for Journals by Title or ISSN
for Articles by Keywords

Publisher: John Wiley and Sons   (Total: 1606 journals)

 A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z  

  First | 9 10 11 12 13 14 15 16 | Last

Oxonomics     Hybrid Journal   (Followers: 1)
Pacific Economic Review     Hybrid Journal   (Followers: 2, SJR: 0.785, h-index: 16)
Pacific Focus     Hybrid Journal   (Followers: 1, SJR: 0.256, h-index: 4)
Pacific Philosophical Quarterly     Hybrid Journal   (Followers: 7, SJR: 0.317, h-index: 12)
Pacing and Clinical Electrophysiology     Hybrid Journal   (Followers: 4, SJR: 0.966, h-index: 69)
Packaging Technology and Science     Hybrid Journal   (Followers: 10, SJR: 0.463, h-index: 24)
Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 3, SJR: 1.092, h-index: 54)
Pain Medicine     Hybrid Journal   (Followers: 5, SJR: 0.776, h-index: 48)
Pain Practice     Hybrid Journal   (Followers: 2, SJR: 0.652, h-index: 25)
Palaeontology     Hybrid Journal   (Followers: 13, SJR: 0.759, h-index: 36)
PAMM : Proceedings in Applied Mathematics and Mechanics     Free  
Papers In Regional Science     Hybrid Journal   (Followers: 6, SJR: 1.315, h-index: 29)
Parasite Immunology     Hybrid Journal   (Followers: 3, SJR: 0.804, h-index: 51)
Parliamentary History     Hybrid Journal   (Followers: 3, SJR: 0.122, h-index: 2)
Particle & Particle Systems Characterization     Hybrid Journal   (SJR: 0.255, h-index: 26)
Pathogens and Disease     Hybrid Journal  
Pathology Intl.     Hybrid Journal   (SJR: 0.657, h-index: 48)
Peace & Change     Hybrid Journal   (Followers: 4)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 4, SJR: 1.295, h-index: 56)
Pediatric Anesthesia     Hybrid Journal   (Followers: 4, SJR: 0.994, h-index: 47)
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 3, SJR: 0.952, h-index: 60)
Pediatric Dermatology     Hybrid Journal   (Followers: 5, SJR: 0.57, h-index: 44)
Pediatric Diabetes     Hybrid Journal   (Followers: 14, SJR: 1.203, h-index: 36)
Pediatric Obesity     Hybrid Journal   (Followers: 4, SJR: 1.156, h-index: 26)
Pediatric Pulmonology     Hybrid Journal   (Followers: 2, SJR: 0.771, h-index: 72)
Pediatric Transplantation     Hybrid Journal   (SJR: 0.557, h-index: 45)
Pediatrics Intl.     Hybrid Journal   (Followers: 3, SJR: 0.366, h-index: 38)
Performance Improvement     Hybrid Journal   (Followers: 2)
Performance Improvement Quarterly     Hybrid Journal   (Followers: 1, SJR: 0.281, h-index: 5)
Periodontology 2000     Hybrid Journal   (Followers: 4, SJR: 1.112, h-index: 66)
Permafrost and Periglacial Processes     Hybrid Journal   (Followers: 3, SJR: 1.772, h-index: 42)
Personal Relationships     Hybrid Journal   (Followers: 3, SJR: 0.659, h-index: 41)
Personality and Mental Health     Hybrid Journal   (Followers: 12, SJR: 0.313, h-index: 6)
Personnel Psychology     Hybrid Journal   (Followers: 21, SJR: 3.339, h-index: 71)
Perspectives In Psychiatric Care     Hybrid Journal   (Followers: 1, SJR: 0.431, h-index: 18)
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 3, SJR: 0.865, h-index: 60)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (Followers: 1, SJR: 0.213, h-index: 6)
Pest Management Science     Hybrid Journal   (Followers: 5, SJR: 0.99, h-index: 64)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 6, SJR: 0.659, h-index: 16)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 22, SJR: 1.397, h-index: 50)
Pharmacology Research & Perspectives     Open Access  
Pharmacotherapy The J. of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 18, SJR: 0.741, h-index: 71)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 1, SJR: 0.108, h-index: 9)
Philosophical Books     Hybrid Journal   (Followers: 7)
Philosophical Investigations     Hybrid Journal   (Followers: 3, SJR: 0.113, h-index: 6)
Philosophical Issues     Hybrid Journal   (Followers: 8, SJR: 0.174, h-index: 1)
Philosophical Perspectives     Hybrid Journal   (Followers: 6)
Philosophy & Public Affairs     Hybrid Journal   (Followers: 17, SJR: 1.818, h-index: 25)
Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 15, SJR: 0.852, h-index: 8)
Philosophy Compass     Hybrid Journal   (Followers: 6, SJR: 0, h-index: 1)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.709, h-index: 86)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 2, SJR: 0.694, h-index: 39)
Phycological Research     Hybrid Journal   (Followers: 2)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.788, h-index: 67)
physica status solidi (b)     Hybrid Journal   (Followers: 1, SJR: 0.775, h-index: 65)
physica status solidi (c)     Hybrid Journal   (Followers: 1, SJR: 0.397, h-index: 27)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (Followers: 1, SJR: 1.275, h-index: 27)
Physik in unserer Zeit     Hybrid Journal  
Physik J.     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (Followers: 1, SJR: 1.358, h-index: 87)
Physiological Entomology     Hybrid Journal   (Followers: 2, SJR: 0.635, h-index: 35)
Physiological Reports     Open Access  
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 27, SJR: 0.273, h-index: 28)
Phytochemical Analysis     Hybrid Journal   (Followers: 1, SJR: 0.703, h-index: 39)
Phytotherapy Research     Hybrid Journal   (SJR: 0.718, h-index: 65)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 3, SJR: 1.86, h-index: 63)
Plant Biotechnology J.     Hybrid Journal   (Followers: 5, SJR: 2.052, h-index: 47)
Plant Breeding     Hybrid Journal   (Followers: 13, SJR: 0.625, h-index: 43)
Plant Pathology     Hybrid Journal   (Followers: 7, SJR: 0.997, h-index: 44)
Plant Species Biology     Hybrid Journal   (Followers: 3, SJR: 0.36, h-index: 25)
Plant, Cell & Environment     Hybrid Journal   (Followers: 4, SJR: 2.158, h-index: 112)
Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.124, h-index: 34)
Poe Studies     Partially Free   (Followers: 5)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 10, SJR: 0.147, h-index: 1)
Policy & Internet     Hybrid Journal   (Followers: 8)
Policy Studies J.     Hybrid Journal   (Followers: 5, SJR: 0.755, h-index: 25)
Political Insight     Partially Free   (Followers: 1)
Political Psychology     Hybrid Journal   (Followers: 17, SJR: 1.126, h-index: 40)
Political Science Quarterly     Hybrid Journal   (Followers: 27, SJR: 0.35, h-index: 23)
Political Studies     Hybrid Journal   (Followers: 24, SJR: 0.922, h-index: 36)
Political Studies Review     Hybrid Journal   (Followers: 14, SJR: 0.837, h-index: 10)
Politics     Hybrid Journal   (Followers: 8, SJR: 0.438, h-index: 9)
Politics & Policy     Hybrid Journal   (Followers: 6, SJR: 0.294, h-index: 5)
Polymer Composites     Hybrid Journal   (Followers: 8, SJR: 0.623, h-index: 49)
Polymer Engineering & Science     Hybrid Journal   (Followers: 13, SJR: 0.62, h-index: 70)
Polymer Intl.     Hybrid Journal   (Followers: 3, SJR: 0.717, h-index: 61)
Polymers for Advanced Technologies     Hybrid Journal   (Followers: 3, SJR: 0.617, h-index: 51)
Population and Development Review     Hybrid Journal   (Followers: 3, SJR: 2.084, h-index: 50)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.42, h-index: 28)
Poverty & Public Policy     Hybrid Journal   (Followers: 13)
Practical Diabetes     Hybrid Journal   (Followers: 4)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 0.958, h-index: 64)
Prescriber     Hybrid Journal   (Followers: 7)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 4)
Preventive Cardiology     Hybrid Journal   (Followers: 3)
Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 26)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (Followers: 2, SJR: 0.268, h-index: 14)
Process Safety Progress     Hybrid Journal   (Followers: 4, SJR: 0.366, h-index: 20)
Production and Operations Management     Hybrid Journal   (Followers: 4, SJR: 2.479, h-index: 57)

  First | 9 10 11 12 13 14 15 16 | Last

Journal Cover   Phytotherapy Research
  [SJR: 0.718]   [H-I: 65]   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  [1606 journals]
  • Differential Regulation of Calcium Signalling Pathways by Components of
           Piper methysticum ('Awa)
    • Authors: L. M. N. Shimoda; A. Showman, J. D. Baker, I. Lange, D. L. Koomoa, A. J. Stokes, R. P. Borris, H. Turner
      Pages: n/a - n/a
      Abstract: Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA‐ergic effects of the well‐characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS‐targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium‐mobilizing activity of traditionally prepared and partially HPLC‐purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin‐sensitive and ‐insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non‐store‐operated pathways. Together with the pepper‐like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP‐like conductances are observed in kava‐treated cells under patch clamp. Thus TRP‐mediated cellular effects may be responsible for some of the reported pharmacology of kava. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T04:48:04.430987-05:
      DOI: 10.1002/ptr.5291
