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Pacific Economic Review     Hybrid Journal   (Followers: 2, SJR: 0.785, h-index: 16)
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: 2, 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: 13, 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: 3)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 4, SJR: 1.295, h-index: 56)
Pediatric Anesthesia     Hybrid Journal   (Followers: 3, 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: 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: 3, 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: 11, SJR: 0.313, h-index: 6)
Personnel Psychology     Hybrid Journal   (Followers: 16, 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: 5, 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: 17, 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   (Followers: 1, 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: 23, 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: 3, 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: 26, 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: 12)
Practical Diabetes     Hybrid Journal   (Followers: 4)
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: 4)
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)

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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  [1604 journals]   [SJR: 0.718]   [H-I: 65]
  • Anti‐inflammatory Activities of Gouania leptostachya Methanol
           Extract and its Constituent Resveratrol
    • Authors: To Thi Mai Dung; Jongsung Lee, Eunji Kim, Byong Chul Yoo, Van Thai Ha, Yong Kim, Deok Hyo Yoon, Sungyoul Hong, Kwang‐Soo Baek, Nak Yoon Sung, Tae Woong Kim, Jong‐Hoon Kim, Jae Youl Cho
      Abstract: Gouania leptostachya DC. var. tonkinensis Pitard. Rhamnaceae is a traditional medicinal plant used in Thailand for treating various inflammatory symptoms. However, no systematic studies have been performed concerning the anti‐inflammatory effects or molecular mechanisms of this plant. The immunopharmacological activities of a methanol extract from the leaves and twigs of G. leptostachya (Gl‐ME) were elucidated based on the gastritis symptoms of mice treated with HCl/EtOH and the inflammatory responses, such as nitric oxide (NO) release and prostaglandin E2 (PGE2) production, from RAW264.7 cells and peritoneal macrophages. Moreover, inhibitory target molecules were also assessed. Gl‐ME dose‐dependently diminished the secretion of NO and PGE2 from LPS‐stimulated RAW264.7 cells and peritoneal macrophages. The gastritis lesions of HCl/EtOH‐treated mice were also attenuated after Gl‐ME treatment. The extract (50 and 300 µg/mL) clearly reduced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)‐2, nuclear translocation of p65/nuclear factor (NF)‐κB, phosphorylation of p65‐activating upstream enzymes, such as protein kinase B (AKT), inhibitor of κBα kinase (IKK), and inhibitor of κB (IκBα), and the enzymatic activity of Src. By HPLC analysis, one of the major components in the extract was revealed as resveratrol with NO and Src inhibitory activities. Moreover, this compound suppressed NO production and HCl/EtOH‐induced gastric symptoms. Therefore, these results suggest that Gl‐ME might be useful as an herbal anti‐inflammatory medicine through the inhibition of Src and NF‐κB activation pathways. The efficacy data of G. leptostachya also implies that this plant could be further tested to see whether it can be developed as potential anti‐inflammatory preparation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-21T05:05:34.817463-05:
      DOI: 10.1002/ptr.5262
  • A Novel Pregnane‐Type Alkaloid from Pachysandra terminalis Inhibits
           Methicillin‐Resistant Staphylococcus aureus In Vitro and In Vivo
    • Authors: Hui Zhao; Xiao‐Yang Wang, Ming‐Kai Li, Zheng Hou, Ying Zhou, Zhou Chen, Jing‐Ru Meng, Xiao‐xing Luo, Hai‐Feng Tang, Xiao‐Yan Xue
      Abstract: A new kind of pregnane‐type alkaloid, 20α‐dimethylamino‐3β‐senecioylamino‐16β‐hydroxy‐pregn‐5‐ene (K‐6), was isolated from Pachysandra terminalis Sieb. et Zucc., and its antibacterial activity against MRSA and MRSE was evaluated. We found that K‐6 showed antibacterial effects against MRSA and MRSE with minimum inhibitory concentration values (25 mg/L), but did not induce antibiotic resistance in bacteria easily. The administration of K‐6 dose‐dependently improved the animal survival rate of mice infected with MRSA, with survival rates of 36.34% and 66.67% in the low‐dose and high‐dose groups, respectively. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. Scanning and transmission electron microscopy analyses indicated that the cytoplasm shrink of bacterial cells led to noticeable gaps between the cell membrane and cell cytoplasm, and the severely damaged cell membrane resulted in leakage of intracellular content, which ultimately caused the lethal effect of K‐6 on bacteria. These findings demonstrated that K‐6 is a potential agent against MRSA and MRSE. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-21T03:33:51.319019-05:
      DOI: 10.1002/ptr.5261
  • A Combination of Glucosyl Hesperidin and Caffeine Exhibits an
           Anti‐obesity Effect by Inhibition of Hepatic Lipogenesis in Mice
    • Authors: Tatsuya Ohara; Koutarou Muroyama, Yoshihiro Yamamoto, Shinji Murosaki
      Abstract: To develop an anti‐obesity agent, we examined the combination effect of glucosyl hesperidin (G‐hesperidin) and caffeine on obesity in mice. High‐fat diet‐induced obese KK mice were fed a low‐fat diet with or without G‐hesperidin, caffeine, or their combination for 2 weeks. Decreases in body weight and significantly lower adipose tissue weight were observed in the combination‐fed mice but not in the G‐hesperidin‐fed or caffeine‐fed mice. DNA microarray analysis of mouse liver suggested that the feeding of G‐hesperidin + caffeine was associated with lower lipogenesis. Therefore, we examined the anti‐lipogenic effect of G‐hesperidin + caffeine in fasted–refed KK mice. Hepatic triglyceride levels were significantly lower in the mice fed G‐hesperidin + caffeine during the refeeding period but not in the mice fed each alone. In addition, hepatic expressions of genes related to lipogenesis, such as sterol regulatory element‐binding protein‐1c or fatty acid synthase, were significantly lower in the mice fed G‐hesperidin + caffeine compared with that in the control mice. These results suggested that G‐hesperidin + caffeine is effective for controlling obesity partly by the inhibition of hepatic lipogenesis. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-20T02:27:52.636435-05:
      DOI: 10.1002/ptr.5258
  • Neuroprotection by Saponins
    • Authors: Aijing Sun; Xianxiang Xu, Junsheng Lin, Xiuling Cui, Ruian Xu
      Abstract: Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones. Their diverse biological activities are ascribed to their different structures. Saponins have long been recognized as key ingredients in traditional Chinese medicine. Accumulated evidence suggests that saponins have significant neuroprotective effects on attenuation of central nervous system disorders, such as stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, our understanding of the mechanisms underlying the observed effects remains incomplete. Based on recently reported data from basic and clinical studies, this review highlights the proposed mechanisms of their neuroprotective function including antioxidant, modulation of neurotransmitters, anti‐apoptosis, anti‐inflammation, attenuating Ca2+ influx, modulating neurotrophic factors, inhibiting tau phosphorylation, and regeneration of neural networks. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-19T02:04:19.507263-05:
      DOI: 10.1002/ptr.5246
  • Complementary Usage of Rhodiola crenulata (L.) in Chronic Obstructive
           Pulmonary Disease Patients: The Effects on Cytokines and T Cells
    • Authors: Shih‐Pin Chen; Rosa Huang Liu, Tsong‐Ming Lu, James Cheng‐Chung Wei, Tzu‐Chin Wu, Wei‐Yu Tsai, Chung‐Hung Tsai, Chi‐Chiang Yang
      Abstract: Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age‐matched, and sex‐matched non‐COPD control subjects. Our results showed that serum levels of IL‐2, IL‐10, and IFN‐γ in COPD patients before treatment are significantly higher than levels in non‐COPD controls (p 
      PubDate: 2014-11-18T05:27:22.558269-05:
      DOI: 10.1002/ptr.5259
  • Gallic Acid Exhibits Risks of Inducing Muscular Hemorrhagic Liposis and
           Cerebral Hemorrhage—Its Action Mechanism and Preventive Strategy
    • Authors: Chiu‐Lan Hsieh; Chien‐Hong Lin, Hui‐Er Wang, Chiung‐Chi Peng, Robert Y. Peng
      Abstract: Gallic acid (3,4,5‐trihydroxybenzoic acid) (GA) occurs in many plants. The adverse effects of GA are seldom cited. GA (6–14 μM) provoked the hemorrhagic liposis of the cervical muscles and intracranial hemorrhage. The cause of these pathological events and the method for prevention are still lacking. Using the chicken embryo model and some selected nutraceutics such as folate, glutathione (GSH), N‐acetylcysteine, and vitamin E (Vit E), we carried out this study. Results revealed that the action mechanism of GA involved (i) inducing hypoxia with upregulated gene hif‐1α and downregulated ratio vegf‐r2/vegf‐a, leading to dys‐vascularization and myopathy; (ii) impairing cytochrome c oxidase; (iii) stimulating creatine kinase and lactate dehydrogenase release; (iv) eliciting carnitine accumulation and liposis via downregulating gene CPT1; (v) suppressing superoxide dismutase and stimulating NO, H2O2, and malondialdehyde; and (vi) depleting erythrocytic and tissue GSH, resulting in hemorrhage. When both Vit E and GSH were applied to the day 1 chicks, a better alleviation effect was revealed. Conclusively, GA potentially exhibits adverse effect by eliciting hemorrhagic liposis of cervical muscles and cerebral hemorrhage. Supplementation with GSH, Vit E, and N‐acetylcysteine is able to ameliorate these adverse effects, warranting the importance of restricting the clinical phytotherapeutic doses of GA and related compounds. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-17T22:37:45.44128-05:0
      DOI: 10.1002/ptr.5249
  • Antioxidant and Anti‐Inflammatory Properties of the Citrus
           Flavonoids Hesperidin and Hesperetin: An Updated Review of their Molecular
           Mechanisms and Experimental Models
    • Authors: Hamideh Parhiz; Ali Roohbakhsh, Fatemeh Soltani, Ramin Rezaee, Mehrdad Iranshahi
      Abstract: Inflammation and oxidative stress are two major causes of various life‐threatening diseases. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from citrus species that have numerous biological properties, particularly antioxidant and anti‐inflammatory. New findings showed that the antioxidant activity of Hsd/Hst was not only limited to its radical scavenging activity, but it augmented the antioxidant cellular defenses via the ERK/Nrf2 signaling pathway as well. Various in vitro and in vivo studies have been conducted to evaluate Hsd, its metabolites, or its synthetic derivatives at reducing inflammatory targets including NF‐κB, iNOS, and COX‐2, and the markers of chronic inflammation. In this review, new findings regarding the molecular targets of Hsd and Hst in the reduction of oxidative stress are discussed. Also, in the anti‐inflammatory section, we provide a summary of significant investigations concerning the mechanisms of action based on the studied inflammation models. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-13T05:15:50.270508-05:
      DOI: 10.1002/ptr.5256
  • Hypoglycaemic Activity of Culinary Pleurotus ostreatus and P. cystidiosus
           Mushrooms in Healthy Volunteers and Type 2 Diabetic Patients on Diet
           Control and the Possible Mechanisms of Action
    • Authors: W. J. A. Banukie N. Jayasuriya; Chandanie A. Wanigatunge, Gita H. Fernando, D. Thusitha U. Abeytunga, T. Sugandhika Suresh
      Abstract: This study determined the oral hypoglycaemic effect of suspensions of freeze dried and powdered (SFDP) Pleurotus ostreatus (P.o) and Pleurotus cystidiosus (P.c), using healthy human volunteers and Type 2 diabetic patients on diet control at a dose of 50 mg/kg/body weight, followed by a glucose load. The possible hypoglycaemic mechanisms were evaluated using rats, by examining intestinal glucose absorption and serum levels of insulin, glucokinase (GK) and glycogen synthase kinase (GSK). The P.o and P.c showed a significant reduction (P 
      PubDate: 2014-11-08T01:45:44.113335-05:
      DOI: 10.1002/ptr.5255
  • Mangiferin Attenuates Renal Fibrosis Through Down‐Regulation of
           Osteopontin in Diabetic Rats
    • Authors: Xia Zhu; Ya‐Qin Cheng, Lei Du, Yu Li, Fan Zhang, Hao Guo, Yao‐Wu Liu, Xiao‐Xing Yin
      Abstract: This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason‐stained positive area of glomeruli, protein expression of type IV collagen, and α‐smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF‐кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF‐кB. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-07T02:43:44.689591-05:
      DOI: 10.1002/ptr.5254
  • Garlic (Allium sativum) Stimulates Lipopolysaccharide‐induced Tumor
           Necrosis Factor‐alpha Production from J774A.1 Murine Macrophages
    • Authors: Jessica Sung; Youssef Harfouche, Melissa De La Cruz, Martha P. Zamora, Yan Liu, James A. Rego, Nancy E. Buckley
      Abstract: Garlic (Allium sativum) is known to have many beneficial attributes such as antimicrobial, antiatherosclerotic, antitumorigenetic, and immunomodulatory properties. In the present study, we investigated the effects of an aqueous garlic extract on macrophage cytokine production by challenging the macrophage J774A.1 cell line with the garlic extract in the absence or presence of lipopolysaccharide (LPS) under different conditions. The effect of allicin, the major component of crushed garlic, was also investigated. Using enzyme‐linked immunosorbent assay and reverse transcriptase‐quantitative polymerase chain reaction, it was found that garlic and synthetic allicin greatly stimulated tumor necrosis factor‐alpha (TNF‐α) production in macrophages treated with LPS. The TNF‐α secretion levels peaked earlier and were sustained for a longer time in cells treated with garlic and LPS compared with cells treated with LPS alone. Garlic acted in a time‐dependent manner. We suggest that garlic, at least partially via its allicin component, acts downstream from LPS to stimulate macrophage TNF‐α secretion. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons, Ltd.
