knee and the wheel and flare reaction of patients suffering from hay fever. They have also been described as cardioprotective and pro‐angiogenic. Toxicity studies have indicated that potassium humate is safe in humans up to a daily dosage of 1 g/kg, whereas fulvic acid is safe in humans up to a daily dosage of 1.8 g per adult. The antiinflammatory action of potassium humate can be contributed to the inhibition of the release of inflammatory‐related cytokines, an adhesion molecule, oxidants and components of the complement system. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-03T02:27:47.336031-05:
      DOI: 10.1002/ptr.5319
  • The Involvement of Serotonin in the Hypoglycemic Effects Produced by
           Administration of the Aqueous Extract of Xylaria nigripes with
           Steroid‐Induced Insulin‐Resistant Rats
    • Authors: Ying‐I Chen; Chung‐Yuh Tzeng, Yu‐Wen Cheng, Tai‐Hao Hsu, Wai Jane Ho, Zeng‐Chin Liang, Chang‐Wei Hsieh, Jason T. C. Tzen, Shih‐Liang Chang
      Abstract: Xylaria nigripes (XN) is a medicinal fungus with a high‐economic value. The aim of this study was to explore the hypoglycemic effects and mechanisms of the XN aqueous extract in steroid‐induced insulin‐resistant (SIIR) rats. Significant hypoglycemic effects were observed 60 min after administration of XN aqueous extract. In normal Wistar, hypoglycemic effects were 21% (the plasma glucose level decreased from 128.6 ± 12.5 to 100.9 ± 10.7 mg/dL). In SIIR, hypoglycemic effects were 26% (the plasma glucose level decreased from 177.6 ± 12.5 to 133.3 ± 29.7 mg/dL) rats refer to their baseline. The signaling proteins for insulin‐receptor substrate‐1 and glucose transporter‐4 increased 0.51‐fold and 1.12‐fold, respectively, as determined by Western blotting; the increase in the proteins was 13% and 9%, respectively, as determined by immunohistochemistry. The serotonin antagonist, α‐p‐chlorophenylalanine, effectively blocked the hypoglycemic effects and increased the signaling protein levels. After XN administration, none of the animals showed significant changes in plasma‐free fatty acids in 60 min. In summary, the XN extract may have hypoglycemic effects in normal Wistar and SIIR rats that may have a serotonin‐related hypoglycemic effect and enhance insulin sensitivity in the SIIR rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-25T02:05:38.513317-05:
      DOI: 10.1002/ptr.5314
  • Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and
           Centella asiatica in Human Liver Microsomes
    • Authors: Jay Savai; Alice Varghese, Nancy Pandita, Meena Chintamaneni
      Abstract: Withania somnifera is commonly used as a rejuvenator, whereas Centella asiatica is well known for its anxiolytic and nootropic effects. The present study aims at investigating the effect of crude extracts and principal phytoconstituents of both the medicinal plants with CYP3A4 and CYP2D6 enzyme activity in human liver microsomes (HLM). Phytoconstituents were quantified in the crude extracts of both the medicinal plants using reverse phase HPLC. Crude extracts and phytoconstituents of W. somnifera showed no significant interaction with both CYP3A4 and CYP2D6 enzymes in HLM. Of the crude extracts of C. asiatica screened in vitro, methanolic extract showed potent noncompetitive inhibition of only CYP3A4 enzyme (Ki—64.36 ± 1.82 µg/mL), whereas ethanol solution extract showed potent noncompetitive inhibition of only CYP2D6 enzyme (Ki—36.3 ± 0.44 µg/mL). The flavonoids, quercetin, and kaempferol showed potent (IC50 values less than 100 μM) inhibition of CYP3A4 activity, whereas quercetin alone showed potent inhibition of CYP2D6 activity in HLM. Because methanolic extract of C. asiatica showed a relatively high percentage content of quercetin and kaempferol than ethanol solution extract, the inhibitory effect of methanolic extract on CYP3A4 enzyme activity could be attributed to the flavonoids. Thus, co‐administration of the alcoholic extracts of C. asiatica with drugs that are substrates of CYP3A4 and CYP2D6 enzymes may lead to undesirable herb‐drug interactions in humans. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-13T04:01:24.010829-05:
      DOI: 10.1002/ptr.5308
  • Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl
           Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells
    • Authors: Yoon Jung Jeon; Seung‐Nam Jung, Hyeyoun Chang, Jieun Yun, Chang Woo Lee, Joonku Lee, Sangho Choi, Oyekanmi Nash, Dong Cho Han, Byoung‐Mog Kwon
      Abstract: Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose‐dependent manner. To identify the active components, a bioassay‐guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down‐regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase‐3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3‐related diseases, including cancer and inflammation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-13T03:41:26.933955-05:
      DOI: 10.1002/ptr.5311
  • The Effect of Zataria multiflora and its Constituent, Carvacrol, on
           Tracheal Responsiveness and Lung Pathology in Guinea Pig Model of COPD
    • Authors: L. Gholami Mahtaj; M.H. Boskabady, N. Mohamadian Roshan
      Abstract: The effects of Zataria multiflora (Z. multiflora) and its constituent, carvacrol, in guinea pigs model of chronic obstructive pulmonary disease (COPD) were examined. Animals were divided into control, COPD, COPD + drinking water containing three concentrations of extract of Z. multiflora (0.4, 0.8 and 1.6 mg/ml), COPD + drinking water containing three concentrations of carvacrol (60, 120 and 240 µg/ml) and COPD + dexamethasone (50 µg/ml). COPD was induced by exposing animals to cigarette smoke for 3 months. Emphysema as a pathological change of the lung and tracheal responsiveness were measured (n = 5 for control and COPD groups and n = 6 for another groups). Tracheal responsiveness (p 
      PubDate: 2015-02-13T03:32:07.203715-05:
      DOI: 10.1002/ptr.5309
  • Protective Effects of Turbinaria ornata and Padina pavonia against
