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Pacific Focus     Hybrid Journal   (Followers: 1, SJR: 0.256, h-index: 4)
Pacific Philosophical Quarterly     Hybrid Journal   (Followers: 7, SJR: 0.317, h-index: 12)
Pacing and Clinical Electrophysiology     Hybrid Journal   (Followers: 4, SJR: 0.966, h-index: 69)
Packaging Technology and Science     Hybrid Journal   (Followers: 10, SJR: 0.463, h-index: 24)
Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 3, SJR: 1.092, h-index: 54)
Pain Medicine     Hybrid Journal   (Followers: 6, SJR: 0.776, h-index: 48)
Pain Practice     Hybrid Journal   (Followers: 2, SJR: 0.652, h-index: 25)
Palaeontology     Hybrid Journal   (Followers: 12, SJR: 0.759, h-index: 36)
PAMM : Proceedings in Applied Mathematics and Mechanics     Free  
Papers In Regional Science     Hybrid Journal   (Followers: 6, SJR: 1.315, h-index: 29)
Parasite Immunology     Hybrid Journal   (Followers: 3, SJR: 0.804, h-index: 51)
Parliamentary History     Hybrid Journal   (Followers: 3, SJR: 0.122, h-index: 2)
Particle & Particle Systems Characterization     Hybrid Journal   (SJR: 0.255, h-index: 26)
Pathogens and Disease     Hybrid Journal  
Pathology Intl.     Hybrid Journal   (SJR: 0.657, h-index: 48)
Peace & Change     Hybrid Journal   (Followers: 4)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 4, SJR: 1.295, h-index: 56)
Pediatric Anesthesia     Hybrid Journal   (Followers: 2, SJR: 0.994, h-index: 47)
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 2, SJR: 0.952, h-index: 60)
Pediatric Dermatology     Hybrid Journal   (Followers: 5, SJR: 0.57, h-index: 44)
Pediatric Diabetes     Hybrid Journal   (Followers: 14, SJR: 1.203, h-index: 36)
Pediatric Obesity     Hybrid Journal   (Followers: 4, SJR: 1.156, h-index: 26)
Pediatric Pulmonology     Hybrid Journal   (Followers: 2, SJR: 0.771, h-index: 72)
Pediatric Transplantation     Hybrid Journal   (SJR: 0.557, h-index: 45)
Pediatrics Intl.     Hybrid Journal   (Followers: 3, SJR: 0.366, h-index: 38)
Performance Improvement     Hybrid Journal   (Followers: 2)
Performance Improvement Quarterly     Hybrid Journal   (Followers: 1, SJR: 0.281, h-index: 5)
Periodontology 2000     Hybrid Journal   (Followers: 2, SJR: 1.112, h-index: 66)
Permafrost and Periglacial Processes     Hybrid Journal   (Followers: 3, SJR: 1.772, h-index: 42)
Personal Relationships     Hybrid Journal   (Followers: 3, SJR: 0.659, h-index: 41)
Personality and Mental Health     Hybrid Journal   (Followers: 10, SJR: 0.313, h-index: 6)
Personnel Psychology     Hybrid Journal   (Followers: 14, SJR: 3.339, h-index: 71)
Perspectives In Psychiatric Care     Hybrid Journal   (Followers: 1, SJR: 0.431, h-index: 18)
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 3, SJR: 0.865, h-index: 60)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (Followers: 1, SJR: 0.213, h-index: 6)
Pest Management Science     Hybrid Journal   (Followers: 4, SJR: 0.99, h-index: 64)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 4, SJR: 0.659, h-index: 16)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 21, SJR: 1.397, h-index: 50)
Pharmacology Research & Perspectives     Open Access  
Pharmacotherapy The J. of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 13, SJR: 0.741, h-index: 71)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 1, SJR: 0.108, h-index: 9)
Philosophical Books     Hybrid Journal   (Followers: 7)
Philosophical Investigations     Hybrid Journal   (Followers: 3, SJR: 0.113, h-index: 6)
Philosophical Issues     Hybrid Journal   (Followers: 8, SJR: 0.174, h-index: 1)
Philosophical Perspectives     Hybrid Journal   (Followers: 6)
Philosophy & Public Affairs     Hybrid Journal   (Followers: 16, SJR: 1.818, h-index: 25)
Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 14, SJR: 0.852, h-index: 8)
Philosophy Compass     Hybrid Journal   (Followers: 7, SJR: 0, h-index: 1)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.709, h-index: 86)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 3, SJR: 0.694, h-index: 39)
Phycological Research     Hybrid Journal   (Followers: 2)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.788, h-index: 67)
physica status solidi (b)     Hybrid Journal   (Followers: 1, SJR: 0.775, h-index: 65)
physica status solidi (c)     Hybrid Journal   (Followers: 1, SJR: 0.397, h-index: 27)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (SJR: 1.275, h-index: 27)
Physik in unserer Zeit     Hybrid Journal  
Physik J.     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (Followers: 1, SJR: 1.358, h-index: 87)
Physiological Entomology     Hybrid Journal   (Followers: 2, SJR: 0.635, h-index: 35)
Physiological Reports     Open Access  
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 20, SJR: 0.273, h-index: 28)
Phytochemical Analysis     Hybrid Journal   (Followers: 1, SJR: 0.703, h-index: 39)
Phytotherapy Research     Hybrid Journal   (SJR: 0.718, h-index: 65)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 2, SJR: 1.86, h-index: 63)
Plant Biotechnology J.     Hybrid Journal   (Followers: 5, SJR: 2.052, h-index: 47)
Plant Breeding     Hybrid Journal   (Followers: 13, SJR: 0.625, h-index: 43)
Plant Pathology     Hybrid Journal   (Followers: 6, SJR: 0.997, h-index: 44)
Plant Species Biology     Hybrid Journal   (Followers: 2, SJR: 0.36, h-index: 25)
Plant, Cell & Environment     Hybrid Journal   (Followers: 4, SJR: 2.158, h-index: 112)
Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.124, h-index: 34)
Poe Studies     Partially Free   (Followers: 5)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 6, SJR: 0.147, h-index: 1)
Policy & Internet     Hybrid Journal   (Followers: 8)
Policy Studies J.     Hybrid Journal   (Followers: 5, SJR: 0.755, h-index: 25)
Political Insight     Partially Free   (Followers: 1)
Political Psychology     Hybrid Journal   (Followers: 14, SJR: 1.126, h-index: 40)
Political Science Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.35, h-index: 23)
Political Studies     Hybrid Journal   (Followers: 22, SJR: 0.922, h-index: 36)
Political Studies Review     Hybrid Journal   (Followers: 14, SJR: 0.837, h-index: 10)
Politics     Hybrid Journal   (Followers: 7, SJR: 0.438, h-index: 9)
Politics & Policy     Hybrid Journal   (Followers: 6, SJR: 0.294, h-index: 5)
Polymer Composites     Hybrid Journal   (Followers: 8, SJR: 0.623, h-index: 49)
Polymer Engineering & Science     Hybrid Journal   (Followers: 13, SJR: 0.62, h-index: 70)
Polymer Intl.     Hybrid Journal   (Followers: 2, SJR: 0.717, h-index: 61)
Polymers for Advanced Technologies     Hybrid Journal   (Followers: 3, SJR: 0.617, h-index: 51)
Population and Development Review     Hybrid Journal   (Followers: 3, SJR: 2.084, h-index: 50)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.42, h-index: 28)
Poverty & Public Policy     Hybrid Journal   (Followers: 11)
Practical Diabetes     Hybrid Journal   (Followers: 3)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 0.958, h-index: 64)
Prescriber     Hybrid Journal   (Followers: 7)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 3)
Preventive Cardiology     Hybrid Journal   (Followers: 3)
Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 26)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (Followers: 2, SJR: 0.268, h-index: 14)
Process Safety Progress     Hybrid Journal   (Followers: 2, SJR: 0.366, h-index: 20)
Production and Operations Management     Hybrid Journal   (Followers: 4, SJR: 2.479, h-index: 57)
Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)
Progress in Neurology and Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.133, h-index: 3)

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Journal Cover Phytotherapy Research
   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  [1602 journals]   [SJR: 0.718]   [H-I: 65]
  • Gelidium elegans, an Edible Red Seaweed, and Hesperidin Inhibit Lipid
           Accumulation and Production of Reactive Oxygen Species and Reactive
