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Pacing and Clinical Electrophysiology     Hybrid Journal   (Followers: 4, SJR: 0.927, h-index: 77)
Packaging Technology and Science     Hybrid Journal   (Followers: 10, SJR: 0.72, h-index: 27)
Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 4, SJR: 1.429, h-index: 58)
Pain Medicine     Hybrid Journal   (Followers: 6, SJR: 0.929, h-index: 55)
Pain Practice     Hybrid Journal   (Followers: 3, SJR: 0.835, h-index: 30)
Palaeontology     Hybrid Journal   (Followers: 13, SJR: 1.111, h-index: 40)
PAMM : Proceedings in Applied Mathematics and Mechanics     Free  
Papers In Regional Science     Hybrid Journal   (Followers: 6, SJR: 1.332, h-index: 34)
Parasite Immunology     Hybrid Journal   (Followers: 4, SJR: 0.916, h-index: 55)
Parliamentary History     Hybrid Journal   (Followers: 5, SJR: 0.151, h-index: 3)
Particle & Particle Systems Characterization     Hybrid Journal   (SJR: 0.226, h-index: 28)
Pathology Intl.     Hybrid Journal   (Followers: 1, SJR: 0.831, h-index: 53)
Peace & Change     Hybrid Journal   (Followers: 4)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 34, SJR: 1.325, h-index: 62)
Pediatric Anesthesia     Hybrid Journal   (Followers: 4, SJR: 0.95, h-index: 53)
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 4, SJR: 1.252, h-index: 67)
Pediatric Dermatology     Hybrid Journal   (Followers: 5, SJR: 0.739, h-index: 50)
Pediatric Diabetes     Hybrid Journal   (Followers: 16, SJR: 1.027, h-index: 43)
Pediatric Obesity     Hybrid Journal   (Followers: 5, SJR: 1.336, h-index: 33)
Pediatric Pulmonology     Hybrid Journal   (Followers: 5, SJR: 1.092, h-index: 77)
Pediatric Transplantation     Hybrid Journal   (SJR: 0.663, h-index: 49)
Pediatrics Intl.     Hybrid Journal   (Followers: 3, SJR: 0.443, h-index: 42)
Performance Improvement     Hybrid Journal   (Followers: 3)
Performance Improvement Quarterly     Hybrid Journal   (Followers: 2, SJR: 0.362, h-index: 7)
Periodontology 2000     Hybrid Journal   (Followers: 4, SJR: 1.467, h-index: 74)
Permafrost and Periglacial Processes     Hybrid Journal   (Followers: 3, SJR: 1.741, h-index: 46)
Personal Relationships     Hybrid Journal   (Followers: 4, SJR: 1.355, h-index: 45)
Personality and Mental Health     Hybrid Journal   (Followers: 12, SJR: 0.39, h-index: 7)
Personnel Psychology     Hybrid Journal   (Followers: 25, SJR: 5.796, h-index: 80)
Perspectives In Psychiatric Care     Hybrid Journal   (Followers: 1, SJR: 0.349, h-index: 20)
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 4, SJR: 1.566, h-index: 66)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (Followers: 2, SJR: 0.283, h-index: 8)
Pest Management Science     Hybrid Journal   (Followers: 5, SJR: 1.262, h-index: 72)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 8, SJR: 0.959, h-index: 20)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 23, SJR: 1.631, h-index: 59)
Pharmacology Research & Perspectives     Open Access  
Pharmacotherapy The J. of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 21, SJR: 0.852, h-index: 78)
Philosophical Books     Hybrid Journal   (Followers: 9)
Philosophical Investigations     Hybrid Journal   (Followers: 3, SJR: 0.162, h-index: 6)
Philosophical Issues     Hybrid Journal   (Followers: 8, SJR: 1.009, h-index: 2)
Philosophical Perspectives     Hybrid Journal   (Followers: 7)
Philosophy & Public Affairs     Hybrid Journal   (Followers: 23, SJR: 1.607, h-index: 29)
Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 19, SJR: 1.629, h-index: 11)
Philosophy Compass     Hybrid Journal   (Followers: 9, SJR: 0.282, h-index: 2)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.764, h-index: 96)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 2, SJR: 0.642, h-index: 42)
Phycological Research     Hybrid Journal   (Followers: 2, SJR: 0.405, h-index: 21)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.81, h-index: 72)
physica status solidi (b)     Hybrid Journal   (Followers: 1, SJR: 0.852, h-index: 70)
physica status solidi (c)     Hybrid Journal   (Followers: 1, SJR: 0.471, h-index: 31)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (Followers: 1, SJR: 1.166, h-index: 32)
Physik in unserer Zeit     Hybrid Journal   (Followers: 1)
Physik J.     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (Followers: 1, SJR: 1.442, h-index: 95)
Physiological Entomology     Hybrid Journal   (Followers: 2, SJR: 0.768, h-index: 38)
Physiological Reports     Open Access   (Followers: 1)
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 26, SJR: 0.396, h-index: 30)
Phytochemical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.959, h-index: 45)
Phytotherapy Research     Hybrid Journal   (SJR: 0.82, h-index: 76)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 3, SJR: 2.572, h-index: 72)
Plant Biotechnology J.     Hybrid Journal   (Followers: 6, SJR: 2.463, h-index: 58)
Plant Breeding     Hybrid Journal   (Followers: 15, SJR: 0.626, h-index: 49)
Plant Pathology     Hybrid Journal   (Followers: 7, SJR: 1.114, h-index: 50)
Plant Species Biology     Hybrid Journal   (Followers: 3, SJR: 0.509, h-index: 26)
Plant, Cell & Environment     Hybrid Journal   (Followers: 5, SJR: 2.821, h-index: 121)
Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.231, h-index: 40)
Poe Studies     Partially Free   (Followers: 5)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 11, SJR: 0.415, h-index: 3)
Policy & Internet     Hybrid Journal   (Followers: 8)
Policy Studies J.     Hybrid Journal   (Followers: 4, SJR: 1.362, h-index: 30)
Political Insight     Partially Free   (Followers: 1)
Political Psychology     Hybrid Journal   (Followers: 17, SJR: 1.885, h-index: 45)
Political Science Quarterly     Hybrid Journal   (Followers: 31, SJR: 0.378, h-index: 26)
Political Studies     Hybrid Journal   (Followers: 23, SJR: 1.107, h-index: 39)
Political Studies Review     Hybrid Journal   (Followers: 15, SJR: 0.488, h-index: 12)
Politics     Hybrid Journal   (Followers: 8, SJR: 0.517, h-index: 12)
Politics & Policy     Hybrid Journal   (Followers: 6, SJR: 0.347, h-index: 8)
Polymer Composites     Hybrid Journal   (Followers: 11, SJR: 0.67, h-index: 53)
Polymer Engineering & Science     Hybrid Journal   (Followers: 13, SJR: 0.572, h-index: 76)
Polymer Intl.     Hybrid Journal   (Followers: 3, SJR: 0.847, h-index: 67)
Polymers for Advanced Technologies     Hybrid Journal   (Followers: 3, SJR: 0.833, h-index: 57)
Population and Development Review     Hybrid Journal   (Followers: 4, SJR: 2.686, h-index: 56)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.836, h-index: 33)
Poverty & Public Policy     Hybrid Journal   (Followers: 13)
Practical Diabetes     Hybrid Journal   (Followers: 5, SJR: 0.175, h-index: 3)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 1.262, h-index: 69)
Prescriber     Hybrid Journal   (Followers: 7)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 3)
Preventive Cardiology     Hybrid Journal   (Followers: 3, SJR: 0.839, h-index: 23)
Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 28, SJR: 0.169, h-index: 21)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (Followers: 3, SJR: 0.381, h-index: 16)
Process Safety Progress     Hybrid Journal   (Followers: 6, SJR: 0.387, h-index: 22)
Production and Operations Management     Hybrid Journal   (Followers: 4, SJR: 2.417, h-index: 62)
Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)
Progress in Neurology and Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.124, h-index: 3)
Progress in Photovoltaics: Research & Applications     Hybrid Journal   (Followers: 7, SJR: 4.314, h-index: 74)
Progress in Structural Engineering and Materials     Hybrid Journal   (Followers: 5)
Project Management J.     Hybrid Journal   (Followers: 29, SJR: 0.497, h-index: 8)
Propellants, Explosives, Pyrotechnics     Hybrid Journal   (Followers: 183, SJR: 0.765, h-index: 37)

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Journal Cover   Phytotherapy Research
  [SJR: 0.82]   [H-I: 76]   [0 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
   Published by John Wiley and Sons Homepage  [1598 journals]
  • Antimicrobial Effects of Blueberry, Raspberry, and Strawberry Aqueous
           Extracts and their Effects on Virulence Gene Expression in Vibrio cholerae
    • Authors: Hazim O. Khalifa; Maki Kamimoto, Toshi Shimamoto, Tadashi Shimamoto
      Abstract: The antimicrobial effects of aqueous extracts of blueberry, raspberry, and strawberry on 13 pathogenic bacteria were evaluated. The minimum inhibitory concentrations and minimum bactericidal concentrations of the extracts were determined before and after neutralization to pH 7.03 ± 0.15. Both Gram‐positive and Gram‐negative pathogenic bacteria were selectively inhibited by the non‐neutralized berries. Blueberry was the best inhibitor, and Vibrio and Listeria were the most sensitive bacteria. After neutralization, blueberry affected only Vibrio and Listeria, whereas the antimicrobial activities of raspberry and strawberry were abolished. The total contents of phenolics, flavonoids, and proanthocyanidins in the extracts were measured with colorimetric methods and were highest in strawberry, followed by raspberry, and then blueberry. We also studied the effects of sub‐bactericidal concentrations of the three berry extracts on virulence gene expression in Vibrio cholerae. Real‐time quantitative reverse transcription–polymerase chain reaction revealed that the three berry extracts effectively repressed the transcription of the tcpA gene. Raspberry also repressed the transcription of the ctxA gene, whereas blueberry and strawberry did not. However, the three berry extracts did not affect the transcription of toxT. These results suggest that the three berry extracts exert potent antimicrobial effects and inhibit the expression of the virulence factors of V. cholerae. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-21T03:05:29.627726-05:
      DOI: 10.1002/ptr.5436
  • The Protective Effect of α‐Hederin, the Active Constituent of
           Nigella sativa, on Lung Inflammation and Blood Cytokines in Ovalbumin
           Sensitized Guinea Pigs
    • Abstract: In the present study, the preventive effect of two different concentrations of α‐hederin, the active constituent of Nigella sativa, on lung inflammation and blood cytokines in ovalbumin sensitized guinea pigs was examined. Forty eight male adult guinea pigs were divided into control (C), sensitized (S) and sensitized pretreated groups; with thymoquinone (S+TQ), low dose (S+LAH) and high dose of α‐hederin (S+HAH) and inhaled fluticasone propionate (S+FP). The lung histopathology and blood levels of IL‐4, IFN‐γ and IL‐17 were assessed. Compared to sensitized animals, all pathological changes improved significantly in pretreated groups (p 
      PubDate: 2015-08-21T02:19:21.605391-05:
      DOI: 10.1002/ptr.5429
  • Distinct Responses of Cytotoxic Ganoderma lucidum Triterpenoids in Human
           Carcinoma Cells
    • Authors: Weimei Ruan; Ying Wei, David G. Popovich
      Abstract: The medicinal mushroom Ganoderma lucidum is well recognized for its effective cancer‐preventative and therapeutic properties, while specific components responsible for these anticancer effects are not well studied. Six triterpenoids that are ganolucidic acid E, lucidumol A, ganodermanontriol, 7‐oxo‐ganoderic acid Z, 15‐hydroxy‐ganoderic acid S, and ganoderic acid DM were isolated and identified from an extract of the mushroom. All compounds reduced cell growth in three human carcinoma cells (Caco‐2, HepG2, and HeLa cells) dose dependently with LC50s from 20.87 to 84.36 μM. Moreover, the six compounds induced apoptosis in HeLa cells with a maximum increase (22%) of sub‐G1 accumulations and 43.03% apoptotic cells in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (15‐hydroxy‐ganoderic acid S treatment). Apoptosis was further confirmed by annexin‐V staining. Four of the compounds also caused apoptosis in Caco‐2 cells with maximum 9.5% increase of sub‐G1 accumulations (7‐oxo‐ganoderic acid Z treatment) and maximum 29.84% apoptotic cells in TUNEL assay (ganoderic acid DM treatment). Contrarily, none of the compounds induced apoptosis in HepG2 cells. The different responses of the three cell lines following these treatments indicated that the bioactive properties of these compounds may vary from cells of different sites of origin and are likely acting under diverse regulatory mechanisms. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-21T02:08:56.7812-05:00
      DOI: 10.1002/ptr.5426
  • Zingerone activates VMAT2 during MPP+‐induced Cell Death
    • Abstract: Parkinson's disease (PD) is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatum. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is used to produce an animal model for PD, and it is converted to 1‐methyl‐4‐phenylpyridine (MPP+) in animals. MPP+ accumulation leads to neuronal cell death. Vesicular monoamine transporter 2 (VMAT2) regulates the accumulation of monoamine neurotransmitters into synaptic vesicles and is involved in neuroprotection against neurotoxin‐induced cell death. Recently, zingerone has been reported to reduce oxidative stress and inhibit inflammation. Therefore, we examined the effect of zingerone on neuronal cell death in a PD model. In an MPP+ and MPTP‐mediated PD model, neuronal cell survival was increased by zingerone without modifying neuroinflammation or reactive oxygen species generation. Zingerone also induced ERK activation and VMAT2 expression, leading to the attenuation of MPP+‐induced neuronal cell death. Our current results suggest that zingerone has a neuroprotective effect in a PD model. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-17T22:51:47.82582-05:0