      PubDate: 2014-11-04T01:47:24.615789-05:
      DOI: 10.1002/ptr.5253
  • Soyasaponins Aa and Ab Exert an Anti‐Obesity Effect in 3T3‐L1
           Adipocytes Through Downregulation of PPARγ
    • Authors: Seung Hwan Yang; Eun‐Kyung Ahn, Jung A Lee, Tai‐Sun Shin, Chigen Tsukamoto, Joo‐won Suh, Itabashi Mei, Gyuhwa Chung
      Abstract: Saponins are a diverse group of biologically functional products in plants. Soyasaponins are usually glycosylated, which give rise to a wide diversity of structures and functions. In this study, we investigated the effects and molecular mechanism of soyasaponins Aa and Ab in regulating adipocyte differentiation and expression of adipogenic marker genes in 3T3‐L1 adipocytes. Soyasaponins Aa and Ab dose‐dependently inhibited the accumulation of lipids and the expression of adiponectin, adipocyte determination and differentiation factor 1/sterol regulatory element binding protein 1c, adipocyte fatty acid‐binding protein 2, fatty acid synthase, and resistin in 3T3‐L1 adipocytes. In addition, soyasaponins Aa and Ab suppressed the transcriptional activity of peroxisome proliferator‐activated receptor γ (PPARγ) in HEK 293T cells. Furthermore, we confirmed that the expression of PPARγ and of CCAAT‐enhancer‐binding protein α (C/EBPα) was suppressed at both the mRNA and protein levels in 3T3‐L1 adipocytes by treatment with soyasaponins Aa and Ab. Taken together, these findings indicate that soyasaponin Aa and Ab markedly inhibit adipocyte differentiation and expression of various adipogenic marker genes through the downregulation of the adipogenesis‐related transcription factors PPARγ and C/EBPα in 3T3‐L1 adipocytes. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-04T01:33:11.684082-05:
      DOI: 10.1002/ptr.5252
  • Formula Optimization of the Jiashitang Scar Removal Ointment and
           Antiinflammatory Compounds Screening by NF‐κB
           Bioactivity‐guided Dual‐luciferase Reporter Assay System
    • Authors: Jie Gao; Jin Tao, Nannan Zhang, Yanjie Liu, Min Jiang, Yuanyuan Hou, Qian Wang, Gang Bai
      Abstract: Inflammation plays a role in scar formation; therefore, decreasing inflammation benefits scar removal. Jiashitang scar removal ointment (JST) is a commercially available traditional Chinese medicinal formulation. It is composed of extracts from Carthamus tinctorius L. (Car), Rheum officinale Baill. (Rhe), Salvia miltiorrhiza Beg. (Sal), and Panax notoginseng (Burk.) F. H. Chen (Pan), which are all herbs with potent antiinflammatory activities. Our aims are to optimize the formula of JST and to elucidate its antiinflammatory active components. Response surface methodology was applied to optimize proportions of the four herb extracts. The antiinflammatory effects were evaluated using in vitro and in vivo models. To screen for active components in this formula, a bioactivity‐based ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry analysis was performed. After optimization, the antiinflammatory effects of the new formula were significantly superior to the original one. Screening identified 13 active ingredients: a series of saffiomin, emodin, salvianolic acid, tanshinone, and triterpenoid saponin derivatives. These active ingredients were predicted to exert nuclear factor‐κB inhibiting effects through MAPK, PI3K/AKT, and NIK‐IKK pathways. In conclusion, the original formula was successfully optimized with more potent antiinflammatory activity. These methods can be applied to researches of other formulas. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-02T23:56:37.642371-05:
      DOI: 10.1002/ptr.5244
  • Effect of Ginkgo Biloba Extract on Lipopolysaccharide‐induced
           Anhedonic Depressive‐like Behavior in Male Rats
    • Authors: Kuei‐Ying Yeh; Sing‐Siang Shou, Yi‐Xuan Lin, Chao‐Cin Chen, Chen‐Yen Chiang, Chien‐Yu Yeh
      Abstract: The peripheral administration of lipopolysaccharide (LPS) induces depressive‐like behavior. Anhedonia is a core symptom of depression, defined as a loss of the capacity to experience pleasure. The present study used the sucrose preference test to investigate the influence of Ginkgo biloba extract (EGb 761) on LPS‐induced anhedonia in male rats. The animals were randomly divided into four groups: (I) vehicle + saline, (II) vehicle + LPS, (III) EGb 761 + saline, and (IV) EGb 761 + LPS. Saline or LPS (100 µg/kg) was administered intraperitoneally 2 h before the sucrose preference test. Sucrose consumption was recorded 2, 4, 6, 13, and 24 h after 100 µg/kg of LPS or saline injection in the dark phase of the light/dark cycle. Dopamine and serotonin levels in the nucleus accumbens were measured. Our results indicated that the vehicle + LPS group exhibited a significant decrease in sucrose intake compared with the vehicle + saline group. The EGb 761 + LPS group showed more sucrose and food consumption than the vehicle + LPS group. Additionally, compared with the EGb 761 + LPS group, the vehicle + LPS group had less dopamine levels in the nucleus accumbens. Treatment with EGb 761 had no effect on water intake. Our results suggest that EGb 761 may be useful for reducing anhedonic depressive‐like behavior. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons, Ltd.