  • Phytochemical and Pharmacological Profile of Vitex negundo
    • Authors: Cheng‐Jian Zheng; Hua‐Qiang Li, Shan‐Cheng Ren, Chuan‐Liang Xu, Khalid Rahman, Lu‐Ping Qin, Ying‐Hao Sun
      Pages: n/a - n/a
      Abstract: The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti‐nociceptive, antiinflammatory, anti‐tumor, anti‐oxidant, insecticidal, antimicrobial, anti‐androgenic, anti‐osteoporotic, anti‐cataract, hepatoprotective and anti‐hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure–activity relationship and their molecular mechanisms of action. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T04:47:58.268409-05:
      DOI: 10.1002/ptr.5303
  • Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from
           Traditional Chinese Herbs
    • Authors: Yong Zhao; Bent Håvard Hellum, Aihua Liang, Odd Georg Nilsen
      Pages: n/a - n/a
      Abstract: The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed by time‐dependent and nicotinamide adenine dinucleotide phosphate‐dependent and reversible inhibition by Lineweaver–Burk plot assessments. Inhibition mechanisms were also assessed by computerized interaction prediction by using the Discovery Studio CDOCKER software (Accelrys, San Diego, CA, USA). Tetrahydropalmatine showed a mechanism‐based inhibition of both CYP1A2 and CYP2D6, and Ber of CYP2D6. Neferine and Ber both showed a nonmechanistic inhibition of CYP1A2. All compounds showed a similar and significant mechanism‐based inhibition of CYP3A4. Tetrahydropalmatine and Ber demonstrated both reversible and irreversible inhibition of CYP2D6 and CYP3A4. Tetrahydropalmatine and Ber displayed H‐bond and several Pi‐bond connections with specific amino acid residues of CYP1A2, CYP2D6 and CYP3A4, giving further knowledge to the identified reversible and irreversible herb–drug interactions. Tetrahydropalmatine and Ber should be considered for herb–drug interactions in clinical therapy until relevant clinical studies are available. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-30T03:03:13.149626-05:
      DOI: 10.1002/ptr.5285
  • Pharmacological Activity of 6‐Gingerol in Dextran Sulphate
           Sodium‐induced Ulcerative Colitis in BALB/c Mice
    • Authors: Babajide O. Ajayi; Isaac A. Adedara, Ebenezer O. Farombi
      Pages: n/a - n/a
      Abstract: Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6‐gingerol in a mouse model of dextran sulphate sodium (DSS)‐induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co‐treated with 6‐gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment‐related effects of 6‐gingerol in DSS‐treated mice. Administration of 6‐gingerol significantly reversed the DSS‐mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6‐gingerol significantly suppressed the circulating concentrations of interleukin‐1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS‐treated mice. 6‐Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS‐treated mice. 6‐Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-29T02:38:40.432521-05:
      DOI: 10.1002/ptr.5286
  • Therapeutic Potential of Resveratrol in Type I Gaucher Disease
    • Authors: Cheong Hoon Seo; June‐Bum Kim
      Pages: n/a - n/a
      Abstract: Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti‐inflammatory, anti‐oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis‐inducing factor (AIF), Bax, cleaved caspase‐3, acetyl‐coenzyme A acetyltransferase 1 (ACAT1), E3‐binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol‐treated patient cells were determined by thin‐layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase‐3 dose‐dependently decreased, while those of ACAT1, E3BP, and CS dose‐dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:54:46.076223-05:
      DOI: 10.1002/ptr.5304
  • Effects of Jitai Tablet, A Traditional Chinese Medicine, on Spontaneous
           Withdrawal Symptoms and Modulation of Dopaminergic Functions in
           Morphine‐Dependent Rats
    • Authors: Shaoang Tu; Jinlong Gao, Jia Liu, Jinming Zhang, Yiyun Huang, Shasha Xu, Mei Han, Jianhui Liang
      Pages: n/a - n/a
      Abstract: Chronic opioid abuse can cause damage to dopamine neurons. However, there are currently no effective pharmacotherapies to reverse this damage, even though progress has been made in the development of therapeutic strategies for opioid dependence. The Jitai tablet (JTT) is a traditional Chinese medicine formulation most commonly used for opioid addiction treatment in China. In a morphine spontaneous withdrawal rat model we investigated the effects of JTT, either given before (pre‐treatment) or after (post‐treatment) morphine administration, on the dopamine system. Our study has shown the following: (1) pre‐ and post‐treatment with JTT were effective at alleviating the wet dog shakes and episodes of writhing; (2) pre‐treatment with JTT inhibited the morphine‐induced decreases in dopamine transporter (DAT), dopamine D2 receptor (D2R) and tyrosine hydroxylase (TH) levels in the striatum (p 
      PubDate: 2015-01-27T04:50:18.412115-05:
      DOI: 10.1002/ptr.5300
  • Inhibition of Wnt/β‐Catenin Pathway by Dehydrocostus Lactone
           and Costunolide in Colon Cancer Cells
    • Authors: Guang‐zhi Dong; Ah‐Ram Shim, Jin Seong Hyeon, Hwa Jin Lee, Jae‐Ha Ryu
      Pages: n/a - n/a
      Abstract: Abnormal activation of β‐catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β‐catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti‐colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β‐catenin. They also suppressed the nuclear translocation of galectin‐3 that is one of the coactivators of β‐catenin in SW‐480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW‐480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti‐colorectal cancer activities through inhibiting Wnt/β‐catenin pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:31:50.643179-05:
      DOI: 10.1002/ptr.5299
  • The Promiscuous and Synergic Molecular Interaction of Polyphenols in
           Bactericidal Activity: An Opportunity to Improve the Performance of
    • Authors: Laura Tomás‐Menor; Enrique Barrajón‐Catalán, Antonio Segura‐Carretero, Nuria Martí, Domingo Saura, Javier A. Menéndez, Jorge Joven, Vicente Micol
      Pages: n/a - n/a
      Abstract: Plant polyphenols are a potential source of new antimicrobial molecules against bacteria because most newly developed antimicrobial agents do not improve the clinical management of infectious diseases. The potential synergism between the major polyphenolic compounds present in a Cistus salviifolius extract, which was characterized by HPLC‐ESI‐MS/MS, was investigated by the isobole method and the fractional inhibitory concentration index determination. Pairwise combinations of selected flavonoids and ellagitannins present in C. salviifolius extract were assayed against the in vitro growth of Staphylococcus aureus. Some combinations revealed synergic effects, resulting in a reduction of the minimum inhibitory concentration required to inhibit 50% growth (MIC50) up to 20 times lower as compared with the individual compounds. Some of the combinations exhibited MIC50 values close to drug potency level (0.5–1 µg/mL). Punicalagin and myricetin were the major contributors in the combinations. The proportion between the compounds in the synergic mixtures is crucial and may explain the superior antimicrobial activity displayed by this extract when compared with other botanical extracts. The rational optimization of these combinations could lead to the design of potent antimicrobial phytopharmaceuticals, which may improve the performance of current antibiotics, taking advantage of the multi‐targeted and synergic molecular interactions of selected polyphenols. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T04:26:12.704628-05:
      DOI: 10.1002/ptr.5296
  • Effect of Resveratrol on the Pharmacokinetics of Carbamazepine in Healthy
           Human Volunteers
    • Authors: Satish Kumar Bedada; Prasad Nearati
      Pages: n/a - n/a
      Abstract: The purpose of the present study was to assess the effect of resveratrol (RSV) pretreatment on CYP3A4 enzyme activity and pharmacokinetics of carbamazepine (CBZ) in healthy human volunteers. The open‐label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC‐MS/MS. In comparison with the control, RSV pretreatment significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC), and half life (t1/2) and significantly decreased apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F), while there was no significant change observed in time to reach maximum concentration (tmax) and elimination rate constant (kel) of CBZ. Furthermore, RSV pretreatment significantly decreased metabolite to parent (CBZE/CBZ) ratios of Cmax and AUC and significantly increased CBZE/CBZ ratios of CL/F and Vd/F, indicating the reduced formation of CBZE to CBZ. The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to RSV‐mediated inhibition of CYP3A4 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CBZ including other CYP3A4 substrates. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-27T01:28:30.851783-05:
      DOI: 10.1002/ptr.5302
  • A Critical Evaluation of the Clinical Evidence for Pomegranate
           Preparations in the Prevention and Treatment of Cardiovascular Diseases
    • Authors: Christian Vlachojannis; Paul Erne, Andreas W. Schoenenberger, Sigrun Chrubasik‐Hausmann
      Pages: n/a - n/a
      Abstract: This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co‐active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose‐finding and long‐term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-22T03:36:42.678012-05:
      DOI: 10.1002/ptr.5280
  • Astragaloside IV Attenuates Injury Caused by Myocardial
           Ischemia/Reperfusion in Rats via Regulation of Toll‐Like Receptor
           4/Nuclear Factor‐κB Signaling Pathway
    • Authors: Meili Lu; Futian Tang, Jing Zhang, Aina Luan, Meng Mei, Chonghua Xu, Suping Zhang, Hongxin Wang, Leonid N. Maslov
      Abstract: Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll‐like receptor 4 (TLR4) and nuclear factor‐κB (NF‐κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF‐κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B‐cell lymphoma‐2 associated X protein and caspase‐3 expressions and increased B‐cell lymphoma‐2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF‐κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-21T04:54:40.07202-05:0
      DOI: 10.1002/ptr.5297
  • Characterisation of Antimicrobial Extracts from Dandelion Root (Taraxacum
           officinale) Using LC‐SPE‐NMR
    • Authors: O. Kenny; N. P. Brunton, D. Walsh, C. M. Hewage, P. McLoughlin, T. J. Smyth
      Abstract: Plant extracts have traditionally been used as sources of natural antimicrobial compounds, although in many cases, the compounds responsible for their antimicrobial efficacy have not been identified. In this study, crude and dialysed extracts from dandelion root (Taraxacum officinale) were evaluated for their antimicrobial properties against Gram positive and Gram negative bacterial strains. The methanol hydrophobic crude extract (DRE3) demonstrated the strongest inhibition of microbial growth against Staphylococcus aureus, methicillin‐resistant S. aureus and Bacillus cereus strains. Normal phase (NP) fractionation of DRE3 resulted in two fractions (NPF4 and NPF5) with enhanced antimicrobial activity. Further NP fractionation of NPF4 resulted in two fractions (NPF403 and NPF406) with increased antimicrobial activity. Further isolation and characterisation of compounds in NPF406 using liquid chromatography solid phase extraction nuclear magnetic resonance LC‐SPE‐NMR resulted in the identification of 9‐hydroxyoctadecatrienoic acid and 9‐hydroxyoctadecadienoic acid, while the phenolic compounds vanillin, coniferaldehyde and p‐methoxyphenylglyoxylic acid were also identified respectively. The molecular mass of these compounds was confirmed by LC mass spectroscopy (MS)/MS. In summary, the antimicrobial efficacy of dandelion root extracts demonstrated in this study support the use of dandelion root as a source of natural antimicrobial compounds. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-21T04:35:36.001171-05:
      DOI: 10.1002/ptr.5276
  • The Anti‐Osteoporosis and Antioxidant Activities of Chemical
           Constituents from Chrysanthemum indicum Flowers
    • Authors: Bui Thi Thuy Luyen; Bui Huu Tai, Nguyen Phuong Thao, Young Mi Lee, Sang Hyun Lee, Hae Dong Jang, Young Ho Kim
      Abstract: Two new compounds, chrysinoneside A (1) and (−)‐trans‐chrysanthenol‐6‐O‐β‐D‐glucopyranoside (2), along with 17 known compounds (3–19) were isolated from Chrysanthemum indicum flowers. The total phenolic and flavonoid contents of various fractions were determined. The EtOAC fraction had the highest total phenolic content (525.84 ± 23.51 mg GAE/g DR) and the total flavonoid content (63.49 ± 3.32 mg QE/g DR). The EtOAc and water fractions showed the greatest peroxyl radical‐scavenging capacity and the ability to reduce Cu(I) ions, with ORAC and CUPRAC values ranging from 24.00 ± 0.44 to 28.06 ± 1.35 and 16.90 ± 0.51 to 49.77 ± 0.97 μM, respectively. Compounds 5–11, 18, and 19 displayed strong effects in both peroxyl radical‐scavenging and reducing capacity assays at a concentration of 10 μM. The anti‐osteoporosis activity of these compounds was also evaluated. Compounds 10, 13, and 19 exhibited the most potent tartrate‐resistant acid phosphatase activity in receptor activator of nuclear factor‐κB ligand‐induced osteoclastic RAW 264.7 cells with values of 105.95 ± 1.18, 110.32 ± 3.95, and 112.58 ± 6.42%, respectively. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-19T05:04:26.090938-05:
      DOI: 10.1002/ptr.5281
  • Quantification of Anthocyanins in Elderberry and Chokeberry Dietary
    • Authors: Christian Vlachojannis; Benno F. Zimmermann, Sigrun Chrubasik‐Hausmann
      Abstract: Elderberry and chokeberry food supplements may be ‘functional food’ in patients with metabolic syndrome or influenza but, for this, adequate amounts of co‐active ingredients must be consumed in the daily dose. This study aimed to quantify the anthocyanin content in three elderberry and six chokeberry products to assess their usefulness as functional food. Analyses were carried out using an established HPLC procedure. The minimum anthocyanin doses for the treatment of metabolic syndrome disorders were estimated as 110 mg per day and 3.5 g per day for influenza. Three products were inappropriate for clinical use. The lowest liquid supplies were achieved with a proprietary elderberry concentrate (11 mL) and a proprietary chokeberry mother juice (100 mL). Clinical studies are now required to prove the effectiveness and adapt the doses according to the clinical symptoms. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-19T04:55:07.868239-05:
      DOI: 10.1002/ptr.5284
  • Effects of the Flavanone combination Hesperetin‐Naringenin, and
           Orange and Grapefruit Juices, on Airway inflammation and Remodeling in a
           murine asthma model
    • Authors: Ensiyeh Seyedrezazadeh; Saeed Kolahian, Amir‐Ali Shahbazfar, Khalil Ansarin, Masoud Pour Moghaddam, Masoud Sakhinia, Ebrahim Sakhinia, Mohammadreza Vafa
      Abstract: We investigated whether flavanones, hesperetin–naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non‐asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra‐alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM‐induced asthma. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-15T23:13:51.903739-05:
      DOI: 10.1002/ptr.5292
  • The Potential Drug–Drug Interactions of Ginkgolide B Mediated by
           Renal Transporters
    • Authors: Zhixia Qiu; Lei Wang, Yu Dai, Weichao Ren, Wenwen Jiang, Xijing Chen, Ning Li
      Abstract: Ginkgolide B (GB) is a selective and strong antagonist of platelet‐activating factor with great benefits in CNS diseases treatment. The renal excretion constitutes the predominant secretory pathway of GB. Here, we investigated the potential role of renal drug transporters in GB urinary excretion. The intravenous administration of GB was conducted at 10 min post‐administration of probenecid (potential inhibitor of organic anion transporters/organic anion transporting polypeptides) or bromosulfophthalein (traditional inhibitor of multi‐drug resistance proteins) in rats. Pretreated with probenecid, the systemic exposure of GB was significantly elevated from 8.319 ± 1.646 to 14.75 ± 1.328 µg · mL−1∙h but with reduced total clearance from 1.17 ± 0.331 to 0.596 ± 0.0573 L · h−1∙kg−1 accompanying no changes in plasma elimination half‐lives compared with control group. With no pronounced effect on metabolic elimination, the decreased total clearance was closely pertained to the reduced renal excretion, indicating the potential effect of organic anion transporters and/or organic anion transporting polypeptides in renal secretory of GB from blood to urine. However, the possible effect of bromosulfophthalein was restricted within a minor extent, suggesting the mild role of multi‐drug resistance protein in GB renal excretion. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-15T01:36:22.408534-05:
      DOI: 10.1002/ptr.5294
  • Influence of Polyphenols on the Physiological Processes in the Skin
    • Authors: Anna Ratz‐Łyko; Jacek Arct, Sławomir Majewski, Katarzyna Pytkowska
      Abstract: In the last decade antioxidants from a group of polyphenols have been proposed as one of the most effective functional ingredients of anti‐ageing properties that counteract the effects of oxidative damage to the skin. It has been shown that the use of polyphenols affects skin protection and mitigates inflammatory conditions of the skin. Numerous studies have confirmed that polyphenols by neutralizing free radicals, antioxidant activity and by their ability to chelate ions of transition metals can effectively reduce the level of nonprotein inflammatory mediators. The biological activity of polyphenols in the skin is primarily determined by their physicochemical properties and the ability to overcome the epidermal barrier as they try to reach appropriate receptors. This study reviews literature on the effects of polyphenols relating to the physiological processes in the skin and role of the major plant polyphenols in cosmetology and dermatology. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T06:15:51.406535-05:
      DOI: 10.1002/ptr.5289
  • Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in
           Hamsters Fed High‐Fat diet
    • Authors: Na Ning; Kai He, Yanzhi Wang, Zongyao Zou, Hao Wu, Xuegang Li, Xiaoli Ye
      Abstract: Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high‐fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up‐regulated low‐density lipoprotein receptor (LDLR) and cholesterol 7α‐hydroxylase (CYP7A1) mRNA and protein expression and down‐regulated apical sodium‐dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up‐regulating LDLR and CYP7A1 mRNA and protein expression, down‐regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T06:08:56.778367-05:
      DOI: 10.1002/ptr.5295
  • Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Induces Gene
           Expression of Anti‐viral Proteins and Inhibits Neuraminidase
    • Authors: Crystal Y.Q. Du; Ken Y.Z. Zheng, Cathy WC Bi, Tina T.X. Dong, Huangquan Lin, Karl W.K. Tsim
      Abstract: Yu Ping Feng San (YPFS), a Chinese herbal decoction comprised of Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu) and Saposhnikoviae Radix (Fangfeng), has been used clinically for colds and flus; however, the action mechanism of which is not known. Previously, we had demonstrated that YPFS could modulate inflammatory response and phagocytosis in exerting anti‐viral and anti‐bacterial effects. Here, we further evaluated the bioactivities of YPFS in gene expression regulated by interferon (IFN) signaling and neuraminidase activity of influenza virus A. Application of YPFS onto cultured murine macrophages, the expressions of mRNAs encoding ribonuclease L (RNaseL), myxovirus (influenza virus) resistance 2 (Mx2), protein kinase R (PKR) and IFN‐stimulated gene 15 (ISG15) were induced from 2 to 30 folds in dose‐dependent manners. In parallel, the transcriptional activity of IFN‐stimulated response element (ISRE), an up stream regulator of the above anti‐viral proteins, was also triggered by YPFS treatment. Conversely, YPFS was found to suppress the neuraminidase activity of influenza virus A in cultured epithelial cells, thereby preventing the viral release and spreading. Taken together, YPFS exerted anti‐bacterial and anti‐viral effects in innate immunity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T05:11:23.524911-05:
      DOI: 10.1002/ptr.5290
  • Isolation of a Novel Antibacterial Phenyl Thioketone from the Seagrass,
           Cymodocea serrulata
    • Authors: K. Mary Elizabeth Gnanambal; Jamila Patterson, Edward J. K. Patterson
      Abstract: A total of 40 extract types of varying polarities from commonly occurring seagrasses were tested for their antibacterial efficiency against 14 clinically isolated human pathogens using agar well diffusion technique. The extracts from acetone of Cymodocea serrulata expressed moderate broad span of activity against a range of gram‐positive and gram‐negative isolates that were at least resistant to five of the commercially available antibiotics at a minimal concentration of 10 µg. The active extracts of C. serrulata that showed maximal inhibitions were purified using column chromatography that afforded six compounds (a–f). Compound f elicited pronounced inhibitions against Escherichia coli with minimal inhibitory concentration values of 1–3 µg concentration using micro‐dilution method. The active compound was identified as phenyl thioketone using various spectral analyses. This is the first investigation that reveals thioketone functionality from this seagrass species possessing antibacterial actions. This study indicates that there are thiocarbonyl groups from marine floral sources too, which could be possibly used for therapeutic purposes. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T04:25:52.954277-05:
      DOI: 10.1002/ptr.5283
  • Multifunctional Activity of Polyphenolic Compounds Associated with a
           Potential for Alzheimer's Disease Therapy from Ecklonia cava
    • Authors: Byoung Wook Choi; Hye Sook Lee, Hyeon‐Cheol Shin, Bong Ho Lee
      Abstract: Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 μM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol‐A (PFF‐A), showed a particularly potent inhibitory activity (IC50 0.95 μM), which is over 100‐fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aβ. Bieckol and PFF‐A inhibited amyloid precursor protein biosynthesis. PFF‐A also showed very strong β‐secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T04:19:29.519985-05:
      DOI: 10.1002/ptr.5282
  • Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian
           Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells
    • Authors: Ya‐Fang Wang; Ting Li, Zheng‐Hai Tang, Lin‐Lin Chang, Hong Zhu, Xiu‐Ping Chen, Yi‐Tao Wang, Jin‐Jian Lu
      Abstract: Baicalein (BA), isolated from the Chinese medicinal herb Scutellariae radix (Huangqin in Chinese), is a flavonoid with various pharmacological effects. Herein, we found that BA only slightly reduced the cell viability on HepG2 cells after 24‐h treatment as determined by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay. However, BA (50 μM) effectively blocked the colony formation. Meanwhile, BA remarkably induced the formation of autophagosomes after 24‐h treatment as determined by immunofluorescence with monodansylcadaverine staining as well as transmission electron microscopy, respectively. Moreover, BA obviously up‐regulated the expression of microtubule‐associated protein 1A/1B‐light chain 3‐II in concentration‐dependent and time‐dependent manners in HepG2 cells. When combined with the autophagy inhibitor chloroquine and BA, the cell viability and colony formation were significantly decreased, indicating that BA triggered protective autophagy, which prevented cell death. Further study showed that BA concentration‐dependently and time‐dependently decreased the expression of p‐AKT (S473), p‐ULK1 (S757) and p‐4EBP1 (T37 and S65), suggesting the involvement of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) in BA‐triggered autophagy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T00:24:05.728965-05:
      DOI: 10.1002/ptr.5298
  • Effects of Total Flavones from Acanthopanax senticosus on L‐type
           Calcium Channels, Calcium Transient and Contractility in Rat Ventricular
    • Authors: Shengjiang Guan; Juanjuan Ma, Xi Chu, Yonggang Gao, Ying Zhang, Xuan Zhang, Fenghua Zhang, Zhenyi Liu, Jianping Zhang, Li Chu
      Abstract: Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L‐type Ca2+ channel currents (ICa‐L) using the whole cell patch‐clamp technique and on intracellular calcium ([Ca2+]i) handling and cell contractility in rat ventricular myocytes with the aid of a video‐based edge‐detection system. Exposure to TFAS resulted in a concentration‐ and voltage‐dependent blockade of ICa‐L, with the half‐maximal inhibitory concentration (IC50) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current–voltage relationship but also shifted the activation and inactivation curves of ICa‐L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca2+]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca2+]i through the direct inhibition of ICa‐L in rat ventricular myocytes and consequent negative effect on myocardial contractility. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T00:09:58.09954-05:0
      DOI: 10.1002/ptr.5278
  • Did Ebola Survivors Use Plant Medicines, and if so, Which Ones'
    • Authors: Solomon Habtemariam; Giovanni Lentini
      Abstract: In the absence of any known therapeutically useful drug or vaccine available to combat Ebola, the disease has emerged as one of the most globally important crisis of the year. In the affected West African regions, no one seems to know what drug to use or even try on Ebola patients, while in the West, the debate on discovering new drugs versus repurposing old ones is heating up. Because Ebola affected countries are highly reliant on traditional medicines, we herewith suggest recording plants used by Ebola survivors as they may serve as sources of novel therapeutic agents in the future. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-14T00:09:49.595739-05:
      DOI: 10.1002/ptr.5279
  • PI3K‐Mediated Proliferation of Fibroblasts by Calendula officinalis
           Tincture: Implication in Wound Healing
    • Authors: Manikarna Dinda; Uma Dasgupta, Namrata Singh, Debasish Bhattacharyya, Parimal Karmakar