      DOI: 10.1002/ptr.5435
  • Corrigendum: An Acute, Double‐Blind, Placebo‐Controlled
           Cross‐over Study of 320 mg and 640 mg Doses of Bacopa
           monnieri (CDRI 08) on Multitasking Stress Reactivity and Mood
    • Authors: Sarah Benson; Luke A. Downey, Con Stough, Mark Wetherell, Andrea Zangara, Andrew Scholey
      PubDate: 2015-08-16T22:22:21.301799-05:
      DOI: 10.1002/ptr.5439
  • Corrigendum: Examining the Nootropic Effects of a Special Extract of
           Bacopa monniera on Human Cognitive Functioning: 90 day
           Double‐Blind Placebo‐Controlled Randomized Trial
    • Authors: Con Stough; Luke A. Downey, Jenny Lloyd, Beata Silber, Stephanie Redman, Chris Hutchison, Keith Wesnes, Pradeep J. Nathan
      PubDate: 2015-08-16T22:21:11.405809-05:
      DOI: 10.1002/ptr.5441
  • Antifolate Activity of Plant Polyphenols against Mycobacterium
    • Authors: Archana Raju; Mariam S. Degani, Mihir P. Khambete, M. K. Ray, M. G. R. Rajan
      Abstract: With the view of exploring phytochemicals as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors, known plant polyphenols from various classes were subjected to detailed docking studies. From this in‐silico screening, seven polyphenols were selected and tested against Mtb H37Rv in whole cell assays. The phytochemicals exhibited potential activity ranging from 3 to 183 µm. These molecules were then tested against the pathogenic and human enzymes in a high‐throughput microtitre assay. Epigallocatechin gallate showed the best activity and selectivity. The in‐silico analysis was in agreement with the assay results. Of these 7 polyphenols, 5 exhibiting minimum inhibitory concentration values of ≤15 µm were tested for synergistic activity with first line drug Ethambutol and second line folate inhibitor para‐amino salicylic acid. Epigallocatechin gallate, Magnolol and Bakuchiol exhibited moderate synergistic association by lowering the minimum inhibitory concentration of these drugs. These simple phytochemicals could hence be considered as leads for further studies, or for preparation of semi‐synthetic derivatives to be used in combination therapy, for increased anti‐tuberculosis activity after validation in‐vivo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-15T01:08:13.944382-05:
      DOI: 10.1002/ptr.5437
  • Corrigendum: An Acute, Double‐Blind, Placebo‐Controlled
           Crossover Study of 320 mg and 640 mg Doses of a Special
           Extract of Bacopa monnieri (CDRI 08) on Sustained Cognitive Performance
    • Authors: Luke A. Downey; James Kean, Fiona Nemeh, Angela Lau, Alex Poll, Rebecca Gregory, Margaret Murray, Johanna Rourke, Brigit Patak, Matthew P. Pase, Andrea Zangara, Justine Lomas, Andrew Scholey, Con Stough
      PubDate: 2015-08-14T04:21:13.831329-05:
      DOI: 10.1002/ptr.5440
  • Phytochemical and Botanical Therapies for Rosacea: A Systematic Review
    • Abstract: Botanical and cosmeceutical therapies are commonly used to treat symptoms of rosacea such as facial erythema, papules/pustule counts, and telangiectasia. These products may contain plant extracts, phytochemicals, and herbal formulations. The objective of this study was to review clinical studies evaluating the use of botanical agents for the treatment of rosacea. MEDLINE and Embase databases were searched for clinical studies evaluating botanical therapies for rosacea. Major results were summarized, and study methodology was analyzed. Several botanical therapies may be promising for rosacea symptoms, but few studies are methodologically rigorous. Several plant extract and phytochemicals effectively improved facial erythema and papule/pustule counts caused by rosacea. Many studies are not methodologically rigorous. Further research is critical, as many botanicals have been evaluated in only one study. Botanical agents may reduce facial erythema and effectively improve papule/pustule counts associated with rosacea. Although promising, further research in the area is imperative. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-14T04:07:01.277721-05:
      DOI: 10.1002/ptr.5432
  • Anti‐lung Cancer Effects of Polyphyllin VI and VII Potentially
           Correlate with Apoptosis In Vitro and In Vivo
    • Authors: Zhufen Lin; Yuting Liu, Fangyuan Li, Jinjun Wu, Guiyu Zhang, Ying Wang, Linlin Lu, Zhongqiu Liu
      Abstract: Polyphyllin VI (PVI) and polyphyllin VII (PVII) derived from Paris polyphylla possess anti‐cancer activities. However, the mechanisms for the anti‐lung cancer effects of PVI and PVII remain poorly understood. In this study, PVI and PVII exhibited inhibitory effects on the proliferation of A549 and NCI‐H1299 cells. PVI and PVII induced G2/M cell cycle arrest and triggered apoptosis. PVI and PVII upregulated the tumor suppressor protein p53 and downregulated cyclin B1. The two treatments significantly increased the expression levels of death receptor 3, death receptor 5, Fas, cleaved PARP, and cleaved caspase‐3. Furthermore, PVI and PVII significantly inhibited the growth of A549 cells in vivo. The tumor inhibitory rates of PVI were 25.74%, 34.62%, and 40.43% at 2, 3, and 4 mg/kg, respectively, and those of PVII were 25.63%, 41.71%, and 40.41% at 1, 2, and 3 mg/kg, respectively. Finally, PVI and PVII regulated the expression of proteins related to the apoptotic pathway in A549 xenografts. In summary, PVI and PVII exhibited strong inhibitory effects on lung cancer cell growth in vitro and in vivo by inducing G2/M cell cycle arrest and triggering apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T22:33:57.164392-05:
      DOI: 10.1002/ptr.5430
  • Paeoniflorin ameliorates ANIT‐induced cholestasis by activating Nrf2
           through an PI3K/Akt‐dependent pathway in rats
    • Authors: Zhe Chen; Xiao Ma, Yun Zhu, Yanling Zhao, Jiabo Wang, Ruisheng Li, Chang Chen, Shizhang Wei, Wenjuan Jiao, Yaming Zhang, Jianyu Li, Lifu Wang, Ruilin Wang, Honghong Liu, Honghui Shen, Xiaohe Xiao
      Abstract: Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha‐naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT‐induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma‐glutamyl transpeptidase (γ‐GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT‐administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate‐cysteine ligase catalytic subunit (GCLc) and glutamate‐cysteine ligase modifier subunit (GCLm) in ANIT‐treated group. In addition, the RNA and protein expression of Akt and nuclear factor‐E2‐related factor‐2 (Nrf2) were also activated by paeoniflorin in ANIT‐induced rats. These findings indicated that paeoniflorin protected ANIT‐induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt‐dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T02:09:39.806322-05:
      DOI: 10.1002/ptr.5431
  • Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of
           Recurrent Urinary Tract Infection'
    • Authors: Jitka Vostalova; Ales Vidlar, Vilim Simanek, Adela Galandakova, Pavel Kosina, Jan Vacek, Jana Vrbkova, Benno F. Zimmermann, Jitka Ulrichova, Vladimir Student
      Abstract: Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent‐to‐treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age‐standardized 12‐month UTI history (p = 0.01)]. The Kaplan–Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T01:20:41.21443-05:0
      DOI: 10.1002/ptr.5427
  • Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian
    • Authors: Mohammad A. Khanfar; Sanaa K. Bardaweel, Mohamed R. Akl, Khalid A. El Sayed
      Abstract: The established anticancer and neuroprotective properties of oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimer's disease development encouraged us to examine the possibility that oleocanthal inhibits mTOR. To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K‐γ. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3‐γ/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose‐dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA‐MB‐231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-07T03:46:17.655965-05:
      DOI: 10.1002/ptr.5434
  • Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic
           Activity: From a Bioactivity‐guided Approach to Comprehensive
           Metabolite Profiling
    • Abstract: Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n‐butanol, and the remaining water fractions was evaluated in streptozotocin‐induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large‐scale untargeted metabolite profiling of methanol extract was performed via UPLC‐PDA and qTOF‐MS (ultra‐performance liquid chromatography photodiode array detection and quadrupole time‐of‐flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O‐caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-03T01:00:28.451313-05:
      DOI: 10.1002/ptr.5424
  • In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida
           spp. and Probiotic Vaginal Microbiota
    • Authors: Maura Di Vito; Paola Mattarelli, Monica Modesto, Antonietta Girolamo, Milva Ballardini, Annunziata Tamburro, Marcello Meledandri, Francesca Mondello
      Abstract: The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO‐VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R‐215 and Lactobacillus acidophilus R‐52) was tested. Both TTO‐VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo‐VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations 
      PubDate: 2015-08-03T00:43:01.936183-05:
      DOI: 10.1002/ptr.5422
  • 3,4,5‐Tricaffeoylquinic Acid Attenuates TRAIL‐induced
           Apoptosis in Human Keratinocytes by Suppressing Apoptosis‐related
           Protein Activation
    • Authors: Da Hee Lee; Yoon Jeong Nam, Min Sung Lee, Dong Suep Sohn, Yong Kyoo Shin, Chung Soo Lee
      Abstract: Caffeoyl derivatives exhibit antiinflammatory and antioxidant effects. However, the effect of 3,4,5‐tricaffeoylquinic acid on the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of 3,4,5‐tricaffeoylquinic acid on TRAIL‐induced apoptosis in human keratinocytes. 3,4,5‐Tricaffeoylquinic acid and oxidant scavengers attenuated the decrease in the cytosolic levels of Bid, Bcl‐2, and survivin proteins; the increase in the levels of cytosolic Bax, p53, and phosphorylated p53; the increase in the levels of phosphorylated p38; the increase in the mitochondrial levels of the voltage‐dependent anion channel; loss of the mitochondrial transmembrane potential; the release of cytochrome c; activation of caspases (8, 9, and 3); cleavage of poly [ADP‐ribose] polymerase‐1; production of reactive oxygen species; the depletion of glutathione (GSH); nuclear damage; and cell death in keratinocytes treated with TRAIL. These results suggest that 3,4,5‐tricaffeoylquinic acid may reduce TRAIL‐induced apoptosis in human keratinocytes by suppressing the activation of the caspase‐8 and Bid pathways and the mitochondria‐mediated cell death pathway. The effect appears to be associated with the inhibitory effect on the production of reactive oxygen species and depletion of GSH. 3,4,5‐Tricaffeoylquinic acid appears to be effective in the prevention of TRAIL‐induced apoptosis‐mediated skin diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-30T00:51:09.126653-05:
      DOI: 10.1002/ptr.5425
  • Therapeutic and Prophylactic Potential of Morama (Tylosema esculentum): A
    • Authors: Walter Chingwaru; Jerneja Vidmar, Petrina T. Kapewangolo, Ofentse Mazimba, Jose Jackson
      Abstract: Tylosema esculentum (morama) is a highly valued traditional food and source of medicine for the San and other indigenous populations that inhabit the arid to semi‐arid parts of Southern Africa. Morama beans are a rich source of phenolic acids, flavonoids, certain fatty acids, non‐essential amino acids, certain phytosterols, tannins and minerals. The plant's tuber contains griffonilide, behenic acid and starch. Concoctions of extracts from morama bean, tuber and other local plants are frequently used to treat diarrhoea and digestive disorders by the San and other indigenous populations. Information on composition and bioactivity of phytochemical components of T. esculentum suggests that the polyphenol‐rich extracts of the bean testae and cotyledons have great potential as sources of chemicals that inhibit infectious microorganisms (viral, bacterial and fungal, including drug‐resistant strains), offer protection against certain non‐communicable diseases and promote wound healing and gut health. The potential antinutritional properties of a few morama components are also highlighted. More research is necessary to reveal the full prophylactic and therapeutic potential of the plant against diseases of the current century. Research on domestication and conservation of the plant offers new hope for sustainable utilisation of the plant. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-21T04:07:19.530086-05:
      DOI: 10.1002/ptr.5419
  • Extract from Ceratonia siliqua Exhibits Depigmentation Properties
    • Authors: Namrita Lall; Navneet Kishore, Saeideh Momtaz, Ahmed Hussein, Sanushka Naidoo, Mabatho Nqephe, Bridget Crampton