      PubDate: 2014-10-24T04:33:27.020913-05:
      DOI: 10.1002/ptr.5247
  • Comparing the Effects of Kamikihito in Japan and
           Kami‐Guibi‐Tang in Korea on Memory Enhancement: Working
           Towards the Development of a Global Study
    • Authors: Hidetoshi Watari; Michiko Shigyo, Norio Tanabe, Michihisa Tohda, Ki‐Ho Cho, Park Su Kyung, Woo Sang Jung, Yutaka Shimada, Naotoshi Shibahara, Tomoharu Kuboyama, Chihiro Tohda
      Abstract: Traditional medicine is widely used in East Asia, and studies that demonstrate its usefulness have recently become more common. However, formulation‐based studies are not globally understood because these studies are country‐specific. There are many types of formulations that have been introduced to Japan and Korea from China. Establishing whether a same‐origin formulation has equivalent effects in other countries is important for the development of studies that span multiple countries. The present study compared the effects of same‐origin traditional medicine used in Japan and Korea in an in vivo experiment. We prepared drugs that had the same origin and the same components. The drugs are called kamikihito (KKT) in Japan and kami‐guibi‐tang (KGT) in Korea. KKT (500 mg extract/kg/day) and KGT (500 mg extract/kg/day) were administered to ddY mice, and object recognition and location memory tests were performed. KKT and KGT administration yielded equivalent normal memory enhancement effects. 3D‐HPLC showed similar, but not identical, patterns of the detected compounds between KKT and KGT. This comparative research approach enables future global clinical studies of traditional medicine to be conducted through the use of the formulations prescribed in each country. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-23T22:13:51.853286-05:
      DOI: 10.1002/ptr.5250
  • The Immunostimulating Role of Lichen Polysaccharides: A Review
    • Authors: Gajendra Shrestha; Larry L. St. Clair, Kim L. O'Neill
      Abstract: The immune system has capacity to suppress the development or progression of various malignancies including cancer. Research on the immunomodulating properties of polysaccharides obtained from plants, microorganisms, marine organisms, and fungi is growing rapidly. Among the various potential sources, lichens, symbiotic systems involving a fungus and an alga and/or a cyanobacterium, show promise as a potential source of immunomodulating compounds. It is well known that lichens produce an abundance of structurally diverse polysaccharides. However, only a limited number of studies have explored the immunostimulating properties of lichen polysaccharides. Published studies have shown that some lichen polysaccharides enhance production of nitrous oxide (NO) by macrophages and also alter the production levels of various proinflammatory and antiinflammatory cytokines (IL‐10, IL‐12, IL‐1β, TNF‐α, and IFN‐α/β) by macrophages and dendritic cells. Although there are only a limited number of studies examining the role of lichen polysaccharides, all results suggest that lichen polysaccharides can induce immunomodulatory responses in macrophages and dendritic cells. Thus, a detailed evaluation of immunomodulatory capacity of lichen polysaccharides could provide a unique opportunity for the discovery of novel therapeutic agents. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-22T04:11:41.18946-05:0
      DOI: 10.1002/ptr.5251
  • Dang Shen [Codonopsis pilosula (Franch.) Nannf] Herbal Formulae for
           Chronic Obstructive Pulmonary Disease: A Systematic Review and
    • Authors: Johannah L. Shergis; Shaonan Liu, Xiankun Chen, Anthony L. Zhang, Xinfeng Guo, Chuanjian Lu, Charlie C. Xue
      Abstract: This systematic review and meta‐analysis assessed the efficacy and safety of Dang shen [Codonopsis pilosula (Franch.) Nannf., root] formulae for the treatment of chronic obstructive pulmonary disease (COPD). English and Chinese databases were searched, and 48 randomized controlled trials were included. Dang shen formulae improved lung function forced expiratory volume in 1 s compared with conventional pharmacotherapy (CP) [mean difference (MD) 0.22 L, 95% confidence interval (CI) 0.13–0.31, p 
      PubDate: 2014-10-22T01:26:20.357693-05:
      DOI: 10.1002/ptr.5248
  • Inhibitory Effects of French Pine Bark Extract, Pycnogenol®, on
           Alveolar Bone Resorption and on the Osteoclast Differentiation
    • Authors: Hideki Sugimoto; Kiyoko Watanabe, Toshizo Toyama, Shun‐suke Takahashi, Shuta Sugiyama, Masaichi‐Chang‐il Lee, Nobushiro Hamada
      Abstract: Pycnogenol® (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non‐infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate‐resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1–100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-21T22:42:47.726099-05:
      DOI: 10.1002/ptr.5245
  • The application of metabolomics in traditional Chinese medicine opens up a
           dialogue between Chinese and Western medicine
    • Authors: Hongxin Cao; Aihua Zhang, Huamin Zhang, Hui Sun, Xijun Wang
      Abstract: Metabolomics provides an opportunity to develop the systematic analysis of the metabolites and has been applied to discovering biomarkers and perturbed pathways which can clarify the action mechanism of traditional Chinese medicines (TCM). TCM is a comprehensive system of medical practice that has been used to diagnose, treat and prevent illnesses more than 3000 years. Metabolomics represents a powerful approach that provides a dynamic picture of the phenotype of biosystems through the study of endogenous metabolites, and its methods resemble those of TCM. Recently, metabolomics tools have been used for facilitating interactional effects of both Western medicine and TCM. We describe a protocol for investigating how metabolomics can be used to open up ‘dialogue’ between Chinese and Western medicine, and facilitate lead compound discovery and development from TCM. Metabolomics will bridge the cultural gap between TCM and Western medicine and improve development of integrative medicine, and maximally benefiting the human. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-21T02:26:23.813576-05:
      DOI: 10.1002/ptr.5240
  • Potent Effects of the Total Saponins from Dioscorea nipponica Makino
           Against Streptozotocin‐Induced Type 2 Diabetes Mellitus in Rats
    • Authors: Hao Yu; Lingli Zheng, Lina Xu, Lianhong Yin, Yuan Lin, Hua Li, Kexin Liu, Jinyong Peng
      Abstract: The aim of the present paper was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against type 2 diabetes mellitus. Streptozotocin (STZ) with high‐fat diet induced type 2 diabetes mellitus (T2DM) rats were treated with TSDN. Some biochemical parameters, target proteins and genes were investigated. The results showed that TSDN decreased the levels of food/water intake, fasting blood glucose and serum lipid parameters, ameliorated oral glucose and insulin tolerance test levels, markedly increased body weight and serum insulin, reduced excess free radicals and affected ossification and renal protection. Histopathological examination indicated that TSDN increased liver glycogen, decreased the production of lipid vacuoles and lightened liver damage. Further investigation showed that TSDN down‐regulated the protein expressions of NF‐κB, GRP78, ATF6, eIF2 and the levels of MAPK phosphorylation and up‐regulated the protein expressions of IRS‐1, GLUT‐4, p‐Akt and p‐AMPK. In addition, TSDN obviously decreased the gene expressions of TNF‐a, IL‐6, PEPCK, G6Pase, GSK‐3β and GSK‐3β activity, and increased the gene expressions of PFK, PK and GK activity. These findings show the anti‐diabetic activity of total saponins from D. nipponica Makino, which should be developed as a new potent drug for treatment of diabetes mellitus in future. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-16T20:23:21.963912-05:
      DOI: 10.1002/ptr.5243
  • Aqueous Extract of Rosmarinus officinalis L. Inhibits Neutrophil Influx
           and Cytokine Secretion
    • Authors: Ana Mara de Oliveira e Silva; Isabel Daufenback Machado, José Roberto Santin, Illana Louise Pereira Melo, Gabriela Vieira Pedrosa, Maria Ines Genovese, Sandra Helena Poliselli Farsky, Jorge Mancini‐Filho
      Abstract: Rosmarinus officinalis L. phenolic compounds have attracted considerable attention because of their antioxidant and antimicrobial properties, including its ability to treat inflammatory disorders. In this work, we investigated the in vivo and in vitro effects of R. officinalis aqueous extract on neutrophil trafficking from the blood into an inflamed tissue, on cell‐derived secretion of chemical mediators, and on oxidative stress. Anti‐inflammatory activity was investigated using carrageenan‐induced inflammation in the subcutaneous tissue of male Wistar rats orally treated with the R. officinalis extract (100, 200, or 400 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (prostaglandin E2 (PGE2), TNF‐α, interleukin 6 (IL‐6), leukotriene B4 (LTB4), and cytokine‐induced neutrophil chemoattractant 1 by enzyme‐linked immunosorbent assay), and the anti‐oxidative profile (super oxide dismutase (SOD), glutathione peroxidase, and thiobarbituric acid reactive substance (TBARS) spectrophotometry) were quantified in the inflamed exudate. N‐Formyl‐methionine‐leucine‐phenylalanine‐induced chemotaxis, lipopolysaccharide‐induced NO2− production (Greiss reaction), and adhesion molecule expression (flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 µg/mL). Animals orally treated with phosphate‐buffered saline and neutrophils incubated with Hank's balanced salt solution were used as control. R. officinalis extract oral treatment caused a dose‐dependent reduction in the neutrophil migration as well as decreased SOD, TBARS, LTB4, PGE2, IL‐6, and TNF‐α levels in the inflamed exudate. In vitro treatment with R. officinalis decreased neutrophil chemotaxis, NO2− production, and shedding of L‐selectin and β2 integrin expressions. Results here presented show that R. officinalis aqueous extract displays important in vivo and in vitro anti‐inflammatory actions by blocking pathways of neutrophil migration and secretion, suggesting its therapeutic application to acute inflammatory reactions. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-15T22:06:01.494171-05:
      DOI: 10.1002/ptr.5238
  • Mechanisms of improvement of intestinal transport of baicalin and puerarin
           by extracts of Radix Angelicae Dahuricae
    • Authors: Xin‐Li Liang; Jing Zhang, Guo‐Wei Zhao, Zhe Li, Yun Luo, Zheng‐Gen Liao, Dong‐Mei Yan
      Abstract: Radix Angelicae Dahuricae is the dried root of Angelicae Dahurica (Fisch.ex Hoffm.) Hook.f. var.formosana (Boiss.) Shan et Yuan (Fam.Umbelliferae). The total coumarins (Cou) and volatile oil (VO) were main active components that drived from Radix Angelicae Dahuricae. Our previous studies have shown that Cou and VO could increase intestinal absorption for transmucosal drug delivery with unknown mechanism. The aim of this study was to investigate the molecular mechanism of Radix Angelicae Dahuricae for improving drug intestinal transport. Caco‐2 cell model was used to study the effect of Radix Angelicae Dahurica on transepithelial electrical resistance. Western blot was used to study its effect on the expression of the actin and ZO‐1, tight junction proteins. The effect of Radix Angelicae Dahurica on the expression of P‐gp protein was investigated using flow cytometry. VO (0.036–2.88 μL/mL) and Cou (0.027–0.54 mg/mL) caused a reversible, time‐ and dose‐dependent decrease in transepithelial electrical resistance. VO and/or Cou could inhibit the expression of the tight junction protein, ZO‐1 and actin. VO and/or Cou also could inhibit the expression of P‐gp. These data suggested that Radix Angelicae Dahurica increased cell permeability by affecting the expression of actin, ZO‐1 or P‐gp, opening the tight junction or inhibiting the efflux induced by P‐gp. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-14T02:21:24.293505-05:
      DOI: 10.1002/ptr.5242
  • Effect of Ginger (Zingiber officinale) on Heavy Menstrual Bleeding: A
           Placebo‐Controlled, Randomized Clinical Trial
    • Authors: Farzaneh Kashefi; Marjan Khajehei, Mohammad Alavinia, Ebrahim Golmakani, Javad Asili
      Pages: n/a - n/a
