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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: 3, SJR: 0.952, h-index: 60)
Pediatric Dermatology     Hybrid Journal   (Followers: 5, SJR: 0.57, h-index: 44)
Pediatric Diabetes     Hybrid Journal   (Followers: 13, 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: 6, 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: 12, 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: 15, SJR: 1.126, h-index: 40)
Political Science Quarterly     Hybrid Journal   (Followers: 25, 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
  • Puerarin: A Review of Pharmacological Effects
    • Abstract: Puerarin is the major bioactive ingredient isolated from the root of the Pueraria lobata (Willd.) Ohwi, which is well known as Gegen (Chinese name) in traditional Chinese medicine. As the most abundant secondary metabolite, puerarin was isolated from Gegen in the late 1950s. Since then, its pharmacological properties have been extensively investigated. It is available in common foods and is used in alternative medicine. It has been widely used in the treatment of cardiovascular and cerebrovascular diseases, diabetes and diabetic complications, osteonecrosis, Parkinson's disease, Alzheimer's disease, endometriosis, and cancer. The beneficial effects of puerarin on the various medicinal purposes may be due to its wide spectrum of pharmacological properties such as vasodilation, cardioprotection, neuroprotection, antioxidant, anticancer, antiinflammation, alleviating pain, promoting bone formation, inhibiting alcohol intake, and attenuating insulin resistance. However, the direct molecular mechanisms and targets remain unclear. This review provides a comprehensive summary of the pharmacological effects of puerarin. Copyright © 2013 John Wiley & Sons, Ltd.
  • Phytotherapy of Benign Prostatic Hyperplasia. A Minireview
    • Abstract: Benign prostate hyperplasia (BPH) is a common condition affecting older men, with an incidence that is age‐dependent. Histological BPH, which typically develops after the age of 40 years, ranges in prevalence from >50% at 60 years to as high as 90% by 85 years of age. Typical symptoms include increased frequency of urination, nocturia, urgency, hesitancy, and weak urine stream. Conventional medicines used for the treatment of BPH include alpha blockers and 5‐alpha reductase inhibitors. This articles review the mode of action, the efficacy, and the safety, including herb‐drug interactions of the most common botanicals (Serenoa repens, Pygeum africanum, Urtica dioica, and Cucurbita pepo) and nutraceuticals (isoflavones, lycopene, selenium, and β‐Sitosterol) in controlling the lower urinary tract symptoms associated to BPH. Copyright © 2013 John Wiley & Sons, Ltd.
  • Safety and Efficacy of Bixa orellana (Achiote, Annatto) Leaf Extracts
    • Abstract: Bixa orellana leaf preparations have been used for many years by indigenous people for a variety of medicinal applications. Published research studies in animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad antimicrobial (antibacterial and antifungal), anti‐inflammatory, analgesic, hypoglycemic, and antidiarrheal activities. No studies have specifically assessed the ability of leaf extracts to inhibit urogenital infections although Bixa products have been used in folkloric medicine to treat gonorrhea and other infections. Few human studies have been conducted and published using Bixa leaf preparations. Many more studies have been conducted and published involving Bixa seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity) studies have been conducted in animals. A 6 month study in humans given 750 mg of leaf powder per day demonstrated no significant or serious adverse effects. Bixa leaf extracts appear to be safe when given under current conditions of use. However, additional human and animal controlled safety and efficacy studies are needed. In addition, detailed chemical analyses are required to establish structure–function relationships. Copyright © 2013 John Wiley & Sons, Ltd.
  • The Isolation of Antiprotozoal Compounds from Libyan Propolis
    • Abstract: Propolis is increasingly being explored as a source of biologically active compounds. Until now, there has been no study of Libyan propolis. Two samples were collected in North East Libya and tested for their activity against Trypanosoma brucei. Extracts from both samples had quite high activity. One of the samples was fractionated and yielded a number of active fractions. Three of the active fractions contained single compounds, which were found to be 13‐epitorulosal, acetyl‐13‐epi‐cupressic acid and 13‐epi‐cupressic acid, which have been described before in Mediterranean propolis. Two of the compounds had a minimum inhibitory concentration value of 1.56 µg/mL against T. brucei. The active fractions were also tested against macrophages infected with Leishmania donovani, and again moderate to strong activity was observed with the compounds having IC50 values in the range 5.1–21.9 µg/mL. Copyright © 2014 John Wiley & Sons, Ltd.