      Abstract: Calendula officinalis, a member of the Asteraceae family, is a flowering plant and has been used for its antibacterial, antifungal, antiviral, antiinflammatory, anticancer and wound healing activity. The mode of action of C. officinalis tincture on wound healing is poorly understood. Here, we investigated the role of C. officinalis tincture (CDOT) on cell viability and wound closure. C. officinalis tincture stimulated both proliferation and migration of fibroblasts in a statistically significant manner in a PI3K‐dependent pathway. The increase in phosphorylation of FAK (Tyr 397) and Akt (Ser 473) was detected after treatment of CDOT. Inhibition of the PI3K pathway by wortmannin and LY294002 decreased both cell proliferation and cell migration. HPLC‐ESI MS revealed the presence of flavonol glycosides as the major compounds of CDOT. Altogether, our results showed that CDOT potentiated wound healing by stimulating proliferation and migration of fibroblast in a PI3K‐dependent pathway, and the identified compounds are likely to be responsible for wound healing activity. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-13T04:02:38.806096-05:
      DOI: 10.1002/ptr.5293
  • A p‐Menth‐1‐ene‐4,7‐diol (EC‐1) from
           Eucalyptus camaldulensis Dhnh. Triggers Apoptosis and Cell Cycle Changes
           in Ehrlich Ascites Carcinoma Cells
    • Authors: Farhadul Islam; Jahan Ara Khanam, Mahbuba Khatun, Natasha Zuberi, Laboni Khatun, Syed Rashel Kabir, Md Abu Reza, MM Ali, M A Rabbi, Vinod Gopalan, Alfred King‐Yin Lam
      Abstract: Anticancer activities of p‐menth‐1‐ene‐4,7‐diol (EC‐1) isolated from Eucalyptus camaldulensis Dhnh. were studied on Ehrlich ascites carcinoma (EAC) cells by MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) assay. Anticancer activities also analyzed in EAC‐bearing mice by assessment of cancer growth inhibition, changes in cancer volume, changes in life span, and hematological parameters. Apoptosis was analyzed by fluorescence microscope, DNA fragmentation assay, and flow cytometry. The expression of apoptosis‐related genes, Bcl‐2, Bcl‐X, PARP‐1, p53, and Bax, were analyzed using polymerase chain reaction (PCR). EC‐1 significantly inhibited proliferation of EAC cells in vivo and restored the altered hematological parameters of EAC‐bearing mice. Cytological observation by fluorescence microscope showed apoptosis of EAC cells upon treatment with EC‐1. Also, DNA fragmentation assay revealed EAC cells' apoptosis following EC‐1 treatment. Increased mRNA expressions of p53 and Bax genes and negative expressions of Bcl‐2 and Bcl‐X were observed in cells treated with EC‐1. These findings confirmed the induction of apoptosis by EC‐1. In addition, MTT assay showed dose‐dependent anticancer activity of EC‐1 against EAC cell. Cell cycle analysis revealed that EC‐1 treatment caused suppression of EAC cells at S phase. To conclude, EC‐1 is a novel anticancer compound and showed antiproliferative and apoptotic activities in cellular and mice models. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-13T03:41:56.647091-05:
      DOI: 10.1002/ptr.5288
  • The Hydrolysed Products of Iridoid Glycosides Can Enhance Imatinib
           Mesylate‐Induced Apoptosis in Human Myeloid Leukaemia Cells
    • Authors: Min‐Beom Kim; Chulwon Kim, Won‐Seok Chung, Jae‐Heung Cho, Dongwoo Nam, Sung‐Hoon Kim, Kwang Seok Ahn
      Abstract: Several studies have demonstrated that deregulated activation of signal transducer and activator of transcription 3 (STAT3) has been associated with survival, proliferation, chemoresistance and angiogenesis of tumour cells. Thus, inhibition of STAT3 expression could be a potent therapeutic approach for cancer treatment. Using several leukaemia cell lines, the effect of the hydrolysed‐catalpol (H‐catalpol) and hydrolysed‐aucubin (H‐aucubin) products on the STAT3 signalling pathway, inhibition of BCR–ABL activation, cellular proliferation and potentiation of imatinib mesylate‐induced apoptosis was investigated. We found that iridoid glycosides (catalpol and aucubin) did not exert any cytotoxicity in the tumour cells, whereas both H‐catalpol and H‐aucubin exhibited significant cytotoxic effects on K562 human myeloid leukaemia cells. Indeed, H‐catalpol and H‐aucubin down‐regulated BCR–ABL phosphorylation and inhibited constitutive STAT3 activation through abrogating upstream JAK2 and c‐Src and constitutive STAT5 activation leading to apoptosis through caspase‐3 activation. Hydrolysed‐catalpol enhanced the apoptosis induced by imatinib mesylate and this correlated with down‐regulation of gene products that mediate cell proliferation (cyclin D1), and cell survival (Bcl‐2, Bcl‐xL and survivin); all known to be regulated by the STAT3. Overall, our results provide novel insight into the role of hydrolysed iridoids in potentially treating leukaemia through the modulation of STAT3 signalling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-13T03:06:51.368405-05:
      DOI: 10.1002/ptr.5272
  • Reversion of Nitrate Tolerance in Rat Aorta Rings by Freeze‐dried
           Red Wine
    • Authors: Fabio Fusi; Giampietro Sgaragli
      Abstract: Chronically administered organic nitrates induce nitrate tolerance and endothelial dysfunction, which limit their therapeutic use. eNOS uncoupling, ROS over‐production, aldehyde dehydrogenase‐2 as well as superoxide dismutase (SOD) oxidative inhibition, and cGMP desensitization are thought to play an important role. Natural polyphenols are effective antioxidants, which might counteract the mechanisms leading to nitrate tolerance. The aim of this work was to verify whether freeze‐dried (dealcoholized) red wine (FDRW) was able to revert glyceryl trinitrate (GTN) tolerance and endothelial dysfunction induced in rat aorta rings with either GTN or diethyldithiocarbamate (DETCA), an irreversible inhibitor of Cu/Zn SOD. GTN induced a concentration‐dependent relaxation of rings pre‐contracted with phenylephrine. GTN spasmolysis was significantly reduced in rings pre‐incubated with either GTN or DETCA. FDRW, at 2.8 µg of gallic acid equivalents (GAE)/mL concentration, was able to revert partially, though significantly, GTN‐induced tolerance but not tolerance and endothelial dysfunction induced by DETCA. This work provides the first evidence in vitro that red wine components, at concentrations comparable to those achieved in human blood after moderate consumption of red wine, revert tolerance to nitrates with a mechanism possibly mediated by SOD. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-10T03:22:10.337361-05:
      DOI: 10.1002/ptr.5287
  • The Genus Trollius—Review of Pharmacological and Chemical Research
    • Authors: Ewa Witkowska‐Banaszczak
      Abstract: Three species of the genus Trollius (Ranunculaceae) are traditionally used to treat upper respiratory tract infections, pharyngitis, tonsillitis, bronchitis, cold with fever, acute tympanitis, aphthae, mouth sore, hemorrhage and pain of gums, acute lymphangitis and acute periostitis. However, only a few studies support its traditional use. These are studies of the biological activity of extracts and/or compounds of selected species of Trollius, but there are no clinical studies proving the effectiveness or possible toxic effects. Until now, the following activity of extracts and/or compounds from certain species of Trollius used in traditional medicine has been proven: antiviral, antibacterial, antiinflammatory and antioxidant. The review showed that flavonoids, mainly C‐glycosides, were characteristic of the species Trollius. Furthermore, other main groups of compounds are carotenoids, organic acids, terpenes, alkaloids, sterols, lactones and carbohydrates. The essential oil mainly contains compounds from the group of benzenoids, nitrogen‐containing compounds, monoterpenoids and sesquiterpenoids, irregular terpenes and macrocyclic epoxide. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-09T02:51:03.351215-05:
      DOI: 10.1002/ptr.5277
  • Anti‐Platelet Activity of Water Dispersible Curcuminoids in Rat
    • Authors: Anikisetty Maheswaraiah; Lingamallu Jaganmohan Rao, Kamatham Akhilender Naidu
      Abstract: Curcuminoids are active principle of turmeric with plethora of health beneficial properties. In this study, we have evaluated for the first time the effect of water dispersible curcuminoids on rat platelet aggregation. Curcuminoids (10–30 µg/mL) significantly inhibited platelet aggregation induced by agonists viz., collagen, ADP and arachidonic acid. Curcuminoids were found to be two‐fold more potent than curcumin in inhibiting platelet aggregation. Intracellular curcuminoid concentration was relatively higher than curcumin in rat platelets. Curcuminoids significantly attenuated thromboxane A2, serotonin levels in rat platelets which play an important role in platelet aggregation. Curcuminoid treatment increased nitric oxide (NO) levels in platelets treated with agonists. Curcuminoids inhibited free radicals such as superoxide anion released from activated platelets, which ultimately inhibits platelet aggregation. Further, curcuminoids inhibited 12‐lipoxygenase activity and formation of 12‐hydroperoxyeicosatetraenoic acid (12‐HPETE) in activated rat platelets which regulates platelet aggregation. The results suggest that curcuminoids have remarkable anti‐platelet activity by modulating multiple mechanisms involved in platelet aggregation. Thus curcuminoids may have a therapeutic potential to prevent platelet activation related disorders. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-09T02:04:58.81682-05:0