      Abstract: Objective: A wide range of herbal plants have been reported to treat various gynecological problems of women. This study was set out to investigate the effect of ginger (Zingiber officinale) on heavy menstrual bleeding (HMB) in high school girls. Methods: Ninety‐two young women who experienced HMB and met the inclusion criteria were recruited in this study. Participants were evaluated for six consecutive menstrual cycles. During 3 assessment cycles, their HMB was confirmed by Pictorial Blood Assessment Chart. They were then randomly allocated to two study groups to receive either ginger or placebo capsules. The participants filled in the same chart during three intervention cycles. Results: The level of menstrual blood loss dramatically declined during the three intervention cycles in ginger‐receiving group. The decrease of blood loss in ginger‐receiving group was significantly more remarkable than that of participants receiving placebo (p 
      PubDate: 2014-10-08T22:32:11.515402-05:
      DOI: 10.1002/ptr.5235
  • Effect of Curcumin on Hepatic Antioxidant Enzymes Activities and Gene
           Expressions in Rats Intoxicated with Aflatoxin B1
    • Authors: S. M. El‐Bahr
      Abstract: Twenty‐eight rats were examined in a 5‐week experiment to investigate the effect of curcumin on gene expression and activities of hepatic antioxidant enzymes in rats intoxicated with aflatoxin B1 (AFB1). The rats were divided into four groups. Rats in 1–4 groups served as control, oral curcumin treated (15 mg/kg body weight), single i.p. dose of AFB1 (3 mg/kg body weight) and combination of single i.p. dose of AFB1 with oral curcumin treated, respectively. AFB1 Liver damage and oxidative stress were evident in untreated AFB1‐intoxicated rats as indicated by a significant elevation in hepatic transaminases, elevation in lipid peroxide biomarkers (thiobarbituric acid reactive substances; TBARS), reduction of reduced glutathione (GSH) concentration, reduction in the activities of antioxidant enzymes namely catalase (CAT), total superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione‐S‐transferase (GST) and down‐regulation of gene expression of these antioxidant enzymes compared to control. Liver sections of rats intoxicated with AFB1 showed a disrupted lobular architecture, scattered necrotic cells and biliary proliferation. Administration of curcumin with AFB1 resulted in amelioration of AFB1‐induced effects compared to untreated AFB1‐intoxicated rats via an up‐regulation of antioxidant enzyme gene expression, activation of the expressed genes and increase in the availability of GSH. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-07T23:07:17.05011-05:0
      DOI: 10.1002/ptr.5239
  • Isoflavones Extracted from Chickpea Cicer arietinum L. Sprouts Induce
           Mitochondria‐Dependent Apoptosis in Human Breast Cancer Cells
    • Authors: Hua Chen; Hai‐Rong Ma, Yan‐Hua Gao, Xue Zhang, Madina Habasi, Rui Hu, Haji Akber Aisa
      Abstract: Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation‐7 (MCF‐7). 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays showed that ICS (10–60 µg/mL) significantly inhibited the proliferation of both cell lines in a time‐dependent and dose‐dependent fashion. Wright‐Giemsa staining as well as annexin V‐fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose‐dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis‐promoting gene Bcl‐2‐associated X protein and decreased the expression of the antiapoptotic gene Bcl‐2. Western blot analysis showed that treatment of SKBr3 and MCF‐7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose‐dependent manner. Flow cytometry assays using the fluorescent probe 3,3′‐dihexyloxacarbocyanine iodide showed a dose‐dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose‐dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-06T23:17:00.423925-05:
      DOI: 10.1002/ptr.5241
  • Pentacyclic Triterpenoids from Spikes of Prunella vulgaris L. Inhibit
           Glycogen Phosphorylase and Improve Insulin Sensitivity in 3T3‐L1
    • Authors: Qian Yu; Jin Qi, Lu Wang, Shou‐Jin Liu, Bo‐Yang Yu
      Pages: n/a - n/a
      Abstract: Phytochemical investigation of methanol extract from the spikes of Prunella vulgaris L. led to the isolation of two new pentacyclic triterpenoid glycosides Vulgasides I (1) and II (2) along with 13 known compounds (3–15). Their structures were established on the basis of nuclear magnetic resonance (1D and 2D) and mass spectroscopic data analysis. All the isolated compounds were screened for glycogen phosphorylase inhibitory activity and also evaluated for their effect on insulin sensitivity in 3T3‐L1 adipocytes. Two new compounds (1, 2) did not demonstrate the glycogen phosphorylase inhibitory activity, but other compounds (3–11) exhibited varying degrees of glycogen phosphorylase inhibitory activity with IC50 values in the range from 30.69 to 68.85 μM. Compounds 3, 6, 7, 11, and 13 demonstrated markedly increased insulin‐mediated glucose consumption in 3T3‐L1 adipocytes. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-03T00:58:30.604692-05:
      DOI: 10.1002/ptr.5228
  • Modulation of Cox‐1, 5‐, 12‐ and 15‐Lox by Popular
           Herbal Remedies Used in Southern Italy Against Psoriasis and Other Skin
    • Authors: Ammar Bader; Francesca Martini, Guillermo R. Schinella, Jose L. Rios, Jose M. Prieto
      Pages: n/a - n/a
      Abstract: Acanthus mollis (Acanthaceae), Achillea ligustica, Artemisia arborescens and Inula viscosa (Asteraceae) are used in Southern Italy against psoriasis and other skin diseases that occur with an imbalanced production of eicosanoids. We here assessed their in vitro effects upon 5‐, 12‐, 15‐LOX and COX‐1 enzymes as well as NFκB activation in intact cells as their possible therapeutic targets. All methanol crude extracts inhibited both 5‐LOX and COX‐1 activities under 200 µg/mL, without significant effects on the 12‐LOX pathway or any relevant in vitro free radical scavenging activity. NFκB activation was prevented by all extracts but A. mollis. Interestingly, A. ligustica, A. arborescens and A. mollis increased the biosynthesis of 15(S)‐HETE, an anti‐inflammatory eicosanoid. A. ligustica (IC50 = 49.5 µg/mL) was superior to Silybum marianum (IC50 = 147.8 µg/mL), which we used as antipsoriatic herbal medicine of reference. Its n‐hexane, dichloromethane and ethyl acetate fractions had also inhibitory effects on the LTB4 biosynthesis (IC50s = 9.6, 20.3 and 68 µg/mL, respectively) evidencing that the apolar extracts of A. ligustica are promising active herbal ingredients for future phytotherapeutical products targeting psoriasis. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2014-10-03T00:16:07.513125-05:
      DOI: 10.1002/ptr.5234
  • A Review of the Receptor Binding and Pharmacological Effects of
    • Authors: Sidney J. Stohs; Michael J. Hartman
      Pages: n/a - n/a
      Abstract: N‐methyltyramine (NMT) is a protoalkaloid isolated from various plant species. It is assumed that NMT is an adrenergic agonist with pharmacological properties similar to other structurally related biogenic amines. Current research studies indicate that NMT is an α‐adrenoreceptor antagonist, and exhibits modest inhibitory (antagonistic) activity with respect to the breakdown of fats (lipolysis). Furthermore, NMT has been shown to enhance appetite and digestion of foods through its stimulatory effects on gastrin and pancreatic secretions. As a consequence, NMT is not an ingredient that should be used in dietary supplements designed to promote weight loss. It may result in an increase in perceived energy by promoting appetite and the digestion and absorption of nutrients while inhibiting the breakdown to fats to energy. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-02T00:10:05.106774-05:
      DOI: 10.1002/ptr.5231
  • In vitro Combinatory Antimicrobial Effect of Plumbagin with Oxacillin and
           Tetracycline against Staphylococcus aureus
    • Authors: Johana Rondevaldova; Pavel Novy, Ladislav Kokoska
      Pages: n/a - n/a
      Abstract: Plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone), a bicyclic naphthoquinone naturally distributed among Plumbago species, has been reported to have antimicrobial activity against a wide range of microorganisms. In this study, plumbagin was examined for its combinatory antimicrobial effect with tetracycline or oxacillin against nine strains of Staphylococcus aureus, including its methicillin‐ and multidrug‐resistant strains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated according to the sum of fractional inhibitory concentration (ΣFIC) indices. Additive interactions were obtained for both combinations against most of the strains tested. Synergy was obtained for combination with oxacillin against two out of seven strains (ΣFIC range 0.273–0.281), both were methicillin resistant. Our results proved plumbagin as a compound suitable for anti‐Staphylococcal combinatory testing. Moreover, to the best of our knowledge, this is the first report of plumbagin synergy with oxacillin against S. aureus strains, including its resistant forms. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-30T05:26:18.705046-05:
      DOI: 10.1002/ptr.5237
  • Extracts from Calendula officinalis Offer in Vitro Protection Against H2O2
           Induced Oxidative Stress Cell Killing of Human Skin Cells
    • Authors: Abdullah M. Alnuqaydan; Claire E. Lenehan, Rachel R. Hughes, Barbara J. Sanderson
      Pages: n/a - n/a
      Abstract: The in vitro safety and antioxidant potential of Calendula officinalis flower head extracts was investigated. The effect of different concentrations (0.125, 0.5, 1.0, 2.0 and 5.0% (v/v)) of Calendula extracts on human skin cells HaCaT in vitro was explored. Doses of 1.0% (v/v) (0.88 mg dry weight/mL) or less showed no toxicity. Cells were also exposed to the Calendula extracts for either 4, 24 or 48 h before being exposed to an oxidative insult (hydrogen peroxide H2O2) for 1 h. Using the MTT cytotoxicity assay, it was observed that two independent extracts of C. officinalis gave time‐dependent and concentration‐dependent H2O2 protection against induced oxidative stress in vitro using human skin cells. Pre‐incubation with the Calendula extracts for 24 and 48 h increased survival relative to the population without extract by 20% and 40% respectively following oxidative challenge. The antioxidant potential of the Calendula extracts was confirmed using a complimentary chemical technique, the DPPH● assay. Calendula extracts exhibited free radical scavenging abilities. This study demonstrates that Calendula flower extracts contain bioactive and free radical scavenging compounds that significantly protect against oxidative stress in a human skin cell culture model. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-30T02:19:11.404107-05:
      DOI: 10.1002/ptr.5236
  • Effect of Hypericum perforatum L. Extract on Insulin Resistance and Lipid
           Metabolic Disorder in High‐Fat‐Diet Induced Obese Mice
    • Authors: Jin‐ying Tian; Rong‐ya Tao, Xiao‐lin Zhang, Qian Liu, Yi‐bo He, Ya‐lun Su, Teng‐fei Ji, Fei Ye
      Pages: n/a - n/a
      Abstract: Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin‐layer chromatography, ultraviolet, high‐performance liquid chromatography (HPLC), and HPLC‐mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic–euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-29T23:55:41.874995-05:
      DOI: 10.1002/ptr.5230
  • Anticancer Activities of Selected Species of North American Lichen
    • Authors: Gajendra Shrestha; Atif M. El‐Naggar, Larry L. St. Clair, Kim L. O'Neill
      Abstract: Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0/G1 stage, and caused apoptosis in a dose‐dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-24T22:52:13.559669-05:
      DOI: 10.1002/ptr.5233
  • Anti‐Inflammatory and Antinociceptive Activity of Urera aurantiaca
    • Authors: R. Riedel; C. Marrassini, C. Anesini, S. Gorzalczany
      Abstract: Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti‐inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti‐inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan‐induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose‐dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis 3‐ethylbenzothiazoline 6‐sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-24T22:08:29.020127-05:
      DOI: 10.1002/ptr.5226
  • Alhagi: A Plant Genus Rich in Bioactives for Pharmaceuticals
    • Authors: Gulzar Muhammad; Muhammad Ajaz Hussain, Farooq Anwar, Muhammad Ashraf, Anwarul‐Hassan Gilani