      Abstract: Skin hyper‐pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L‐tyrosine as a substrate and showed diphenolase activity. The extract further significantly lowered tyrosinase mRNA levels in B16‐F10 mouse melanocytes. Bioassay‐guided fractionation led to the isolation of six compounds. Compounds (−)‐epicatechin‐3‐O‐gallate, 1,2,3,6‐tetra‐O‐galloyl‐ß‐D‐glucose and gallocatechin‐3‐O‐gallate showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30 µg/mL, respectively. These compounds also exhibited L‐DOPA activities with IC50 values of >200, 150 and 200 µg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non‐irritant with irritancy potential of −34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-20T04:33:50.189768-05:
      DOI: 10.1002/ptr.5420
  • Antiamoebic and Antigiardial Activity of Clerodane Diterpenes from Mexican
           Salvia Species Used for the Treatment of Diarrhea
    • Abstract: Terpenoids from Salvia species have been identified to possess biological properties as antiprotozoal agents. Here, we evaluated the antiamoebic and antigiardial activities of 14 known clerodane and modified clerodane‐type diterpenes isolated from five Mexican Salvia species against Entamoeba histolytica and Giardia lamblia, and analyzed the effects of the functionalities in decalin ring or in the whole clerodane framework to visualize the structural requirements necessary to produce an antiprotozoal activity. Among these, linearolactone was the most active clerodane diterpene against both protozoa with IC50 values of 22.9 μM for E. histolytica and of 28.2 μM in the case of G. lamblia. In this context it may be a lead compound for the development of novel therapeutic agent for the treatment of diarrhea and dysentery. The remaining diterpenes assayed showed moderate to weak activity against both protozoa. These findings give support to the use of Salvia species in the traditional medicine from México for the treatment of diarrhea. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-16T22:55:30.11824-05:0
      DOI: 10.1002/ptr.5421
  • Lupeol Protects Against Cerulein‐Induced Acute Pancreatitis in Mice
    • Abstract: Lupeol is a triterpenoid commonly found in fruits and vegetables and is known to exhibit a wide range of biological activities, including antiinflammatory and anti‐cancer effects. However, the effects of lupeol on acute pancreatitis specifically have not been well characterized. Here, we investigated the effects of lupeol on cerulein‐induced acute pancreatitis in mice. Acute pancreatitis was induced via an intraperitoneal injection of cerulein (50 µg/kg). In the lupeol treatment group, lupeol was administered intraperitoneally (10, 25, or 50 mg/kg) 1 h before the first cerulein injection. Blood samples were taken to determine serum cytokine and amylase levels. The pancreas was rapidly removed for morphological examination and used in the myeloperoxidase assay, trypsin activity assay, and real‐time reverse transcription polymerase chain reaction. In addition, we isolated pancreatic acinar cells using a collagenase method to examine the acinar cell viability. Lupeol administration significantly attenuated the severity of pancreatitis, as was shown by reduced pancreatic edema, and neutrophil infiltration. In addition, lupeol inhibited elevation of digestive enzymes and cytokine levels, such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1, and interleukin (IL)‐6. Furthermore, lupeol inhibited the cerulein‐induced acinar cell death. In conclusion, these results suggest that lupeol exhibits protective effects on cerulein‐induced acute pancreatitis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-16T04:33:20.435491-05:
      DOI: 10.1002/ptr.5423
  • Oxidative Stress Responses to Nigella sativa Oil Concurrent with a
           Low‐Calorie Diet in Obese Women: A Randomized, Double‐Blind
           Controlled Clinical Trial
    • Authors: Nazli Namazi; Reza Mahdavi, Mohammad Alizadeh, Safar Farajnia
      Abstract: The aim of the present study was to determine the effects of Nigella sativa (NS) oil concurrent with a low‐calorie diet on lipid peroxidation and oxidative status in obese women. In this double‐blind placebo‐controlled randomized clinical trial, 50 volunteer obese (body mass index = 30–35 kg/m2) women aged 25–50 years old were recruited. Participants were randomly divided into intervention (n = 25) and placebo (n = 25) groups. They received a low‐calorie diet with 3 g/day NS oil or low‐calorie diet with 3 g/day placebo for 8 weeks. Forty‐nine women (intervention group = 25; placebo group = 24) completed the trial. NS oil concurrent with a low‐calorie diet decreased weight in the NS group compared to the placebo group (−4.80 ± 1.50 vs. −1.40 ± 1.90 kg; p 
      PubDate: 2015-07-14T22:56:08.570371-05:
      DOI: 10.1002/ptr.5417
  • A polymethoxy flavonoids‐rich Citrus aurantium extract ameliorates
           ethanol‐induced liver injury through modulation of AMPK and
           Nrf2‐related signals in a binge drinking mouse model
    • Abstract: Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor‐α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP‐activated protein kinase (AMPK) and nuclear factor E2‐related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase‐1, NAD(P)H quinone oxidoreductase 1, and γ‐glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti‐inflammatory, and antiapoptotic activity against ethanol‐induced liver injury. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T09:59:09.764987-05:
      DOI: 10.1002/ptr.5415
  • Effects of Lonicera japonica Thunb. on Type 2 Diabetes via
           PPAR‐γ Activation in Rats
    • Authors: Jae Min Han; Mi Hye Kim, You Yeon Choi, Haesu Lee, Jongki Hong, Woong Mo Yang
      Abstract: Lonicera japonica Thunb. (Caprifoliaceae) is a traditional herbal medicine and has been used to treat diabetic symptoms. Notwithstanding its use, the scientific basis on anti‐diabetic properties of L. japonica is not yet established. This study is designed to investigate anti‐diabetic effects of L. japonica in type 2 diabetic rats. L. japonica was orally administered at the dose of 100 mg/kg in high‐fat diet‐fed and low‐dose streptozotocin‐induced rats. After the treatment of 4 weeks, L. japonica reduced high blood glucose level and homeostatic model assessment of insulin resistance in diabetic rats. In addition, body weight and food intake were restored by the L. japonica treatment. In the histopathologic examination, the amelioration of damaged β‐islet in pancreas was observed in L. japonica‐treated diabetic rats. The administration of L. japonica elevated peroxisome proliferator‐activated receptor gamma and insulin receptor subunit‐1 protein expressions. The results demonstrated that L. japonica had anti‐diabetic effects in type 2 diabetic rats via the peroxisome proliferator‐activated receptor gamma regulatory action of L. japonica as a potential mechanism. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T09:55:35.538741-05:
      DOI: 10.1002/ptr.5413
  • Potent Insulin Secretagogue from Scoparia dulcis Linn of Nepalese Origin
    • Abstract: Ethno‐botanical inspired isolation from plant Scoparia dulcis Linn. (Sweet Broomweed) yielded six compounds, coixol (1), glutinol (2), glutinone (3), friedelin (4), betulinic acid (5), and tetratriacontan‐1‐ol (6). There structures were identified using mass and 1D‐ and 2D‐NMR spectroscopy techniques. Compounds 1–6 were evaluated for their insulin secretory activity on isolated mice islets and MIN‐6 pancreatic β‐cell line, and compounds 1 and 2 were found to be potent and mildly active, respectively. Compound 1 was further evaluated for insulin secretory activity on MIN‐6 cells. Compound 1 was subjected to in vitro cytotoxicity assay against MIN‐6, 3T3 cell lines, and islet cells, and in vivo acute toxicity test in mice that was found to be non‐toxic. The insulin secretory activity of compounds 1 and 2 supported the ethno‐botanic uses of S. dulcis as an anti‐diabetic agent. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T09:50:41.514169-05:
      DOI: 10.1002/ptr.5412
  • Differential Inhibition of T Lymphocyte Proliferation and Cytokine
           Synthesis by [6]‐Gingerol, [8]‐Gingerol, and
    • Authors: Megan Bernard; Suzanne J. Furlong, Melanie R. Power Coombs, David W. Hoskin
      Abstract: [6]‐Gingerol, [8]‐gingerol, and [10]‐gingerol are pungent components of fresh ginger, extracts of which inhibit various components of the inflammatory response. Because little is known regarding the effect of gingerols with different unbranched alkyl side chain lengths on the activation and effector function of T lymphocytes, we compared the effects of [6]‐gingerol, [8]‐gingerol, and [10]‐gingerol on murine T lymphocyte proliferation, expression of CD25 and CD69 activation markers, cytokine synthesis, and interleukin (IL)‐2 receptor signaling. All three gingerols inhibited DNA synthesis by T lymphocytes, as well as interferon‐γ synthesis. In contrast, only [8]‐gingerol and [10]‐gingerol inhibited CD25 and CD69 expression, and IL‐2 synthesis. None of the gingerols affected IL‐4 synthesis. Exogenous IL‐2 enhanced T lymphocyte proliferation in the presence of [6]‐gingerol but did not significantly increase T lymphocyte proliferation in the presence of [8]‐gingerol or [10]‐gingerol. In line with this finding, [8]‐gingerol and [10]‐gingerol impaired IL‐2‐induced proliferation of CTLL‐2 cells, but constitutive CD25 expression was unaffected, indicating inhibition of IL‐2 receptor signaling. In general, [10]‐gingerol and [8]‐gingerol were more potent inhibitors of T lymphocytes than [6]‐gingerol. Suppression of T lymphocyte responses by gingerols suggests that these phytochemicals may be beneficial in chronic inflammatory conditions associated with excessive or inappropriate T lymphocyte activation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:51:04.302563-05:
      DOI: 10.1002/ptr.5414
  • Constipation and Botanical Medicines: An Overview
    • Authors: Carla Cirillo; Raffaele Capasso
      Abstract: Constipation affects 14% of the adult population globally, mainly women, and significantly impacts on health‐related quality of life. The causes of constipation are mainly three: lifestyle related (functional constipation), disease related, and drug induced. Constipation can generate considerable suffering, including abdominal pain and distension, anorexia, and nausea. The value of some therapeutic measures such as increased fluid intake, physical activity, diet rich in fiber, and nutritional supplements recommended for the relief of constipation is still questionable. The treatment of constipation can be carried out not only with traditional drugs but also with herbal medicines or with nutraceuticals, which are used to prevent or treat the disorder. We have reviewed the most common botanical laxatives such as senna, cascara, frangula, aloe, and rhubarb and their use in the treatment of constipation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:48:22.078572-05:
      DOI: 10.1002/ptr.5410
  • Cytotoxic Impact of Costunolide Isolated from Costus speciosus on Breast
           Cancer via Differential Regulation of Cell Cycle—An In‐vitro
           and In‐silico Approach
    • Authors: Anita Roy; Rajalakshmi Manikkam
      Abstract: Costunolide, a sesquiterpene lactone, is a biologically active molecule found in most of the medicinally valuable plants. The present study aims to evaluate the anticancer property of costunolide isolated from Costus speciosus against breast cancer cell lines (MCF‐7 and MDA‐MB‐231). Costunolide effectively reduced the viability of both MCF‐7 and MDA‐MB‐231 cell lines at an IC50 value of 40 μM. Flow cytometric analysis revealed costunolide mediated cell cycle arrest at G2/M phase in both the cell types. Western blotting results confirmed the alterations in the expression of cell cycle regulators (cyclin D1, D3, CDK‐4, CDK‐6, p18 INK4c, p21 CIP1/Waf‐1 and p27 KIP1) and apoptosis inducers (caspase‐3 and caspase‐9) upon costunolide treatment in comparison with their expressions in normal breast cell line (MCF‐10A). Costunolide mediated downregulation of positive cell cycle regulators and upregulation of negative cell cycle regulators were related to the induction of apoptosis in cancer cells. The above results were validated with in‐silico results that predicted stable interactions between costunolide and cancer targets. Thus costunolide effectively induced breast cancer cell apoptosis targeting cell cycle regulation, and the compound can be used as an effective herbal therapeutic molecule to treat breast cancer with further explorations. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:48:17.124578-05:
      DOI: 10.1002/ptr.5408

  •        3,6‐Dimethoxy‐6″,6″‐Dimethyl‐(7,8,2″,3″)‐Chromeneflavone,
           a Flavonoid Isolated from Lonchocarpus Araripensis Benth. (Fabaceae),
           Reduces Nociceptive Behaviour in Mice
    • Abstract: Lonchocarpus araripensis Benth. is largely distributed in the northeast region of Brazil. It is popularly known as ‘sucupira’. Recent studies have shown that some species of Lonchocarpus have interesting pharmacological activities. In this study, we evaluated the antinociceptive effect of a flavone isolated from L. araripensis. The chemical examination resulted in the isolation of 3,6‐dimethoxy‐6″,6″‐dimethyl‐(7,8,2″,3″)‐chromeneflavone (DDF). The structure of the compound was established by spectral analysis. Antinociceptive activity of DDF was evaluated by measuring nociception by acetic acid, formalin and hot plate tests. The rota rod test was used to evaluate motor coordination. The results demonstrated that DDF was able to prevent acetic‐acid‐writhing‐induced nociception (p 
