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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: 4, 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: 18, 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: 5, 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: 18, 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: 13, SJR: 0.852, h-index: 8)
Philosophy Compass     Hybrid Journal   (Followers: 6, SJR: 0, h-index: 1)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.709, h-index: 86)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 2, 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: 26, 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: 16, SJR: 1.126, h-index: 40)
Political Science Quarterly     Hybrid Journal   (Followers: 27, 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: 13)
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: 3, 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
  • 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
  • Xanthine Oxidase Inhibitory Activity of Extracts Prepared from
           Polygonaceae Species
    • Abstract: The xanthine oxidase (XO) inhibitory activity of aqueous and organic extracts of 27 selected species belonging in five genera (Fallopia, Oxyria, Persicaria, Polygonum and Rumex) of the family Polygonaceae occurring in the Carpathian Basin were tested in vitro. From different plant parts (aerial parts, leaves, flowers, fruits and roots), a total of 196 extracts were prepared by subsequent extraction with methanol and hot H2O and solvent–solvent partition of the MeOH extract yielding n‐hexane, chloroform and 50% MeOH subextracts. It was found that the chloroform subextracts and/or the remaining 50% MeOH extracts of Fallopia species (F. bohemica, F. japonica and F. sachalinensis), Rumex species (R. acetosa, R. acetosella, R. alpinus, R. conglomeratus, R. crispus, R. hydrolapathus, R. pulcher, R. stenophyllus, R. thyrsiflorus, R. obtusifolius subsp. subalpinus, R. patientia) and Polygonum bistorta, Polygonum hydropiper, Polygonum lapathifolium and Polygonum viviparum demonstrated the highest XO inhibitory activity (>85% inhibition) at 400 µg/mL. The IC50 values of the active extracts were also determined. On the basis of the results, these plants, and especially P. hydropiper and R. acetosella, are considered worthy of activity‐guided phytochemical investigations. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anti‐fibrotic and Anti‐tumorigenic Effects of Rhein, a Natural
           Anthraquinone Derivative, in Mammalian Stellate and Carcinoma Cells
    • Abstract: Anthraquinone compounds have been recognized to possess antiinflammatory, anti‐fibrotic and anti‐tumour properties and thus applied in human and veterinary therapeutics as active substances of medicinal products. Amongst the anthraquinones isolated from Rheum palmatum, also known as da‐huang, rhein was detected as one of the highest metabolite contents in the bloodstream of mammals. The biological activities of rhein therefore deserve detailed investigation. In this study, we aimed to delineate the mechanism of inhibitory actions of rhein on fibrotic and tumorigenic processes by means of various biochemical assays, such as immunofluorescent staining, real‐time polymerase chain reaction (PCR) and western blotting analyses in rat pancreatic stellate cells (LTC‐14), human pancreatic ductal adenocarcinoma cells (PANC‐1) and human colon carcinoma cells (SW480 and SW620). Our results demonstrated that the application of rhein notably suppressed the mRNA and protein levels of various fibrotic and tumorigenic mediators including alpha‐smooth muscle actin, type I collagen, fibronectin, N‐cadherin and matrix metalloproteinases in the testing mammalian cells. The mechanism of the suppressive actions of rhein was associated with the modulation of the sonic hedgehog and serine‐threonine kinase signalling pathways. In conclusion, we suggest that rhein may serve as a therapeutic or an adjuvant agent in anti‐fibrotic and anti‐tumorigenic approaches. Copyright © 2014 John Wiley & Sons, Ltd.
  • Changes in 5‐hydroxytryptamine and Cortisol Plasma Levels in
           Menopausal Women After Inhalation of Clary Sage Oil
  • Anti‐inflammatory Effects of Ginsenosides Rg5, Rz1, and Rk1:
           Inhibition of TNF‐α‐induced NF‐κB,
           COX‐2, and iNOS transcriptional expression
    • Abstract: In the course of this experiment on the anti‐inflammatory effect of ginsenosides, protopanaxdiol ginsenosides have shown inhibition activities in inflammatory responses: NF‐κB, COX‐2, and iNOS were induced by TNF‐α. The responses of this experiment were evaluated by NF‐κB‐luciferase assay and RT‐PCR experiment of COX‐2 and iNOS genes. The NF‐κB expressions were inhibited by ginsenosides Rd, Rg5, Rz1, and Rk1 in a dose‐dependent manner. The IC50 values were 3.47, 0.61, 0.63, and 0.75 μM, respectively. Particularly, ginsenosides Rg5, Rz1, and Rk1 as converted ginsenosides from primary protopanaxdiol ginsenosidess significantly inhibited COX‐2 and iNOS gene expression. These inhibition levels were similar to sulfasalazine as reference material. Copyright © 2014 John Wiley & Sons, Ltd.