  • Review on Liver Inflammation and Antiinflammatory Activity of Andrographis
           paniculata for Hepatoprotection
    • Abstract: Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation. Copyright © 2014 John Wiley & Sons, Ltd.
  • Turmeric Toxicity in A431 Epidermoid Cancer Cells Associates with
           Autophagy Degradation of Anti‐apoptotic and Anti‐autophagic
           p53 Mutant
    • Abstract: The keratinocyte‐derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin‐mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small‐interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric‐treated or Curcumin‐treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53. Copyright © 2014 John Wiley & Sons, Ltd.
  • A Pilot Study on the Effectiveness of a Rose Hip Shell Powder in Patients
           Suffering from Chronic Musculoskeletal Pain
    • Abstract: We carried out a 3‐month preliminary investigation on the effectiveness of a rose hip shell powder and its mechanism of action. Of 52 patients suffering from acute exacerbations of low back pain (n = 39) or knee pain (n = 13), 29 had participated earlier in the pilot study with the pseudofruit powder Litozin®. After assessing the baseline values, patients were offered up to 20 g of a rose hip shell powder per day. Patients were encouraged to adjust the daily dose upwards or downwards according to their symptoms for the period of 3 months. The examination for possible effectiveness was by intention‐to‐treat analysis with last observation carried forward. There was no difference in any generic or disease‐specific outcome variables between the patients consuming the rose hip shell powder and those consuming the pseudofruit powder Litozin® in the previous surveillance study. A human protein array system and fractions from the rose powders were used to study their effect on cytokine expression in vitro. The data indicate that lipophilic rose hip fractions from the shell and the pseudofruit inhibit cytokine expression and that the shell powder may be the better starting material for a future rose hip extract prepared with a lipophilic solvent. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anti‐inflammatory Effects of Ginsenosides Rg5, Rz1, and Rk1:
           Inhibition of TNF‐α‐induced NF‐κB,
           COX‐2, and iNOS transcriptional expression
    • Abstract: In the course of this experiment on the anti‐inflammatory effect of ginsenosides, protopanaxdiol ginsenosides have shown inhibition activities in inflammatory responses: NF‐κB, COX‐2, and iNOS were induced by TNF‐α. The responses of this experiment were evaluated by NF‐κB‐luciferase assay and RT‐PCR experiment of COX‐2 and iNOS genes. The NF‐κB expressions were inhibited by ginsenosides Rd, Rg5, Rz1, and Rk1 in a dose‐dependent manner. The IC50 values were 3.47, 0.61, 0.63, and 0.75 μM, respectively. Particularly, ginsenosides Rg5, Rz1, and Rk1 as converted ginsenosides from primary protopanaxdiol ginsenosidess significantly inhibited COX‐2 and iNOS gene expression. These inhibition levels were similar to sulfasalazine as reference material. Copyright © 2014 John Wiley & Sons, Ltd.
  • Antiinflammatory, Antioxidant, and Immunological Effects of Carum copticum
           L. and Some of Its Constituents
    • Abstract: Carum copticum L. has been used traditionally for its various therapeutic effects. The plant contains various components such as thymol and carvacrol. Different therapeutic effects such as antifungal, antioxidant, antibacterial, antiparasitic, and antilipidemic were described for the plant and its constituents. Therefore, antiinflammatory, antioxidant, and immunological effects of C. copticum and its constituents, thymol and carvacrol, were discussed in the present review. Previous studies have shown potent antiinflammatory, antioxidant, and immunological effects for C. copticum and its constituents, thymol and carvacrol. Therefore, the plant and its constituents have therapeutic values in several inflammatory and immunological disorders as well as in the oxidative stress conditions. Copyright © 2014 John Wiley & Sons, Ltd.