      PubDate: 2015-07-14T08:47:08.141689-05:
      DOI: 10.1002/ptr.5418
  • Dual Effects of Liquiritigenin on the Proliferation of Bone Cells:
           Promotion of Osteoblast Differentiation and Inhibition of Osteoclast
    • Authors: Kaho Uchino; Kuniaki Okamoto, Eiko Sakai, Erika Yoneshima, Mayumi Iwatake, Yutaka Fukuma, Kazuhisa Nishishita, Takayuki Tsukuba
      Abstract: Bone is constantly controlled by a balance between osteoblastic bone formation and osteoclastic bone resorption. Liquiritigenin is a plant‐derived flavonoid and has various pharmacological effects, such as antioxidative, antitumor, and antiinflammatory effects. Here, we show that liquiritigenin has dual effects on the proliferation of bone cells, regarding the promotion of osteoblast differentiation and the inhibition of osteoclast differentiation. Liquiritigenin‐treated murine osteoblastic MC3T3‐E1 cells showed an increased alkaline phosphatase activity and enhanced phosphorylation of Smad1/5 compared with untreated cells. Moreover, liquiritigenin inhibited osteoclast differentiation, its bone‐resorption activity through slightly decreased the phosphorylation of extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase, and inhibitor of nuclear factor kappa Bα; however, the phosphorylation of Akt and p38 slightly increased in bone marrow‐derived osteoclasts. The expression levels of the osteoclast marker proteins nuclear factor of activated T‐cell cytoplasmic‐1, Src, and cathepsin K diminished. These results suggest that liquiritigenin may be useful as a therapeutic and/or preventive agent for osteoporosis or inflammatory bone diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:46:57.664656-05:
      DOI: 10.1002/ptr.5416
  • Asiaticoside Inhibits TNF‐α‐Induced Endothelial
           Hyperpermeability of Human Aortic Endothelial Cells
    • Authors: Lai Yen Fong; Chin Theng Ng, Zainul Amiruddin Zakaria, Mohamad Taufik Hidayat Baharuldin, Abdul Kadir Arifah, Muhammad Nazrul Hakim, Ahmad Zuraini
      Abstract: The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor‐alpha (TNF‐α), a pro‐atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF‐α in human aortic endothelial cells (HAEC). TNF‐α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)‐dextran. Asiaticoside pretreatment significantly suppressed TNF‐α‐induced increased permeability. Asiaticoside also prevented TNF‐α‐induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF‐α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti‐hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D‐induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF‐α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F‐actin organization. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:37:57.735185-05:
      DOI: 10.1002/ptr.5404
  • Thymoquinone Inhibition of Acquisition and Expression of
           Alcohol‐Induced Behavioral Sensitization
    • Authors: Muhammad Sona Khan; Aneela Gohar, Ghulam Abbas, Wajahat Mahmood, Khalid Rauf, Robert D. E. Sewell
      Abstract: Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol‐induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose‐dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T07:28:48.996394-05:
      DOI: 10.1002/ptr.5409
  • Chemical Constituents of Euonymus alatus (Thunb.) Sieb. and Their PTP1B
           and α‐Glucosidase Inhibitory Activities
    • Abstract: Phytochemical study on the corks of Euonymus alatus resulted in the isolation of a novel 3‐hydroxycoumarinflavanol (23), along with ten triterpenoids (1–10), ten phenolic derivatives (11–20), and two flavonoid glycosides (21 and 22). Their structures were determined by extensive 1D and 2D‐nuclear magnetic resonance spectroscopic and mass spectrometry data analysis. Furthermore, their inhibitory effects against the protein tyrosine phosphatases 1B (PTP1B) and α‐glucosidase enzyme activity were evaluated. Compounds 6, 7, 9, 15, 19, and 23 were non‐competitive inhibitors, exhibiting most potency with IC50 values ranging from 5.6 ± 0.9 to 18.4 ± 0.3 µm, against PTP1B. Compound 3 (competitive), compounds 5 and 15 (mixed‐competitive) displayed potent inhibition with IC50 values of 15.1 ± 0.7, 23.6 ± 0.6 and 14.8 ± 0.9 µm, respectively. Moreover, compounds 15, 20, and 23 exhibited potent inhibition on α‐glucosidase with IC50 values of 10.5 ± 0.8, 9.5 ± 0.6, and 9.1 ± 0.5 µm, respectively. Thus, these active ingredients may have value as new lead compounds for the development of new antidiabetic agents. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T07:28:18.988798-05:
      DOI: 10.1002/ptr.5411
  • Phloroglucinol Protects INS‐1 Pancreatic β‐cells Against
           Glucotoxicity‐Induced Apoptosis
    • Authors: Mi Hwa Park; Ji Sook Han
      Abstract: Decreasing numbers, and impaired function, of pancreatic β‐cells are key factors in the development of type 2 diabetes. This study was designed to investigate whether phloroglucinol protected pancreatic β‐cells against glucotoxicity‐induced apoptosis using a rat insulinoma cell line (INS‐1). High glucose treatment (30 mM) induced INS‐1 cell death; however, the level of glucose‐induced apoptosis was significantly reduced in cells treated with 100‐μM phloroglucinol. Treatment with 10–100‐μM phloroglucinol increased cell viability and decreased intracellular levels of reactive oxygen species, nitric oxide, and lipid peroxidation dose‐dependently in INS‐1 cells pretreated with high glucose. Furthermore, phloroglucinol treatment markedly reduced the protein expression of Bax, cytochrome c, and caspase 9, while increasing anti‐apoptotic Bcl‐2 protein expression. Cell death type was examined using annexin V/propidium iodide staining, revealing that phloroglucinol markedly reduced high glucose‐induced apoptosis. These results demonstrated that phloroglucinol could be useful as a potential therapeutic agent for the protection of pancreatic β‐cells against glucose‐induced apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-07T03:30:50.137997-05:
      DOI: 10.1002/ptr.5407
  • Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5
           Up‐Regulation, ROS Generation, Modulation of Bcl‐2 and IAP
           Family Members
    • Abstract: Pachymic acid (PA) is a lanostane‐type triterpenoid derived from Poria cocos mushroom that possess various biological effects such as anti‐cancer, antiinflammatory and anti‐metastasis effects. In this study, we investigated the anti‐cancer effects of PA in EJ bladder cancer cells. The results showed that PA significantly inhibited proliferation of EJ cells in a dose‐dependent manner. PA induced accumulation of sub‐G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in EJ cells in a dose‐dependent manner. PA also induces activation of caspase‐3, ‐8 and ‐9, and subsequent cleavage of poly (ADP‐ribose) polymerase, and significantly suppressed the inhibitor of apoptosis protein family proteins in a dose‐dependent manner. Furthermore, PA activates Bid and induced the loss of mitochondrial membrane potential (ΔΨm) with up‐regulated pro‐apoptotic proteins (Bax and Bad), down‐regulated anti‐apoptotic proteins (Bcl‐2 and Bcl‐xL) and cytochrome c release. In turn, PA increased the generation of reactive oxygen species (ROS); also, the ROS production was blocked by N‐acetyl‐L‐cysteine. The expressions of TNF‐related apoptosis inducing ligand and death receptor 5 were up‐regulated by PA in a dose‐dependent manner, suggesting extrinsic pathway also involved in PA‐induced apoptosis. This study provides evidence that PA might be useful in the treatment of human bladder cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-07T03:28:19.687546-05:
      DOI: 10.1002/ptr.5402
  • Becatamide Found in Houttuynia cordata Suppresses P‐selectin
           Expression Via Inhibiting COX Enzyme, Not Increasing cAMP in Platelets
    • Authors: Jae B. Park
      Abstract: Atherosclerosis is a well‐known inflammatory cardiovascular disease. Recent studies suggested potential anti‐atherosclerosis effects of becatamide found in Houttuynia cordata. Therefore, in this study, we investigated potential effect of becatamide (1) and its analogues (enferamide (2), veskamide (3), oretamide (4) and amkamide (5)) on cyclooxygenase (COX)‐1 and ‐2 and the production of cyclic adenosine monophosphate (cAMP), which are critically involved in platelet activation. Among them, becatamide was the most potent compound able to inhibit COX‐1 (IC50 = 0.27 µm) and ‐2 (IC50 = 0.78 µm) (p  veskamide > enferamide > oretamide > amkamide. As a result of the inhibition, the production of thromboxane B2 and P‐selectin expression were suppressed by 35% (p 
      PubDate: 2015-06-26T00:47:17.842447-05:
      DOI: 10.1002/ptr.5391
  • Effect of Serenoa Repens on Oxidative Stress, Inflammatory and Growth
           Factors in Obese Wistar Rats with Benign Prostatic Hyperplasia
    • Abstract: Serenoa repens has been widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms; however, most of the studies have been conducted in individuals with normal weight and not obese. In this study, the effects of a lipidic extract of S. repens, in markers of oxidative stress, inflammation, and growth factors, in obese rats with testosterone‐induced prostatic hyperplasia, were investigated. Total nitrites, malondialdehyde, total glutathione, superoxide dismutase (SOD), and catalase activity were measured; in addition, assays for inflammatory cytokines TNF‐α, IL‐1β, IL‐6 and the growth factors basic fibroblast growth factor (FGFb) and vascular endothelial growth factor (VEGF) were performed. The obese rats had a higher prostate weight compared with controls. S. repens significantly decreased prostate weight, total nitrites, and malondialdehyde; improved total glutathione, SOD, and catalase activity; and significantly reduced inflammatory (TNF‐α, IL‐1β and IL‐6) and growth factors (VEGF and FGFb). S. repens showed high antioxidant and antiinflammatory activity in obese rats, suggesting that their use could be beneficial in the treatment of benign prostatic hyperplasia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-24T03:21:32.753432-05:
      DOI: 10.1002/ptr.5406
  • A Preliminary Investigation on the Antimicrobial Activity of
           Listerine®, Its Components, and of Mixtures Thereof
    • Abstract: Listerine® is one of the most popular mouthwashes worldwide and claims to combat harmful bacteria. In the past century, its recipe was changed from an essential oil mouthwash to a five‐component mixture (thymol, menthol, eucalyptol, and methyl salicylate dissolved in 27% ethanol). The aim of this study was to get preliminary information about the antimicrobial activities of individual Listerine® components and their mixtures. We tested the bacterial strains Streptococcus mutans, Enterococcus faecalis, and Eikenella corrodens and the yeast Candida albicans. The established minimum inhibitory concentration (MIC) assay and the minimum bactericidal/fungicidal concentration (MBC/MFC) assay were applied. None of the combinations of two phenols at the concentrations contained within Listerine® were associated with either an additive or synergistic effect. Thymol had lower MIC and MBC/MFC values than the other Listerine® components and Listerine® against E. corrodens and C. albicans. The mixtures consisting of eucalyptol, methyl salicylate, and thymol were the most effective against S. mutans and E. faecalis and more effective than Listerine®. Our results demonstrate that the phenols and their concentrations as contained within Listerine® could be further optimized in terms of selecting those which increase their general effectiveness, at concentrations that do not induce harm. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-24T02:29:48.86281-05:0
      DOI: 10.1002/ptr.5399
  • Paris Saponin VII Inhibits the Migration and Invasion in Human A549 Lung
           Cancer Cells
    • Authors: Lei Fan; Yuhua Li, Yang Sun, Jing Han, Zhenggang Yue, Jin Meng, Xutao Zhang, Feng Zhang, Qibing Mei
      Abstract: Metastasis is the main cause of death in lung cancer. Targeting the process of metastasis is a strategy to lung cancer treatment. Trillium tschonoskii Maxim., a traditional Chinese medicine, has been used for treatment of many diseases, including cancer. This study aims to determine the anti‐metastatic effect of paris saponin VII (PS VII) which was extracted from T. tschonoskii Maxim. by using human lung cancer cell line A549 cells. Our results showed that PS VII could significantly suppress the viability as well as cell migration and invasion abilities of A549 cells in a concentration‐dependent manner. PS VII reduced the activity of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 by elevating the expression of TIMP1/2. These data indicated that PS VII could reduce the metastatic capability of A549 cells, probably through up‐regulating the expression of TIMP1/2. These findings demonstrated a new therapeutic potential for PS VII in anti‐metastatic therapy of lung cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-24T02:21:11.697583-05:
      DOI: 10.1002/ptr.5389
  • Consumption of Argan Oil Improves Anti‐Oxidant and Lipid Status in
           Hemodialysis Patients
    • Authors: Rachid Eljaoudi; Driss Elkabbaj, Abdelali Bahadi, Azeddine Ibrahimi, Mohammed Benyahia, Mourad Errasfa