  • Biliary Excretion of Glycyrrhetinic Acid: Glucuronide‐Conjugate
           Determination Following a Pharmacokinetic Study of Rat Bile
    • Abstract: Liquorice is a commonly prescribed herb in traditional Chinese medicine with the primary constituent, glycyrrhetinic acid (GA) responsible for the toxic effects arising from its chronic consumption. Hepatic transformation and biliary excretion of GA are significant and well‐documented pharmacokinetic pathways in humans, while glucuronide conjugates are the major identified metabolites. Here we report the role of bile in GA bioconversion in rats; this being achieved following intravenous administration of GA to Sprague–Dawley rats at a dose of 2 mg/kg with bile fluid analyzed for 3 h post‐injection using HPLC. The maximum concentration of glucuronides was detected about 30 min post‐administration, while the cumulative biliary excretion of glucuronides after 3 h was found to be 63.6 ± 6.4%. Our findings indicate a relatively high rate of biliary excretion for GA via the formation of glucuronide conjugates, and as a result of these findings, glucuronidation can be firmly regarded as a primary detoxification pathway for GA in rats. Copyright © 2014 John Wiley & Sons, Ltd.
  • Autophagy Activation and Antiviral Activity by a Licorice Triterpene
    • Abstract: The triterpene glycyrrhizic acid (GRA), the main product from the Glycyrrhiza glabra medicinal plant, is known for its antiinflammatory and antimicrobial activity. In this work, GRA was studied for its ability to induce the autophagic process activator Beclin 1 in epithelial cells and to observe how this property could influence its antiviral activity. After 24 h of treatment, GRA induced a Beclin 1 production that was more than twofold higher than that produced by rapamycin, used as a reference compound. When the compounds were added to HeLa cells together with the viruses, GRA demonstrated a strong antiherpes simplex virus type 1 (HSV1) activity, whereas rapamycin had no activity. However, if the compounds were added to the cells 24 h before the viruses, GRA induced the production of an even higher amount of Beclin 1 and showed an improved antiviral effect; under these conditions, rapamycin was also able to exert a significant anti‐HSV1 activity. In conclusion, GRA is a strong inducer of the autophagy activator Beclin 1, which establishes a resistance state to HSV1 replication. Copyright © 2014 John Wiley & Sons, Ltd.
  • Apple Polyphenol Extracts Protect Against Aspirin‐induced Gastric
           Mucosal Damage in Rats
    • Abstract: The protective role of two apple polyphenol extracts, Douglas‐FB (FB) and Douglas‐EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague–Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10‐day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10−2 m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10‐day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Protective Effects of a Polyphenol‐Enriched Protein Powder on
           Exercise‐Induced Susceptibility to Virus Infection
    • 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.
  • Phytochemistry and Antileishmanial Activity of the Leaf Latex of Aloe
           calidophila Reynolds
    • Abstract: Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC50 values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, 1H NMR, and 13C NMR spectral data. The isolated compounds showed strong antileishmanial activity with IC50 values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC50 = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost‐effective antileishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.
  • Involvement of Cerebral Nervous System Areas and Cytokines on
           Antihyperalgesic and Anti‐Inflammatory Activities of Kielmeyera
           rugosa Choisy (Calophyllaceae) in Rodents
    • 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.