  • Evaluation of the Effect of Curcumin Capsules on Glyburide Therapy in
           Patients with Type‐2 Diabetes Mellitus
    • Abstract: This study aimed to assess the possible beneficial effects of curcumin capsules as lipid‐lowering effects and as a permeability glycoprotein (P‐gp) inhibitor on the pharmacokinetics and pharmacodynamics of glyburide and as a P‐gp substrate with glyburide in patients with type‐2 diabetes mellitus. Open‐label, randomized control trial was carried out for 11 days on eight type‐2 diabetic patients on glyburide therapy. On the first day of the study, following the administration of 5 mg of glyburide, blood samples were collected from the patients at various time intervals ranging from 0.5 to 24 h. Blood sampling was repeated on the 11th day of the study, after treating the patients with curcumin for ten consecutive days. Glyburide concentrations changed at the second hour, Cmax was unchanged, the glucose levels were decreased, Area Under first Movement Curre (AUMC) was increased, and no patient has experienced the hypoglycaemia. The low‐density lipoprotein, very‐low‐density lipoprotein and triglycerides were decreased significantly, and the high‐density lipoprotein content increased. The co‐administration of curcumin capsules with glyburide may be beneficial to the patients in better glycaemic control. The lipid lowering and antidiabetic properties of the curcumin show as a potential future drug molecule. Copyright © 2014 John Wiley & Sons, Ltd.
  • A Chemically Standardized Extract of Ziziphus jujuba Fruit (Jujube)
           Stimulates Expressions of Neurotrophic Factors and Anti‐oxidant
           Enzymes in Cultured Astrocytes
    • Abstract: The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as a health supplement worldwide. To study the role of jujube in brain benefits, the expression of neurotrophic factors and anti‐oxidant enzymes in the jujube‐treated cultured astrocytes was determined. Application of a chemical standardized water extract of jujube in cultured astrocytes for 24 h stimulated the expressions of nerve growth factor, brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor in a concentration‐dependent manner. The pre‐treatment with H89, a protein kinase A inhibitor, attenuated the jujube‐induced expression of neurotrophic factors. In parallel, the treatment of jujube water extract induced the transcriptional expressions of the enzymes responsible for anti‐oxidation, i.e. NAD(P)H: quinine oxidoreductase 1, glutamate‐cysteine ligase catalytic subunit, glutamate‐cysteine ligase modifier subunit and glutathione S‐transferase, in a concentration‐dependent manner. These results proposed the benefits of jujube in regulating expressions of neurotrophic factors and anti‐oxidant enzymes in cultured astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.
  • Apple Polyphenol Extracts Protect Against Aspirin‐induced Gastric
           Mucosal Damage in Rats
    • Abstract: The protective role of two apple polyphenol extracts, Douglas‐FB (FB) and Douglas‐EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague–Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10‐day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10−2 m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10‐day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Antidepressant Effects of Ginseng Total Saponins in Male
           C57BL/6 N Mice by Enhancing Hippocampal Inhibitory Phosphorylation
           of GSK‐3β
    • Abstract: Ginseng total saponins (GTS) are principal bioactive ingredients of Panax ginseng. In this study, we investigated the antidepressant effect of GTS on the corticosterone‐induced mouse depression model and explored the underlying mechanism. Corticosterone (20 mg kg−1 d−1) was subcutaneously administered for 22 d to induce the model, before doses of GTS (12.5, 25, and 50 mg kg−1 d−1) or fluoxetine (10 mg kg−1 d−1) were subsequently given by gavage. On day 20 and 21, depression‐like behavior was observed via a forced swimming test and a tail suspension test respectively. At 6 h after the last dose of corticosterone (day 22), all mice were sacrificed followed by serum corticosterone assays and Western blot analysis. The results showed that GTS (25 and 50 mg kg−1 d−1) treatments relieved depression‐like behavior without altering the elevated serum corticosterone levels. Furthermore, GTS treatments raised the down‐regulated levels of hippocampal glycogen synthase kinase‐3β (GSK‐3β) inhibitory phosphorylation. In contrast, fluoxetine (10 mg kg−1 d−1) treatment reversed the increased corticosterone level and had no effect on the decreased GSK‐3β inhibitory phosphorylation. These findings confirmed the antidepressant effect of GTS in the corticosterone‐induced mouse depression model. Enhancing GSK‐3β inhibitory phosphorylation may be one of the underlying mechanisms. Copyright © 2013 John Wiley & Sons, Ltd.
  • Ginsenoside Rg3 Up‐regulates the Expression of Vascular Endothelial
           Growth Factor in Human Dermal Papilla Cells and Mouse Hair Follicles
    • Abstract: Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real‐time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3‐stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose‐dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up‐regulated by Rg3 in a dose‐dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up‐regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. Copyright © 2013 John Wiley & Sons, Ltd.