      DOI: 10.1002/ptr.5274
  • Orally Delivered Sour Cherry Seed Extract (SCSE) Affects Cardiovascular
           and Hematological Parameters in Humans
    • Authors: Zoltan Csiki; Agnes Papp‐Bata, Attila Czompa, Aniko Nagy, Istvan Bak, Istvan Lekli, Andras Javor, David D. Haines, Gyorgy Balla, Arpad Tosaki
      Abstract: In the present study, we investigated the effects of sour cherry seed extract (SCSE) on a variety of systemic processes that contribute to general health and viability of human subjects. The experiments were conducted according to a double‐blind protocol in which six healthy individuals were administered 250‐mg/day SCSE for 14 days, while four were treated with placebo. Peripheral blood was collected before and after the treatment period. Samples were analyzed for levels of selected cells, enzymes, or metabolites. Subjects that received SCSE showed increases in the values of mean cell volume, serum transferrin, mean peroxidase index, and representation of peripheral blood lymphocytes. On the other hand, decreases were observed in circulating neutrophils and ferritin levels. Changes observed in the present study do not fit into a clear pattern that might yield additional in‐depth understanding of SCSE‐mediated alterations in physiologic responses. The most encouraging result of the present study is the absence of any indication of toxicity by subjects consuming the extract. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-09T01:27:10.568876-05:
      DOI: 10.1002/ptr.5273
  • Phytochemicals and Their Potential Usefulness in Inflammatory Bowel
    • Authors: Sahil J. Somani; Ketan P. Modi, Anuradha S. Majumdar, Bhakti N. Sadarani
      Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unclear etiology, namely ulcerative colitis and Crohn's disease. Various drug therapies including aminosalicylates and immunomodulators have been approved for use; they have shown to produce diverse side effects. To overcome these limitations of the current therapeutics for IBD, extensive research is underway to identify drugs that are effective and free of undesirable side effects. Recently, various naturally occurring phytochemicals that cover a wide range of chemical entities such as polyphenols, terpeniods, flavonoids, and alkaloids have received attention as alternative candidates for IBD therapy. These phytochemicals act by modulating the immune response, various transcription factors, or reduce cytokine secretion. This review summarizes the findings of recent studies on phytochemicals as therapeutic agents in the management of IBD. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-09T00:41:00.451666-05:
      DOI: 10.1002/ptr.5271
  • Anti‐Proliferative Effects of Polyphenols from Pomegranate Rind
           (Punica granatum L.) on EJ Bladder Cancer Cells Via Regulation of
           p53/miR‐34a Axis
    • Authors: Benhong Zhou; Huilan Yi, Jun Tan, Yue Wu, Gang Liu, Zhenpeng Qiu
      Abstract: miRNAs and their validated miRNA targets appear as novel effectors in biological activities of plant polyphenols; however, limited information is available on miR‐34a mediated cytotoxicity of pomegranate rind polyphenols in cancer cell lines. For this purpose, cell viability assay, Realtime quantitative PCR for mRNA quantification, western blot for essential protein expression, p53 silencing by shRNA and miR‐34a knockdown were performed in the present study. EJ cell treatment with 100 µg (GAE)/mL PRE for 48 h evoked poor cell viability and caspase‐dependent pro‐apoptosis appearance. PRE also elevated p53 protein and triggered miR‐34a expression. The c‐Myc and CD44 were confirmed as direct targets of miR‐34a in EJ cell apoptosis induced by PRE. Our results provide sufficient evidence that polyphenols in PRE can be potential molecular clusters to suppress bladder cancer cell EJ proliferation via p53/miR‐34a axis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-01-08T23:09:06.116776-05:
      DOI: 10.1002/ptr.5267
  • Xanthine Oxidase Inhibitory Activity of Extracts Prepared from
           Polygonaceae Species
    • Authors: Orsolya Orbán-Gyapai; Ildikó Lajter, Judit Hohmann, Gusztáv Jakab, Andrea Vasas
      Abstract: The xanthine oxidase (XO) inhibitory activity of aqueous and organic extracts of 27 selected species belonging in five genera (Fallopia, Oxyria, Persicaria, Polygonum and Rumex) of the family Polygonaceae occurring in the Carpathian Basin were tested in vitro. From different plant parts (aerial parts, leaves, flowers, fruits and roots), a total of 196 extracts were prepared by subsequent extraction with methanol and hot H2O and solvent–solvent partition of the MeOH extract yielding n‐hexane, chloroform and 50% MeOH subextracts. It was found that the chloroform subextracts and/or the remaining 50% MeOH extracts of Fallopia species (F. bohemica, F. japonica and F. sachalinensis), Rumex species (R. acetosa, R. acetosella, R. alpinus, R. conglomeratus, R. crispus, R. hydrolapathus, R. pulcher, R. stenophyllus, R. thyrsiflorus, R. obtusifolius subsp. subalpinus, R. patientia) and Polygonum bistorta, Polygonum hydropiper, Polygonum lapathifolium and Polygonum viviparum demonstrated the highest XO inhibitory activity (>85% inhibition) at 400 µg/mL. The IC50 values of the active extracts were also determined. On the basis of the results, these plants, and especially P. hydropiper and R. acetosella, are considered worthy of activity‐guided phytochemical investigations. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-12-16T01:14:32.527813-05:
      DOI: 10.1002/ptr.5275
  • Anti‐fibrotic and Anti‐tumorigenic Effects of Rhein, a Natural
           Anthraquinone Derivative, in Mammalian Stellate and Carcinoma Cells
    • Authors: Siu Wai Tsang; Zhao-Xiang Bian
      Abstract: Anthraquinone compounds have been recognized to possess antiinflammatory, anti‐fibrotic and anti‐tumour properties and thus applied in human and veterinary therapeutics as active substances of medicinal products. Amongst the anthraquinones isolated from Rheum palmatum, also known as da‐huang, rhein was detected as one of the highest metabolite contents in the bloodstream of mammals. The biological activities of rhein therefore deserve detailed investigation. In this study, we aimed to delineate the mechanism of inhibitory actions of rhein on fibrotic and tumorigenic processes by means of various biochemical assays, such as immunofluorescent staining, real‐time polymerase chain reaction (PCR) and western blotting analyses in rat pancreatic stellate cells (LTC‐14), human pancreatic ductal adenocarcinoma cells (PANC‐1) and human colon carcinoma cells (SW480 and SW620). Our results demonstrated that the application of rhein notably suppressed the mRNA and protein levels of various fibrotic and tumorigenic mediators including alpha‐smooth muscle actin, type I collagen, fibronectin, N‐cadherin and matrix metalloproteinases in the testing mammalian cells. The mechanism of the suppressive actions of rhein was associated with the modulation of the sonic hedgehog and serine‐threonine kinase signalling pathways. In conclusion, we suggest that rhein may serve as a therapeutic or an adjuvant agent in anti‐fibrotic and anti‐tumorigenic approaches. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-12-16T00:28:45.314068-05:
      DOI: 10.1002/ptr.5266
  • Anti‐allergic Effect of Intranasal Administration of Type‐A
           Procyanidin Polyphenols Based Standardized Extract of Cinnamon Bark in
           Ovalbumin Sensitized BALB/c Mice
    • Authors: Urmila M. Aswar; Amit D. Kandhare, Vishwaraman Mohan, Prasad A. Thakurdesai
      Abstract: The objective of the present work was to evaluate anti‐allergic effects of intranasal administration of type‐A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP‐CZ) in ovalbumin (OVA)‐induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1–G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2–G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14–21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4–G6 received TAPP‐CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP‐CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA‐induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP‐CZ showed anti‐allergic efficacy in animal model of AR. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-12-12T02:13:18.65218-05:0
      DOI: 10.1002/ptr.5269
  • Therapeutic Potential of Cannabinoids in Counteracting