  • Evaluation of the Effect of Curcumin Capsules on Glyburide Therapy in
           Patients with Type‐2 Diabetes Mellitus
    • Abstract: This study aimed to assess the possible beneficial effects of curcumin capsules as lipid‐lowering effects and as a permeability glycoprotein (P‐gp) inhibitor on the pharmacokinetics and pharmacodynamics of glyburide and as a P‐gp substrate with glyburide in patients with type‐2 diabetes mellitus. Open‐label, randomized control trial was carried out for 11 days on eight type‐2 diabetic patients on glyburide therapy. On the first day of the study, following the administration of 5 mg of glyburide, blood samples were collected from the patients at various time intervals ranging from 0.5 to 24 h. Blood sampling was repeated on the 11th day of the study, after treating the patients with curcumin for ten consecutive days. Glyburide concentrations changed at the second hour, Cmax was unchanged, the glucose levels were decreased, Area Under first Movement Curre (AUMC) was increased, and no patient has experienced the hypoglycaemia. The low‐density lipoprotein, very‐low‐density lipoprotein and triglycerides were decreased significantly, and the high‐density lipoprotein content increased. The co‐administration of curcumin capsules with glyburide may be beneficial to the patients in better glycaemic control. The lipid lowering and antidiabetic properties of the curcumin show as a potential future drug molecule. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Isolation of Antiprotozoal Compounds from Libyan Propolis
    • Abstract: Propolis is increasingly being explored as a source of biologically active compounds. Until now, there has been no study of Libyan propolis. Two samples were collected in North East Libya and tested for their activity against Trypanosoma brucei. Extracts from both samples had quite high activity. One of the samples was fractionated and yielded a number of active fractions. Three of the active fractions contained single compounds, which were found to be 13‐epitorulosal, acetyl‐13‐epi‐cupressic acid and 13‐epi‐cupressic acid, which have been described before in Mediterranean propolis. Two of the compounds had a minimum inhibitory concentration value of 1.56 µg/mL against T. brucei. The active fractions were also tested against macrophages infected with Leishmania donovani, and again moderate to strong activity was observed with the compounds having IC50 values in the range 5.1–21.9 µg/mL. Copyright © 2014 John Wiley & Sons, Ltd.
  • Turmeric Toxicity in A431 Epidermoid Cancer Cells Associates with
           Autophagy Degradation of Anti‐apoptotic and Anti‐autophagic
           p53 Mutant
    • Abstract: The keratinocyte‐derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin‐mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small‐interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric‐treated or Curcumin‐treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53. Copyright © 2014 John Wiley & Sons, Ltd.
  • Antiinflammatory, Antioxidant, and Immunological Effects of Carum copticum
           L. and Some of Its Constituents
    • Abstract: Carum copticum L. has been used traditionally for its various therapeutic effects. The plant contains various components such as thymol and carvacrol. Different therapeutic effects such as antifungal, antioxidant, antibacterial, antiparasitic, and antilipidemic were described for the plant and its constituents. Therefore, antiinflammatory, antioxidant, and immunological effects of C. copticum and its constituents, thymol and carvacrol, were discussed in the present review. Previous studies have shown potent antiinflammatory, antioxidant, and immunological effects for C. copticum and its constituents, thymol and carvacrol. Therefore, the plant and its constituents have therapeutic values in several inflammatory and immunological disorders as well as in the oxidative stress conditions. Copyright © 2014 John Wiley & Sons, Ltd.
  • Effects of Eucommia ulmoides Extract on Longitudinal Bone Growth Rate in
           Adolescent Female Rats
    • 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.
  • Therapeutic Potential of Cannabinoids in Counteracting
           Chemotherapy‐induced Adverse Effects: An Exploratory Review
    • Abstract: Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy‐associated bone loss, chemotherapy‐induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy‐induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anti‐allergic Effect of Intranasal Administration of Type‐A
           Procyanidin Polyphenols Based Standardized Extract of Cinnamon Bark in
           Ovalbumin Sensitized BALB/c Mice
    • Abstract: The objective of the present work was to evaluate anti‐allergic effects of intranasal administration of type‐A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP‐CZ) in ovalbumin (OVA)‐induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1–G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2–G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14–21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4–G6 received TAPP‐CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP‐CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA‐induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP‐CZ showed anti‐allergic efficacy in animal model of AR. Copyright © 2014 John Wiley & Sons, Ltd.
  • Ellagic Acid Suppresses Lipid Accumulation by Suppressing Early Adipogenic
           Events and Cell Cycle Arrest
    • Abstract: Ellagic acid (EA) is a natural polyphenol found in various fruits and vegetables. In this study, we examined the inhibitory effect of EA on fat accumulation in 3T3‐L1 cells during adipogenesis. Our data showed that EA reduced fat accumulation by down‐regulating adipogenic markers such as peroxisome proliferator activated receptor γ (PPARγ) and the CCAAT/enhancer binding protein α (C/EBPα) at the mRNA and protein levels in a dose‐dependent manner. We found that the decrease in adipogenic markers resulted from reduced expression of some early adipogenic transcription factors such as KLF4, KLF5, Krox20, and C/EBPβ within 24 h. Also, these inhibitions were correlated with down‐regulation of TG synthetic enzymes, causing inhibition of triglyceride (TG) levels in 3T3‐L1 cells investigated by ORO staining and in zebrafish investigated by TG assay. Additionally, the cell cycle analysis showed that EA inhibited cell cycle progression by arresting cells at the G0/G1 phase. Copyright © 2014 John Wiley & Sons, Ltd.