  • Weight Reduction Effect of Puerh Tea in Male Patients with Metabolic
    • Abstract: Puerh tea has been proposed to promote weight loss and favorably modify glucose, insulin and blood lipids. This study tested the effect of daily Puerh tea consumption for 3 months on weight and body mass index (BMI), and select metabolic parameters. The effect of daily Puerh tea intake on weight, BMI and changes in glucose, HbA1c and lipids was evaluated in patients with metabolic syndrome. The patients (N = 70) were randomized into two groups: those taking Puerh tea extract capsule (333 mg Puerh tea extract) three times a day and those taking a placebo tea for 3 months. There was a decrease in body weight of 1.3 kg in the Puerh tea group (p = 0.077) versus 0.23 kg in the placebo arm (p = 0.186). There was also a slight decrease in BMI 0.47 kg/m2 in the Puerh tea group (p = 0.076) versus 0.09 kg/m2 in the placebo arm (p = 0.185), suggesting a trend of weight change, but without statistical significance. Subgroup analysis of the male patients demonstrated statistically significant improvements in body weight reduction (p = 0.004) and BMI (p = 0.004). However, the change in other metabolic parameters (cholesterol or triglyceride) or HbA1c was not statistically significant. Intake of Puerh tea for 3 months was associated with a slight reduction in body weight and BMI, especially in the male patients. Therefore, daily Puerh tea consumption may be an alternative choice to modify body weight. Copyright © 2014 John Wiley & Sons, Ltd.
  • Functional and Morphological Effects of Grape Seed Proanthocyanidins on
           Peripheral Neuropathy in Rats with Type 2 Diabetes Mellitus
    • Abstract: Grape seed proanthocyanidins (GSPs) possess a broad spectrum of pharmacological and therapeutic properties. The aim of this study was to examine the effect of GSPs on functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. Diabetic rats were induced by two injections of 25 mg streptozotocin/kg body weight and 8 weeks of a high‐carbohydrate/high‐fat diet. GSPs were then administrated to the rats for 16 weeks. Thermal and mechanical sensitivity thresholds and nerve conductive velocity were measured to evaluate peripheral nerve function. Light microscopy was used with special stains to observe the morphological changes in the central and peripheral nervous systems. Calcium (Ca2+) homeostasis and ATPase activities in the sciatic nerves were also determined. In diabetic rats receiving GSP treatment (especially at the 500 mg/kg dose), the abnormal peripheral nerve function and impaired nervous tissues (L4 to L5 spinal cord segments, L5 dorsal root ganglion, and sciatic nerves) were improved to a significant extent. Moreover, 500 mg/kg GSP treatment significantly reduced the concentration of free Ca2+ and elevated Ca2+‐ATPase activity in sciatic nerves. These results suggest that GSPs may prevent early functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. Copyright © 2013 John Wiley & Sons, Ltd.
  • Hyperoside Regulates the Level of Thymic Stromal Lymphopoietin through
           Intracellular Calcium Signalling
    • Abstract: Hyperoside (HYP) is the principle active component of Crataegus pinnatifida. Thymic stromal lymphopoietin (TSLP) plays a vital role in the pathogenesis of allergic reactions. Here, we investigated how HYP regulates the levels of TSLP in a human mast cell line, HMC‐1 cells. We analyzed the levels of TSLP by treatment with HYP in phorbol myristate acetate plus calcium ionophore A23187‐stimulated HMC‐1 cells with ELISA and a polymerase chain reaction analysis. We also analyzed the pathway that HYP regulates TSLP by measuring the level of fluorescent intracellular calcium and using a Western blot analysis. HYP decreased the level of intracellular calcium in stimulated HMC‐1 cells. It also significantly decreased the production and mRNA expression of TSLP in stimulated HMC‐1 cells. It significantly decreased the levels of receptor‐interacting protein 2 and active caspase‐1 in stimulated HMC‐1 cells. HYP significantly decreased the translocation of NF‐κB into the nucleus and degradation of IκBα in the cytoplasm in stimulated HMC‐1 cells. Furthermore, it significantly decreased the production and mRNA expression of interleukin‐1β and interleukin‐6 in stimulated HMC‐1 cells. Taken together, our findings establish HYP as a potential agent for the treatment of allergic reactions. Copyright © 2013 John Wiley & Sons, Ltd.