           Chemotherapy‐induced Adverse Effects: An Exploratory Review
    • Authors: Sattar Ostadhadi; Mahdieh Rahmatollahi, Ahmad-Reza Dehpour, Reza Rahimian
      Abstract: Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy‐associated bone loss, chemotherapy‐induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy‐induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-12-12T01:33:40.113193-05:
      DOI: 10.1002/ptr.5265
  • Ellagic Acid Suppresses Lipid Accumulation by Suppressing Early Adipogenic
           Events and Cell Cycle Arrest
    • Authors: Mi-Seon Woo; Hyeon-Son Choi, Min-Jung Seo, Hui-Jeon Jeon, Boo-Yong Lee
      Abstract: Ellagic acid (EA) is a natural polyphenol found in various fruits and vegetables. In this study, we examined the inhibitory effect of EA on fat accumulation in 3T3‐L1 cells during adipogenesis. Our data showed that EA reduced fat accumulation by down‐regulating adipogenic markers such as peroxisome proliferator activated receptor γ (PPARγ) and the CCAAT/enhancer binding protein α (C/EBPα) at the mRNA and protein levels in a dose‐dependent manner. We found that the decrease in adipogenic markers resulted from reduced expression of some early adipogenic transcription factors such as KLF4, KLF5, Krox20, and C/EBPβ within 24 h. Also, these inhibitions were correlated with down‐regulation of TG synthetic enzymes, causing inhibition of triglyceride (TG) levels in 3T3‐L1 cells investigated by ORO staining and in zebrafish investigated by TG assay. Additionally, the cell cycle analysis showed that EA inhibited cell cycle progression by arresting cells at the G0/G1 phase. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-12-02T06:36:37.585143-05:
      DOI: 10.1002/ptr.5264
  • Effects of Vitexin on the Pharmacokinetics and mRNA Expression of CYP
           Isozymes in Rats
    • Authors: Xin-shuai Wang; Xiao-chen Hu, Gui-ling Chen, Xiang Yuan, Rui-na Yang, Shuo Liang, Jing Ren, Jia-chun Sun, Guo-qiang Kong, She-gan Gao, Xiao-shan Feng
      Abstract: In traditional therapy with Chinese medicine, vitexin has several pharmacological properties, including antinociceptive, antispasmodic, antioxidant, antimyeloperoxidase, and α‐glucosidase inhibitory activities. Recently, vitexin was shown to protect the heart against ischemia/reperfusion injury in an in vitro model by inhibiting apoptosis. The purpose of this study was to find out whether vitexin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), and midazolam (5 mg/kg), was given as oral administration to rats treated with short or long period of intravenous vitexin via the caudal vein. Blood samples were collected at a series of time points, and the concentrations of probe drugs in plasma were determined by HPLC‐mass spectrometry (MS)/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real‐time reverse transcription‐polymerase chain reaction was performed to determine the effects of vitexin on the mRNA expression of CYP1A2, CYP2C11, and CYP3A1 in rat liver. Treatment with short or long period of vitexin had no effects on rat CYP1A2. However, CYP3A1 enzyme activity was inhibited by vitexin in a concentration‐dependent and time‐dependent manner. Furthermore, CYP2C11 enzyme activity was induced after short period treatment but inhibited after long period of vitexin treatment. The mRNA expression results were in accordance with the pharmacokinetic results. In conclusion, vitexin can either inhibit or induce activities of CYP2C11 and CYP3A1. Therefore, caution is needed when vitexin is co‐administered with some CYP2C11 or CYP3A1 substrates in clinic, which may result in treatment failure and herb–drug interactions. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-12-01T05:24:23.79479-05:0
      DOI: 10.1002/ptr.5260
  • Anti‐Leishmanial, Anti‐Inflammatory and Antimicrobial
           Activities of Phenolic Derivatives from Tibouchina paratropica
    • Authors: María I. Tracanna; Antonio M. Fortuna, Angel V. Contreras Cárdenas, Alexandra K. Marr, W. Robert McMaster, Anaximandro Gómez-Velasco, Eugenio Sánchez-Arreola, Luis Ricardo Hernández, Horacio Bach
      Abstract: A new phenolic derivative, 2,8‐dihydroxy‐7H‐furo[2,3‐f]chromen‐7‐one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti‐parasitic activity against Leishmania donovani (IC50 = 0.809 µg/mL). In addition, an 85% reduction in the secretion of the pro‐inflammatory cytokine IL‐6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti‐inflammatory IL‐10 was observed. Compound 2 showed neither anti‐parasitic nor anti‐inflammatory properties. In addition, no cytotoxic activities were observed against the human‐derived macrophage THP‐1 cells. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-24T02:40:58.279261-05:
      DOI: 10.1002/ptr.5263
  • Curcumin Combined with Oxaliplatin Effectively Suppress Colorectal
           Carcinoma in vivo Through Inducing Apoptosis
    • Authors: Li-da Guo; Yong-qing Shen, Xiao-han Zhao, Li-jian Guo, Zhi-jun Yu, Duo Wang, Li-meng Liu, Jing-ze Liu
      Abstract: Studies have shown chemopreventive and/or chemotherapeutic effects of several curcumin‐based combinatorial treatments on colorectal cancer cells. However, their in vivo effects remain unclear. This study has demonstrated the therapeutic effect of curcumin and oxaliplatin, alone or in combination, on subcutaneously xenografted LoVo human colorectal cancer cells in immunodeficient (nu/nu) mice in vivo. Combinatorial administration of curcumin and oxaliplatin evidently inhibited the growth of colorectal cancer in nude mice, which was significantly more effective than either agent alone. Curcumin combined with oxaliplatin treatment induced apoptosis, accompanied by ultrastructural changes and cell cycle arrest in S and G2/M phases. Further mechanism analysis indicated that while the number of apoptotic tumor cells and the expression of Bax, caspase‐3, and poly (ADP‐ribose) polymerase (PARP) increased significantly, the expression of Bcl‐2, survivin, HSP70, pro‐caspase‐3, and pro‐PARP were dramatically suppressed in tumor cells after the treatment with combinatorial curcumin and oxaliplatin for 22 days. Taken together, the present study has demonstrated that administration of combined curcumin and oxaliplatin effectively suppressed colorectal carcinoma in vivo through inducing apoptosis and thus may provide an effective treatment for colorectal carcinoma. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-24T02:01:38.556908-05:
      DOI: 10.1002/ptr.5257
  • Anti‐inflammatory Activities of Gouania leptostachya Methanol
           Extract and its Constituent Resveratrol
    • Authors: To Thi Mai Dung; Jongsung Lee, Eunji Kim, Byong Chul Yoo, Van Thai Ha, Yong Kim, Deok Hyo Yoon, Sungyoul Hong, Kwang‐Soo Baek, Nak Yoon Sung, Tae Woong Kim, Jong‐Hoon Kim, Jae Youl Cho
      Abstract: Gouania leptostachya DC. var. tonkinensis Pitard. Rhamnaceae is a traditional medicinal plant used in Thailand for treating various inflammatory symptoms. However, no systematic studies have been performed concerning the anti‐inflammatory effects or molecular mechanisms of this plant. The immunopharmacological activities of a methanol extract from the leaves and twigs of G. leptostachya (Gl‐ME) were elucidated based on the gastritis symptoms of mice treated with HCl/EtOH and the inflammatory responses, such as nitric oxide (NO) release and prostaglandin E2 (PGE2) production, from RAW264.7 cells and peritoneal macrophages. Moreover, inhibitory target molecules were also assessed. Gl‐ME dose‐dependently diminished the secretion of NO and PGE2 from LPS‐stimulated RAW264.7 cells and peritoneal macrophages. The gastritis lesions of HCl/EtOH‐treated mice were also attenuated after Gl‐ME treatment. The extract (50 and 300 µg/mL) clearly reduced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)‐2, nuclear translocation of p65/nuclear factor (NF)‐κB, phosphorylation of p65‐activating upstream enzymes, such as protein kinase B (AKT), inhibitor of κBα kinase (IKK), and inhibitor of κB (IκBα), and the enzymatic activity of Src. By HPLC analysis, one of the major components in the extract was revealed as resveratrol with NO and Src inhibitory activities. Moreover, this compound suppressed NO production and HCl/EtOH‐induced gastric symptoms. Therefore, these results suggest that Gl‐ME might be useful as an herbal anti‐inflammatory medicine through the inhibition of Src and NF‐κB activation pathways. The efficacy data of G. leptostachya also implies that this plant could be further tested to see whether it can be developed as potential anti‐inflammatory preparation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-21T05:05:34.817463-05:
      DOI: 10.1002/ptr.5262
  • A Novel Pregnane‐Type Alkaloid from Pachysandra terminalis Inhibits
           Methicillin‐Resistant Staphylococcus aureus In Vitro and In Vivo
    • Authors: Hui Zhao; Xiao‐Yang Wang, Ming‐Kai Li, Zheng Hou, Ying Zhou, Zhou Chen, Jing‐Ru Meng, Xiao‐xing Luo, Hai‐Feng Tang, Xiao‐Yan Xue