      Abstract: Alhagi, a plant genus from family Fabaceae, is widely distributed in many countries of Asia, Australia and Europe. Commonly known as camel thorn, Alhagi has many species famous for feed and folk medicinal uses. Different species of Alhagi such as Alhagi pseudalhagi, A. graecorum, A. sparsifolia, A. kirgisorum, A. maurorum, A. camelorum and A. persarum have been explored for their antioxidant potential and nutritive value along with various medicinal properties. A wide array of pharmacologically active secondary metabolites such as flavonoids, alkaloids (alhacidin and alhacin), steroids, pseudalhagin A, phospholipids and polysaccharides have been reported from different parts of Alhagi species. A broad range of biological activities such as antioxidant, cardiovascular, anti‐ulcer, hepatoprotective, antispasmodic, antidiarrheal, antinociceptive, antipyretic, anti‐inflammatory, anti‐rheumatic, antibacterial and antifungal have been ascribed to different parts of Alhagi. In addition, Alhagi plants are also valued as a rich source of digestible protein and important minerals. This review focuses on the medicinal applications and detailed profile of high‐value bioactive phytochemicals along with pharmacological attributes and therapeutic potential of these multi‐purpose plants. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-24T21:52:47.057306-05:
      DOI: 10.1002/ptr.5222
  • A Novel Diterpene Skeleton: Identification of a Highly Aromatic, Cytotoxic
           and Antioxidant
           5‐Methyl‐10‐demethyl‐abietane‐type Diterpene
           from Premna serratifolia
    • Authors: Solomon Habtemariam; George K. Varghese
      Abstract: Premna serratifolia Linn. (syn: . P. corymbosa (Burm. f.) Merr., P. integrifolia L. and P. obtusifolia R. Br.) is a member of the Verbenaceae family that is extensively used in the Ayurvedic system of medicine in India. As part of our continuous pharmacological and phytochemical studies on medicinal plants, we have screened the methanolic extracts of leaves, root bark (RB) and root wood of P. serratifolia for cytotoxic activity against two cancer cell lines: SHSY‐5Y neuroblastoma and B16 melanoma cells. The RB extract that showed promising activity was fractionated using solvents of increasing polarity followed by a combination of Sephadex LH‐20 column and Combiflash chromatography as well as HPLC to afford the active principle. Comprehensive spectroscopic analysis including 1D and 2D NMR (COSY, HMQC, HMBC, NOESY) and MS analysis revealed the identity of the isolated compound as 11,12,16‐trihydroxy‐2‐oxo‐5‐methyl‐10‐demethyl‐abieta‐1[10],6,8,11,13‐pentene that appears to be a novel compound based on a new diterpene skeleton. The cytotoxic activity of the isolated compound was 21 and 23 times higher than the crude extract against the SHSY‐5Y and B16 cells, respectively. The novel compound also possesses in vitro antioxidant effects as evidenced by the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging effect where an IC50 value of 20.4 ± 1.3 μM was obtained. In comparison, the positive control, caffeic acid, showed an IC50 value of 14.4 ± 1.6 μM. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-22T23:47:30.765105-05:
      DOI: 10.1002/ptr.5229
  • Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter
           pylori Based on Inhibition of Urease
    • Authors: Xiao‐Dan Yu; Jian‐Hui Xie, Yong‐Hong Wang, Yu‐Cui Li, Zhi‐Zhun Mo, Yi‐Feng Zheng, Ji‐Yan Su, Ye‐er Liang, Jin‐Zhi Liang, Zi‐Ren Su, Ping Huang
      Abstract: The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H. pylori and jack bean in concentration‐dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver‐Burk plots indicated that the type of inhibition was non‐competitive against H. pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA‐inactivated urease assay showed DL‐dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H. pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H. pylori infection. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-22T02:48:39.479258-05:
      DOI: 10.1002/ptr.5227
  • Modulating Potential of L‐Sulforaphane in the Expression of
           Cytochrome P450 to Identify Potential Targets for Breast Cancer
           Chemoprevention and Therapy Using Breast Cell Lines
    • Authors: Barbara Licznerska; Hanna Szaefer, Iwona Matuszak, Marek Murias, Wanda Baer‐Dubowska
      Abstract: The L‐sulforaphane (SFN) component of broccoli sprout showed anticancer activity in several preclinical studies including breast cancer. Estrogens are considered major risk factors in breast carcinogenesis. The aim of this study was to evaluate the effect of SFN on the expression of cytochrome P450 involved in the estrogen metabolism in breast cancer cell lines MCF7 and MDA‐MB‐231 and in non‐tumorigenic MCF10A cell line. The expression of CYP19, CYP1A1, 1A2, 1B1 was determined at the transcript and protein levels. There were found some remarkable differences in the effect of SFN at a dose of 5 µmol/L on CYP19 expression: in ER(+) MCF7 significant reduction, in ER(−) MDA‐MB‐231 an increased expression and unchanged expression in MCF10A cell line. The effect of SFN on CYPs (1A1, 1A2, 1B1) involved in estrogen catabolism was to a lesser extent dependent on breast cell line. The slightly reduced CYP1A1 protein level was observed in all cell lines tested. An increased level of CYP1A2 and decreased level of CYP1B1 expression were found in MCF10A. These results indicate that the naturally occurring L isomer of SFN may affect the expression of P450s involved in estrogen metabolism. This effect may contribute to the anticancer activity of SFN in breast tissue. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-19T01:17:05.011063-05:
      DOI: 10.1002/ptr.5232
  • Phloroglucinols from Anti‐Microbial Deposit‐Resins of
           Australian Stingless Bees (Tetragonula carbonaria)
    • Authors: C. Flavia Massaro; Thomas J. Smyth, W. Franklin Smyth, Tim Heard, Sara D. Leonhardt, Mohammad Katouli, Helen M. Wallace, Peter Brooks
      Abstract: Stingless bees accumulate deposits of plant resins that are mixed with beeswax to produce propolis. Previous studies have reported anti‐microbial constituents of stingless bee (Tetragonula carbonaria) propolis from East Australia, but several components remained to be characterized. In the search of natural products yet unreported for Australian propolis, four bee deposit‐resins of T. carbonaria bees were analysed by gas and liquid chromatography mass spectrometry with accurate mass measurements. Ethanolic extracts of the deposit‐resins were tested in vitro against Staphylococcus aureus ATCC 25983 and Pseudomonas aeruginosa ATCC 27853 by the agar diffusion method. Phloroglucinols, flavonoids and isoprenoids were identified in samples. The crude extracts showed strong anti‐staphylococcal effects but were less active against the Gram‐negative bacterium. The diagnostic data enabled the identification of markers that can be used for profiling other Australian propolis sources and to target the isolation of bioactive phloroglucinols in future studies against antibiotic resistant S. aureus strains. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-18T00:23:10.854374-05:
      DOI: 10.1002/ptr.5225
  • Expression of BDNF and TH mRNA in the Brain Following Inhaled
           Administration of α‐Pinene
    • Authors: Hikaru Kasuya; Narumi Okada, Mika Kubohara, Tadaaki Satou, Yoshinori Masuo, Kazuo Koike
      Abstract: Essential oils are mainly administered by inhalation. Administration by inhalation is considered to occur through two pathways, neurological transfer and pharmacological transfer. However, the relationship between the two routes is not clear. To clarify this relationship, we administered α‐pinene, which has an anxiolytic‐like effect, to mice. Emotional behavior and accumulation and expression of relevant mRNAs in the brain (brain‐derived neurotrophic factor (BDNF); tyrosine hydroxylase (TH)) were examined following inhaled administration of α‐pinene (10 μL/L air for 60 or 90 min). To evaluate the anxiolytic‐like effect, the elevated plus maze (EPM) test was used. Inhalation of α‐pinene for 60 min produced a significant increase in the total distance traveled in the EPM test compared with control (water). The concentration of α‐pinene in the brain after 60 min of inhalation was significantly increased compared with that after 90 min of inhalation. The expression of BDNF mRNA in the olfactory bulb and in the hippocampus was almost the same after 60 min of inhalation compared to that after 90 min of inhalation. The expression of TH mRNA in the midbrain after 60 min of inhalation was significantly increased compared with that of the control. Thus, an increase in α‐pinene in the brain induces an increase in TH mRNA expression and increases locomotor activity. The anxiolytic‐like effect may be related to both neurological transfer and pharmacological transfer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-17T02:46:32.332697-05:
      DOI: 10.1002/ptr.5224
  • The Standardized BHH10 Extract, a Combination of Astragalus membranaceus,
           Cinnamomum cassia, and Phellodendron amurense, Reverses Bone Mass and
           Metabolism in a Rat Model of Postmenopausal Osteoporosis
    • Authors: Jeong‐Eun Huh; Soo‐Jeong Kim, Jung‐Won Kang, Dong‐Woo Nam, Do‐Young Choi, Dong‐Suk Park, Jae‐Dong Lee
      Abstract: Jasin‐hwan‐gagambang (BHH10), a modified prescription of Jasin‐hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)‐induced rats. Sprague–Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17β‐estradiol (E2). BHH10 treatment significantly inhibited OVX‐induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low‐density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C‐telopeptide type 1 collagen, and bone morphogenetic protein‐2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10‐treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN‐treated or E2‐treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2014-09-17T02:33:17.413168-05:
      DOI: 10.1002/ptr.5218
  • Modulation of Radiation‐Induced Alterations in Oxidative Stress and
           Cytokine Expression in Lung Tissue by Panax Ginseng Extract
    • Authors: Seong Soon Jang; Hyeong Geug Kim, Jong Min Han, Jin Seok Lee, Min Kyung Choi, Gil Ja Huh, Chang Gue Son
      Abstract: We investigated the modulating effect of Panax ginseng extract (PGE) on radiation‐induced lung injury (RILI) by measuring early changes in oxidative stress levels, cytokine expression, and the histopathology of mouse lung tissue treated with high dose of X‐ray radiation. The mice were pretreated with 25, 50, and 100‐mg/kg doses of PGE orally for four consecutive days, and their thoraces were then exposed to 15‐Gy X‐ray radiation 1 h after the last administration of PGE on day 4. The pretreatments with 50 and 100 mg/kg PGE led to significant reductions in the elevation of lipid peroxidation levels at 2 and 10 days, respectively, after irradiation. The mice pretreated with PGE exhibited dose‐dependent reductions in the irradiation‐induced production of tumor necrosis factor α and transforming growth factor β1 cytokines 10 days after irradiation, with these reductions nearly reaching the control levels after the 100‐mg/kg dose. Furthermore, together with providing significant protection against reductions in catalase activity and glutathione content, pretreatment with 100 mg/kg PGE resulted in a marked attenuation of the severity of inflammatory changes in lung tissue 10 days after irradiation. A high pretreatment dose of PGE may be a useful pharmacological approach for protection against RILI. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-15T01:25:54.24004-05:0
      DOI: 10.1002/ptr.5223
  • Chemical Composition and Antimicrobial Activity of the Essential Oil of
           Apricot Seed
    • Authors: Hyun‐hee Lee; Jeong‐Hyun Ahn, Ae‐Ran Kwon, Eun Sook Lee, Jin‐Hwan Kwak, Yu‐Hong Min
      Abstract: In traditional oriental medicine, apricot (Prunus armeniaca L.) seed has been used to treat skin diseases such as furuncle, acne vulgaris and dandruff, as well as coughing, asthma and constipation. This study describes the phytochemical profile and antimicrobial potential of the essential oil obtained from apricot seeds (Armeniacae Semen). The essential oil isolated by hydrodistillation was analysed by gas chromatography–mass spectroscopy. Benzaldehyde (90.6%), mandelonitrile (5.2%) and benzoic acid (4.1%) were identified. Disc diffusion, agar dilution and gaseous contact methods were performed to determine the antimicrobial activity against 16 bacteria and two yeast species. The minimum inhibitory concentrations ranged from 250 to 4000, 500 to 2000 and 250 to 1000 µg/mL for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The minimum inhibitory doses by gaseous contact ranged from 12.5 to 50, 12.5 to 50 and 3.13 to 12.5 mg/L air for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The essential oil exhibited a variable degree of antimicrobial activity against a range of bacteria and yeasts tested. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-15T00:59:17.065597-05:
      DOI: 10.1002/ptr.5219
  • Tolerance of Phellodendron amurense Bark Extract (Nexrutine®) in
           Patients with Human Prostate Cancer
    • Authors: Gregory P. Swanson; William E. Jones, Chul S. Ha, Carol A. Jenkins, Addanki Pratap Kumar, Joseph Basler