           Nitrogen Species in 3T3-L1 and RAW264.7 Cells
    • Authors: Hui-Jeon Jeon; Min-Jung Seo, Hyeon-Son Choi, Ok-Hwan Lee, Boo-Yong Lee
      Pages: n/a - n/a
      Abstract: Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3-L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose-dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide-induced nitric oxide production was significantly reduced in G. elegans extract-treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-15T21:57:27.017879-05:
      DOI: 10.1002/ptr.5186
  • Autophagy Activation and Antiviral Activity by a Licorice Triterpene
    • Authors: Samuela Laconi; Maria A. Madeddu, Raffaello Pompei
      Pages: n/a - n/a
      Abstract: The triterpene glycyrrhizic acid (GRA), the main product from the Glycyrrhiza glabra medicinal plant, is known for its antiinflammatory and antimicrobial activity. In this work, GRA was studied for its ability to induce the autophagic process activator Beclin 1 in epithelial cells and to observe how this property could influence its antiviral activity. After 24 h of treatment, GRA induced a Beclin 1 production that was more than twofold higher than that produced by rapamycin, used as a reference compound. When the compounds were added to HeLa cells together with the viruses, GRA demonstrated a strong antiherpes simplex virus type 1 (HSV1) activity, whereas rapamycin had no activity. However, if the compounds were added to the cells 24 h before the viruses, GRA induced the production of an even higher amount of Beclin 1 and showed an improved antiviral effect; under these conditions, rapamycin was also able to exert a significant anti-HSV1 activity. In conclusion, GRA is a strong inducer of the autophagy activator Beclin 1, which establishes a resistance state to HSV1 replication. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T19:32:09.58923-05:0
      DOI: 10.1002/ptr.5189
  • A Review of the Pharmacological Effects of Piceatannol on Cardiovascular
    • Authors: Yee-Ling Tang; Shun-Wan Chan
      Pages: n/a - n/a
      Abstract: The incidence of cardiovascular diseases (CVDs) is high in both developed and developing countries. It has a high global rate of mortality and causes heavy social burden. Drugs are available for managing or treating CVDs and its complications. Consumption of dietary supplements or functional foods for reducing the risk of CVDs has also gained wide recognition by the general public. Piceatannol, an analog and metabolite of resveratrol, is a natural stilbene commonly found in the skin of grapes and wine. Piceatannol is believed to be a potent compound with certain cardiovascular therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, and angiogenesis. It also has vasorelaxation and antioxidant activities. A comprehensive review of piceatannol concludes that piceatannol has the potential to be developed into health products for the cardiovascular system to help modern society reduce the high CVD incidence. However, further investigations are warranted in order to increase the bioavailability and understand the biological mechanisms and safety of using piceatannol. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T19:31:38.361145-05:
      DOI: 10.1002/ptr.5185
  • Review of Plants and Their Constituents in the Therapy of Cerebral
    • Authors: Effat Behravan; Bibi Marjan Razavi, Hossein Hosseinzadeh
      Pages: n/a - n/a
      Abstract: Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to cerebral hypoxia and thus to the death of neuronal cells or stroke. The limited number of medicines currently available for patients following ischemic stroke and insufficient data on efficiency of these chemicals in the treatment of stroke led us to the search for novel therapeutic approaches. Recent studies have focused on the possible capacity of natural compounds extracted from vegetables and fruits, to prevent human disabilities caused by cerebral ischemia. In this review, we will discuss some plants and their constituents that may protect brain ischemia or delay the neurological disorders following a stroke. We have reviewed different studies in scientific databases that investigate herbal compounds and their effects on cerebral ischemia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T19:30:22.966765-05:
      DOI: 10.1002/ptr.5187
  • Anxiolytic-Like Effect of Illicium verum Fruit Oil, trans-Anethole and
           Related Compounds in Mice
    • Authors: Michiyo Miyagawa; Tadaaki Satou, Chihiro Yukimune, Ayumi Ishibashi, Haruna Seimiya, Hideo Yamada, Toshio Hasegawa, Kazuo Koike
      Pages: n/a - n/a
      Abstract: The fruit of Illicium verum Hook. f. (star anise) is used by many as a spice. The fragrance of I. verum fruit is characteristically anise-like. In this study, hexane-extracted I. verum fruit oil (IVO), trans-anethole as the main component, and related compounds (propiophenone, 4′-methoxy-propiophenone, trans-β-methylstyrene) were analyzed in order to clarify the emotional effect of inhaling the fragrance of I. verum fruit. As a result, although 4 μL/L air IVO did not exhibit an anxiolytic-like effect, 1 μL/L air trans-anethole exhibited a significant effect (p 
      PubDate: 2014-06-11T19:21:50.92941-05:0
      DOI: 10.1002/ptr.5190
  • Modulating Effects of Pycnogenol® on Oxidative Stress and DNA Damage
           Induced by Sepsis in Rats
    • Authors: Gökçe Taner; Sevtap Ayd��n, Merve Bacanl��, Zehra Sar��göl, Tolga Şahin, A. Ahmet Başaran, Nurşen Başaran
      Pages: n/a - n/a
      Abstract: The aim of this study was to evaluate the protective effects of Pycnogenol® (Pyc), a complex plant extract from the bark of French maritime pine, on oxidative stress parameters (superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and total glutathione (GSH) and malondialdehyde (MDA) levels), an inflammatory cytokine (tumor necrosis factor alpha (TNF-α) level) and also DNA damage in Wistar albino rats. Rats were treated with 100 mg/kg intraperitonally Pyc following the induction of sepsis by cecal ligation and puncture. The decreases in MDA levels and increases in GSH levels, and SOD and GPx activities were observed in the livers and kidneys of Pyc-treated septic rats. Plasma TNF-α level was found to be decreased in the Pyc-treated septic rats. In the lymphocytes, kidney, and liver tissue cells of the sepsis-induced rats, Pyc treatment significantly decreased the DNA damage and oxidative base damage using standard alkaline assay and formamidopyrimidine DNA glycosylase-modified comet assay, respectively. In conclusion, Pyc treatment might have a role in the prevention of sepsis-induced oxidative damage not only by decreasing DNA damage but also increasing the antioxidant status and DNA repair capacity in rats. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T07:30:52.528985-05:
      DOI: 10.1002/ptr.5184
  • Black Tea Extract and its Thearubigins Relieve the
           Sildenafil‐Induced Delayed Gut Motility in Mice: A Possible Role of
           Nitric Oxide
    • Authors: Hussam A. S. Murad; Hossam M. Abdallah
      Abstract: In this study we hypothesize that a standardized black tea aqueous extract (BTE) and thearubigins, its main polyphenolic pigments, will improve sildenafil‐induced delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty groups of mice (n = 8) were given a phenol red meal, and three sets of experiments were performed. In the first and second sets, effects of different concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in combinations, on GE and SIT were measured. In the third set, influence of nω‐Nitro‐l‐arginine methyl ester hydrochloride (l‐NAME) pretreatment on effects of these treatments was tested.Black tea extract (3% and 4.5%) and thearubigins (50 and 60 mg/kg) dose‐dependently increased GE and SIT, whereas BTE 6% and thearubigins 70 mg/kg did not affect them. Sildenafil dose‐dependently reduced both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l‐NAME with sildenafil (5 mg/kg) reversed its motility‐delaying effects. Pretreatment with l‐NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% + sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a standardized BTE and its thearubigins improve the sildenafil‐induced delayed gut motility in mice. This improvement was partially blocked by l‐NAME suggesting a possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be considered a reliever therapy for the sildenafil‐induced dyspepsia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-03T20:03:23.448158-05:
      DOI: 10.1002/ptr.5183
  • Sulforaphane Suppresses LPS‐Induced or TPA‐Induced
           Downregulation of PDCD4 in RAW 264.7 Cells
    • Authors: Jong-Ho Cho; Young-Woo Kim, Young-Sam Keum
      Abstract: Sulforaphane is a natural chemopreventive isothiocyanate and abundantly found in various cruciferous vegetables. Although chemopreventive activity of sulforaphane is well documented, the detailed biochemical mechanism(s), underlying how it regulates the protein translation process to antagonize pro‐inflammatory responses are largely unclear. In the present study, we show that lipopolysaccharide (LPS) or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) treatment reduces cellular levels of PDCD4, and this event is mediated by affecting both transcription and proteolysis in RAW 264.7 cells. We show that LPS‐mediated or TPA‐mediated PDCD4 downregulation is catalyzed by the activation of intracellular Akt1 or S6K1 kinases and that sulforaphane suppresses LPS‐induced or TPA‐induced Akt1 or S6K1 activation, thereby resulting in the attenuation of PDCD4 downregulation in RAW 264.7 cells. We propose that sulforaphane suppression of PDCD4 downregulation serves as a novel molecular mechanism to control proliferation in response to pro‐inflammatory signals. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-03T20:02:40.855852-05:
      DOI: 10.1002/ptr.5171
  • Antiangiogenic Activity of Xanthomicrol and Calycopterin, Two
           Polymethoxylated Hydroxyflavones in Both In Vitro and Ex Vivo Models
    • Authors: Hassan Abbaszadeh; Soltan Ahmad Ebrahimi, Maziar Mohammad Akhavan
      Abstract: Our previous studies had shown xanthomicrol and calycopterin, two plant‐derived flavonoids, to have selective antiproliferative activity against some malignant cell lines. The present study is focused on the investigation of antiangiogenic potential of these two flavonoids, using in vitro and ex vivo models. Xanthomicrol and calycopterin were found to have potent inhibitory effects on microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to completely block microvessel sprouting at 10 µg/mL, and calycopterin suppressed microvessel outgrowth by 89% at 5 µg/mL. Suramin and thalidomide, used at 20 µg/mL as positive controls, inhibited microvessel formation by 23% and 64%, respectively. The flavones also inhibited endothelial cell tube formation and human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 µg/mL. In order to delineate the underlying mechanisms of antiangiogenic activity of these flavones, we investigated the influences of xanthomicrol and calycopterin on expression of vascular endothelial growth factor (VEGF) and basic‐fibroblast growth factor (b‐FGF) in endothelial cells. These flavones were able to inhibit VEGF expression at 0.5, 5, and 10 µg/mL, but they had little or no effect on b‐FGF expression. These findings suggest that xanthomicrol and calycopterin possess potent antiangiogenic activities, which may be due to their inhibitory influences on VEGF expression. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-03T19:59:53.601826-05:
      DOI: 10.1002/ptr.5179
  • Pomegranate Juice and Prostate Cancer: Importance of the Characterisation
           of the Active Principle
    • Authors: Sigrun Chrubasik-Hausmann; Christian Vlachojannis, Benno Zimmermann
      Abstract: Two exploratory clinical studies investigating proprietary pomegranate products showed a trend of effectiveness in increasing prostate‐specific antigen doubling time in patients with prostate cancer. A recent clinical study did not support these results. We therefore analysed a lot of the marketed pomegranate blend for co‐active pomegranate compounds. The high‐performance liquid chromatography method was used to detect punicalagin, ellagic acid and anthocyanins. Total polyphenoles were determined by the Folin–Ciocalteu method using gallic acid as reference. The results show that the co‐active compounds in the daily dose of the pomegranate blend were far below those previously tested and that the photometric assessment is not reliable for the standardisation of study medications. Not pomegranate but the low amount of co‐active compounds in the proprietary pomegranate blend was responsible for its clinical ineffectiveness. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-03T19:57:39.119941-05:
      DOI: 10.1002/ptr.5181
  • Zerumbone Suppresses IL‐1β‐induced Cell Migration and
           Invasion by Inhibiting IL‐8 and MMP‐3 Expression in Human
           Triple‐negative Breast Cancer Cells
    • Authors: Jeonghun Han; Soo Youn Bae, Soo-Jin Oh, Jeongmin Lee, Jun Ho Lee, Hyun-chul Lee, Se Kyung Lee, Won Ho Kil, Seok Won Kim, Seok Jin Nam, Sangmin Kim, Jeong Eon Lee
      Abstract: Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial‐mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)‐1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL‐1β‐induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL‐1β‐induced cell migration and invasion in breast cancer cells. The levels of IL‐8 and matrix metalloproteinase (MMP)‐3 mRNA were analyzed by real‐time polymerase chain reaction. The levels of secreted IL‐8 and MMP‐3 protein were analyzed by enzyme‐linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL‐8 and MMP‐3 expression were significantly increased by IL‐1β treatment in Hs578T and MDA‐MB231 cells. On the other hand, IL‐1β‐induced IL‐8 and MMP‐3 expression was decreased by ZER. Finally, IL‐1β‐induced cell migration and invasion were decreased by ZER in Hs578T and MDA‐MB231 cells. ZER suppresses IL‐1β‐induced cell migration and invasion by inhibiting IL‐8 expression and MMP‐3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple‐negative breast cancer patients. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-30T08:58:34.438437-05:
      DOI: 10.1002/ptr.5178
  • Growth Inhibition Effects of Isoalantolactone on K562/A02 Cells:
           Caspase‐dependent Apoptotic Pathways, S Phase Arrest, and
           Downregulation of Bcr/Abl
    • Authors: Hong Cai; Xiuxiang Meng, Yuzhong Li, Chuihui Yang, Yong Liu
      Abstract: Isoalantolactone, a sesquiterpene lactone, is the active component of Inula helenium (Compositae). It has been reported that isoalantolactone has the capacity to inhibit tumor cell growth through induction of apoptosis. The purposes of this study were to evaluate the effects of isoalantolactone on the human erythroleukemia drug‐resistant cell line K562/A02 and to provide evidence of its function as a potent therapeutic agent in patients with chronic myelogenous leukemia with the Bcr/Abl phenotype. Our results showed that isoalantolactone significantly inhibited K562/A02 cell growth by downregulating Bcr/Abl expression. Isoalantolactone also induced apoptosis via increase generation of reactive oxygen species, modulation of the protein levels of Bcl‐2 family members, caspase activation, poly ADP‐ribose polymerase (PARP) cleavage, and release of cytochrome c. We also observed that isoalantolactone inhibited proliferation by inducing cell cycle arrest in the S phase. Taken together, all these findings support that growth inhibition effects of isoalantolactone on K562/A02 cells may be mediated through caspase‐dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-27T19:51:59.301536-05:
      DOI: 10.1002/ptr.5182
  • Catechin‐based Procyanidins from Peumus boldus Mol. Aqueous Extract
           Inhibit Helicobacter pylori Urease and Adherence to Adenocarcinoma Gastric
    • Authors: Edgar Pastene; Víctor Parada, Marcia Avello, Antonieta Ruiz, Apolinaria García
      Abstract: In this work, the anti‐Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay‐guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP‐HPLC; HILIC‐HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50 = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin‐derived proanthocyanidins (LC‐MS and phloroglucinolysis). The anti‐adherent effect of boldo was assessed by co‐culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti‐adherent effect in a concentration‐dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti‐urease activity and anti‐adherent effect against H. pylori, properties directly linked with the presence of catechin‐derived proanthocyanidins. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-22T23:07:30.275286-05:
      DOI: 10.1002/ptr.5176
  • Umbelliferone Increases the Expression of Adipocyte‐Specific Genes
           in 3 T3‐L1 Adipocyte
    • Authors: Jarinyaporn Naowaboot; Choon Hee Chung, Ran Choi, Patchareewan Pannangpetch
      Abstract: Umbelliferone (UMB), a natural product of coumarin family, has been shown to reduce blood glucose and to improve lipid profiles in streptozotocin (STZ)‐induced diabetic rats. Our objective was to examine the effect of UMB on adipogenesis by investigating its stimulatory effect on lipid accumulation and mRNA expression of adipogenic transcription factors and adipocyte‐specific genes in 3 T3‐L1 preadipocyte culture. An Oil Red O staining was used to monitor lipid accumulation, and we found that UMB treatment at concentration range of 10–100 μM significantly increased lipid accumulation of differentiating 3 T3‐L1 cells. At the molecular level of adipogenesis, we examined the mRNA expression of adipogenic transcription factors, peroxisome proliferator‐activated receptor γ, CCAAT/enhancer‐binding protein α, and sterol regulatory element‐binding protein 1c. Those transcription factors were increased by UMB at 10–100 μM. Interestingly, UMB also stimulated the mRNA expression of adipocyte‐specific genes, adipocyte fatty acid‐binding protein, lipoprotein lipase, fatty acid synthase, fatty acid translocase, and adiponectin. Our findings indicate that the stimulatory effect of UMB on adipocyte differentiation likely occurs through up‐regulation of adipogenic transcription factors and downstream adipocyte‐specific gene expression. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-22T23:07:13.071804-05:
      DOI: 10.1002/ptr.5180
  • Curcuminoid Treatment for Knee Osteoarthritis: A Randomized
           Double‐Blind Placebo‐Controlled Trial
    • Authors: Yunes Panahi; Ali-Reza Rahimnia, Mojtaba Sharafi, Gholamhossein Alishiri, Amin Saburi, Amirhossein Sahebkar
      Abstract: Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long‐term adverse events of currently available medications including non‐steroidal anti‐inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti‐inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double‐blind placebo‐control parallel‐group clinical trial was conducted among patients with mild‐to‐moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p 
      PubDate: 2014-05-22T21:07:36.38166-05:0
      DOI: 10.1002/ptr.5174
  • Biliary Excretion of Glycyrrhetinic Acid: Glucuronide‐Conjugate
           Determination Following a Pharmacokinetic Study of Rat Bile
    • Authors: Yang Lu; Jing Jing, Weichao Ren, Jing Zhu, Zhixia Qiu, Ning Li, Xiaonan Li, Di Zhao, Harendra S. Parekh, Xijing Chen
      Abstract: Liquorice is a commonly prescribed herb in traditional Chinese medicine with the primary constituent, glycyrrhetinic acid (GA) responsible for the toxic effects arising from its chronic consumption. Hepatic transformation and biliary excretion of GA are significant and well‐documented pharmacokinetic pathways in humans, while glucuronide conjugates are the major identified metabolites. Here we report the role of bile in GA bioconversion in rats; this being achieved following intravenous administration of GA to Sprague–Dawley rats at a dose of 2 mg/kg with bile fluid analyzed for 3 h post‐injection using HPLC. The maximum concentration of glucuronides was detected about 30 min post‐administration, while the cumulative biliary excretion of glucuronides after 3 h was found to be 63.6 ± 6.4%. Our findings indicate a relatively high rate of biliary excretion for GA via the formation of glucuronide conjugates, and as a result of these findings, glucuronidation can be firmly regarded as a primary detoxification pathway for GA in rats. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-21T21:30:27.879206-05:
      DOI: 10.1002/ptr.5170
  • Proanthocyanin Content in Cranberry CE Medicinal Products
    • Authors: Sigrun Chrubasik-Hausmann; Christian Vlachojannis, Benno F. Zimmermann
      Abstract: The CE marking is a statutory marking for certain products sold within the European Economic Area. Medicinal products with a CE label are not regulated by the European Medicines Agency but are licensed according to the directives of the European Community. We have analysed the proanthocyanin (PAC) content of four cranberry CE products by both a photometric (DMAC method using 4‐dimethylamino‐cinnamic‐aldehyde as colouring reagent) and a high‐performance liquid chromatography assay and have compared the daily dosages recommended for the products by their manufacturers with benchmark doses obtained from the literature. For all CE products, the identified DMAC values for the PAC content per unit were below those declared. For two of the CE medicinal products, not even the manufacturers' maximum daily dosages have type A PAC contents that would have any chance of providing the health benefits promised on the product information sheets; the other two might have some chance, but only at maximum dosage (nine capsules per day for one of them). CE medicinal products should be better controlled by regulatory authorities to prevent consumers from buying and taking doses that are inadequate to provide the benefits claimed. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-21T21:17:57.542956-05:
      DOI: 10.1002/ptr.5172
  • α‐Glucosidase Inhibitors from the Stems of Embelia ribes
    • Authors: Phu Hoang Dang; Hai Xuan Nguyen, Nhan Trung Nguyen, Hanh Ngoc Thi Le, Mai Thanh Thi Nguyen
      Abstract: From the ethyl acetate extract of the stems of Embelia ribes (Myrsinaceae), a new alkenylresorcinol, embeliphenol A (1), together with 11 known compounds have been isolated. Their structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α‐glucosidase inhibitory activity in a concentration‐dependent manner, except for 2 and 9. Compounds 1, 3–6, 8, and 12 showed more potent inhibitory activity, with IC50 values ranging from 10.4 to 116.7 μM, than that of a positive control acarbose (IC50, 214.5 μM). Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-21T21:16:45.901205-05:
      DOI: 10.1002/ptr.5175
  • Antihyperalgesic Effects of an Aqueous Stem Bark Extract of Mangifera
           indica L.: Role of Mangiferin Isolated from the Extract
    • Authors: Bárbara B. Garrido-Suárez; Gabino Garrido, Mary Elena García, René Delgado-Hernández