           Azoxymethane‐Induced Colon Carcinogenesis through Modulation of PPAR
           Gamma, NF‐κB and Oxidative Stress
    • Authors: Ayman M. Mahmoud; Ehab M. Abdella, Azza M. El‐Derby, Eman M. Abdella
      Abstract: The aim of this study was to investigate the antiproliferative and protective effects of the brown seaweeds, Turbinaria ornata and Padina pavonia, against azoxymethane (AOM)‐induced colon carcinogenesis in mice. Both algal extracts showed anti‐proliferative effects on the human carcinoma cell line HCT‐116 in vitro, with T. ornata demonstrating a more potent effect. Male albino Swiss mice received intraperitoneal injections of AOM (10 mg/kg) once a week for two consecutive weeks and 100 mg/kg of either T. ornata or P. pavonia extracts. AOM‐induced mice exhibited alterations in the histological structure of the colon, elevated lipid peroxidation and nitric oxide, declined glutathione content and reduced activity of superoxide dismutase and glutathione peroxidase. In addition, AOM induced downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and p53 mRNA expression, with concomitant upregulation of nuclear factor‐kappa B (NF‐κB) in colon tissue. Administration of either algal extract markedly alleviated the recorded alterations. In conclusion, the current study suggests that T. ornata and P. pavonia, through their antioxidant and anti‐inflammatory effects, are able to attenuate colon inflammation by downregulating NF‐κB expression. Furthermore, the protective effects of both algae against AOM‐initiated carcinogenesis were attributed, at least in part, to their ability to upregulate colonic PPARγ and p53 expression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-12T00:17:22.01702-05:0
      DOI: 10.1002/ptr.5310
  • Anti‐HIV‐1 Integrase Activity and Molecular Docking Study of
           Compounds from Caesalpinia  sappan L.
    • Authors: Supinya Tewtrakul; Prapaporn Chaniad, Somsak Pianwanit, Chatchanok Karalai, Chanita Ponglimanont, Orapun Yodsaoue
      Abstract: Caesalpinia sappan L. (Caesalpiniaceae) has been traditionally used as blood tonic, expectorant, and astringent by boiling with water. Searching for HIV‐1 integrase (IN) inhibitors from this plant is a promising approach. The EtOH extract of C. sappan and its isolated compounds were tested for their anti‐HIV‐1 IN effect using the multiplate integration assay, and the active compounds were determined for their mechanisms by molecular docking technique. Extraction from the heartwoods and roots of C. sappan led to the isolation of nine compounds. Among the compounds tested, sappanchalcone (2) displayed the strongest effect against HIV‐1 IN with an IC50 value of 2.3 μM followed by protosappanin A (9, IC50 = 12.6 μM). Structure‐activity relationships of compounds from C. sappan were found, in which the vicinal hydroxyl moiety were essential for anti‐HIV‐1 IN effect of compounds 2 and 9 by binding with the amino acid residues Gln148 and Thr66 in the core domain of the HIV‐ 1 IN enzyme, respectively. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-11T06:41:26.45842-05:0
      DOI: 10.1002/ptr.5307
  • Corosolic Acid Exhibits Anti‐angiogenic and
           Anti‐lymphangiogenic Effects on In Vitro Endothelial Cells and on an
           In Vivo CT‐26 Colon Carcinoma Animal Model
    • Authors: Ki Hyun Yoo; Jong‐Hwa Park, Dae Young Lee, Jeon Hwang‐Bo, Nam In Baek, In Sik Chung
      Abstract: We describe the anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid, a pentacyclic triterpenoid isolated from Cornus kousa Burg. A mouse colon carcinoma CT‐26 animal model was employed to determine the in vivo anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid. Corosolic acid induced apoptosis in CT‐26 cells, mediated by the activation of caspase‐3. In addition, it reduced the final tumor volume and the blood and lymphatic vessel densities of tumors, indicating that it suppresses in vivo angiogenesis and lymphangiogenesis. Corosolic acid inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells. In addition, corosolic acid decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin‐1. Pretreatment with corosolic acid decreased the phosphorylation of focal adhesion kinase (FAK) and ERK1/2, suggesting that corosolic acid contains anti‐angiogenic activity that can suppress FAK signaling induced by angiopoietin‐1. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-02T21:48:33.330524-05:
      DOI: 10.1002/ptr.5306
  • Apoptotic Effects of the Extracts of Cordyceps militaris via Erk
           Phosphorylation in a Renal Cell Carcinoma Cell Line
    • Authors: Kazuhiro Yamamoto; Hiroaki Shichiri, Atsushi Uda, Kazuhiko Yamashita, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai
      Abstract: Cordyceps militaris (CM) is gaining attention as a traditional medicinal food, but its molecular biological mechanisms for anti‐cancer activity are not identified or clarified. We aimed to elucidate the synthesizing apoptotic effects of CM extracts and to determine the biological effects of CM extract against cordycepin alone in a renal cell carcinoma (RCC) cell line. CM extract showed higher effects of growth inhibition, apoptotic effect, and cell cycle arrest than cordycepin alone. Moreover, CM extract activated extracellular signal‐regulated kinase (Erk) highly more than cordycepin alone. We suggest that cordycepin and CM extract induced apoptosis via the activation of Erk dominantly and AMP‐activated protein kinase slightly; CM extract has more potent effects on apoptotic effects associated with Erk activation than cordycepin alone. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-02T21:31:40.659915-05:
      DOI: 10.1002/ptr.5305
  • Natural Sesquiterpene Lactones Enhance Oxacillin and Gentamicin
           Effectiveness Against Pathogenic Bacteria Without Antibacterial Effects on
           Beneficial Lactobacilli
    • Authors: Elena Cartagena; Mariana Alva, Susana Montanaro, Alicia Bardón