      Abstract: Phellodendron amurense bark extract (Nexrutine®) has shown a favorable effect on prostate cancer in vivo and in vitro. We evaluated its tolerance in patients undergoing surgery or radiation for prostate cancer. Patients received Nexrutine® orally (500 mg tid) either 1 to 2 months preoperatively or 1 to 2 months prior to and with radiation therapy. Common Terminology Criteria for Adverse Events were used to measure tolerance. In total, 21 patients (9 surgery and 12 radiation) underwent treatment. During the Nexrutine® alone component, there were two transient grade 3 toxicities (hypokalemia and urinary incontinence). There was no grade 4 toxicity. For the combined Nexrutine® and radiation component, no additional patients suffered a grade 3 toxicity. All the toxicities were transient. By the end of the neoadjuvant treatment, 81% of the patients had a decline in prostate‐specific antigen. This is the first report of patients with prostate cancer being treated with P. amurense bark extract, and it was very well tolerated. Toxicities were minimal and self‐limited. This compound can be safely used in further evaluation of a treatment effect on cancer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-09T21:36:29.73631-05:0
      DOI: 10.1002/ptr.5221
  • Evaluation of Inhibitory Effects of Caffeic acid and Quercetin on Human
           Liver Cytochrome P450 Activities
    • Authors: Himanshu Rastogi; Snehasis Jana
      Abstract: When herbal drugs and conventional allopathic drugs are used together, they can interact in our body which can lead to the potential for herb–drug interactions. This work was conducted to evaluate the herb–drug interaction potential of caffeic acid and quercetin mediated by cytochrome P450 (CYP) inhibition. Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of caffeic acid and quercetin. IC50, Ki values, and the types of inhibition were determined. Both caffeic acid and quercetin were potent competitive inhibitors of CYP1A2 (Ki = 1.16 and 0.93 μM, respectively) and CYP2C9 (Ki = 0.95 and 1.67 μM, respectively). Caffeic acid was a potent competitive inhibitor of CYP2D6 (Ki = 1.10 μM) and a weak inhibitor of CYP2C19 and CYP3A4 (IC50 > 100 μM). Quercetin was a potent competitive inhibitor of CYP 2C19 and CYP3A4 (Ki = 1.74 and 4.12 μM, respectively) and a moderate competitive inhibitor of CYP2D6 (Ki = 18.72 μM). These findings might be helpful for safe and effective use of polyphenols in clinical practice. Our data indicated that it is necessary to study the in vivo interactions between drugs and pharmaceuticals with dietary polyphenols. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-08T01:38:07.903895-05:
      DOI: 10.1002/ptr.5220
  • Anti‐Proliferative Properties of Kahweol in Oral Squamous Cancer
           Through the Regulation Specificity Protein 1
    • Authors: Jung‐Il Chae; Young‐Joo Jeon, Jung‐Hyun Shim
      Abstract: Kahweol, the coffee‐specific deterpene, has been shown to have potential anti‐cancer effects against several cancers. However, the molecular mechanisms underlying the anti‐cancer activity of kahweol have not yet established. In this study, we investigated whether kahweol could show anti‐cancer effects on oral squamous cell lines (OSCCs), HN22 and HSC4. We conducted an 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxy‐phenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay, 4′‐6‐diamidino2‐phenylindole (DAPI) staining, propidium iodide staining, immunocytochemistry, and Western blot analysis for the characterization of kahweol and the underlying signaling pathway. We determined that kahweol‐treated cells showed significantly decreased cell viability and increased nuclear condensation and an increased sub‐G1 population in OSCCs. Interestingly, suppression of the transcription factor specificity protein 1 (Sp1) was followed by induced apoptosis by kahweol in a dose‐dependent manner. In addition, kahweol modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and anti‐apoptotic proteins, resulting in apoptosis. Taken together, results from these findings suggest that kahweol may be a potential anti‐cancer drug candidate to induce apoptotic cell death through downregulation of Sp1 in OSCCs. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-08T01:30:43.228251-05:
      DOI: 10.1002/ptr.5217
  • Evaluation of Hemostatic and Anti‐inflammatory Activities of
           Extracts from Different Lagochilus Species in Experimental Animals:
           Comparison of Different Extractives and Sources
    • Authors: Ying Jiao; Pei‐Hua Chen, Ai‐Zhen Xiong, Zheng‐Tao Wang, Karl Wah‐Keung Tsim, Gui‐Xin Chou, Hong Xu
      Abstract: Different members of Lagochilus genus have been used in folkloric medicine to treat hemorrhages and inflammation. However, only a few species of them have received scientific attention supporting their efficacy. Here, the hemostatic and antiinflammatory activities of five Lagochilus species were determined and compared by using in vivo assays. The results showed that the extracts of Lagochilus lanatonodus and Lagochilus diacanthophyllus showed better hemostatic activities among five species. The high doses of L. lanatonodus extracts were able to shorten the values of thrombin time, activated partial thromboplastin time and prothrombin time in a rat model. Moreover, the extracts of L. lanatonodus and L. diacanthophyllus showed strong inhibitory effects on the acute phase of inflammation in both xylene‐induced ear edema mouse model and carrageenan‐induced paw edema rat model. In parallel, the treatment of these extracts modulated the expressions of those inflammatory parameters, that is, nitric oxide, prostaglandin E2, inducible nitric oxide synthase, malondialdehyde and superoxide dismutase. L. lanatonodus and L. diacanthophyllus showed better hemostatic and antiinflammatory activities in several test models: these results therefore supported the folkloric utilization. L. lanatonodus was found to be the most active Lagochilus species. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-29T23:39:58.93252-05:0
      DOI: 10.1002/ptr.5216
  • Cancer Patients at Risk of Herb/Food Supplement–Drug Interactions: A
           Systematic Review
    • Authors: Saud M. Alsanad; Elizabeth M. Williamson, Rachel L. Howard
      Abstract: Herbal medicines and dietary supplements are commonly taken by patients with cancer, leading to concern over interactions with conventional medicines. A literature search was carried out to identify published studies exploring supplement use by patients with a cancer diagnosis. A total of 818 articles were retrieved using the key words, but only 41 are judged to be relevant based on title. Following the review of the abstracts, ten papers were considered to be potentially relevant, but of these, only two met the selection criteria, and three additional papers were identified from published reviews. Of 806 patients surveyed, 433 (53.7%) were reported to be taking combinations of supplements and drugs, and 167 incidents of risk were identified, affecting 60 patients (13.9%). The interactions identified were mainly theoretical and not supported by clinical data. No studies reported any adverse events associated with these combinations; most did not record the actual drug combinations taken, and the risk potential of some supplements appears to have been over‐estimated. More effort should be made to investigate supplement use in this vulnerable patient group, based on sound evidence of plausible interaction, not only to avoid harm but also to provide reassurance where appropriate if the patient wishes to take a particular supplement. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-26T06:09:30.043259-05:
      DOI: 10.1002/ptr.5213
  • The Protective Effects of Rhodiola crenulata Extracts on Drosophila
           melanogaster Gut Immunity Induced by Bacteria and SDS Toxicity
    • Authors: Caixia Zhu; Fachun Guan, Chao Wang, Li Hua Jin
      Abstract: The aim of this study was to observe the effect of the Rhodiola crenulata extracts on gut immunity of Drosophila melanogaster. Wild‐type flies fed standard cornmeal–yeast medium were used as controls. Experimental groups were supplemented with 2.5% R. crenulata aqueous extracts in standard medium. Survival rate was determined by feeding pathogenic microorganisms and toxic compounds. The levels of reactive oxygen species and dead cells were detected by dihydroethidium and 7‐amino‐actinomycin D staining, respectively. The expression of antimicrobial peptides was evaluated by quantitative polymerase chain reaction, and morphological change of the intestine was imaged by an Axioskop 2 plus microscope. The results demonstrate that R. crenulata increased the survival rates of adult flies and expression of antimicrobial peptide genes after pathogen or toxic compound ingestion. Moreover, decreased levels of reactive oxygen species and epithelial cell death were associated with results in improved intestinal morphology. The pharmacological action of R. crenulata from Tibet was greater than that from Sichuan. These results indicate that the R. crenulata extracts from Tibet had better pharmacological effect on D. melanogaster gut immunity after ingestion of pathogens and toxic compounds. These results may provide the pharmacological basis for prevention of inflammatory diseases of the intestine. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-22T04:34:08.631529-05:
      DOI: 10.1002/ptr.5215
  • Effects of Supplementation with Heracleum persicum Fruit Extract on Serum
           Lipids in Patients Undergoing Coronary Angiography: A Pilot Trial
    • Authors: Yahya Dadjo; Yunes Panahi, Bahram Pishgoo, Amirhossein Sahebkar, Hamidreza Taghipour, Ahmad Akbari, Shahram Parvin
      Abstract: Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the Iranian traditional medicine and also a safe and common dietary spice. The present pilot study aimed to investigate the impact of supplementation with H. persicum fruits on serum lipid concentrations in a group of patients with minimal coronary artery disease. Subjects who were diagnosed with  0.05). However, serum triglycerides levels were reduced after H. persicum extract supplementation in a borderline significant manner (p = 0.063). Short‐term supplementation with H. persicum fruit extract might be used as an adjunctive treatment for patients with hypertriglyceridemia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-19T06:11:39.153698-05:
      DOI: 10.1002/ptr.5214
  • Effect of Kuwanon G Isolated from the Root Bark of Morus alba on
           Ovalbumin‐induced Allergic Response in a Mouse Model of Asthma
    • Authors: Hyo Won Jung; Seok Yong Kang, Jong Seong Kang, A Ryun Kim, Eun‐Rhan Woo, Yong‐Ki Park
      Pages: n/a - n/a
      Abstract: The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)‐induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA‐specific IgE and Th2 cytokines (IL‐4, IL‐5, and IL‐13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA‐specific IgE and IL‐4, IL‐5, and IL‐13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-13T06:05:25.635971-05:
      DOI: 10.1002/ptr.5191
  • Alkali‐Soluble Polysaccharide, Isolated from Lentinus edodes,
           Induces Apoptosis and G2/M Cell Cycle Arrest in H22 Cells Through
           Microtubule Depolymerization
    • Authors: Ru‐xu You; Jin‐yu Liu, Shi‐jun Li, Liu Wang, Kai‐ping Wang, Yu Zhang
      Pages: n/a - n/a
      Abstract: The aim of the study was to evaluate the pro‐apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN‐induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca2+. In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN‐induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti‐tumour effect of LTN. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-11T06:28:19.018762-05:
      DOI: 10.1002/ptr.5209
  • Antiinflammatory Properties of the Stem‐bark of Anopyxis klaineana
           and its Major Constituent, Methyl Angolensate
    • Authors: Evelyn A. Mireku; Abraham Y. Mensah, Merlin L. K. Mensah, Derek A. Tocher, Solomon Habtemariam
      Pages: n/a - n/a
      Abstract: Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West African folkloric medicines that has never been investigated for its pharmacological effects or phytochemical constituents. In the present study, the antiinflammatory properties of the stem‐bark extracts were evaluated using the carrageenan‐induced paw oedema model in chicks. The petroleum ether, ethyl acetate and methanol extracts all showed a time and dose‐dependent antiinflammatory effect over the 5‐h observation period. Phytochemical analysis of the most active extract (methanol extract) yielded the principal constituent that was identified as methyl angolensate through extensive spectroscopic and X‐ray analysis studies. Although slightly less potent (ED50, 4.05 ± 0.0034 mg/kg, orally) than the positive control, diclofenac (ED50, 2.49 ± 0.023, intraperitoneally n = 5), this first ever compound isolated from A. klaineana showed promising antiinflammatory activity that may account to some of the reported medicinal uses of the plant. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-11T05:59:44.307133-05:
      DOI: 10.1002/ptr.5212
  • Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and
           Hairless Mice
    • Authors: Eunson Hwang; Sang‐Yong Park, Hyun Ji Lee, Tae Youp Lee, Zheng‐wang Sun, Tae Hoo Yi
      Abstract: Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin‐6, and MMP‐1 were significantly suppressed, and type I procollagen expression was stimulated in UVB‐irradiated and GA‐treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP‐1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor‐β1. Our data indicate that GA is a potential candidate for the prevention of UVB‐induced premature skin aging. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-08T01:33:04.742814-05:
      DOI: 10.1002/ptr.5198
  • Eugenia punicifolia (Kunth) DC. as an Adjuvant Treatment for Type‐2
           Diabetes Mellitus: A non‐Controlled, Pilot Study
    • Authors: Débora Simone Sales; Fabio Carmona, Bruna Cestari Azevedo, Silvia Helena Taleb‐Contini, Ana Carolina Duó Bartolomeu, Fernando B. Honorato, Edson Z. Martinez, Ana Maria Soares Pereira
      Abstract: Type‐2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type‐2 DM. Fifteen patients were enrolled in a pilot, non‐controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid‐stimulating hormone, C‐reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin‐3‐O‐rhamnoside, quercetin‐3‐O‐galactoside, quercetin‐3‐O‐xyloside, quercetin‐3‐O‐rhamnoside, kaempferol‐3‐O‐rhamnoside, phytol, gallic acid, and trans‐caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type‐2 DM and deserve further investigation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-06T07:40:47.985891-05:
      DOI: 10.1002/ptr.5206
  • Lipid‐Lowering Effects of Curcumin in Patients with Metabolic
           Syndrome: A Randomized, Double‐Blind, Placebo‐Controlled Trial
    • Authors: Yi‐Sun Yang; Ying‐Fang Su, Hui‐Wen Yang, Yu‐Hsien Lee, Janet I. Chou, Kwo‐Chang Ueng
      Abstract: Human studies of curcumin extract on lipid‐lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty‐five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high‐density lipoprotein cholesterol (HDL‐C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p 
      PubDate: 2014-08-06T07:35:50.344871-05:
      DOI: 10.1002/ptr.5197
  • Effects of Smilaxchinoside A and Smilaxchinoside C, Two Steroidal
           Glycosides from Smilax riparia, on Hyperuricemia in a Mouse Model
    • Authors: Xiao‐Hui Wu; Chong‐Zhi Wang, Jun Zhang, Shu‐Qing Wang, Lide Han, Yan‐Wen Zhang, Chun‐Su Yuan
      Abstract: The roots and rhizomes of Smilax riparia, called ‘Niu‐Wei‐Cai’ in traditional Chinese medicine, are believed to be effective in treating the symptoms of gout. However, the active constituents and their uricosuric mechanisms are unknown. In this study, we isolated two steroidal glycosides, named smilaxchinoside A and smilaxchinoside C, from the total saponins obtained from the ethanol extract of the roots of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We observed that these two steroidal glycosides possess potent uricosuric activities, and the observed effects accompanied the reduction of renal mURAT1 and the inhibition of xanthine oxidase, which contribute to the enhancement of uric acid excretion and the reduction of hyperuricemia‐induced renal dysfunction. Smilaxchinoside A and smilaxchinoside C may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-06T00:13:47.100955-05:
      DOI: 10.1002/ptr.5207
  • Investigation of the Efficacy of Adjunctive Therapy with
           Bioavailability‐Boosted Curcuminoids in Major Depressive Disorder
    • Authors: Yunes Panahi; Roghayeh Badeli, Nima Karami, Amirhossein Sahebkar
      Abstract: Current medications have limited efficacy in controlling the symptoms of major depressive disorder (MDD), and are associated with several adverse events on long‐term use. Curcuminoids are extremely safe and multifunctional phytopharmaceuticals that have been shown to alleviate depressive symptoms in a variety of experimental models. The present study aimed to investigate the efficacy of curcuminoids as an add‐on to standard antidepressants in patients with MDD. One hundred and eleven subjects were assigned to standard antidepressive therapy plus curcuminoids–piperine combination (1000–10 mg/day; n = 61) or standard antidepressive therapy alone (n = 50) for a period of 6 weeks. Efficacy measures were changes in the psychological status on the basis of the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI‐II). The BDI‐II and HADS total and subscale scores were reduced by the end of trial in both study groups. There were significantly greater reductions in total HADS score and subscales of anxiety and depression in the curcuminoids versus control group (p 
      PubDate: 2014-08-04T06:26:29.744501-05:
      DOI: 10.1002/ptr.5211
  • Effects of Five Ayurvedic Herbs on Locomotor Behaviour in a Drosophila
           melanogaster Parkinson's Disease Model
    • Authors: R. L. M. Jansen; B. Brogan, A. J. Whitworth, E. J. Okello
      Abstract: Current conventional treatments for Parkinson's disease (PD) are aimed at symptom management, as there is currently no known cure or treatment that can slow down its progression. Ayurveda, the ancient medical system of India, uses a combination of herbs to combat the disease. Herbs commonly used for this purpose are Zandopa (containing Mucuna pruriens), Withania somnifera, Centella asiatica, Sida cordifolia and Bacopa monnieri. In this study, these herbs were tested for their potential ability to improve climbing ability of a fruit fly (Drosophila melanogaster) PD model based on loss of function of phosphatase and tensin‐induced putative kinase 1 (PINK1). Fruit flies were cultured on food containing individual herbs or herbal formulations, a combination of all five herbs, levodopa (positive control) or no treatment (negative control). Tests were performed in both PINK1 mutant flies and healthy wild‐type (WT) flies. A significant improvement in climbing ability was observed in flies treated with B. monnieri compared with untreated PINK1 mutant flies. However, a significant decrease in climbing ability was observed in WT flies for the same herb. Centella asiatica also significantly decreased climbing ability in WT flies. No significant effects were observed with any of the other herbs in either PINK1 or WT flies compared with untreated flies. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-04T06:01:37.095359-05:
      DOI: 10.1002/ptr.5199
  • The Protective Effects of a Polyphenol‐Enriched Protein Powder on
           Exercise‐Induced Susceptibility to Virus Infection
    • Authors: Maryam Ahmed; Dru A. Henson, Matthew C. Sanderson, David C. Nieman, Nicholas D. Gillitt, Mary Ann Lila
      Abstract: Prolonged and intensive exercise induces transient immunosuppression and is associated with an increased risk and severity of infections. The goal of this study was to characterize the antiviral and antibacterial properties of the bioactive metabolites of a blueberry–green tea‐polyphenol soy protein complex (PSPC) in the serum of supplemented subjects during a 3‐day intensified training period. Long‐distance runners, randomly divided into two groups, ingested 40 g/day PSPC or placebo (soy protein and colorings) for 17 days, with a 3‐day running period inserted at day 14. Blood serum samples were collected pre‐14 days and post‐14 days supplementation, and immediately and 14 h after the third day of running. The post‐exercise serum from both groups significantly promoted the growth of Escherichia coli and Staphylococcus aureus in culture by 20–70%, but returned to normal levels following recovery. Furthermore, the serum from subjects ingesting PSPC did not display antibacterial properties at any time point. In contrast, there was a significant difference in the ability of serum from PSPC‐supplemented versus placebo‐supplemented athletes to protect cells in culture from killing by vesicular stomatitis virus following strenuous exercise. In addition, the serum of subjects who ingested PSPC significantly delayed an exercise‐induced increase in virus replication. These results indicate that polyphenol complexes containing blueberry and green tea have the potential to protect athletes from virus infections following rigorous exercise. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T03:21:43.671858-05:
      DOI: 10.1002/ptr.5208
  • Involvement of Cerebral Nervous System Areas and Cytokines on
           Antihyperalgesic and Anti‐Inflammatory Activities of Kielmeyera
           rugosa Choisy (Calophyllaceae) in Rodents
    • Authors: M.S. Melo; R.G. Brito, P.L. Santos, P.C.L. Nogueira, V.R.S. Moraes, M.C.P. Matos, J.N.S. Ferro, E.O. Barreto, W. Lucca Junior, M.A. Botelho, L.J. Quintans Junior
      Abstract: Kielmeyera rugosa is a medicinal plant known in Northeastern Brazil as ‘pau‐santo’, and it is used in the treatment of several tropical diseases such as malaria, schistosomiasis, and leishmaniasis. We evaluated antihyperalgesic and anti‐inflammatory activities of methanol stem extract of K. rugosa (MEKR) in mice. The mechanical hyperalgesia induced by carrageenan and tumor necrosis factor‐alpha (TNF‐α), prostaglandin E2, and dopamine were assessed. We also investigated the anti‐inflammatory effect of MEKR on carrageenan‐induced pleurisy and paw edema. Ninety minutes after the treatment, the animals were submitted to an imunofluorescence for Fos protein. MEKR (100, 200, and 400 mg/kg; p.o.) inhibited the development of mechanical hypernociception and edema. MEKR significantly decreased TNF‐α and interleukin 1β levels in pleural lavage and suppressed the recruitment of leukocytes. MEKR (1, 10, and 100 mg/mL) did not produce cytotoxicity, determined using the methyl‐thiazolyl‐tetrazolium assay in vitro. The locomotor activity was not affected. MEKR activated significantly the bulb olfactory, piriform cortex, and periaqueductal gray of the central nervous system. Our results provide first time evidence to propose that MEKR attenuates mechanical hyperalgesia and inflammation, in part, through an activation of central nervous system areas, mainly the periaqueductal gray and piriform cortex areas. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T01:46:38.761566-05:
      DOI: 10.1002/ptr.5205
  • Effects of Eucommia ulmoides Extract on Longitudinal Bone Growth Rate in
           Adolescent Female Rats
    • Authors: Ji Young Kim; Jeong‐Il Lee, MiKyung Song, Donghun Lee, Jungbin Song, Soo Young Kim, Juyeon Park, Ho‐Young Choi, Hocheol Kim
      Abstract: Eucommia ulmoides is one of the popular tonic herbs for the treatment of low back pain and bone fracture and is used in Korean medicine to reinforce muscles and bones. This study was performed to investigate the effects of E. ulmoides extract on longitudinal bone growth rate, growth plate height, and the expressions of bone morphogenetic protein 2 (BMP‐2) and insulin‐like growth factor 1 (IGF‐1) in adolescent female rats. In two groups, we administered a twice‐daily dosage of E. ulmoides extract (at 30 and 100 mg/kg, respectively) per os over 4 days, and in a control group, we administered vehicle only under the same conditions. Longitudinal bone growth rate in newly synthesized bone was observed using tetracycline labeling. Chondrocyte proliferation in the growth plate was observed using cresyl violet dye. In addition, we analyzed the expressions of BMP‐2 and IGF‐1 using immunohistochemistry. Eucommia ulmoides extract significantly increased longitudinal bone growth rate and growth plate height in adolescent female rats. In the immunohistochemical study, E. ulmoides markedly increased BMP‐2 and IGF‐1 expressions in the proliferative and hypertrophic zones. In conclusion, E. ulmoides increased longitudinal bone growth rate by promoting chondrogenesis in the growth plate and the levels of BMP‐2 and IGF‐1. Eucommia ulmoides could be helpful for increasing bone growth in children who have growth retardation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T00:34:35.834751-05:
      DOI: 10.1002/ptr.5195
  • Apple Polyphenol Extracts Protect Against Aspirin‐induced Gastric
           Mucosal Damage in Rats
    • Authors: Gunaranjan Paturi; Christine A. Butts, Kerry L. Bentley‐Hewitt, Tony K. McGhie, Zaid S. Saleh, Andrew McLeod
      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.