  • Effects of Vitexin on the Pharmacokinetics and mRNA Expression of CYP
           Isozymes in Rats
    • Abstract: In traditional therapy with Chinese medicine, vitexin has several pharmacological properties, including antinociceptive, antispasmodic, antioxidant, antimyeloperoxidase, and α‐glucosidase inhibitory activities. Recently, vitexin was shown to protect the heart against ischemia/reperfusion injury in an in vitro model by inhibiting apoptosis. The purpose of this study was to find out whether vitexin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), and midazolam (5 mg/kg), was given as oral administration to rats treated with short or long period of intravenous vitexin via the caudal vein. Blood samples were collected at a series of time points, and the concentrations of probe drugs in plasma were determined by HPLC‐mass spectrometry (MS)/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real‐time reverse transcription‐polymerase chain reaction was performed to determine the effects of vitexin on the mRNA expression of CYP1A2, CYP2C11, and CYP3A1 in rat liver. Treatment with short or long period of vitexin had no effects on rat CYP1A2. However, CYP3A1 enzyme activity was inhibited by vitexin in a concentration‐dependent and time‐dependent manner. Furthermore, CYP2C11 enzyme activity was induced after short period treatment but inhibited after long period of vitexin treatment. The mRNA expression results were in accordance with the pharmacokinetic results. In conclusion, vitexin can either inhibit or induce activities of CYP2C11 and CYP3A1. Therefore, caution is needed when vitexin is co‐administered with some CYP2C11 or CYP3A1 substrates in clinic, which may result in treatment failure and herb–drug interactions. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anti‐Leishmanial, Anti‐Inflammatory and Antimicrobial
           Activities of Phenolic Derivatives from Tibouchina paratropica
    • Abstract: A new phenolic derivative, 2,8‐dihydroxy‐7H‐furo[2,3‐f]chromen‐7‐one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti‐parasitic activity against Leishmania donovani (IC50 = 0.809 µg/mL). In addition, an 85% reduction in the secretion of the pro‐inflammatory cytokine IL‐6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti‐inflammatory IL‐10 was observed. Compound 2 showed neither anti‐parasitic nor anti‐inflammatory properties. In addition, no cytotoxic activities were observed against the human‐derived macrophage THP‐1 cells. Copyright © 2014 John Wiley & Sons, Ltd.
  • Curcumin Combined with Oxaliplatin Effectively Suppress Colorectal
           Carcinoma in vivo Through Inducing Apoptosis
    • Abstract: Studies have shown chemopreventive and/or chemotherapeutic effects of several curcumin‐based combinatorial treatments on colorectal cancer cells. However, their in vivo effects remain unclear. This study has demonstrated the therapeutic effect of curcumin and oxaliplatin, alone or in combination, on subcutaneously xenografted LoVo human colorectal cancer cells in immunodeficient (nu/nu) mice in vivo. Combinatorial administration of curcumin and oxaliplatin evidently inhibited the growth of colorectal cancer in nude mice, which was significantly more effective than either agent alone. Curcumin combined with oxaliplatin treatment induced apoptosis, accompanied by ultrastructural changes and cell cycle arrest in S and G2/M phases. Further mechanism analysis indicated that while the number of apoptotic tumor cells and the expression of Bax, caspase‐3, and poly (ADP‐ribose) polymerase (PARP) increased significantly, the expression of Bcl‐2, survivin, HSP70, pro‐caspase‐3, and pro‐PARP were dramatically suppressed in tumor cells after the treatment with combinatorial curcumin and oxaliplatin for 22 days. Taken together, the present study has demonstrated that administration of combined curcumin and oxaliplatin effectively suppressed colorectal carcinoma in vivo through inducing apoptosis and thus may provide an effective treatment for colorectal carcinoma. Copyright © 2014 John Wiley & Sons, Ltd.
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