      Abstract: This is a report on the synergistic interactions (SIs) between melampolide‐type sesquiterpene lactones 1–8 from Acanthospermum hispidum DC., and oxacillin or gentamicin, against four pathogenic strains of Staphylococcus aureus and Enterococcus faecalis; two of them were multi‐resistant strains obtained from chronic infectious processes. Our results showed that all associations of 1–8 with antibiotics (ATBs) are more effective than pure ATBs to control pathogenic strains of S. aureus and E. faecalis. The most relevant SIs were observed when the major lactone of A. hispidum, acanthospermal B [5], was combined with gentamicin (protein synthesis inhibitor) against an ex vivo culture of methicillin‐resistant S. aureus SAR 1, displaying a significant MIC reduction in 5 (312.5 to 78.1 µg/mL), and gentamicin (120 µg/mL to 3 µg/mL). Compound 4 improved the antibiotic potency of oxacillin (cell wall synthesis inhibitor) against ampicillin‐resistant E. faecalis (60 µg/mL to 1.5 µg/mL). It is important to remark that three beneficial lactobacilli were resistant to 1–8 and their mixtures with gentamicin or oxacillin in effective concentrations against pathogenic bacteria. Synergism between ATBs and phytochemicals is a therapeutically helpful concept to improve ATB efficacy and prevent resistance. The present results show that selective SIs occur between melampolides and gentamicin or oxacillin, and open a new field of research. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-02-02T01:23:35.949148-05:
      DOI: 10.1002/ptr.5301
  • Differential Regulation of Calcium Signalling Pathways by Components of
           Piper methysticum ('Awa)
    • Authors: L. M. N. Shimoda; A. Showman, J. D. Baker, I. Lange, D. L. Koomoa, A. J. Stokes, R. P. Borris, H. Turner
      Abstract: Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA‐ergic effects of the well‐characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS‐targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium‐mobilizing activity of traditionally prepared and partially HPLC‐purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin‐sensitive and ‐insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non‐store‐operated pathways. Together with the pepper‐like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP‐like conductances are observed in kava‐treated cells under patch clamp. Thus TRP‐mediated cellular effects may be responsible for some of the reported pharmacology of kava. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T04:48:04.430987-05:
      DOI: 10.1002/ptr.5291
  • Phytochemical and Pharmacological Profile of Vitex negundo
    • Authors: Cheng‐Jian Zheng; Hua‐Qiang Li, Shan‐Cheng Ren, Chuan‐Liang Xu, Khalid Rahman, Lu‐Ping Qin, Ying‐Hao Sun
      Abstract: The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti‐nociceptive, antiinflammatory, anti‐tumor, anti‐oxidant, insecticidal, antimicrobial, anti‐androgenic, anti‐osteoporotic, anti‐cataract, hepatoprotective and anti‐hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure–activity relationship and their molecular mechanisms of action. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T04:47:58.268409-05:
      DOI: 10.1002/ptr.5303
  • Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from
           Traditional Chinese Herbs
    • Authors: Yong Zhao; Bent Håvard Hellum, Aihua Liang, Odd Georg Nilsen
      Abstract: The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed by time‐dependent and nicotinamide adenine dinucleotide phosphate‐dependent and reversible inhibition by Lineweaver–Burk plot assessments. Inhibition mechanisms were also assessed by computerized interaction prediction by using the Discovery Studio CDOCKER software (Accelrys, San Diego, CA, USA). Tetrahydropalmatine showed a mechanism‐based inhibition of both CYP1A2 and CYP2D6, and Ber of CYP2D6. Neferine and Ber both showed a nonmechanistic inhibition of CYP1A2. All compounds showed a similar and significant mechanism‐based inhibition of CYP3A4. Tetrahydropalmatine and Ber demonstrated both reversible and irreversible inhibition of CYP2D6 and CYP3A4. Tetrahydropalmatine and Ber displayed H‐bond and several Pi‐bond connections with specific amino acid residues of CYP1A2, CYP2D6 and CYP3A4, giving further knowledge to the identified reversible and irreversible herb–drug interactions. Tetrahydropalmatine and Ber should be considered for herb–drug interactions in clinical therapy until relevant clinical studies are available. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T03:03:13.149626-05:
      DOI: 10.1002/ptr.5285
  • Pharmacological Activity of 6‐Gingerol in Dextran Sulphate
           Sodium‐induced Ulcerative Colitis in BALB/c Mice
    • Authors: Babajide O. Ajayi; Isaac A. Adedara, Ebenezer O. Farombi
      Abstract: Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6‐gingerol in a mouse model of dextran sulphate sodium (DSS)‐induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co‐treated with 6‐gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment‐related effects of 6‐gingerol in DSS‐treated mice. Administration of 6‐gingerol significantly reversed the DSS‐mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6‐gingerol significantly suppressed the circulating concentrations of interleukin‐1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS‐treated mice. 6‐Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS‐treated mice. 6‐Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-29T02:38:40.432521-05:
      DOI: 10.1002/ptr.5286
  • Therapeutic Potential of Resveratrol in Type I Gaucher Disease
    • Authors: Cheong Hoon Seo; June‐Bum Kim
      Abstract: Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti‐inflammatory, anti‐oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis‐inducing factor (AIF), Bax, cleaved caspase‐3, acetyl‐coenzyme A acetyltransferase 1 (ACAT1), E3‐binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol‐treated patient cells were determined by thin‐layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase‐3 dose‐dependently decreased, while those of ACAT1, E3BP, and CS dose‐dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:54:46.076223-05:
      DOI: 10.1002/ptr.5304
  • Effects of Jitai Tablet, A Traditional Chinese Medicine, on Spontaneous
           Withdrawal Symptoms and Modulation of Dopaminergic Functions in
           Morphine‐Dependent Rats
    • Authors: Shaoang Tu; Jinlong Gao, Jia Liu, Jinming Zhang, Yiyun Huang, Shasha Xu, Mei Han, Jianhui Liang
      Abstract: Chronic opioid abuse can cause damage to dopamine neurons. However, there are currently no effective pharmacotherapies to reverse this damage, even though progress has been made in the development of therapeutic strategies for opioid dependence. The Jitai tablet (JTT) is a traditional Chinese medicine formulation most commonly used for opioid addiction treatment in China. In a morphine spontaneous withdrawal rat model we investigated the effects of JTT, either given before (pre‐treatment) or after (post‐treatment) morphine administration, on the dopamine system. Our study has shown the following: (1) pre‐ and post‐treatment with JTT were effective at alleviating the wet dog shakes and episodes of writhing; (2) pre‐treatment with JTT inhibited the morphine‐induced decreases in dopamine transporter (DAT), dopamine D2 receptor (D2R) and tyrosine hydroxylase (TH) levels in the striatum (p 
      PubDate: 2015-01-27T04:50:18.412115-05:
      DOI: 10.1002/ptr.5300
  • Inhibition of Wnt/β‐Catenin Pathway by Dehydrocostus Lactone
           and Costunolide in Colon Cancer Cells
    • Authors: Guang‐zhi Dong; Ah‐Ram Shim, Jin Seong Hyeon, Hwa Jin Lee, Jae‐Ha Ryu
      Abstract: Abnormal activation of β‐catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β‐catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti‐colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β‐catenin. They also suppressed the nuclear translocation of galectin‐3 that is one of the coactivators of β‐catenin in SW‐480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW‐480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti‐colorectal cancer activities through inhibiting Wnt/β‐catenin pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:31:50.643179-05:
      DOI: 10.1002/ptr.5299
  • Effect of Resveratrol on the Pharmacokinetics of Carbamazepine in Healthy
           Human Volunteers
    • Authors: Satish Kumar Bedada; Prasad Nearati
      Abstract: The purpose of the present study was to assess the effect of resveratrol (RSV) pretreatment on CYP3A4 enzyme activity and pharmacokinetics of carbamazepine (CBZ) in healthy human volunteers. The open‐label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC‐MS/MS. In comparison with the control, RSV pretreatment significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC), and half life (t1/2) and significantly decreased apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F), while there was no significant change observed in time to reach maximum concentration (tmax) and elimination rate constant (kel) of CBZ. Furthermore, RSV pretreatment significantly decreased metabolite to parent (CBZE/CBZ) ratios of Cmax and AUC and significantly increased CBZE/CBZ ratios of CL/F and Vd/F, indicating the reduced formation of CBZE to CBZ. The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to RSV‐mediated inhibition of CYP3A4 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CBZ including other CYP3A4 substrates. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T01:28:30.851783-05:
      DOI: 10.1002/ptr.5302
  • A Critical Evaluation of the Clinical Evidence for Pomegranate
           Preparations in the Prevention and Treatment of Cardiovascular Diseases
    • Authors: Christian Vlachojannis; Paul Erne, Andreas W. Schoenenberger, Sigrun Chrubasik‐Hausmann
      Abstract: This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co‐active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose‐finding and long‐term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-22T03:36:42.678012-05:
      DOI: 10.1002/ptr.5280
  • The Potential Drug–Drug Interactions of Ginkgolide B Mediated by
           Renal Transporters
    • Authors: Zhixia Qiu; Lei Wang, Yu Dai, Weichao Ren, Wenwen Jiang, Xijing Chen, Ning Li
      Abstract: Ginkgolide B (GB) is a selective and strong antagonist of platelet‐activating factor with great benefits in CNS diseases treatment. The renal excretion constitutes the predominant secretory pathway of GB. Here, we investigated the potential role of renal drug transporters in GB urinary excretion. The intravenous administration of GB was conducted at 10 min post‐administration of probenecid (potential inhibitor of organic anion transporters/organic anion transporting polypeptides) or bromosulfophthalein (traditional inhibitor of multi‐drug resistance proteins) in rats. Pretreated with probenecid, the systemic exposure of GB was significantly elevated from 8.319 ± 1.646 to 14.75 ± 1.328 µg · mL−1∙h but with reduced total clearance from 1.17 ± 0.331 to 0.596 ± 0.0573 L · h−1∙kg−1 accompanying no changes in plasma elimination half‐lives compared with control group. With no pronounced effect on metabolic elimination, the decreased total clearance was closely pertained to the reduced renal excretion, indicating the potential effect of organic anion transporters and/or organic anion transporting polypeptides in renal secretory of GB from blood to urine. However, the possible effect of bromosulfophthalein was restricted within a minor extent, suggesting the mild role of multi‐drug resistance protein in GB renal excretion. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-15T01:36:22.408534-05:
      DOI: 10.1002/ptr.5294
  • Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in
           Hamsters Fed High‐Fat diet
    • Authors: Na Ning; Kai He, Yanzhi Wang, Zongyao Zou, Hao Wu, Xuegang Li, Xiaoli Ye