      PubDate: 2014-07-28T06:20:14.25098-05:0
      DOI: 10.1002/ptr.5210
  • A Review of the Pharmacological Effects of Piceatannol on Cardiovascular
    • Authors: Yee‐Ling Tang; Shun‐Wan Chan
      First page: 1581
      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 on Liver Inflammation and Antiinflammatory Activity of Andrographis
           paniculata for Hepatoprotection
    • Authors: Lee Suan Chua
      First page: 1589
      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.
      PubDate: 2014-07-10T03:56:53.450811-05:
      DOI: 10.1002/ptr.5193
  • Changes in 5‐hydroxytryptamine and Cortisol Plasma Levels in
           Menopausal Women After Inhalation of Clary Sage Oil
    • Authors: Kyung‐Bok Lee; Eun Cho, Young‐Sook Kang
      First page: 1599
      Abstract: The purpose of this study was to examine the antidepressant‐like effects of clary sage oil on human beings by comparing the neurotransmitter level change in plasma. The voluntary participants were 22 menopausal women in 50's. Subjects were classified into normal and depression tendency groups using each of Korean version of Beck Depression Inventory‐I (KBDI‐I), KBDI‐II, and Korean version of Self‐rating Depression Scale. Then, the changes in neurotransmitter concentrations were compared between two groups. After inhalation of clary sage oil, cortisol levels were significantly decreased while 5‐hydroxytryptamine (5‐HT) concentration was significantly increased. Thyroid stimulating hormone was also reduced in all groups but not statistically significantly. The different change rate of 5‐HT concentration between normal and depression tendency groups was variable according to the depression measurement inventory. When using KBDI‐I and KBDI‐II, 5‐HT increased by 341% and 828% for the normal group and 484% and 257% for the depression tendency group, respectively. The change rate of cortisol was greater in depression tendency groups compared with normal groups, and this difference was statistically significant when using KBDI‐II (31% vs. 16% reduction) and Self‐rating Depression Scale inventory (36% vs. 8.3% reduction). Among three inventories, only KBDI‐II differentiated normal and depression tendency groups with significantly different cortisol level. Finally, clary sage oil has antidepressant‐like effect, and KBDI‐II inventory may be the most sensitive and valid tool in screening for depression status or severity. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-06T23:05:17.820968-05:
      DOI: 10.1002/ptr.5163
  • 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
      First page: 1606
      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
  • Proanthocyanin Content in Cranberry CE Medicinal Products
    • Authors: Sigrun Chrubasik‐Hausmann; Christian Vlachojannis, Benno F. Zimmermann
      First page: 1612
      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
  • 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 da 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
      First page: 1615
      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
  • 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
      First page: 1625
      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
  • 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
      First page: 1632
      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
  • 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
      First page: 1637
      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
  • 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
      First page: 1646
      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
  • 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
      First page: 1654
      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
  • 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
      First page: 1661
      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
  • Umbelliferone Increases the Expression of Adipocyte‐Specific Genes
           in 3 T3‐L1 Adipocyte
    • Authors: Jarinyaporn Naowaboot; Choon Hee Chung, Ran Choi, Patchareewan Pannangpetch
      First page: 1671
      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
  • Pomegranate Juice and Prostate Cancer: Importance of the Characterisation
           of the Active Principle
    • Authors: Sigrun Chrubasik‐Hausmann; Christian Vlachojannis, Benno Zimmermann
      First page: 1676
      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
  • 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
      First page: 1679
      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
  • 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
      First page: 1687
      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
  • 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
      First page: 1692
      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
  • 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
      First page: 1701
      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
  • 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
      First page: 1710
      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
  • A Pilot Study on the Effectiveness of a Rose Hip Shell Powder in Patients
           Suffering from Chronic Musculoskeletal Pain
    • Authors: S. Chrubasik‐Hausmann; C. Chrubasik, E. Neumann, U. Müller‐Ladner
      First page: 1720
      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.
      PubDate: 2014-07-17T02:39:23.665587-05:
      DOI: 10.1002/ptr.5192
  • A Chemically Standardized Extract of Ziziphus jujuba Fruit (Jujube)
           Stimulates Expressions of Neurotrophic Factors and Anti‐oxidant
           Enzymes in Cultured Astrocytes
    • Authors: Jianping Chen; Artemis L. Yan, Kelly Y. C. Lam, Candy T. W. Lam, Ning Li, Ping Yao, Aizhen Xiong, Tina T. X. Dong, Karl W. K. Tsim
      First page: 1727
      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.
      PubDate: 2014-07-28T05:21:06.635852-05:
      DOI: 10.1002/ptr.5202
  • Effect of Crude Extract of Eugenia jambolana Lam. on Human Cytochrome P450
    • Authors: Santhivardhan Chinni; Anil Dubala, Jayasankar Kosaraju, Rizwan Basha Khatwal, M. N. Satish Kumar, Elango Kannan
      First page: 1731
      Abstract: The fruit of Eugenia jambolana Lam. is very popular for its anti‐diabetic property. Previous studies on the crude extract of E. jambolana (EJE) have successfully explored the scientific basis for some of its traditional medicinal uses. Considering its wide use and consumption as a seasonal fruit, the present study investigates the ability of E. jambolana to interact with cytochrome P450 enzymes. The standardized EJE was incubated with pooled human liver microsomes to assess the CYP2C9‐, CYP2D6‐, and CYP3A4‐mediated metabolism of diclofenac, dextromethorphan, and testosterone, respectively. The metabolites formed after the enzymatic reactions were quantified by high performance liquid chromatography. EJE showed differential effect on cytochrome P450 activities with an order of inhibitory potential as CYP2C9 > CYP3A4 > CYP2D6 having IC50 of 76.69, 359.02, and 493.05 µg/mL, respectively. The selectivity of EJE for CYP2C9 rather than CYP3A4 and CYP2D6 led to perform the enzyme kinetics to explicate the mechanism underlying the inhibition of CYP2C9‐mediated diclofenac 4′‐hydroxylation. EJE was notably potent in inhibiting the reaction in a non‐competitive manner with Ki of 84.85 ± 5.27 µg/mL. The results revealed the CYP2C9 inhibitory potential of EJE with lower Ki value suggesting that EJE should be examined for its potential pharmacokinetic and pharmacodynamic interactions when concomitantly administered with other drugs. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-03-04T00:13:26.828865-05:
      DOI: 10.1002/ptr.5137
  • The Puzzling Issue of ‘Vehicle‐Treated Control’ when
           Using Ethanol as Drug Carrier for MCF‐7 Cells
    • Authors: Robbie Yat‐Kan Chan; Kenneth Ka‐Ho Lee, Wai‐Yeung Wong, Johnny Cheuk‐On Tang, Kim‐Hung Lam, Chor‐Hing Cheng, Fung‐Yi Lau, Stanton Hon‐Lung Kok, Roberto Gambari, Chung‐Hin Chui
      First page: 1735
      Abstract: Ethanol has been commonly used as a vehicle for drug discovery purpose in vitro. The human breast cancer MCF‐7 estrogen dependent cell line is a common in vitro model used for hormonal therapy study. However, special precaution is suggested when ethanol is used in pharmacological tests as solvent in order to evaluate the biological activity of potential drugs especially concerning about the MCF‐7. Ethanol was shown to stimulate the proliferation of this estrogen receptor positive cell line. Here, we have further demonstrated that the dose responsive stimulatory effect of ethanol on the MCF‐7 cells after pre‐incubating the breast carcinoma cells with phenol red‐free medium and stripped fetal bovine serum. Our findings open a discussion for the evaluation of ethanol as solvent for drug discovery and screening when using MCF‐7 cells as a testing model. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-04-09T20:16:02.303323-05:
      DOI: 10.1002/ptr.5153
  • Increased Susceptibility of Staphylococcus aureus Small Colony Variant to
           Tea Tree Oil: Comment on Cuaron et al. 2014
    • Authors: Jakub Kwiecinski
      First page: 1737
      PubDate: 2014-04-27T19:56:14.613012-05:
      DOI: 10.1002/ptr.5159
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