  • A New Phenolic Component from Triticum aestivum Sprouts and its Effects on
           LPS‐Stimulated Production of Nitric oxide and TNF‐α in
           RAW 264.7 Cells
    • Abstract: An unusual new phenolic component, triticumoside (1), and eight known compounds, isoorientin (2), isoscoparin (3), (2R)‐2‐O‐β‐D‐glucopyranosyloxy‐4,7‐dimethoxy‐2H‐1,4‐benzoxazin‐3(4H)‐one (4), adenosine (5), β‐sitosterol (6), daucosterol (7), 6′‐O‐linolenoyl daucosterol (8), α‐tocopherol (9), were isolated from Triticum aestivum sprouts. The hybrid structure of 1, which is a hybrid between a flavone and a polyoxygenated benzene, is rarely found in natural sources. In addition, the effects of these compounds on LPS‐induced NO and TNF‐α production in RAW 264.7 cells were evaluated. At a concentration of 2.0 μM, compounds 2–4 significantly inhibited the production of both NO and TNF‐α. Compound 1 exhibited inhibitory activity on the secretion of TNF‐α at concentrations as low as 2.0 μM, but it did not reduce NO levels at any of the tested concentrations. Copyright © 2013 John Wiley & Sons, Ltd.
  • Flavonoids from Sophora moorcroftiana and their Synergistic Antibacterial
           Effects on MRSA
    • Abstract: Synergy is now a widely recognized approach that has direct applicability for new pharmaceuticals. The ethanolic extract of the aerial parts of the herb Sophora moorcroftiana showed significant antibacterial activity against drug‐resistant Staphylococcus aureus, and its minimum inhibitory concentration (MIC) was 8 µg/mL. In a phytochemical study of the extract, five flavonoids were obtained. However, the isolates exhibited antibacterial activity in the range of 32–128 µg/mL, which was weaker than the extract. In combination with antibiotics, the antibacterially inactive compound genistein (1) and diosmetin (4) showed significant synergistic activity against drug‐resistant S. aureus. In combination with norfloxacin, genistein (1) reduced the MIC to 16 µg/mL and showed synergy against strain SA1199B with a fractional inhibitory concentration index (FICI) of 0.38. With the antibiotics norfloxacin, streptomycin and ciprofloxacin, diosmetin (4) showed synergy against SA1199B, RN4220 and EMRSA‐15, with FICI values of 0.38, 0.38 and 0.09, respectively. In an efflux experiment to elucidate a plausible mechanism for the observed synergy, genistein showed marginal inhibition of the NorA efflux protein. Copyright © 2013 John Wiley & Sons, Ltd.
  • Phytochemistry and Antileishmanial Activity of the Leaf Latex of Aloe
           calidophila Reynolds
    • Abstract: Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC50 values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, 1H NMR, and 13C NMR spectral data. The isolated compounds showed strong antileishmanial activity with IC50 values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC50 = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost‐effective antileishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.
  • Effect of Fucoxanthin Alone and in Combination with D‐glucosamine
           Hydrochloride on Carrageenan/kaolin‐induced Experimental Arthritis
           in Rats
    • Abstract: The objective of the present study was to investigate the effect of the fucoxanthin (FUCO) alone and in combination with glucosamine hydrochloride (GAH) on carrageenan/kaolin‐induced inflammatory arthritis model in rats and to explore its underlying mechanisms. Joint swelling, muscle weight ratio (%), histopathological examination and scoring, and proteoglycan degradation were examined. Pro‐inflammatory interleukin (IL‐1β) and tumor necrosis (TNF‐α) levels, cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase(iNOS) protein expression and nitric oxide (NO) level in knee synovial tissue extract were analyzed using enzyme‐linked immunosorbent assay, western blotting analysis, and Griess reagent assay, respectively. FUCO and FUCO + GAH not only may significantly reduce degrees of knee joint swelling and prevent against muscle atrophy, but also may significantly attenuate inflammation in synovial tissue, cartilage erosion, and proteoglycan loss. The efficacies of FUCO + GAH were stronger than that of GAH or FUCO. FUCO alone and FUCO + GAH can significantly inhibit upregulation of COX‐2 and iNOS protein expressions, decrease of IL‐1β and TNF‐α levels, and reduce NO production in knee synovial tissue extract. These results indicated that FUCO is an effective anti‐arthritis agent through an antiinflammation mechanism. FUCO may enhance therapeutic effect of GAH on rat arthritis through mechanism of antiinflammation. Copyright © 2013 John Wiley & Sons, Ltd.