      Abstract: Objective: Virgin Argan oil (VAO) is of interest in oxidative stress and lipid profile because of its fat composition and antioxidant compounds. We investigated the effect of VAO consumption on lipid profile and antioxidant status in hemodialysis patients after a 4‐week period of consumption. Methods: In a crossover, controlled trial, 37 patients (18 men, 19 women) with end‐stage renal disease on maintenance hemodialysis, were randomly assigned to a 4‐week VAO diet. Fasting plasma lipids, vitamin E and oxidized LDL (ox‐LDL) were analyzed. Malondialdehyde (MDA) was determined before and after hemodialysis session. Results: There was no significant change in serum total cholesterol and ox‐LDL. However, VAO consumption decreased the levels of triglyceride (p = 0.03), total cholesterol (p = 0.02) and low‐density lipoprotein (p = 0.03) and increased the levels of high‐density lipoprotein (p = 0.01). Plasma vitamin E contents significantly increased from baseline only in VAO‐group (p 
      PubDate: 2015-06-23T00:35:26.51914-05:0
      DOI: 10.1002/ptr.5405
  • Anti‐TNF‐α Activity of Brazilian Medicinal Plants and
           Compounds from Ouratea semiserrata
    • Abstract: Several plant species are used in Brazil to treat inflammatory diseases and associated conditions. TNF‐α plays a pivotal role on inflammation, and several plant extracts have been assayed against this target, both in vitro and in vivo. The effect of 11 Brazilian medicinal plants on TNF‐α release by LPS‐activated THP‐1 cells was evaluated. The plant materials were percolated with different solvents to afford 15 crude extracts, whose effect on TNF‐α release was determined by ELISA. Among the evaluated extracts, only Jacaranda caroba (Bignoniaceae) presented strong toxicity to THP‐1 cells. Considering the 14 non‐toxic extracts, TNF‐α release was significantly reduced by seven of them (inhibition > 80%), originating from six plants, namely Cuphea carthagenensis (Lythraceae), Echinodorus grandiflorus (Alismataceae), Mansoa hirsuta (Bignoniaceae), Ouratea semiserrata (Ochnaceae), Ouratea spectabilis and Remijia ferruginea (Rubiaceae). The ethanol extract from O. semiserrata leaves was fractionated over Sephadex LH‐20 and RP‐HPLC to give three compounds previously reported for the species, along with agathisflavone and epicatechin, here described for the first time in the plant. Epicatechin and lanceoloside A elicited significant inhibition of TNF‐α release, indicating that they may account for the effect produced by O. semiserrata crude extract. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-22T03:23:45.058363-05:
      DOI: 10.1002/ptr.5401
  • Blood Glucose‐lowering Effect of T. procumbens L.: A Pilot
           Clinical Study in Individuals with Type 2 Diabetes
    • Authors: Gauri S. Desai; Shirish V. Desai, Rajendra S. Gavaskar, Vanisree Mulabagal, Yonnie Wu, Suresh T. Mathews
      Abstract: Traditional knowledge, in vitro studies, and studies using animal models suggest that Tridax procumbens L. exhibits blood glucose‐lowering properties and antiinflammatory effects. In this study, we evaluated the blood glucose‐lowering effect of T. procumbens supplementation in individuals with type 2 diabetes. An extract (asava) of T. procumbens L. was prepared following Ayurveda guidelines. Chemical and microbial analyses indicated presence of phenolics, flavonoids, and carotenoids, and absence of microbial contamination, aflatoxins, heavy metals, and pesticide residues. A chemical fingerprint of T. procumbens L. asava, developed using Ultra high pressure liquid chromatography/electron spray ionization‐mass spectrometry (UPLC/ESI‐MS) in negative mode, suggest the presence of several compounds including polyphenols. T. procumbens asava demonstrated strong total antioxidant capacity, Fe3+ reducing potential, Fe2+ chelation, H2O2 scavenging activity, and inhibition of lipid peroxidation. We recruited 20 type 2 diabetic individuals from Kolhapur, India. Participants received 15 mL of T. procumbens asava, twice daily, for 4 weeks, while continuing their prescribed antidiabetic medications. Fasting blood glucose decreased by 11% in men (p 
      PubDate: 2015-06-22T03:03:28.038241-05:
      DOI: 10.1002/ptr.5394
  • 5,7‐Dihydroxy‐6‐Methoxy‐Flavonoids Eliminate
           HIV‐1 D3‐transfected Cytoprotective Macrophages by Inhibiting
           the PI3K/Akt Signaling Pathway
    • Abstract: Flavonoids, well‐documented secondary metabolites in many vegetables and plants, exhibit antiinflammatory, anti‐oxidant, anti‐microbial, and anticancer activities. However, their cytotoxic effects against human immunodeficiency virus type 1 (HIV‐1)‐infected cytoprotective macrophages have not been studied. In the present study, we investigated their effects and their molecular mechanisms. Treatment with flavonoids in the presence of lipopolysaccharide (LPS)/cycloheximide (CHX) potently eliminated HIV‐1 Tat‐transduced cytoprotective human microglial CHME5 cells; the 5,7‐dihydroxy‐6‐methoxy‐flavonoids oroxylin A and tectorigenin, at a concentration of 10 μM, most potently eliminated the cytoprotective phenotype. These flavonoids eliminated Tat‐transduced CHME5 cells, D3‐transfected CHME5 cells, and HIV‐1 D3‐infected human primary macrophages, in a dose‐dependent manner. Furthermore, oroxylin A and tectorigenin potently inhibited LPS/CHX‐induced phosphorylation of phosphoinositide 3‐kinase (PI3K), pyruvate dehydrogenase lipoamide kinase isozyme 1, Akt, and glycogen synthase kinase‐3β in the Tat‐transduced cells, D3‐transfected CHME5 cells, and D3‐infected human primary macrophages. Based on these findings, 5,7‐dihydroxy‐6‐methoxy‐flavonoids may eliminate HIV‐1 infected cytoprotective macrophages by inhibiting the PI3K/Akt signaling pathway and deliver anti‐HIV‐1 effects in vivo by shortening the lifespan of infected macrophages. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-22T02:28:06.953132-05:
      DOI: 10.1002/ptr.5388
  • Salicin from Willow Bark can Modulate Neurite Outgrowth in Human
           Neuroblastoma SH‐SY5Y Cells
    • Abstract: Salicin from willow bark has been used throughout centuries in China and Europe for the treatment of pain, headache, and inflammatory conditions. Recently, it could be demonstrated that salicin binds and activates the bitter taste receptor TAS2R16. Studies on rodent tissues showed the general expression of bitter taste receptors (TAS2Rs) in rodent brain. Here, we demonstrate the expression of hTAS2R16 in human neuronal tissues and the neuroblastoma cell line SH‐SY5Y. The functionality was analyzed in the neuroblastoma cell line SH‐SY5Y after stimulation with salicin, a known TAS2R16 agonist. In this setting salicin induced in SH‐SY5Y cells phosphorylation of ERK and CREB, the key transcription factor of neuronal differentiation. PD98059, an inhibitor of the ERK pathway, as well as probenecid, a TAS2R16 antagonist, inhibited receptor phosphorylation as well as neurite outgrowth. These data show that salicin might modulate neurite outgrowth by bitter taste receptor activation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-19T05:19:44.438953-05:
      DOI: 10.1002/ptr.5400
  • Dietary Doses of Sulforaphane Affect Hepatic Drug Metabolizing Enzymes in
           Spontaneously Hypertensive Rats
    • Authors: Anik Amin; Margarita CanGongora, Fawzy Elbarbry
      Abstract: We previously demonstrated that exposure of spontaneously hypertensive rats (SHR) to dietary doses of sulforaphane (SF) results in resisting the progressive rise in blood pressure that is normally seen in these rats. This study investigates the potential effect of SF on hepatic drug metabolizing enzymes (DME) in SHR. The activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase (mEH) were measured in hepatic microsomes using specific probe substrates and/or polyclonal antibodies. Cytosolic fraction was utilized to measure protein level and activity of major antioxidant systems. The high dose SF resulted in a significant reduction of activity and apoproteins level of CYP1A2 and CYP2C9 and activities of CYP2B1/2 and mEH. No effect of SF was observed on the rest of the studied CYP enzymes. Both doses of SF resulted in a significant induction of both hepatic glutathione level and activities of superoxide dismutase and catalase. Activities of hepatic glutathione‐S‐transferases, glutathione reductase, and glutathione peroxidase were significantly induced only with the high dose. This study demonstrates that dietary doses of SF modulate the activity or protein expression of DME. Additionally, induction of the impaired antioxidant system in SHR may explain the blood pressure lowering effect of SF in this rat model. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-18T01:29:50.905812-05:
      DOI: 10.1002/ptr.5397
  • Inhibition of UDP‐Glucuronosyltransferases (UGTs) Activity by
           constituents of Schisandra chinensis
    • Abstract: Structure–activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine‐Diphosphate) UDP‐glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb–drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9‐mediated metabolism. In conclusion, in silico‐in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-18T01:27:36.354289-05:
      DOI: 10.1002/ptr.5395
  • Quantitative Evaluation of the Mechanism Underlying the Biotransportation
           of the Active Ingredients in Puerariae lobatae Radix and
           Chuanxiong rhizoma
    • Abstract: The objective of this study was to establish a quantitative method to evaluate the biotransportation of a drug across the cell membrane. Through the application of the law of mass conservation, the drug transportation rate was calculated based on Fick's law of passive diffusion and the Michaelis–Menten equation. The overall membrane‐transportation rate was the sum of the passive diffusion rate and the carrier‐mediated diffusion rate, which were calculated as the transportation mass divided by the respective rate. The active ingredients of Puerariae lobatae Radix and Chuanxiong rhizoma, namely, puerarin and ferulic acid, respectively, were used as two model drugs. The transportation rates of puerarin and ferulic acid were obtained by fitting a model that includes both Fick's law of diffusion and the Michaelis–Menten equation. Compared with the overall transportation, the carrier‐mediated transport and passive diffusion of 1.59 mmol/L puerarin were −35.07% and 64.93%, respectively, whereas the respective transportation modes of 0.1 mmol/L ferulic acid were −35.40% and 64.60%, respectively. Verapamil and MK‐571 increased the overall transport rate and ratio, and MK‐571 treatment changed the carrier‐mediated transport from negative to positive. However, the transport rate and ratio of ferulic acid did not change significantly. The cell transportation mechanisms of puerarin and ferulic acid primarily involve simple passive diffusion and carrier‐mediated transportation. Moreover, P‐glycoprotein and multidrug resistance‐associated protein efflux proteins, and other transportation proteins were found to be involved in the transportation of puerarin. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-15T02:17:03.601756-05:
      DOI: 10.1002/ptr.5393
  • Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke‐induced
           Gastric Epithelial–Mesenchymal Transition in Mice
    • Authors: Zhaofeng Liang; Rui Wu, Wei Xie, Hao Geng, Li Zhao, Chunfeng Xie, Jieshu Wu, Shanshan Geng, Xiaoting Li, Mingming Zhu, Weiwei Zhu, Jianyun Zhu, Cong Huang, Xiao Ma, Caiyun Zhong, Hongyu Han
      Abstract: Tobacco smoke (TS) has been shown to cause gastric cancer. Epithelial–mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. Mitogen‐activated protein kinase (MAPK) pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study, we investigated the effects of TS on MAPK pathway activation and EMT alterations in the stomach of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12 weeks resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2), the Jun N‐terminal kinase (JNK), p38, and ERK5 MAPK pathways as well as activator protein 1 (AP‐1) proteins in stomach. TS reduced the mRNA and protein expression levels of the epithelial markers E‐cadherin and ZO‐1, while the mRNA and protein expression levels of the mesenchymal markers vimentin and N‐cadherin were increased. Treatment of curcumin effectively abrogated TS‐triggered gastric activation of ERK1/2 and JNK MAPK pathways, AP‐1 proteins, and EMT alterations. These results suggest for the first time the protective effects of curcumin in long‐term TS exposure‐induced gastric MAPK activation and EMT, thus providing new insights into the pathogenesis and chemoprevention of TS‐associated gastric cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-14T23:07:44.565783-05:
      DOI: 10.1002/ptr.5398
  • Schisandrin C Ameliorates Learning and Memory Deficits by
           Aβ1–42‐induced Oxidative Stress and Neurotoxicity in Mice
    • Authors: Xin Mao; Zhengzheng Liao, Lin Guo, Xuan Xu, Bo Wu, Mengjie Xu, Xu Zhao, Kaishun Bi, Ying Jia
      Abstract: Schisandrin C (SCH‐C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH‐C on memory impairment and further research on pathological changes in Aβ1–42‐induced Alzheimer's disease mice. Mice were administration with SCH‐C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y‐maze test, active avoidance test and Morris water maze test in all groups, and the level of Aβ1–42 and neuronal injury induced by Aβ1–42 were reversed remarkably following SCH‐C treatment compared with sham group; meanwhile the impairment of short‐term or working memory was dramatically improved. In addition, SCH‐C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH‐C offers protection against Aβ1–42‐induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-14T22:49:48.362028-05:
      DOI: 10.1002/ptr.5390
  • Equol, a Metabolite of Daidzein, Is More Efficient than Daidzein for Bone
           Formation in Growing Female Rats
    • Authors: Yuko Tousen; Hajimu Ishiwata, Yoshiko Ishimi, Sachie Ikegami
      Abstract: Few studies have examined the effects of isoflavones and particularly equol, a metabolite of the isoflavone daidzein, on bone formation during the growth period in animals. The present study investigated the effects of orally administered daidzein or equol on bone formation and bone mineral density in growing female rats. Female Sprague‐Dawley rats, aged 3 weeks, were divided into four groups (n = 8 per group) as follows: rats were orally administered a corn oil, 8 mg/day of daidzein, 4 mg/day of equol or 8 mg/day of equol in corn oil for 4 weeks. Daidzein and equol increased the bone mineral density of growing female rats by stimulating bone formation without exhibiting a substantial effect on the weight of their reproductive organs. Bone growth caused by increased bone mineralizing surface and bone formation rate in rats administered with equol was approximately twice that of rats administered with daidzein. These results suggest that equol might be more efficient than daidzein for bone formation in growing female rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-11T01:17:43.78504-05:0
      DOI: 10.1002/ptr.5387
  • New Activities for Isolated Compounds from Convolvulus
           austro‐aegyptiacus as Anti‐ulcerogenic,
           Anti‐Helicobacter pylori and Their Mimic Synthesis Using
           Bio‐guided Fractionation
    • Abstract: Bio‐guided fractionation of the total alcoholic extract of Convolvulus austro‐aegyptiacus was screened for its anti‐ulcerogenic activity, using an absolute‐ethanol‐induced ulcer model at 500 and 1000 mg/kg doses. Two compounds were isolated from the butanol extract of C. austro‐aegyptiacus and identified by 1H and 13C nuclear magnetic resonance as scopoletin and scopolin. The isolated compounds (50 mg/kg) showed a remarkable anti‐ulcerogenic activity because they exhibited control‐ulcer protection by 16.7% and 90.8%, respectively. The acute toxicity study showed that the extract is highly safe; the median lethal dose (LD50) was more than 4000 mg/kg. Moreover, the obtained results were confirmed by the sub‐chronic toxicity because the rats that have been administered 1000 mg/kg of the extract for 15 consecutive days showed no alteration in the liver and kidney functions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-10T23:09:08.660853-05:
      DOI: 10.1002/ptr.5379
  • 6‐Acetoxy Cyperene, a Patchoulane‐type Sesquiterpene Isolated
           from Cyperus rotundus Rhizomes Induces Caspase‐dependent Apoptosis
           in Human Ovarian Cancer Cells
    • Abstract: Cyperus rotundus (Cyperaceae) has been widely used in traditional medicine for the treatment of various diseases, including cancer. Although an anti‐tumour effect has been suggested for C. rotundus, the anti‐tumour effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The n‐hexane fraction of an ethanol extract of C. rotundus rhizomes was found to inhibit cell growth in ovarian cancer (A2780, SKOV3 and OVCAR3) and endometrial cancer (Hec1A and Ishikawa) cells. Among the thirteen sesquiterpenes isolated from the n‐hexane fraction, some patchoulane‐type compounds, but not eudesmane‐type compounds, showed moderate cytotoxic activity in human ovarian cancer cells. In particular, the patchoulane sesquiterpene 6‐acetoxy cyperene had the most potent cytotoxicity. In this regard, propidium iodide/Annexin V staining and terminal deoxynucleotidyl transferase dUTP (deoxynucleotide triphosphate) nick end labeling assay were performed to study cell cycle progression and apoptosis. 6‐acetoxy cyperene induced apoptosis, as shown by the accumulation of sub‐G1 and apoptotic cells. Furthermore, treatment with 6‐acetoxy cyperene stimulated the activation of caspase‐3, caspase‐8 and caspase‐9 and poly(ADP‐ribose)polymerase in a dose‐dependent manner. Pretreatment with caspase inhibitors neutralized the pro‐apoptotic activity of 6‐acetoxy cyperene. Taken together, these data suggest that 6‐acetoxy cyperene, a patchoulane‐type sesquiterpene isolated from C. rotundus rhizomes, is an anti‐tumour compound that causes caspase‐dependent apoptosis in ovarian cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-10T01:53:55.222237-05:
      DOI: 10.1002/ptr.5385
  • Natural Products Useful in Respiratory Disorders: Focus on
           Side‐Effect Neutralizing Combinations
    • Abstract: This review summarizes literature related to medicinal plants reputed in traditional medical systems for treatment of asthma and coughs. The plants that are pharmacologically investigated for their effectiveness in such conditions, along with respective experimental protocol details, are also discussed. Some of plant origin compounds, which are considered useful as antitussive and antiasthmatic agents, are described as well. Chrysoeriol, a constituent of Aspalathus linearis (Fabaceae) was observed to be selective for relaxant effect in airways (through K+ channel activation), compared with other smooth muscles. We reported that Hypericum perforatum (Hyperieaceae), Andropogon muricatus (Poaceae), Juniper excelsa (Coniferae) and Nepeta cataria (Lamiaceae) exhibit bronchodilatory action, mediated through combination of Ca++ antagonist and phospohodiesrase inhibitory mechanisms, which scientifically explains their medicinal use in asthma. Hyocyamus niger (Solanaceae), Artemisia vulgaris (Compositae), Fumaria parviflora (Fumariaceae) and Terminalia bellerica (Combretaceae) caused bronchodilation via dual blockade of muscarinic receptors and Ca++ influx. Acorus calamus (Araceae), Carum roxburghianum (Apiaceae), Lens culinaris (Fabaceae) and Lepidium sativum (Cruciferae) mediate bronchodilatation through multiple pathways: anticholinergic and inhibition of Ca++ channels and PDE enzyme(s). In conclusion, this review presents an analysis of different novel combinations of pharmacological activities in medicinal plants with side effect‐neutralizing/synergistic potential, setting new trends in the therapeutic options for hyperactive respiratory disorders such as asthma and cough. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-10T01:53:24.012638-05:
      DOI: 10.1002/ptr.5380
  • Tyrosinase and Cholinesterase Inhibitory Potential and Flavonoid
           Characterization of Viola odorata L. (Sweet Violet)
    • Authors: Ilkay Erdogan Orhan; Fatma Sezer Senol, Sinem Aslan Erdem, I. Irem Tatli, Murat Kartal, Sevket Alp
      Abstract: Inhibitory potential of the dichloromethane, ethyl acetate, ethanol, and aqueous extracts of Viola odorata L. (VO) was investigated against tyrosinase (TYR) and cholinesterases by microplate assays. The antioxidant activity was tested using six in vitro assays. Only the ethanol extract inhibited TYR (80.23 ± 0.87% at 100 µg mL−1), whereas none of them were able to inhibit cholinesterases. The extracts were more able to scavenge NO radical (31.98 ± 0.53–56.68 ± 1.10%) than other radicals tested, and displayed low to moderate activity in the rest of the assays. HPLC analysis revealed that the aqueous extract of VO contained a substantial amount of vitexin (18.81 ± 0.047 mg g−1 extract), while the ethanol extract also possessed rutin (1.31 ± 0.013 mg g−1 extract) and vitexin (4.65 ± 0.103 mg g−1 extract). Furthermore, three flavonoids (rutin, isovitexin, and kaempferol‐6‐glucoside) were isolated from the ethanol extract. This is the first report on TYR inhibitory activity of VO as well as presence of vitexin and isovitexin in this species. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-09T04:02:59.19184-05:0
      DOI: 10.1002/ptr.5378
  • Alpinia katsumadai Extracts Inhibit Adhesion and Invasion of Campylobacter
           jejuni in Animal and Human Foetal Small Intestine Cell Lines
    • Abstract: Alpinia katsumadai is used in traditional Chinese medicine for abdominal distention, pain, and diarrhoea. Campylobacter jejuni is the most common cause of bacterial food‐borne diarrhoeal illnesses worldwide. Adhesion to gut epithelium is a prerequisite in its pathogenesis. The antimicrobial, cytotoxic, and anti‐adhesive activities of a chemically characterised extract (SEE) and its residual material of hydrodistillation (hdSEE‐R) from A. katsumadai seeds were evaluated against C. jejuni. Minimal inhibitory concentrations for SEE and hdSEE‐R were 0.5 mg/mL and 0.25 mg/mL, respectively, and there was no cytotoxic influence in the anti‐adhesion tests, as these were performed at much lower concentrations of these tested plant extracts. Adhesion of C. jejuni to pig (PSI) and human foetal (H4) small‐intestine cell lines was significantly decreased at lower concentrations (0.2 to 50 µg/mL). In the same concentration range, the invasiveness of C. jejuni in PSI cells was reduced by 45% to 65% when they were treated with SEE or hdSEE‐R. The hdSEE‐R represents a bioactive waste with a high phenolic content and an anti‐adhesive activity against C. jejuni and thus has the potential for use in pharmaceutical and food products. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-09T03:07:56.259338-05:
      DOI: 10.1002/ptr.5396
  • Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in
           High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetic Rats
    • Authors: Jarinyaporn Naowaboot; Nuntiya Somparn, Suphaket Saentaweesuk, Patchareewan Pannangpetch
      Abstract: Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-08T05:53:44.538507-05:
      DOI: 10.1002/ptr.5392
  • Inhibition of Osteoclast Differentiation by Ginsenoside Rg3 in RAW264.7
           Cells via RANKL, JNK and p38 MAPK Pathways Through a Modulation of
           Cathepsin K: An In Silico and In Vitro Study
    • Abstract: Various studies have demonstrated that overexpression of cathepsin K (Cat‐K) causes excessive bone loss, which ultimately leads to a variety of bone diseases including osteoporosis. Therefore, inhibition of Cat‐K signifies a potential therapeutic target in osteoporosis treatment. Ginsenoside Rg3 is one of the most promising compound of Panax ginseng Meyer (P. ginseng) with numerous biological activities. Thus, in recent study the inhibitory effect of Rg3 isolated from P. ginseng was investigated in order to impede the osteoclast activity by an in silico approach followed by in vitro study validation using RAW264.7 cells through the investigation of different biological activity prediction such as absorption distribution metabolism and excretion (ADMET) properties against Cat‐K protein. The docking results of our study showed that Rg3 is a non‐toxic compound and may act as a drug‐like molecule. Additionally, the molecular interaction of Rg3 with the active residues of Cat‐K markedly describes its inhibitory effects on osteoclastogenesis. Findings of the present study exhibited that Rg3 significantly reduced receptor activator of nuclear factor kappa B ligand (RANKL)‐induced tartrate‐resistant acid phosphatase (TRAP) activity, pit formation (actin rings), and TRAP‐positive multinucleated cells development in RAW264.7 cells. Furthermore, Rg3 dose‐dependently reduced the mRNA expression levels of osteoclast‐specific markers such as RANK, TRAP, and Cat‐K induced by RANKL through the down regulation of p38, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase (JNK) pathways. In conclusion, in silico docking study and in vitro validation together suggested that Rg3 inhibits osteoclastogenesis and reduces bone resorption through the inhibition of Cat‐K. Therefore, Rg3 might be a useful therapeutic agent for the treatment of osteoporosis and proper bone formation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-08T05:40:30.283349-05:
      DOI: 10.1002/ptr.5374
  • Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia
           HL‐60 Cells
    • Abstract: Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro‐apoptotic events in cancerous cells. However, the literature related to the anti‐cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase‐3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time‐dependent and dose‐dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase‐3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti‐cancer properties. Moreover, it opens new possibilities of application of cork by‐products, being more efficient in the sector of cork‐based agriculture. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-05T03:49:02.754766-05:
      DOI: 10.1002/ptr.5364
  • Studies on Bronchodilator Activity of Salvia officinalis (Sage): Possible
           Involvement of K+ Channel Activation and Phosphodiesterase Inhibition