      Abstract: Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high‐fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up‐regulated low‐density lipoprotein receptor (LDLR) and cholesterol 7α‐hydroxylase (CYP7A1) mRNA and protein expression and down‐regulated apical sodium‐dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up‐regulating LDLR and CYP7A1 mRNA and protein expression, down‐regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T06:08:56.778367-05:
      DOI: 10.1002/ptr.5295
  • Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Induces Gene
           Expression of Anti‐viral Proteins and Inhibits Neuraminidase
    • Authors: Crystal Y.Q. Du; Ken Y.Z. Zheng, Cathy WC Bi, Tina T.X. Dong, Huangquan Lin, Karl W.K. Tsim
      Abstract: Yu Ping Feng San (YPFS), a Chinese herbal decoction comprised of Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu) and Saposhnikoviae Radix (Fangfeng), has been used clinically for colds and flus; however, the action mechanism of which is not known. Previously, we had demonstrated that YPFS could modulate inflammatory response and phagocytosis in exerting anti‐viral and anti‐bacterial effects. Here, we further evaluated the bioactivities of YPFS in gene expression regulated by interferon (IFN) signaling and neuraminidase activity of influenza virus A. Application of YPFS onto cultured murine macrophages, the expressions of mRNAs encoding ribonuclease L (RNaseL), myxovirus (influenza virus) resistance 2 (Mx2), protein kinase R (PKR) and IFN‐stimulated gene 15 (ISG15) were induced from 2 to 30 folds in dose‐dependent manners. In parallel, the transcriptional activity of IFN‐stimulated response element (ISRE), an up stream regulator of the above anti‐viral proteins, was also triggered by YPFS treatment. Conversely, YPFS was found to suppress the neuraminidase activity of influenza virus A in cultured epithelial cells, thereby preventing the viral release and spreading. Taken together, YPFS exerted anti‐bacterial and anti‐viral effects in innate immunity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T05:11:23.524911-05:
      DOI: 10.1002/ptr.5290
  • Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian
           Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells
    • Authors: Ya‐Fang Wang; Ting Li, Zheng‐Hai Tang, Lin‐Lin Chang, Hong Zhu, Xiu‐Ping Chen, Yi‐Tao Wang, Jin‐Jian Lu
      Abstract: Baicalein (BA), isolated from the Chinese medicinal herb Scutellariae radix (Huangqin in Chinese), is a flavonoid with various pharmacological effects. Herein, we found that BA only slightly reduced the cell viability on HepG2 cells after 24‐h treatment as determined by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay. However, BA (50 μM) effectively blocked the colony formation. Meanwhile, BA remarkably induced the formation of autophagosomes after 24‐h treatment as determined by immunofluorescence with monodansylcadaverine staining as well as transmission electron microscopy, respectively. Moreover, BA obviously up‐regulated the expression of microtubule‐associated protein 1A/1B‐light chain 3‐II in concentration‐dependent and time‐dependent manners in HepG2 cells. When combined with the autophagy inhibitor chloroquine and BA, the cell viability and colony formation were significantly decreased, indicating that BA triggered protective autophagy, which prevented cell death. Further study showed that BA concentration‐dependently and time‐dependently decreased the expression of p‐AKT (S473), p‐ULK1 (S757) and p‐4EBP1 (T37 and S65), suggesting the involvement of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) in BA‐triggered autophagy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T00:24:05.728965-05:
      DOI: 10.1002/ptr.5298
  • The Genus Trollius—Review of Pharmacological and Chemical Research
    • Authors: Ewa Witkowska‐Banaszczak
      First page: 475
      Abstract: Three species of the genus Trollius (Ranunculaceae) are traditionally used to treat upper respiratory tract infections, pharyngitis, tonsillitis, bronchitis, cold with fever, acute tympanitis, aphthae, mouth sore, hemorrhage and pain of gums, acute lymphangitis and acute periostitis. However, only a few studies support its traditional use. These are studies of the biological activity of extracts and/or compounds of selected species of Trollius, but there are no clinical studies proving the effectiveness or possible toxic effects. Until now, the following activity of extracts and/or compounds from certain species of Trollius used in traditional medicine has been proven: antiviral, antibacterial, antiinflammatory and antioxidant. The review showed that flavonoids, mainly C‐glycosides, were characteristic of the species Trollius. Furthermore, other main groups of compounds are carotenoids, organic acids, terpenes, alkaloids, sterols, lactones and carbohydrates. The essential oil mainly contains compounds from the group of benzenoids, nitrogen‐containing compounds, monoterpenoids and sesquiterpenoids, irregular terpenes and macrocyclic epoxide. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-09T02:51:03.351215-05:
      DOI: 10.1002/ptr.5277
  • Influence of Polyphenols on the Physiological Processes in the Skin
    • Authors: Anna Ratz‐Łyko; Jacek Arct, Sławomir Majewski, Katarzyna Pytkowska
      First page: 509
      Abstract: In the last decade antioxidants from a group of polyphenols have been proposed as one of the most effective functional ingredients of anti‐ageing properties that counteract the effects of oxidative damage to the skin. It has been shown that the use of polyphenols affects skin protection and mitigates inflammatory conditions of the skin. Numerous studies have confirmed that polyphenols by neutralizing free radicals, antioxidant activity and by their ability to chelate ions of transition metals can effectively reduce the level of nonprotein inflammatory mediators. The biological activity of polyphenols in the skin is primarily determined by their physicochemical properties and the ability to overcome the epidermal barrier as they try to reach appropriate receptors. This study reviews literature on the effects of polyphenols relating to the physiological processes in the skin and role of the major plant polyphenols in cosmetology and dermatology. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T06:15:51.406535-05:
      DOI: 10.1002/ptr.5289
  • Characterisation of Antimicrobial Extracts from Dandelion Root (Taraxacum
           officinale) Using LC‐SPE‐NMR
    • Authors: O. Kenny; N. P. Brunton, D. Walsh, C. M. Hewage, P. McLoughlin, T. J. Smyth
      First page: 526
      Abstract: Plant extracts have traditionally been used as sources of natural antimicrobial compounds, although in many cases, the compounds responsible for their antimicrobial efficacy have not been identified. In this study, crude and dialysed extracts from dandelion root (Taraxacum officinale) were evaluated for their antimicrobial properties against Gram positive and Gram negative bacterial strains. The methanol hydrophobic crude extract (DRE3) demonstrated the strongest inhibition of microbial growth against Staphylococcus aureus, methicillin‐resistant S. aureus and Bacillus cereus strains. Normal phase (NP) fractionation of DRE3 resulted in two fractions (NPF4 and NPF5) with enhanced antimicrobial activity. Further NP fractionation of NPF4 resulted in two fractions (NPF403 and NPF406) with increased antimicrobial activity. Further isolation and characterisation of compounds in NPF406 using liquid chromatography solid phase extraction nuclear magnetic resonance LC‐SPE‐NMR resulted in the identification of 9‐hydroxyoctadecatrienoic acid and 9‐hydroxyoctadecadienoic acid, while the phenolic compounds vanillin, coniferaldehyde and p‐methoxyphenylglyoxylic acid were also identified respectively. The molecular mass of these compounds was confirmed by LC mass spectroscopy (MS)/MS. In summary, the antimicrobial efficacy of dandelion root extracts demonstrated in this study support the use of dandelion root as a source of natural antimicrobial compounds. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-21T04:35:36.001171-05:
      DOI: 10.1002/ptr.5276
  • Effects of Total Flavones from Acanthopanax senticosus on L‐type
           Calcium Channels, Calcium Transient and Contractility in Rat Ventricular
    • Authors: Shengjiang Guan; Juanjuan Ma, Xi Chu, Yonggang Gao, Ying Zhang, Xuan Zhang, Fenghua Zhang, Zhenyi Liu, Jianping Zhang, Li Chu
      First page: 533
      Abstract: Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L‐type Ca2+ channel currents (ICa‐L) using the whole cell patch‐clamp technique and on intracellular calcium ([Ca2+]i) handling and cell contractility in rat ventricular myocytes with the aid of a video‐based edge‐detection system. Exposure to TFAS resulted in a concentration‐ and voltage‐dependent blockade of ICa‐L, with the half‐maximal inhibitory concentration (IC50) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current–voltage relationship but also shifted the activation and inactivation curves of ICa‐L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca2+]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca2+]i through the direct inhibition of ICa‐L in rat ventricular myocytes and consequent negative effect on myocardial contractility. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T00:09:58.09954-05:0
      DOI: 10.1002/ptr.5278
  • The Anti‐Osteoporosis and Antioxidant Activities of Chemical
           Constituents from Chrysanthemum indicum Flowers
    • Authors: Bui Thi Thuy Luyen; Bui Huu Tai, Nguyen Phuong Thao, Young Mi Lee, Sang Hyun Lee, Hae Dong Jang, Young Ho Kim
      First page: 540
      Abstract: Two new compounds, chrysinoneside A (1) and (−)‐trans‐chrysanthenol‐6‐O‐β‐D‐glucopyranoside (2), along with 17 known compounds (3–19) were isolated from Chrysanthemum indicum flowers. The total phenolic and flavonoid contents of various fractions were determined. The EtOAC fraction had the highest total phenolic content (525.84 ± 23.51 mg GAE/g DR) and the total flavonoid content (63.49 ± 3.32 mg QE/g DR). The EtOAc and water fractions showed the greatest peroxyl radical‐scavenging capacity and the ability to reduce Cu(I) ions, with ORAC and CUPRAC values ranging from 24.00 ± 0.44 to 28.06 ± 1.35 and 16.90 ± 0.51 to 49.77 ± 0.97 μM, respectively. Compounds 5–11, 18, and 19 displayed strong effects in both peroxyl radical‐scavenging and reducing capacity assays at a concentration of 10 μM. The anti‐osteoporosis activity of these compounds was also evaluated. Compounds 10, 13, and 19 exhibited the most potent tartrate‐resistant acid phosphatase activity in receptor activator of nuclear factor‐κB ligand‐induced osteoclastic RAW 264.7 cells with values of 105.95 ± 1.18, 110.32 ± 3.95, and 112.58 ± 6.42%, respectively. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-19T05:04:26.090938-05:
      DOI: 10.1002/ptr.5281
  • Multifunctional Activity of Polyphenolic Compounds Associated with a
           Potential for Alzheimer's Disease Therapy from Ecklonia cava
    • Authors: Byoung Wook Choi; Hye Sook Lee, Hyeon‐Cheol Shin, Bong Ho Lee
      First page: 549
      Abstract: Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 μM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol‐A (PFF‐A), showed a particularly potent inhibitory activity (IC50 0.95 μM), which is over 100‐fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aβ. Bieckol and PFF‐A inhibited amyloid precursor protein biosynthesis. PFF‐A also showed very strong β‐secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T04:19:29.519985-05:
      DOI: 10.1002/ptr.5282
  • Isolation of a Novel Antibacterial Phenyl Thioketone from the Seagrass,
           Cymodocea serrulata
    • Authors: K. Mary Elizabeth Gnanambal; Jamila Patterson, Edward J. K. Patterson
      First page: 554