  • Apoptosis Induction by 13‐Acetoxyrolandrolide through the
           Mitochondrial Intrinsic Pathway
    • Abstract: The aim of this study was to evaluate the mechanisms of cytotoxicity of the sesquiterpene lactone 13‐acetoxyrolandrolide, a nuclear factor kappa B (NF‐κB) inhibitor that was previously isolated from Rolandra fruticosa. The effects associated with the inhibition of the NF‐κB pathway included dose‐dependent inhibition of the NF‐κB subunit p65 (RelA) and inhibition of upstream mediators IKKβ and oncogenic Kirsten rat sarcoma (K‐Ras). The inhibitory concentration of 13‐acetoxyrolandrolide on K‐Ras was 7.7 µm. The downstream effects of the inhibition of NF‐κB activation were also investigated in vitro. After 24 h of treatment with 13‐acetoxyrolandrolide, the mitochondrial transmembrane potential was depolarized in human colon cancer (HT‐29) cells. The mitochondrial oxidative phosphorylation was also negatively affected, and reduced levels of nicotinamine adenine dinucleotide phosphate (NAD(P)H) were detected after 2 h of 13‐acetoxyrolandrolide exposure. Furthermore, the expression of the pro‐apoptotic protein caspase‐3 increased in a concentration‐dependent manner. Cell flow cytometry showed that 13‐acetoxyrolandrolide induced cell cycle arrest at G1, indicating that the treated cells had undergone caspase‐3‐mediated apoptosis, indicating negative effects on cancer cell proliferation. These results suggest that 13‐acetoxyrolandrolide inhibits NF‐κB and K‐Ras and promotes cell death mediated through the mitochondrial apoptotic pathway. Copyright © 2013 John Wiley & Sons, Ltd.
  • Trametenolic Acid B Reverses Multidrug Resistance in Breast Cancer Cells
           Through Regulating the Expression Level of P‐Glycoprotein
    • Abstract: Trametenolic acid B (TAB) is the main active composition of Trametes lactinea (Berk.) Pat which possesses anti‐tumor activities. There was no report its antitumor effect through regulating P‐glycoprotein (P‐gp) so far, due to P‐gp over expression is one of the most important mechanisms contributing to the multiple drug resistance phenotype. The present aim was to investigate the effects of TAB on P‐gp in multidrug‐resistant cells; Paclitaxel‐resistant cell line MDA‐MB‐231/Taxol was established by stepwise exposure for 10 months. MDA‐MB‐231 cells and MDA‐MB‐231/Taxol cells were treated with TAB, and their growth was evaluated using MTT assays. Paclitaxel accumulation in the cells was analyzed by high performance liquid chromatogram (HPLC). The activity of P‐gp was detected by intracellular accumulation of rhodamine123 (Rho123), and the protein expression of P‐gp was evaluated using western blot. Results indicated that the IC50 of MDA‐MB‐231/Taxol to paclitaxel (Taxol) was 33 times higher than that of nature MDA‐MB‐231. TAB increased the intracellular concentration of Taxol and inhibited the activity of P‐gp and suppressed the expression of P‐gp in MDA‐MB‐231/Taxol cells. Our present results showed that TAB could reverse Taxol resistance in MDA‐MB‐231/Taxol cells, mainly inhibiting the activity of P‐gp and down‐regulating the expression level of P‐gp, and then enhancing the accumulation of chemotherapy agents. © 2013 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
  • Acute, Reproductive Toxicity and Two‐generation Teratology Studies
           of a Standardized Quassinoid‐rich Extract of Eurycoma longifolia
           Jack in Sprague–Dawley Rats
    • Abstract: The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up‐and‐down acute toxicity were investigated in Sprague–Dawley rats orally treated with quassinoid‐rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non‐treated animals. The TAF273‐treated dams decreased in percentage of pre‐implantation loss, post‐implantation loss and late resorption. No toxic symptoms were observed on the TAF273‐treated pregnant female rats and their foetuses were normal. The no‐observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10‐fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.