    • Abstract: The aqueous methanolic extract of the aerial parts of Salvia officinalis (So.Cr) was studied to provide possible underlying mechanism(s) for its medicinal use in asthma using the in vivo bronchodilatory assay and isolated tracheal preparations. S. officinalis (1–10 mg/kg) dose‐dependently inhibited carbachol (CCh)‐induced bronchospasm in anesthetized rats with three‐fold greater potency than the positive control, aminophylline. In tracheal preparations, So.Cr inhibited the low K+ (25 mM)‐induced contractions. Pretreatment of the tissues with 4‐aminopyridine reversed the inhibitory effect of the plant extract against low K+, whereas glibenclamide did not show any effect, thus showing the involvement of voltage‐sensitive K+ channels. When tested against the CCh‐induced pre‐contractions for the involvement of any additional mechanism, interestingly, the extract showed a dose‐dependent (0.03–0.1 mg/mL) inhibitory effect and shifted the inhibitory concentration response curves of isoprenaline to the left, thus showing phosphodiesterase enzyme inhibitory‐like action, similar to that of papaverine. These results indicate that the crude extract of S. officinalis possesses bronchodilatory activity mediated predominantly via activation of voltage‐dependent K+ channels and inhibition of phosphodiesterase enzyme; thus, this study provides sound pharmacological basis for its medicinal use in hyperactive airways disorders such as asthma and cough. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-06-01T00:52:07.358341-05:
      DOI: 10.1002/ptr.5384
  • The Antioxidant Effect of Fermented Papaya Preparation in the Oral Cavity
    • Authors: E. Fibach; I. Ginsburg
      Abstract: Oxidative stress has been recognized to play important roles in various diseases, including of the oral cavity. However, nutritional supplementation of antioxidants to ameliorate the consequences of oxidative stress is debatable. One caveat is that oxidative status is often measured under non‐physiological conditions. Here, we investigated the antioxidant potential of fermented papaya preparation (FPP), a product of yeast fermentation of Carica papaya Linn, under conditions that prevail in the oral cavity. Employing highly sensitive luminol‐dependent chemiluminescence assays, we show that its antioxidant capacity was augmented by saliva (up to 20‐fold, p 
      PubDate: 2015-05-31T22:04:58.066505-05:
      DOI: 10.1002/ptr.5381
  • Effects of Artemetin on Nitric Oxide Release and Protection against
           Peroxidative Injuries in Porcine Coronary Artery Endothelial Cells
    • Authors: Elena Grossini; Patrizia Marotta, Serena Farruggio, Lorenzo Sigaudo, Fatima Qoqaiche, Giulia Raina, Veronica Giuli, David Mary, Giovanni Vacca, Federica Pollastro
      Abstract: Artemetin is one of the main components of Achillea millefolium L. and Artemisia absinthium, which have long been used for the treatment of various diseases. To date, however, available information about protective effects of their extracts on the cardiovascular system is scarce. Therefore, we planned to analyze the effects of artemetin on nitric oxide (NO) release and the protection exerted against oxidation in porcine aortic endothelial (PAE) cells. In PAE, we examined the modulation of NO release caused by artemetin and the involvement of muscarinic receptors, β2‐adrenoreceptors, estrogenic receptors (ER), protein‐kinase A, phospholipase‐C, endothelial‐NO‐synthase (eNOS), Akt, extracellular‐signal‐regulated kinases 1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK). Moreover, in cells treated with hydrogen peroxide, the effects of artemetin were examined on cell survival, glutathione (GSH) levels, apoptosis, mitochondrial membrane potential and transition pore opening. Artemetin increased eNOS‐dependent NO production by the involvement of muscarinic receptors, β2‐adrenoreceptors, ER and all the aforementioned kinases. Furthermore, artemetin improved cell viability in PAE that were subjected to peroxidation by counteracting GSH depletion and apoptosis and through the modulation of mitochondrial function. In conclusion, artemetin protected endothelial function by acting as antioxidant and antiapoptotic agent and through the activation of ERK1/2 and Akt. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-29T12:09:48.720655-05:
      DOI: 10.1002/ptr.5386
  • Involvement of Renin–Angiotensin System Inhibition, the Potential
           Risk of Danshen in the Treatment of Pregnancy‐Induced Hypertension
    • Authors: Baofang Liang; Jianwei Su
      PubDate: 2015-05-25T03:05:56.54065-05:0
      DOI: 10.1002/ptr.5383
  • Incidence and Causes of Aconitum Alkaloid Poisoning in Hong Kong from 1989
           to 2010
    • First page: 1107
      Abstract: Aconite roots contain Aconitum alkaloids, which are highly toxic cardiotoxins and neurotoxins. In this review, the main objective was to determine the incidence and causes of Aconitum alkaloid poisoning in Hong Kong between 1989 and 2010, based on six published reports from the territory‐wide poison control units. In the New Territories East of Hong Kong, the incidence of aconite poisoning showed a sudden and sustained decrease from 0.60 (1989–1991) to 0.16 (1992–1993) and 0.17 (1996–1998) per 100 000 population, after publicity measures in late 1991 to promote awareness of the toxicity of aconite roots. In the whole of Hong Kong, the incidence of aconite poisoning was even lower in January 2000–June 2004 (0.03 per 100 000 population). However, aconite poisoning became more common again in April 2004–July 2009 and 2008–2010 (0.15 and 0.28 per 100 000 population). Overdoses and use of inadequately processed aconite roots were important causes. As from 2004 to 2009, ‘hidden’ aconite poisoning (toxicity caused by contaminants in other dispensed herbs) emerged as an important cause. It is important to continue the safety monitoring of potent herbs and the networking of poison control units. Further systematic studies would be required to identify the likely sources of contamination of herbs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-14T03:52:59.231857-05:
      DOI: 10.1002/ptr.5370
  • Efficacy and Safety of White Willow Bark (Salix alba) Extracts
    • Authors: Mohd Shara; Sidney J. Stohs
      First page: 1112
      Abstract: Willow bark extract has been used for thousands of years as an anti‐inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti‐inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti‐inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor‐α and nuclear factor‐kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non‐steroidal anti‐inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate‐sensitive individuals. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-22T04:31:20.539222-05:
      DOI: 10.1002/ptr.5377
  • Comparative Study of the Biological Activity of Allantoin and Aqueous
           Extract of the Comfrey Root
    • First page: 1117
      Abstract: This study investigates the biological activity of pure allantoin (PA) and aqueous extract of the comfrey (Symphytum officinale L.) root (AECR) standardized to the allantoin content. Cell viability and proliferation of epithelial (MDCK) and fibroblastic (L929) cell line were studied by using MTT test. Anti‐irritant potential was determined by measuring electrical capacitance, erythema index (EI) and transepidermal water loss of artificially irritated skin of young healthy volunteers, 3 and 7 days after application of creams and gels with PA or AECR. Pure allantoin showed mild inhibitory effect on proliferation of both cell lines at concentrations 40 and 100 µg/ml, but more pronounced on MDCK cells. Aqueous extract of the comfrey root effect on cell proliferation in concentrations higher than 40 µg/ml was significantly stimulatory for L929 but inhibitory for MDCK cells. Pharmaceutical preparations that contained AECR showed better anti‐irritant potential compared with PA. Creams showed better effect on hydration and EI compared with the gels that contained the same components. Our results indicate that the biological activity of the comfrey root extract cannot be attributed only to allantoin but is also likely the result of the interaction of different compounds present in AECR. Topical preparations that contain comfrey extract may have a great application in the treatment of skin irritation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-16T03:53:15.399453-05:
      DOI: 10.1002/ptr.5356
  • Influence of a Specialized Trigonella foenum‐graecum Seed Extract
           (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy
           Menstruating Women, a Randomised Placebo Controlled Study
    • Authors: Amanda Rao; Elizabeth Steels, Gavin Beccaria, Warrick J. Inder, Luis Vitetta
      First page: 1123
      Abstract: The aim of the study was to evaluate the effect of Trigonella foenum‐graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo‐controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum‐graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self‐administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI‐20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum‐graecum may be a useful treatment for increasing sexual arousal and desire in women. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-24T01:55:12.889074-05:
      DOI: 10.1002/ptr.5355
  • Memory Enhancement of Acteoside (Verbascoside) in a Senescent Mice Model
           Induced by a Combination of d‐gal and AlCl3
    • First page: 1131
      Abstract: Acteoside, also known as verbascoside or orobanchin, is a common compound found in many important medicinal plants including the Chinese herb Cistanche deserticola Y. C. Ma, which is used for its neuroprotective and memory enhancement properties. We have investigated the effects of acteoside using a senescent mouse model induced by a combination of chronic intraperitoneal administration of d‐gal (60 mg/kg/day) and oral administration AlCl3 (5 mg/kg/day) once daily for 90 days. After 60 days, acteoside (30, 60, and 120 mg/kg/day) was orally administered once daily for 30 days. The memory enhancing effects of acteoside were evaluated using the Morris water maze test. The results showed that 30–120 mg/kg/day of acteoside reduced the escape latency in finding the platform, and increased the number of crossings of the platform. A 30–120 mg/kg/day of acteoside increased significantly the expression of nerve growth factor and tropomycin receptor kinase A mRNA and protein in the hippocampus, measured using real‐time RT‐PCR, immunohistochemical analysis, and western blotting. These results support the use of C. deserticola for memory enhancement and indicate that the effects of acteoside are induced via promotion of nerve growth factor and tropomycin receptor kinase A expression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T04:30:32.826548-05:
      DOI: 10.1002/ptr.5357
  • The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the
           Senescent Mouse Model Induced by a Combination of d‐gal and AlCl3
    • First page: 1137
      Abstract: Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d‐galactose and AlCl3, and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step‐down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase‐3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase‐3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-21T04:30:42.537855-05:
      DOI: 10.1002/ptr.5358
  • In Vitro Assessment of the Anticancer Potential of Evodiamine in Human
           Oral Cancer Cell Lines
    • First page: 1145
      Abstract: Evodiamine, a bioactive alkaloid, has been regarded as having antioxidant, antiinflammatory, and anticancer properties. In the present study, we explored the effects of evodiamine on cell growth and apoptosis in human oral cancer cell lines. Our data revealed that evodiamine significantly inhibited the proliferation of human oral cancer cells and resulted in the cleavages of PARP (poly (ADP‐ribose) polymerase) and caspase‐3, in addition to causing the typical characteristics of apoptosis. Evodiamine also increased Bax protein levels and caused translocation of Bax into mitochondria and Bax oligomerization. In addition, evodiamine decreased expression of myeloid cell leukemia (Mcl‐1) at the transcriptional modification, and knockdown of Mcl‐1 clearly resulted in an increase in expression of Bax and active Bax, resulting in induction of apoptosis. Evodiamine reduced expression of phosphorylated AKT, and LY294002 potentiated evodiamine‐induced apoptosis by regulating Mcl‐1 protein. Our results suggest that evodiamine induces apoptosis in human oral cancer cells through the AKT pathway. These findings provide a rationale for its clinical application in the treatment of oral cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-04-22T21:33:05.760396-05:
      DOI: 10.1002/ptr.5359
  • Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with
           Cancer Drugs in Rhabdomyosarcoma Cell Lines
    • First page: 1152
      Abstract: Synergistic effect of supercritical CO2 extracts of Curcuma species with conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger) (CA) extract showed the highest levels of cytotoxicity with inhibitory concentration IC50 values of 7.133 µg/ml and 7.501 µg/ml for SJRH30 and RD cell lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma xanthorrhiza (Javanese turmeric) extracts. CA showed synergistic cytotoxic effects with vinblastine (VBL) and cyclophosphamide (CP) as indicated by the combination index values of
      PubDate: 2015-05-04T00:59:49.030551-05:
      DOI: 10.1002/ptr.5360
  • Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe
           Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of
           Neutrophil Activation
    • Authors: Tao Wen; Wenjun Xu, Lianchun Liang, Junhong Li, Xiaorong Ding, Xiao Chen, Jianhua Hu, Aiping Lv, Xiuhui Li
      First page: 1161