      Abstract: This study aimed to assess the effects of a Mangifera indica stem bark extract (MSBE) and mangiferin (MG) on pain‐related acute behaviors in the formalin 5% test. Rats received repeated oral MSBE (125–500 mg/kg) once daily for 7 days before formalin injection. Other four groups with the same treatments were performed in order to study the effect of MSBE on the formalin‐induced long‐term secondary mechano‐hyperalgesia at 7 days after the injury by means of the pin‐prick method. Additional groups received a single oral MSBE dose (250 mg/kg) plus ascorbic acid (1 mg/kg, i.p.). Also, repeated oral MG doses (12.5–50 mg/kg) during 7 days were administered. MSBE decreased licking/biting and flinching behaviors only in phase II and reduced the long‐term formalin injury‐induced secondary chronic mechano‐hyperalgesia. The combination of MSBE plus ascorbic acid produced a reinforcement of this effect for flinching behavior, advising that antioxidant mechanisms are involved, at least in part, in these actions. Chronic administration of MG reproduced the effects of MSBE. For the first time, the antihyperalgesic effects of MSBE and MG in formalin 5% test, a recommended concentration for studying the antinociceptive activity of nitric oxide‐related and N‐methyl‐d‐aspartate‐related compounds, were reported. These results could represent an important contribution to explain the analgesic ethnobotanical effects recognized to M. indica and other species containing MG. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-21T21:07:16.768525-05:
      DOI: 10.1002/ptr.5177
  • Guarana (Paullinia cupana Mart.) Prevents β‐Amyloid
           Aggregation, Generation of Advanced Glycation‐end Products (AGEs),
           and Acrolein‐Induced Cytotoxicity on Human Neuronal‐Like Cells
    • Authors: Leonardo Silva Bittencourt; Fares Zeidán-Chuliá, Francini Kiyono Jorge Yatsu, Carlos Eduardo Schnorr, Karla Suzana Moresco, Eduardo Antônio Kolling, Daniel Pens Gelain, Valquiria Linck Bassani, José Cláudio Fonseca Moreira
      Abstract: Advanced glycation end‐products (AGEs) are considered potent molecules capable of promoting neuronal cell death and participating in the development of neurodegenerative disorders such as Alzheimer's disease (AD). Previous studies have shown that AGEs exacerbate β‐amyloid (Aβ) aggregation and AGE‐related cross‐links are also detected in senile plaques. Acrolein (ACR) is an α, β‐unsaturated aldehyde found in the environment and thermally processed foods, which can additionally be generated through endogenous metabolism. The role of ACR in AD is widely accepted in the literature. Guarana (Paullinia cupana Mart.) is popularly consumed by the population in Brazil, mainly for its stimulant activity. In the present study, we showed that guarana (10, 100, and 1000 µg/mL) is able to prevent protein glycation, β‐amyloid aggregation, in vitro methylglyoxal, glyoxal, and ACR (20 μM)‐induced toxicity on neuronal‐like cells (SH‐SY5Y). Since these are considered typical AD pathological hallmarks, we propose that guarana may deserve further research as a potential therapeutic agent in such a neurodegenerative disease. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-19T22:24:28.05784-05:0
      DOI: 10.1002/ptr.5173
  • Dark Chocolate: An Obesity Paradox or a Culprit for Weight Gain'
    • Authors: Grace Farhat; Sandra Drummond, Lorna Fyfe, E. A. S. Al-Dujaili
      First page: 791
      Abstract: Obesity remains a major public health challenge, and its prevalence is dramatically increasing. Diet and exercise are typically recommended to prevent and manage obesity; however, the results are often conflicting. Polyphenols, a class of phytochemicals that have been shown to reduce the risk factors for diabetes type II and cardiovascular diseases, are recently suggested as complementary agents in the management of obesity through several mechanisms such as decreasing fat absorption and/or fat synthesis. Dark chocolate, a high source of polyphenols, and flavanols in particular, has lately received attention for its possible role in modulating obesity because of its potential effect on fat and carbohydrate metabolism, as well as on satiety. This outcome was investigated in animal models of obesity, cell cultures and few human observational and clinical studies. The research undertaken to date has shown promising results, with the possible implication of cocoa/dark chocolate in the modulation of obesity and body weight through several mechanisms including decreasing the expression of genes involved in fatty acid synthesis, reducing the digestion and absorption of fats and carbohydrates and increasing satiety. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-09-02T21:49:27.159464-05:
      DOI: 10.1002/ptr.5062
  • Ferns and Lycopods—A Potential Treasury of Anticancer Agents but
           Also a Carcinogenic Hazard
    • Authors: Pavel Tomšík
      First page: 798
      Abstract: Many species of seedless vascular plants—ferns and lycopods—have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity‐guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds—especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids—were isolated and found to be cytotoxic, particularly pro‐apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern‐derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns—not only the well‐known Bracken (Pteridium)—may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-03T02:31:21.626617-05:
      DOI: 10.1002/ptr.5070
  • Phytotherapy of Opioid Dependence and Withdrawal Syndrome: A Review
    • Authors: Seyed Meghdad Tabatabai; Saeedeh Dashti, Fatemeh Doosti, Hossein Hosseinzadeh
      First page: 811
      Abstract: Development of tolerance and dependence is a major problem associated with opioid treatment. Withdrawal syndrome is common between medical and illicit users of these agents. Phytomedicine has shown promise in the treatment of this complicated psychosomatic condition. In this study, the effects of plant extracts and active components on morphine dependence and withdrawal syndrome are discussed. Proper keywords were used to search through PubMed, Google Scholar, and SciVerse, as well as two local scientific databases, and All relevant results (original articles, meeting abstracts, patents, etc.) published from 2000 to 2013 were chosen for final review. A total of 35 plant species were studied on this subject. Plants from Lamiaceae, Ranunculaceae, and Apiaceae families were especially effective. A few studies were carried out on human subjects and the rest in animal models. Opioid dependence and withdrawal syndrome remain an intimidating challenge. Nonetheless, plants and their derivatives are suitable sources for their treatment. Although there are several plants shown to be effective in animal models, few clinical studies are available. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-22T07:44:58.330734-05:
      DOI: 10.1002/ptr.5073
  • Traditional Plant Aphrodisiacs and Male Sexual Dysfunction
    • Authors: Anthony J Bella; Rany Shamloul
      First page: 831
      Abstract: Introduction: There has been a long history of man's fascination with better and stronger sex drive and performance across different cultures. Several literature texts from the Hindu, Egyptian, Chinese and Roman civilizations document the human endless search for substances that can enhance sexual experiences and/or treat erectile dysfunction. Aim: This review will discuss the current research done on the most popular plant aphrodisiacs and provide evidence to support or discourage the use of any of them to enhance sexual desire and/or function in men. Methods: We review the current evidence on the use of natural substances as aphrodisiacs. Results: We found very little evidence to support the use of plant aphrodisiacs in the treatment of male sexual dysfunction. The vast majority of studies were conducted on animals with very few clinical studies. Available data suggest a beneficial effect of ginseng as a pro‐sexual supplement and not an independent treatment for male sexual dysfunction. Conclusions: Trans‐culturally, many herbal therapies show some potential benefits in improving men's sexual function; however, adequate studies on the specific benefits and health risks associated with their use are needed. We strongly recommend the design and execution of well‐controlled clinical studies to determine the efficacy and safety of plant aphrodisiacs. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-29T04:00:21.721458-05:
      DOI: 10.1002/ptr.5074
  • Biological Effects of the Aqueous Extract of Bridelia grandis Stem Bark on
           Normal and Neoplastic Human Cells: An In Vitro Preliminary Evaluation
    • Authors: Enrica Capelli; Tatiana Ngueyem, Enrica Lanza, Vittorio Bertone, Sergio Barni
      First page: 836
      Abstract: The aim of the work is to investigate the effects of Bridelia grandis (Pierre ex Hutch) stem bark water extract on human HeLa cancer cells and normal monocytes treated in vitro, evaluating the morphological modifications with light and electron microscopy. The phytocomplex obtained from B. grandis caused a significant decrease in the mitotic index of both HeLa cancer cells and normal monocytes. In addition, a reduction of the typical aneuploid‐polyploid pattern has been observed in HeLa cells after treatment. Various alterations at fine structural level, both in neoplastic (HeLa cells) and normal (monocytes) cells have been observed. In particular, electron‐dense cells containing condensed mitochondria, autophagic vacuoles and dense spherical cytoplasmic inclusions have been observed. The results show that B. grandis water extracts have an antiproliferative effect on human cells, with a different effect on neoplastic and normal cells. The antiproliferative effect is accompanied by the appearance of various subcellular alterations. The morphological alterations observed are likely to represent the condition of ‘dark cell’ as a possible preliminary phase towards the autophagic and/or apoptotic cell death. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-07-30T02:25:34.908261-05:
      DOI: 10.1002/ptr.5051
  • Quercetin and EGCG Exhibit Chemopreventive Effects in Cholangiocarcinoma
           Cells via Suppression of JAK/STAT Signaling Pathway
    • Authors: Laddawan Senggunprai; Veerapol Kukongviriyapan, Auemduan Prawan, Upa Kukongviriyapan
      First page: 841
      Abstract: Quercetin and epigallocatechin‐3‐gallate (EGCG) are dietary phytochemicals with antiinflammatory and antitumor effects. In the present study, we examined the effects of these two compounds on Janus‐like kinase (JAK)/signal transduction and transcription (STAT) pathway of cholangiocarcinoma (CCA) cells, because CCA is one of the aggressive cancers with very poor prognosis and JAK/STAT pathway is critically important in inflammation and carcinogenesis. The results showed that the JAK/STAT pathway activation by proinflammatory cytokine interleukin‐6 and interferon‐γ in CCA cells was suppressed by pretreatment with quercetin and EGCG, evidently by a decrease of the elevated phosphorylated‐STAT1 and STAT3 proteins in a dose‐dependent manner. The cytokine‐mediated up‐regulation of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule‐1 (ICAM‐1) via JAK/STAT cascade was abolished by both quercetin and EGCG pretreatment. Moreover, these flavonoids also could inhibit growth and cytokine‐induced migration of CCA cells. Pretreatment with specific JAK inhibitors, AG490 and piceatannol, abolished cytokine‐induced iNOS and ICAM‐1 expression. These results demonstrate beneficial effects of quercetin and EGCG in the suppression of JAK/STAT cascade of CCA cells. Quercetin and EGCG would be potentially useful as cancer chemopreventive agents against CCA. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-08-30T01:11:20.884663-05:
      DOI: 10.1002/ptr.5061
  • Antimutagenic Potential and Modulation of Carcinogen‐Metabolizing
           Enzymes by Ginger Essential Oil
    • Authors: Kottarapat Jeena; Vijayasteltar B. Liju, Ramanath Viswanathan, Ramadasan Kuttan
      First page: 849
      Abstract: Essential oil extracted from ginger (GEO) was evaluated for its mutagenicity to Salmonella typhimurium TA 98, TA 100, TA 102, and TA 1535 strains with and without microsomal activation. GEO was found to be non‐mutagenic up to a concentration of 3 mg/plate. It was also assessed for antimutagenic potential against direct acting mutagens such as sodium azide, 4‐nitro‐o‐phenylenediamine, N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, tobacco extract, and 2‐acetamidoflourene, which needs microsomal activation. GEO significantly inhibited (p 
      PubDate: 2013-09-10T21:43:40.365389-05:
      DOI: 10.1002/ptr.5064
  • High Throughput Screening of Natural Products for Anti‐mitotic
           Effects in MDA‐MB‐231 Human Breast Carcinoma Cells
    • Authors: E. Mazzio; R. Badisa, N. Mack, S. Deiab, K. F. A. Soliman
      First page: 856
      Abstract: Some of the most effective anti‐mitotic microtubule‐binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust National Cancer Institute botanical screenings. In this study, a high‐through put microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015–0.5 mg/mL) relative to paclitaxel for anti‐mitotic effects (independent of toxicity) on proliferation of MDA‐MB‐231 cells. The data obtained showed that less than 1.34 % of the extracts tested showed inhibitory growth (IG50) properties
      PubDate: 2013-09-17T22:37:36.441343-05:
      DOI: 10.1002/ptr.5065
  • Silymarin Improves Vascular Function of Aged Ovariectomized Rats
    • Authors: Buket Demirci; Turhan Dost, Filiz Gokalp, Mustafa Birincioglu
      First page: 868
      Abstract: Both aging and estrogen depletion lead to endothelial dysfunction, which is the main reason of many cardiovascular diseases. Previous reports have shown that cell protective effect of silymarin (SM) depends on its antioxidant and phytoestrogenic properties. We investigated the effect of SM on vascular stiffness of aged menopausal rats and the involvement of estrogenic activity in this effect. Isolated rat aortas were obtained from 22‐month‐old rats, after 18 months of ovariectomy (OVX) follow‐up. Each ring was incubated in tissue bath either with SM (50 mg/L) and 17β‐estradiol (10 μM, E2) or in the presence of SM/fulvestrant (50 mg/L, 10 μM). Endothelium‐intact rings were precontracted with phenylephrine (0.001–30 μM) or high potassium (40 mM); endothelium‐dependent/independent relaxant responses were obtained using acetylcholine (0.001–30 μM) and sodium nitroprusside (0.0001–3 μM), respectively. While phenylephrine sensitivity was significantly increased in OVX rats, relaxations were significantly less in aged OVX rats compared with young rats. In spite of the presence of estrogen antagonist, immediate SM treatment restored the endothelial function and vascular tone better than estrogen replacement. Additionally, as a complementary and alternative medicine, it does not cause estrogenic side effects when taken acutely. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-09-30T09:33:40.487164-05:
      DOI: 10.1002/ptr.5067
  • The Effect of Black Seed (Nigella sativa) Extract on FOXO3 Expression in
           HepG2 Cells
    • Authors: Michael J. Haas; Luisa Onstead-Haas, Emad Naem, Alexis Arnold, Nathcelly Rohrbaugh, Megan Flowers, Arshag D. Mooradian
      First page: 873
      Abstract: Black seed extracts are known to alter cellular metabolism through multiple signaling pathways. Since Forkhead box transcription factor 3 (FOXO3) has a significant role in regulating cellular metabolism, the effect of lipid extracts of black seed (Sativa nigella) on FOXO3 levels and AKT and 5‐AMP activated protein kinase α (AMPKα) signaling was measured in HepG2 hepatoma cells. FOXO3 levels, phosphorylation, and nuclear exclusion were measured by Western blot, as were AKT and AMPK expression and activity using phosphorylation‐specific antibodies. Apolipoprotein A‐I expression, a black seed‐responsive gene, was measured by Western blot. Treatment with black seed extract increased FOXO3 phosphorylation and decreased its expression. In contrast to control cells where FOXO3 was located primarily in the nucleus, in black seed‐treated HepG2 cells, FOXO3 was localized primarily to the cytoplasm. These changes in FOXO3 phosphorylation, expression, and localization were accompanied by increased AKT activity. Black seed also decreased AMPKα activity but increased AMPKα expression. Lipid extracts from black seeds inhibit FOXO3 activity and thereby modulate the expression of FOXO3‐dependent genes. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-02T23:21:34.454853-05:
      DOI: 10.1002/ptr.5069
  • Liquiritigenin Restores Osteoblast Damage through Regulating Oxidative
           Stress and Mitochondrial Dysfunction
    • Authors: Eun Mi Choi; Kwang Sik Suh, Young Soon Lee
      First page: 880
      Abstract: We investigated the protective effect of liquiritigenin, one of the flavonoids present in Glycyrrhizae radix, against antimycin A‐induced mitochondrial dysfunction in MC3T3‐E1 osteoblast cells. Osteoblastic MC3T3‐E1 cells were pre‐incubated with liquiritigenin before treatment with antimycin A, and markers of mitochondrial function and oxidative damage were examined. In addition, the effects of liquiritigenin on the activation of phosphoinositide 3‐kinase (PI3K) were examined in MC3T3‐E1 cells. Liquiritigenin protected MC3T3‐E1 cells from antimycin A‐induced cell death. However, the PI3K inhibitor, LY294002, significantly attenuated liquiritigenin‐mediated cell survival, indicating the involvement of PI3K in the cytoprotective effect of liquiritigenin. Pretreatment with liquiritigenin prior to antimycin A exposure significantly reduced antimycin A‐induced PI3K inactivation, mitochondrial membrane potential dissipation, complex IV inactivation, and ATP loss. Liquiritigenin also reduced mitochondrial superoxide generation, nitrotyrosine production, and cardiolipin peroxidation during mitochondrial complex inhibition with antimycin A. Taken together, the results of this study show that modulation of PI3K, antioxidant effects, and the attenuation of mitochondrial dysfunction by liquiritigenin represent an important mechanism for its protection of osteoblasts against cytotoxicity resulting from mitochondrial oxidative stress. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-03T02:05:30.056167-05:
      DOI: 10.1002/ptr.5071
  • Hypolipemic Effect of Garcinia cambogia in Obese Women
    • Authors: Carlos A. R. Vasques; Ricardo Schneider, Luiz C. Klein-Júnior, Andressa Falavigna, Ivone Piazza, Simone Rossetto
      First page: 887
      Abstract: Garcinia cambogia seems to promote weight reduction and improvement on lipid profile by its major compound, hydroxycitric acid (HCA), blocking ATP‐citratelyase, potentially inhibiting lipogenesis. Furthermore, it is suggested that its extract is able to change the adipokine levels. Thus, the aim of this study was to analyse the effect of G. cambogia on the lipid profile, endocrine, calorimetric and anthropometric parameters of obese women. The women (BMI > 25 kg/m2; age 25–60 years), divided in treated (n = 30) and control (n = 13) groups, received 2.4 g (800 mg 3×/day) of garcinia extract (50% of HCA) or placebo during 60 days, respectively, as well as dietary control. Weight, BMI, waist–hip ratio and percentage of fat mass, resting metabolic rate, respiratory coefficient, triglycerides (TG), total cholesterol, HDL and LDL, leptin and insulin serum levels were evaluated. TG was significantly reduced in the treated group (p = 0.0002) and the post‐treatment variation was different compared to the placebo group (p = 0.04). No significant response was observed on other variables of the lipid profile, or on the anthropometric and calorimetric parameters. Leptin and insulin levels did not change significantly after the treatment. The short‐term treatment with G. cambogia demonstrated a hypotriglyceridemic effect, which does not appear to be related to changes in leptinemia. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-17T02:44:18.042808-05:
      DOI: 10.1002/ptr.5076
  • Panax notoginseng Attenuates Experimental Colitis in the
           Azoxymethane/Dextran Sulfate Sodium Mouse Model
    • Authors: Xiao-Dong Wen; Chong-Zhi Wang, Chunhao Yu, Lei Zhao, Zhiyu Zhang, Adiba Matin, Yunwei Wang, Ping Li, Shu-Yuan Xiao, Wei Du, Tong-Chuan He, Chun-Su Yuan
      First page: 892
      Abstract: Patients suffering from inflammatory bowel disease are at a high risk of developing colorectal cancer. To assess the anticancer potential of botanicals, in this study, we evaluated the effects of Panax notoginseng on azoxymethane/dextran sulfate sodium (DSS)‐induced colitis. One week after A/J mice received azoxymethane, the animals received DSS for 8 days or were supplemented with P. notoginseng extract, at 30 or 90 mg/kg. DSS‐induced colitis was scored with the disease activity index. The severity of the inflammatory lesions was evaluated by a colon tissue histological assessment. The expression of inducible nitric oxide synthase and cyclooxygenase‐2 (COX‐2) were also explored. We observed that the effects of P. notoginseng on the reduction of colon inflammation, expressed in disease activity index score, were in a dose‐related manner (p 
      PubDate: 2013-10-21T02:19:16.199233-05:
      DOI: 10.1002/ptr.5066
  • An In Vitro and Molecular Informatics Study to Evaluate the Antioxidative
           and β‐hydroxy‐β‐methylglutaryl‐CoA
           Reductase Inhibitory Property of Ficus virens Ait
    • Authors: Danish Iqbal; M. Salman Khan, Mohd. S. Khan, Saheem Ahmad, Ashwini K. Srivastava
      First page: 899
      Abstract: The present study is initially intended to evaluate antioxidant and β‐hydroxy‐β‐methylglutaryl‐CoA reductase (HMGR) inhibitory property of Ficus virens Ait., first by in vitro analyses followed by a corroboratory molecular informatics study. Our results show that of all the sequentially extracted fraction of F. virens bark and leaves extract, F. virens bark methanol extract exhibits strong radical scavenging, antioxidant and oxidative DNA damage protective activity, which is well correlated with its total phenolic content. In addition, F. virens bark methanol extract, which is non‐cytotoxic, significantly and non‐covalently inhibit the HMGR activity (IC50 = 3.45 ± 0.45 µg/ml) in comparison with other extracts. The mechanistic aspect of this inhibition activity is authenticated by molecular docking study of bioactive compounds as revealed from gas chromatography–mass spectrometry data, with HMGR. The analysis for the first time indicates that quinic acid (ΔG: −8.11 kcal/mol) and paravastatin (ΔG: −8.22 kcal/mol) exhibit almost same binding energy, while other compounds also showed good binding energy, suggesting that quinic acid alone or in combination with other major bioactive compound is probably responsible for HMGR inhibitory property of the extract and plausibly can be used in in vivo system for the management, prevention, and alleviation of hypercholesterolemia as well as hypercholesterolemia‐induced oxidative stress. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-22T08:02:20.372049-05:
      DOI: 10.1002/ptr.5077
  • Pentalinon andrieuxii Root Extract is Effective in the Topical Treatment
           of Cutaneous Leishmaniasis Caused by Leishmania mexicana
    • Authors: Claudio M. Lezama-Dávila; Li Pan, Angelica P. Isaac-Márquez, Cesar Terrazas, Steve Oghumu, Ricardo Isaac-Márquez, MY Pech-Dzib, Joseph Barbi, Edward Calomeni, Narasimham Parinandi, A. Douglas Kinghorn, Abhay R. Satoskar
      First page: 909