      Abstract: A total of 40 extract types of varying polarities from commonly occurring seagrasses were tested for their antibacterial efficiency against 14 clinically isolated human pathogens using agar well diffusion technique. The extracts from acetone of Cymodocea serrulata expressed moderate broad span of activity against a range of gram‐positive and gram‐negative isolates that were at least resistant to five of the commercially available antibiotics at a minimal concentration of 10 µg. The active extracts of C. serrulata that showed maximal inhibitions were purified using column chromatography that afforded six compounds (a–f). Compound f elicited pronounced inhibitions against Escherichia coli with minimal inhibitory concentration values of 1–3 µg concentration using micro‐dilution method. The active compound was identified as phenyl thioketone using various spectral analyses. This is the first investigation that reveals thioketone functionality from this seagrass species possessing antibacterial actions. This study indicates that there are thiocarbonyl groups from marine floral sources too, which could be possibly used for therapeutic purposes. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T04:25:52.954277-05:
      DOI: 10.1002/ptr.5283
  • Quantification of Anthocyanins in Elderberry and Chokeberry Dietary
    • Authors: Christian Vlachojannis; Benno F. Zimmermann, Sigrun Chrubasik‐Hausmann
      First page: 561
      Abstract: Elderberry and chokeberry food supplements may be ‘functional food’ in patients with metabolic syndrome or influenza but, for this, adequate amounts of co‐active ingredients must be consumed in the daily dose. This study aimed to quantify the anthocyanin content in three elderberry and six chokeberry products to assess their usefulness as functional food. Analyses were carried out using an established HPLC procedure. The minimum anthocyanin doses for the treatment of metabolic syndrome disorders were estimated as 110 mg per day and 3.5 g per day for influenza. Three products were inappropriate for clinical use. The lowest liquid supplies were achieved with a proprietary elderberry concentrate (11 mL) and a proprietary chokeberry mother juice (100 mL). Clinical studies are now required to prove the effectiveness and adapt the doses according to the clinical symptoms. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-19T04:55:07.868239-05:
      DOI: 10.1002/ptr.5284
  • A p‐Menth‐1‐ene‐4,7‐diol (EC‐1) from
           Eucalyptus camaldulensis Dhnh. Triggers Apoptosis and Cell Cycle Changes
           in Ehrlich Ascites Carcinoma Cells
    • Authors: Farhadul Islam; Jahan Ara Khanam, Mahbuba Khatun, Natasha Zuberi, Laboni Khatun, Syed Rashel Kabir, Md Abu Reza, MM Ali, M A Rabbi, Vinod Gopalan, Alfred King‐Yin Lam
      First page: 573
      Abstract: Anticancer activities of p‐menth‐1‐ene‐4,7‐diol (EC‐1) isolated from Eucalyptus camaldulensis Dhnh. were studied on Ehrlich ascites carcinoma (EAC) cells by MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) assay. Anticancer activities also analyzed in EAC‐bearing mice by assessment of cancer growth inhibition, changes in cancer volume, changes in life span, and hematological parameters. Apoptosis was analyzed by fluorescence microscope, DNA fragmentation assay, and flow cytometry. The expression of apoptosis‐related genes, Bcl‐2, Bcl‐X, PARP‐1, p53, and Bax, were analyzed using polymerase chain reaction (PCR). EC‐1 significantly inhibited proliferation of EAC cells in vivo and restored the altered hematological parameters of EAC‐bearing mice. Cytological observation by fluorescence microscope showed apoptosis of EAC cells upon treatment with EC‐1. Also, DNA fragmentation assay revealed EAC cells' apoptosis following EC‐1 treatment. Increased mRNA expressions of p53 and Bax genes and negative expressions of Bcl‐2 and Bcl‐X were observed in cells treated with EC‐1. These findings confirmed the induction of apoptosis by EC‐1. In addition, MTT assay showed dose‐dependent anticancer activity of EC‐1 against EAC cell. Cell cycle analysis revealed that EC‐1 treatment caused suppression of EAC cells at S phase. To conclude, EC‐1 is a novel anticancer compound and showed antiproliferative and apoptotic activities in cellular and mice models. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-13T03:41:56.647091-05:
      DOI: 10.1002/ptr.5288
  • Effects of the Flavanone combination Hesperetin‐Naringenin, and
           Orange and Grapefruit Juices, on Airway inflammation and Remodeling in a
           murine asthma model
    • Authors: Ensiyeh Seyedrezazadeh; Saeed Kolahian, Amir‐Ali Shahbazfar, Khalil Ansarin, Masoud Pour Moghaddam, Masoud Sakhinia, Ebrahim Sakhinia, Mohammadreza Vafa
      First page: 591
      Abstract: We investigated whether flavanones, hesperetin–naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non‐asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra‐alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM‐induced asthma. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-15T23:13:51.903739-05:
      DOI: 10.1002/ptr.5292
  • Astragaloside IV Attenuates Injury Caused by Myocardial
           Ischemia/Reperfusion in Rats via Regulation of Toll‐Like Receptor
           4/Nuclear Factor‐κB Signaling Pathway
    • Authors: Meili Lu; Futian Tang, Jing Zhang, Aina Luan, Meng Mei, Chonghua Xu, Suping Zhang, Hongxin Wang, Leonid N. Maslov
      First page: 599
      Abstract: Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll‐like receptor 4 (TLR4) and nuclear factor‐κB (NF‐κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF‐κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B‐cell lymphoma‐2 associated X protein and caspase‐3 expressions and increased B‐cell lymphoma‐2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF‐κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-21T04:54:40.07202-05:0
      DOI: 10.1002/ptr.5297
  • PI3K‐Mediated Proliferation of Fibroblasts by Calendula officinalis
           Tincture: Implication in Wound Healing
    • Authors: Manikarna Dinda; Uma Dasgupta, Namrata Singh, Debasish Bhattacharyya, Parimal Karmakar
      First page: 607