  • Hair Growth‐Promoting Effect of Carthamus tinctorius Floret Extract
    • Abstract: The florets of Carthamus tinctorius L. have traditionally been used for hair growth promotion. This study aimed to examine the potential of hydroxysafflor yellow A‐rich C. tinctorius extract (CTE) on hair growth both in vitro and in vivo. The effect of CTE on cell proliferation and hair growth‐associated gene expression in dermal papilla cells and keratinocytes (HaCaT) was determined. In addition, hair follicles from mouse neonates were isolated and cultured in media supplemented with CTE. Moreover, CTE was applied topically on the hair‐shaved skin of female C57BL/6 mice, and the histological profile of the skin was investigated. C. tinctorius floret ethanolic extract promoted the proliferation of both dermal papilla cells and HaCaT and significantly stimulated hair growth‐promoting genes, including vascular endothelial growth factor and keratinocyte growth factor. In contrast, CTE suppressed the expression of transforming growth factor‐β1 that is the hair loss‐related gene. Furthermore, CTE treatment resulted in a significant increase in the length of cultured hair follicles and stimulated the growth of hair with local effects in mice. The results provided the preclinical data to support the potential use of CTE as a hair growth‐promoting agent. Copyright © 2013 John Wiley & Sons, Ltd.
  • Antitubercular and Antibacterial Activity of Quinonoid Natural Products
           Against Multi‐Drug Resistant Clinical Isolates
    • Abstract: Multi‐drug resistant Mycobacterium tuberculosis and other bacterial pathogens represent a major threat to human health. In view of the critical need to augment the current drug regime, we have investigated therapeutic potential of five quinonoids, viz. emodin, diospyrin, plumbagin, menadione and thymoquinone, derived from natural products. The antimicrobial activity of quinonoids was evaluated against a broad panel of multi‐drug and extensively drug‐resistant tuberculosis (M/XDR‐TB) strains, rapid growing mycobacteria and other bacterial isolates, some of which were producers of β‐lactamase, Extended‐spectrum β‐lactamase (ESBL), AmpC β‐lactamase, metallo‐beta‐lactamase (MBL) enzymes, as well as their drug‐sensitive ATCC counterparts. All the tested quinones exhibited antimycobacterial and broad spectrum antibacterial activity, particularly against M. tuberculosis (lowest MIC 0.25 µg/mL) and Gram‐positive bacteria (lowest MIC  emodin ~ menadione ~ thymoquinone > diospyrin, whereas their antibacterial efficacy was plumbagin > menadione ~ thymoquinone > diospyrin > emodin. Furthermore, this is the first evaluation performed on these quinonoids against a broad panel of drug‐resistant and drug‐sensitive clinical isolates, to the best of our knowledge. Copyright © 2013 John Wiley & Sons, Ltd.
  • Cannabidiol Promotes Amyloid Precursor Protein Ubiquitination and
           Reduction of Beta Amyloid Expression in SHSY5YAPP+ Cells Through
           PPARγ Involvement
    • Abstract: The amyloidogenic cascade is regarded as a key factor at the basis of Alzheimer's disease (AD) pathogenesis. The aberrant cleavage of amyloid precursor protein (APP) induces an increased production and a subsequent aggregation of beta amyloid (Aβ) peptide in limbic and association cortices. As a result, altered neuronal homeostasis and oxidative injury provoke tangle formation with consequent neuronal loss. Cannabidiol (CBD), a Cannabis derivative devoid of psychotropic effects, has attracted much attention because it may beneficially interfere with several Aβ‐triggered neurodegenerative pathways, even though the mechanism responsible for such actions remains unknown. In the present research, the role of CBD was investigated as a possible modulating compound of APP processing in SHSY5YAPP+ neurons. In addition, the putative involvement of peroxisome proliferator‐activated receptor‐γ (PPARγ) was explored as a candidate molecular site responsible for CBD actions. Results indicated the CBD capability to induce the ubiquitination of APP protein which led to a substantial decrease in APP full length protein levels in SHSY5YAPP+ with the consequent decrease in Aβ production. Moreover, CBD promoted an increased survival of SHSY5YAPP+ neurons, by reducing their long‐term apoptotic rate. Obtained results also showed that all, here observed, CBD effects were dependent on the selective activation of PPARγ. Copyright © 2013 John Wiley & Sons, Ltd.