      Abstract: Cutaneous leishmaniasis (CL) manifests as localized skin lesions, which lead to significant tissue destruction and disfigurement. In the Yucatan Peninsula, Mayan traditional healers use Pentalinon andrieuxii Muell.‐Arg. (Apocynaceae) roots for the topical treatment of CL. Here, we studied the effect of P. andrieuxii root hexane extract (PARE) on the parasites and host cells in vitro and examined its efficacy in the topical treatment of CL caused by Leishmania mexicana. PARE exhibited potent antiparasitic activity in vitro against promastigotes as well as amastigotes residing in macrophages. Electron microscopy of PARE‐treated parasites revealed direct membrane damage. PARE also activated nuclear factor kappaB and enhanced interferon‐γ receptor and MHC class II expression and TNF‐α production in macrophages. In addition, PARE induced production of the Th1 promoting cytokine IL‐12 in dendritic cells as well as enhanced expression of the co‐stimulatory molecules CD40, CD80, and CD86. In vivo studies showed that L. mexicana‐infected mice treated by topical application of PARE resulted in the significant reduction in lesion size and parasite burden compared to controls. These findings indicate that PARE could be used as an alternative therapy for the topical treatment of CL. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-11-08T04:10:29.771266-05:
      DOI: 10.1002/ptr.5079
  • A Fraction Containing Kaempferol‐3,4′‐dimethylether from
           Larrea divaricata Cav. Induces Macrophage Activation on Mice Infected with
           Candida albicans
    • Authors: Renzo Martino; Fernando Canale, Valeria Sülsen, Rosario Alonso, Roberto Davicino, Aida Mattar, Claudia Anesini, Blas Micalizzi
      First page: 917
      Abstract: Larrea divaricata Cav. is a plant growing in South America. Both the infusion and a derived fraction (F1) of L. divaricata have proved to have immunomodulatory properties. Moreover, F1 can activate macrophages obtained from mice infected with Candida albicans. In this work, F1 was administrated to infected animals, and the state and type of activation of resident macrophages were studied. Results showed that F1 was able to activate macrophages obtained from infected mice by both classical and alternative pathways, probably by inducing a translocation of nuclear factor kappa‐B. F1 increases not only the lysosomal activity of macrophages but also the production of phagosomal superoxide anion as a consequence of the activation of the Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) complex. F1 induced an increase in the macrophage capacity to kill the fungus, which was reflected in a decrease in the levels of colonization of organs. A main flavonoid, kaempferol‐3,4′‐dimethylether, was identified in F1 by HPLC. This compound increased in vitro production of nitric oxide in heat‐killed C. albicans‐stimulated macrophages. The flavonoid could thus be considered one of the responsible molecules mediating the overall effects of F1 on the immune system in infected animals. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-11-26T20:54:41.690604-05:
      DOI: 10.1002/ptr.5086
  • Suppression of Lipopolysaccharide‐stimulated Cytokine/Chemokine
           Production in Skin Cells by Sandalwood Oils and Purified
           α‐santalol and β‐santalol
    • Authors: M. Sharma; C. Levenson, R. H. Bell, S. A. Anderson, J. B. Hudson, C. C. Collins, M. E. Cox
      First page: 925
      Abstract: Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme‐linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co‐cultured human dermal fibroblasts and neo‐epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α‐santalol and β‐santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α‐santalol and β‐santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α‐santalol and β‐santalol also suppressed lipopolysaccharide‐induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co‐cultures. The ability of SOs to mimic ibuprofen non‐steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-12-06T22:58:36.867726-05:
      DOI: 10.1002/ptr.5080
  • Targeted Metabolomic Study Indicating Glycyrrhizin's Protection against
           Acetaminophen‐induced Liver Damage through Reversing Fatty Acid
    • Authors: Jian Yu; Yang-Shen Jiang, Yuan Jiang, Yan-Fang Peng, Zhuang Sun, Xiao-Nan Dai, Qiu-Ting Cao, Ying-Ming Sun, Jing-Chun Han, Ya-Jie Gao
      First page: 933
      Abstract: The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen‐induced liver toxicity. Seven‐day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2‐ to 3‐month‐old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen‐induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra‐fast liquid chromatography coupled to triple time‐of‐flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin‐treated, acetaminophen‐treated, and glycyrrhizin + acetaminophen‐treated groups. Long‐chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long‐chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen‐induced liver damage through reversing fatty acid metabolism. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-10-31T04:13:16.17758-05:0
      DOI: 10.1002/ptr.5072
  • Inhibitory Effect of Bacopasides on Spontaneous Morphine Withdrawal
           Induced Depression in Mice
    • Authors: Khalid Rauf; Fazal Subhan, Muzaffar Abbas, Syed Mobasher Ali, Gowhar Ali, Muhammad Ashfaq, Ghulam Abbas
      First page: 937
      Abstract: Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A3, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20–65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt‐ext BM contained Bacoside A3 as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A3. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-11-14T22:58:45.975392-05:
      DOI: 10.1002/ptr.5081
  • Modulation of Melanin Synthesis by Rengyolone Isolated from the Root of
           Eurya emarginata in Melan‐a Cells
    • Authors: Jin Hee Kim; Sang Chul Jeong, Jae Sung Hwang, Eun Sook Lee, Sang Myung Lee
      First page: 940
      Abstract: In the course of screening for the melanogenesis inhibitors, rengyolone was isolated from Eurya emarginata (Thumb) Makino. Its chemical structure was determined on the basis of spectroscopic analysis including mass spectroscopy and nuclear magnetic resonance analysis. Rengyolone inhibited potent melanogenesis in melan‐a cells with an IC50 value of 65 μM without cytotoxicity. Also, rengyolone showed a melanin biosynthesis inhibition zone in a culture plate of Streptomyces bikiniensis, which is commonly used as an indicator organism. Moreover, rengyolone dramatically reduced protein expression of melanogenic enzyme, tyrosinase. Furthermore, rengyolone presented inhibition on the body pigmentation in zebrafish model system and decreased melanin contents and tyrosinase activity. These results suggest that rengyolone isolated from E. emarginata may be an effective skin‐whitening agent that regulates the expression of melanogenic enzymes. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-11-19T23:20:27.895626-05:
      DOI: 10.1002/ptr.5082
  • Lipolytic Activity of Svetol®, a Decaffeinated Green Coffee Bean
    • Authors: John Flanagan; Antoine Bily, Yohan Rolland, Marc Roller
      First page: 946
      Abstract: The beneficial health effects of chlorogenic acids (CGAs), major components of coffee beans, are well known and have been attributed to multiple mechanisms of action. However, the lipolytic activity of CGAs does not appear to have been reported. We studied the effects of varying concentrations of Svetol®, a decaffeinated green coffee bean extract enriched in CGAs, on the liberation of free fatty acids from human adipocytes following short‐term (2 h) and long‐term (192 h) exposure. The results showed that although lipolytic activity observed following short‐term incubation could be tentatively linked to residual caffeine traces in the sample, longer‐term exposure clearly showed the effects of Svetol® on release of free fatty acids, and this effect was not due to caffeine. The results of this study provide a further mechanism by which to explain the long‐term health benefits of CGAs and Svetol®. Copyright © 2013 John Wiley & Sons, Ltd.
      PubDate: 2013-12-12T01:30:18.484516-05:
      DOI: 10.1002/ptr.5085
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