      Abstract: Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post‐medication, the MPO, S100A8/A9, histone, and interleukin‐6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide‐stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-09T02:51:59.35239-05:0
      DOI: 10.1002/ptr.5361
  • Preclinical Pharmacokinetics and Pharmacodynamics and Content Analysis of
           Gnetol in Foodstuffs
    • Authors: Connie M. Remsberg; Stephanie E. Martinez, Bolanle C. Akinwumi, Hope D. Anderson, Jody K. Takemoto, Casey L. Sayre, Neal M. Davies
      First page: 1168
      Abstract: Studies were undertaken to evaluate the bioavailability in rats and content analysis of gnetol in Gnetum gnemon products reported to contain gnetol and to examine the pharmacological properties of gnetol in in vitro models including anti‐inflammatory/analgesic, antidiabetic, anti‐adipogenesis, and anticancer activity. Male Sprague–Dawley rats were cannulated and dosed either intravenously with gnetol (10 mg/kg) or orally (100 mg/kg). Various methanolic extractions of G. gnemon products were quantified. Gnetol's effect on cell viability in selected cell lines with or without inflammatory stimulus was assessed. α‐Amylase and α‐glucosidase inhibition was evaluated. Cyclooxygenase (COX)‐1, COX‐2, and histone deacetylase inhibition and adipogenesis inhibition were examined. After oral and intravenous administration, gnetol was detected in both serum and urine as the parent compound and as a glucuronidated metabolite. The bioavailability of gnetol was determined to be 6%. Gnetol is rapidly glucuronidated and is excreted in urine and via nonrenal routes. Gnetol was found to exist as an aglycone and as a glycoside in G. gnemon products. Gnetol showed concentration‐dependent reductions in cell viability in cancer cell lines with greatest activity in colorectal cancer and potent COX‐1, histone deacetylase, and weak COX‐2 activities along with limited reduction in inflammation. Gnetol also possessed concentration‐dependent alpha‐amylase, alpha‐glucosidase, and adipogenesis activities. Pretreatment of mice with gnetol was able to increase the latency period to response in analgesia models. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-04T01:41:59.548364-05:
      DOI: 10.1002/ptr.5363
  • Modulation of Cytochrome P450 Activity by 18β‐Glycyrrhetic Acid
           and its Consequence on Buspirone Pharmacokinetics in Rats
    • First page: 1188
      Abstract: The aim of this study was to elucidate the inhibition mechanism of 18β‐glycyrrhetic acid (GLY) on cytochrome P450 (CYP) activity and in vivo pharmacokinetic consequences of single GLY dose in rats. An in vitro CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous and oral buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral GLY in rats. In the in vitro CYP inhibition study, CYP3A was involved in the metabolism of GLY. Moreover, GLY inhibited CYP3A activity with an IC50 of 20.1 ± 10.7 μM via a mixed inhibition mechanism. In the in vivo rat pharmacokinetic study, single oral GLY dose enhanced the area under plasma concentration–time curve (AUC) of intravenous and oral BUS, but the extent of increase in AUC was only minimal (1.12–1.45 fold). These results indicate that GLY can inhibit the in vitro CYP3A‐mediated drug metabolism in RLM via a mixed inhibition mechanism. However, the impact of single oral GLY dose on the pharmacokinetics of BUS in rats was limited, showing that GLY could function as merely a weak inhibitor for CYP3A‐mediated drug metabolism in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-23T09:05:50.670082-05:
      DOI: 10.1002/ptr.5365
  • In vivo Antimalarial Activity of α‐Mangostin and the New
           Xanthone δ‐Mangostin
    • First page: 1195
      Abstract: Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α‐mangostin and a new compound, δ‐mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α‐Mangostin was more active against the resistant Plasmodium falciparum chloroquine‐resistant (FCR3) strain (IC50 = 0.2 ± 0.01 μM) than δ‐mangostin (IC50 = 121.2 ± 1.0 μM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-05T08:58:22.257848-05:
      DOI: 10.1002/ptr.5362
  • Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin
           (Corilagin) Rich Extracts of Phyllanthus amarus in
           Carrageenan‐induced Thermal and Mechanical Chronic Muscle
    • Authors: Atul R. Chopade; F. J. Sayyad
      First page: 1202
      Abstract: The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-14T01:10:50.434932-05:
      DOI: 10.1002/ptr.5366
  • Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are
           Mediated Through Dual Inhibition of Ca++ Influx and Phosphodiesterase
    • First page: 1211
      Abstract: This study describes the antidiarrheal and antispasmodic activities of the hydro‐alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action explored along with activity‐directed fractionation. Bp.Cr and its aqueous (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in‐vivo and in‐vitro assays. The crude extract (100–300 mg/kg) showed 20 and 60% protection of castor oil‐induced diarrhea in mice. In isolated rabbit jejunum, Bp.Cr like papaverine inhibited spontaneous and high K+ (80 mM)‐induced contractions equi‐potently. In guinea‐pig ileum, Bp.Cr showed a moderate spasmogenic effect. The activity‐directed fractionation revealed that the spasmolytic activity was concentrated in the organic fractions and spasmogenic component in the aqueous fraction. Amongst the organic fractions, BP.DCM and Bp.Pet inhibited spontaneous and high K+‐induced contractions equi‐potently, while Bp.But, like verapamil was more potent against high K+. The crude extract and its organic fractions caused rightward shift in the Ca++‐concentration response curves (CRCs), similar to verapamil, and all except Bp.But potentiated the isoprenaline‐inhibitory CRCs to the left, similar to papaverine. The results of this study indicate that the crude extract of B. polystachya possesses antidiarrheal and antispasmodic activities, mediated possibly through dual inhibition of Ca++ influx and phospodiesterase enzyme. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-14T03:19:27.2465-05:00
      DOI: 10.1002/ptr.5367
  • An Effect of Oak‐Wood Extract (Robuvit®) on Energy State of
           Healthy Adults—A Pilot Study
    • First page: 1219
      Abstract: The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) – polyphenolic extract obtained from the wood of oak Quercus robur – on the healthy elderly individuals using energy subscale scores of the Activation – Deactivation Adjective Check List. Analysis was focused on the comparison of pre‐post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre‐treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
      PubDate: 2015-05-18T01:05:15.525509-05:
      DOI: 10.1002/ptr.5368
  • Inhibition of Myeloid Cell Leukemia 1 and Activation of Caspases Are
           Critically Involved in Gallotannin‐induced Apoptosis in Prostate
           Cancer Cells
    • First page: 1225
      Abstract: Although gallotannin contained in several medicinal plants was known to have multi‐biological activities, such as antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and antitumor effects, the underlying apoptotic mechanism of gallotannin is not fully understood so far. Thus, in the present study, the apoptotic mechanism of gallotannin was elucidated in DU145, PC‐3, and M2182 prostate cancer cells in association with myeloid cell leukemia 1 (Mcl‐1) signaling. Gallotannin exerted dose‐dependent cytotoxicity in DU145, PC‐3, and M2182 prostate cancer cells. Also, gallotannin showed apoptotic morphological features and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and sub‐G1 accumulation in three prostate cancer cell lines. Consistently, gallotannin cleaved poly (ADP‐ribose) polymerase (PARP) and attenuated the expression of procaspases 9 and 3 in three prostate cancer cell lines. Furthermore, gallotannin attenuated the expression of survival genes such as Mcl‐1, B‐cell lymphoma 2, and B‐cell lymphoma 2 extra large in three prostate cancer cell lines. Interestingly, overexpression of Mcl‐1 reversed the ability of gallotannin to cleave PARP and increase sub‐G1 population in three prostate cancer cell lines. Conversely, silencing of Mcl‐1 enhanced apoptosis by gallotannin in three prostate cancer cell lines by FACSCalibur (Becton Dickinson, Franklin Lakes, NJ, USA). Taken together, our findings demonstrate that inhibition of Mcl‐1 and activation of caspases are critically involved in gallotannin‐induced apoptosis in prostate cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-27T03:15:08.394691-05:
      DOI: 10.1002/ptr.5371
  • Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing
           DNA Methylation
    • Authors: Apei Jiang; Xuemin Wang, Xiaoyun Shan, Yuan Li, Pengqi Wang, Pan Jiang, Qing Feng
      First page: 1237
      Abstract: Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor β (RARβ), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RARβ has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RARβ is a major mechanism for its silencing in tumors. Recently, curcumin has been considered as a potential DNA methyltransferase inhibitor. Herein, we demonstrated that curcumin significantly elevate RARβ expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RARβ promoter methylation in lung cancer A549 and H460 cells. Mechanistic study demonstrated that curcumin was able to downregulate the mRNA levels of DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective effect against weight loss because of tumor burden. Tumor growth was strongly repressed by curcumin treatment. As the results from in vitro, RARβ mRNA were increased and DNMT3b mRNA were decreased by curcumin treatment compared with the mice in control group. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo‐preventive agent for lung cancer through reactivation of RARβ. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-15T08:45:41.8658-05:00
      DOI: 10.1002/ptr.5373
  • Relationship Between Emotional Behavior in Mice and the Concentration of
           (+)‐α‐Santalol in the Brain
    • Authors: Tadaaki Satou; Yuko Ogawa, Kazuo Koike
      First page: 1246
      Abstract: We previously reported finding anxiolytic‐like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)‐α‐santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)‐α‐santalol by inhalation or intraperitoneal injection, we assessed anxiolytic‐like and locomotor activities using elevated‐plus maze tests. We also examined the relationship between the emotional behavior and the (+)‐α‐santalol brain concentration. Anxiolytic‐like activity was not observed immediately after administration or after water‐immersion stress for 24 h for either the (+)‐α‐santalol 2 μL/L air inhalation or the (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)‐α‐santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water‐immersion stress for 24 h. The brain (+)‐α‐santalol concentration was 2.6 µg/g tissue after (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)‐α‐santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic‐like activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-19T00:45:35.582483-05:
      DOI: 10.1002/ptr.5372
  • Transcriptomic Analysis Reveals Wound Healing of Morus alba Root Extract
           by Up‐Regulating Keratin Filament and CXCL12/CXCR4 Signaling
    • First page: 1251
      Abstract: Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA‐mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real‐time cell analysis and real‐time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose‐dependent manner on Kera‐308 cell line, and up‐regulated keratin expression including wound‐induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up‐regulated mRNA associated keratin filaments and toward a more up‐regulated mRNA level of C‐X‐C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-25T02:55:36.84349-05:0
      DOI: 10.1002/ptr.5375
  • The Influence of Aconitum carmichaelii Debx. on the Pharmacokinetic
           Characteristics of Main Components in Rheum palmatum L.
    • First page: 1259
      Abstract: Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines, and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata was the basic herb pair applied in many Chinese traditional prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb anthraquinones as the main marker constituents were investigated. In the present study, pharmacokinetic differences of rhubarb anthraquinones were detected after oral administration of extract of Rheum palmatum L. and compatibility with Aconitum carmichaelii Debx. After oral administration, no difference of peak time can be found for anthraquinones between rhubarb group and compatibility group. But Cmax and area under the curve of aloe‐emodin, emodin and chrysophanol in compatibility group were significantly higher than that in rhubarb group. Although the Cmax of rhein in compatibility group was much lower than that in rhubarb group, the area under the curve value was similar in two groups. The clearance and t1/2 of rhubarb anthraquinone were also changed after compatibility. The change of pharmacokinetics characteristics of rhubarb anthraquinone after compatibility may be caused by the drug–drug interaction medicated by chemical reaction and cytochromes P450. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-05-12T01:43:38.817337-05:
      DOI: 10.1002/ptr.5369
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