      Abstract: Calendula officinalis, a member of the Asteraceae family, is a flowering plant and has been used for its antibacterial, antifungal, antiviral, antiinflammatory, anticancer and wound healing activity. The mode of action of C. officinalis tincture on wound healing is poorly understood. Here, we investigated the role of C. officinalis tincture (CDOT) on cell viability and wound closure. C. officinalis tincture stimulated both proliferation and migration of fibroblasts in a statistically significant manner in a PI3K‐dependent pathway. The increase in phosphorylation of FAK (Tyr 397) and Akt (Ser 473) was detected after treatment of CDOT. Inhibition of the PI3K pathway by wortmannin and LY294002 decreased both cell proliferation and cell migration. HPLC‐ESI MS revealed the presence of flavonol glycosides as the major compounds of CDOT. Altogether, our results showed that CDOT potentiated wound healing by stimulating proliferation and migration of fibroblast in a PI3K‐dependent pathway, and the identified compounds are likely to be responsible for wound healing activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-13T04:02:38.806096-05:
      DOI: 10.1002/ptr.5293
  • Safranal of Crocus sativus L. Inhibits Inducible Nitric Oxide Synthase and
           Attenuates Asthma in a Mouse Model of Asthma
    • Authors: Syed Imran Bukhari; Bijay Pattnaik, Sheikh Rayees, Sanjana Kaul, Manoj K. Dhar
      First page: 617
      Abstract: The present study involves evaluation of antioxidant potential of Crocus sativus and its main constituents, safranal (SFN) and crocin (CRO), in bronchial epithelial cells, followed antiinflammatory potential of the active constituent safranal, in a murine model of asthma. To investigate the antioxidizing potential of Crocus sativus and its main constituents in bronchial epithelial cells, the stress was induced in these cells by a combination of different cytokines that resulted in an increase in nitric oxide production (NO), induced nitric oxide synthase (iNOS) levels, peroxynitrite ion generation, and cytochrome c release. Treatment with saffron and its constituents safranal and crocin resulted in a decrease of NO, iNOS levels, peroxynitrite ion generation, and prevented cytochrome c release. However, safranal significantly reduced oxidative stress in bronchial epithelial cells via iNOS reduction besides preventing apoptosis in these cells. In the murine model of asthma study, antiinflammatory role of safranal was characterized by increased airway hyper‐responsiveness, airway cellular infiltration, and epithelial cell injury. Safranal pretreatment to these allergically inflamed mice lead to a significant decrease in airway hyper‐responsiveness and airway cellular infiltration to the lungs. It also reduced iNOS production, bronchial epithelial cell apoptosis, and Th2 type cytokine production in the lungs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-03-10T04:57:22.240213-05:
      DOI: 10.1002/ptr.5315
  • Reversion of Nitrate Tolerance in Rat Aorta Rings by Freeze‐dried
           Red Wine
    • Authors: Fabio Fusi; Giampietro Sgaragli
      First page: 628
      Abstract: Chronically administered organic nitrates induce nitrate tolerance and endothelial dysfunction, which limit their therapeutic use. eNOS uncoupling, ROS over‐production, aldehyde dehydrogenase‐2 as well as superoxide dismutase (SOD) oxidative inhibition, and cGMP desensitization are thought to play an important role. Natural polyphenols are effective antioxidants, which might counteract the mechanisms leading to nitrate tolerance. The aim of this work was to verify whether freeze‐dried (dealcoholized) red wine (FDRW) was able to revert glyceryl trinitrate (GTN) tolerance and endothelial dysfunction induced in rat aorta rings with either GTN or diethyldithiocarbamate (DETCA), an irreversible inhibitor of Cu/Zn SOD. GTN induced a concentration‐dependent relaxation of rings pre‐contracted with phenylephrine. GTN spasmolysis was significantly reduced in rings pre‐incubated with either GTN or DETCA. FDRW, at 2.8 µg of gallic acid equivalents (GAE)/mL concentration, was able to revert partially, though significantly, GTN‐induced tolerance but not tolerance and endothelial dysfunction induced by DETCA. This work provides the first evidence in vitro that red wine components, at concentrations comparable to those achieved in human blood after moderate consumption of red wine, revert tolerance to nitrates with a mechanism possibly mediated by SOD. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-10T03:22:10.337361-05:
      DOI: 10.1002/ptr.5287
  • Did Ebola Survivors Use Plant Medicines, and if so, Which Ones'
    • Authors: Solomon Habtemariam; Giovanni Lentini
      First page: 632
      Abstract: In the absence of any known therapeutically useful drug or vaccine available to combat Ebola, the disease has emerged as one of the most globally important crisis of the year. In the affected West African regions, no one seems to know what drug to use or even try on Ebola patients, while in the West, the debate on discovering new drugs versus repurposing old ones is heating up. Because Ebola affected countries are highly reliant on traditional medicines, we herewith suggest recording plants used by Ebola survivors as they may serve as sources of novel therapeutic agents in the future. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T00:09:49.595739-05:
      DOI: 10.1002/ptr.5279
  • Complementary Usage of Rhodiola crenulata (L.) in Chronic Obstructive
           Pulmonary Disease Patients: The Effects on Cytokines and T Cells
    • Authors: Shih‐Pin Chen; Rosa Huang Liu, Tsong‐Ming Lu, James Cheng‐Chung Wei, Tzu‐Chin Wu, Wei‐Yu Tsai, Chung‐Hung Tsai, Chi‐Chiang Yang
      First page: 518
      Abstract: Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age‐matched, and sex‐matched non‐COPD control subjects. Our results showed that serum levels of IL‐2, IL‐10, and IFN‐γ in COPD patients before treatment are significantly higher than levels in non‐COPD controls (p 
      PubDate: 2014-11-18T05:27:22.558269-05:
      DOI: 10.1002/ptr.5259
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