  • β‐Sitosterol Enhances Cellular Glutathione Redox Cycling by
           Reactive Oxygen Species Generated From Mitochondrial Respiration:
           Protection Against Oxidant Injury in H9c2 Cells and Rat Hearts
    • Abstract: Herba Cistanches (Cistanche deserticola Y. C. Ma) is a ‘Yang‐invigorating’ tonic herb in Chinese medicine. Preliminary chemical analysis indicated that β‐sitosterol (BS) is one of the chemical constituents in an active fraction of Herba Cistanches. To investigate whether BS is an active ingredient of Herba Cistanches, the effects of BS on H9c2 cells and rat hearts were examined. The results indicated that BS stimulated the mitochondrial ATP generation capacity in H9c2 cells, which was associated with the increased production of mitochondrial reactive oxygen species. BS also stimulated mitochondrial state 3 and state 4 respiration, with the resultant decrease in coupling efficiency. BS produced an up‐regulation of cellular glutathione redox cycling and protected against hypoxia/reoxygenation‐induced apoptosis in H9c2 cells. However, the protective effect of BS against myocardial ischemia/reperfusion injury was seen in female but not male rats ex vivo. The cardioprotection afforded by BS was likely mediated by an up‐regulation of mitochondrial glutathione redox cycling in female rat hearts. In conclusion, the ensemble of results suggests that BS is an active ingredient of Herba Cistanches. The gender‐dependent effect of BS on myocardial protection will further be investigated. Copyright © 2013 John Wiley & Sons, Ltd.
  • FOLFOX 4 Combined with Herbal Medicine for Advanced Colorectal Cancer: A
           Systematic Review
    • Abstract: This systematic review evaluates the clinical evidence for the addition of herbal medicines (HMs) to FOLFOX 4 for advanced colorectal cancer (ACRC) in terms of tumor response rate (tRR), survival, quality of life and reduction in adverse events (AEs). Seven electronic databases were searched for randomized controlled trials (RCTs) of FOLFOX4 combined with HMs compared to FOLFOX4 alone. Outcome data for 13 randomized controlled trials were analysed using Review Manager 5.1. Risk of bias for objective outcomes including tumor response and survival was judged as low. Publication bias was not evident. Meta‐analyses found the addition of HMs improved tRR (RR 1.25, 95%CI 1.06–1.47, I2 = 0%), one year survival (RR 1.51, 95%CI 1.19–1.90, I2 = 0%) and quality of life in terms of Karnofsky Performance Status (KPS) gained (RR 1.84, 95%CI 1.54‐2.19, I2 = 0%); alleviated grade 3 and 4 chemotherapy‐related AEs for neutropenia (RR 0.33, 95%CI 0.18‐0.60, I2 = 0%), nausea and vomiting (RR 0.34, 95%CI 0.17‐0.67, I2 = 0%) and neurotoxicity (RR 0.39, 95%CI 0.15‐1.00, I2 = 0%), compared to FOLFOX4 alone. The most frequently used herbs were Astragalus membranaceus, Panax ginseng, Atractylodes macrocephala, Poria cocos, Coix lachryma‐jobi and Sophora flavescens. In experimental studies, each of these herbs has shown actions that could have contributed to improved tumor response. Copyright © 2013 John Wiley & Sons, Ltd.
  • Effect of Terminalia chebula Extract and Chlorhexidine on Salivary pH and
           Periodontal Health: 2 Weeks Randomized Control Trial
    • Abstract: A double blind, randomized, controlled study with three parallel treatment groups was done to evaluate the efficacy of a Terminalia chebula 10% mouth rinse compared with chlorhexidine 0.12% mouth rinse, applied two times daily for 2 weeks, in the treatment of dental plaque and gingivitis. Seventy‐eight patients were included in the study. The efficacy variables were periodontal indices on days 0, 7 and 14 after commencement of therapy. Twenty six patients received chlorhexidine mouth rinse, twenty six Terminalia chebula mouth rinse and twenty six received saline solution. The clinical parameters were significantly reduced by both chlorhexidine and Terminalia chebula mouth rinse although no significant difference was seen between the two groups (P > 0.05). This study demonstrated that Terminalia chebula mouth rinse is effective in reducing microbial plaque, gingival inflammation and neutralizing salivary pH. Copyright © 2013 John Wiley & Sons, Ltd.
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