      Abstract: A new kind of pregnane‐type alkaloid, 20α‐dimethylamino‐3β‐senecioylamino‐16β‐hydroxy‐pregn‐5‐ene (K‐6), was isolated from Pachysandra terminalis Sieb. et Zucc., and its antibacterial activity against MRSA and MRSE was evaluated. We found that K‐6 showed antibacterial effects against MRSA and MRSE with minimum inhibitory concentration values (25 mg/L), but did not induce antibiotic resistance in bacteria easily. The administration of K‐6 dose‐dependently improved the animal survival rate of mice infected with MRSA, with survival rates of 36.34% and 66.67% in the low‐dose and high‐dose groups, respectively. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. Scanning and transmission electron microscopy analyses indicated that the cytoplasm shrink of bacterial cells led to noticeable gaps between the cell membrane and cell cytoplasm, and the severely damaged cell membrane resulted in leakage of intracellular content, which ultimately caused the lethal effect of K‐6 on bacteria. These findings demonstrated that K‐6 is a potential agent against MRSA and MRSE. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-21T03:33:51.319019-05:
      DOI: 10.1002/ptr.5261
  • Complementary Usage of Rhodiola crenulata (L.) in Chronic Obstructive
           Pulmonary Disease Patients: The Effects on Cytokines and T Cells
    • Authors: Shih‐Pin Chen; Rosa Huang Liu, Tsong‐Ming Lu, James Cheng‐Chung Wei, Tzu‐Chin Wu, Wei‐Yu Tsai, Chung‐Hung Tsai, Chi‐Chiang Yang
      Abstract: Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age‐matched, and sex‐matched non‐COPD control subjects. Our results showed that serum levels of IL‐2, IL‐10, and IFN‐γ in COPD patients before treatment are significantly higher than levels in non‐COPD controls (p 
      PubDate: 2014-11-18T05:27:22.558269-05:
      DOI: 10.1002/ptr.5259
  • Antioxidant and Anti‐Inflammatory Properties of the Citrus
           Flavonoids Hesperidin and Hesperetin: An Updated Review of their Molecular
           Mechanisms and Experimental Models
    • Authors: Hamideh Parhiz; Ali Roohbakhsh, Fatemeh Soltani, Ramin Rezaee, Mehrdad Iranshahi
      Abstract: Inflammation and oxidative stress are two major causes of various life‐threatening diseases. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from citrus species that have numerous biological properties, particularly antioxidant and anti‐inflammatory. New findings showed that the antioxidant activity of Hsd/Hst was not only limited to its radical scavenging activity, but it augmented the antioxidant cellular defenses via the ERK/Nrf2 signaling pathway as well. Various in vitro and in vivo studies have been conducted to evaluate Hsd, its metabolites, or its synthetic derivatives at reducing inflammatory targets including NF‐κB, iNOS, and COX‐2, and the markers of chronic inflammation. In this review, new findings regarding the molecular targets of Hsd and Hst in the reduction of oxidative stress are discussed. Also, in the anti‐inflammatory section, we provide a summary of significant investigations concerning the mechanisms of action based on the studied inflammation models. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-13T05:15:50.270508-05:
      DOI: 10.1002/ptr.5256
  • Comparing the Effects of Kamikihito in Japan and
           Kami‐Guibi‐Tang in Korea on Memory Enhancement: Working
           Towards the Development of a Global Study
    • Authors: Hidetoshi Watari; Michiko Shigyo, Norio Tanabe, Michihisa Tohda, Ki‐Ho Cho, Park Su Kyung, Woo Sang Jung, Yutaka Shimada, Naotoshi Shibahara, Tomoharu Kuboyama, Chihiro Tohda
      Abstract: Traditional medicine is widely used in East Asia, and studies that demonstrate its usefulness have recently become more common. However, formulation‐based studies are not globally understood because these studies are country‐specific. There are many types of formulations that have been introduced to Japan and Korea from China. Establishing whether a same‐origin formulation has equivalent effects in other countries is important for the development of studies that span multiple countries. The present study compared the effects of same‐origin traditional medicine used in Japan and Korea in an in vivo experiment. We prepared drugs that had the same origin and the same components. The drugs are called kamikihito (KKT) in Japan and kami‐guibi‐tang (KGT) in Korea. KKT (500 mg extract/kg/day) and KGT (500 mg extract/kg/day) were administered to ddY mice, and object recognition and location memory tests were performed. KKT and KGT administration yielded equivalent normal memory enhancement effects. 3D‐HPLC showed similar, but not identical, patterns of the detected compounds between KKT and KGT. This comparative research approach enables future global clinical studies of traditional medicine to be conducted through the use of the formulations prescribed in each country. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-23T22:13:51.853286-05:
      DOI: 10.1002/ptr.5250
  • The Immunostimulating Role of Lichen Polysaccharides: A Review
    • Authors: Gajendra Shrestha; Larry L. St. Clair, Kim L. O'Neill
      Abstract: The immune system has capacity to suppress the development or progression of various malignancies including cancer. Research on the immunomodulating properties of polysaccharides obtained from plants, microorganisms, marine organisms, and fungi is growing rapidly. Among the various potential sources, lichens, symbiotic systems involving a fungus and an alga and/or a cyanobacterium, show promise as a potential source of immunomodulating compounds. It is well known that lichens produce an abundance of structurally diverse polysaccharides. However, only a limited number of studies have explored the immunostimulating properties of lichen polysaccharides. Published studies have shown that some lichen polysaccharides enhance production of nitrous oxide (NO) by macrophages and also alter the production levels of various proinflammatory and antiinflammatory cytokines (IL‐10, IL‐12, IL‐1β, TNF‐α, and IFN‐α/β) by macrophages and dendritic cells. Although there are only a limited number of studies examining the role of lichen polysaccharides, all results suggest that lichen polysaccharides can induce immunomodulatory responses in macrophages and dendritic cells. Thus, a detailed evaluation of immunomodulatory capacity of lichen polysaccharides could provide a unique opportunity for the discovery of novel therapeutic agents. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-22T04:11:41.18946-05:0
      DOI: 10.1002/ptr.5251
  • The application of metabolomics in traditional Chinese medicine opens up a
           dialogue between Chinese and Western medicine
    • Authors: Hongxin Cao; Aihua Zhang, Huamin Zhang, Hui Sun, Xijun Wang
      First page: 159
      Abstract: Metabolomics provides an opportunity to develop the systematic analysis of the metabolites and has been applied to discovering biomarkers and perturbed pathways which can clarify the action mechanism of traditional Chinese medicines (TCM). TCM is a comprehensive system of medical practice that has been used to diagnose, treat and prevent illnesses more than 3000 years. Metabolomics represents a powerful approach that provides a dynamic picture of the phenotype of biosystems through the study of endogenous metabolites, and its methods resemble those of TCM. Recently, metabolomics tools have been used for facilitating interactional effects of both Western medicine and TCM. We describe a protocol for investigating how metabolomics can be used to open up ‘dialogue’ between Chinese and Western medicine, and facilitate lead compound discovery and development from TCM. Metabolomics will bridge the cultural gap between TCM and Western medicine and improve development of integrative medicine, and maximally benefiting the human. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-21T02:26:23.813576-05:
      DOI: 10.1002/ptr.5240
  • Dang Shen [Codonopsis pilosula (Franch.) Nannf] Herbal Formulae for
           Chronic Obstructive Pulmonary Disease: A Systematic Review and
    • Authors: Johannah L. Shergis; Shaonan Liu, Xiankun Chen, Anthony L. Zhang, Xinfeng Guo, Chuanjian Lu, Charlie C. Xue
      First page: 167
      Abstract: This systematic review and meta‐analysis assessed the efficacy and safety of Dang shen [Codonopsis pilosula (Franch.) Nannf., root] formulae for the treatment of chronic obstructive pulmonary disease (COPD). English and Chinese databases were searched, and 48 randomized controlled trials were included. Dang shen formulae improved lung function forced expiratory volume in 1 s compared with conventional pharmacotherapy (CP) [mean difference (MD) 0.22 L, 95% confidence interval (CI) 0.13–0.31, p 
      PubDate: 2014-10-22T01:26:20.357693-05:
      DOI: 10.1002/ptr.5248
  • Neuroprotection by Saponins
    • Authors: Aijing Sun; Xianxiang Xu, Junsheng Lin, Xiuling Cui, Ruian Xu
      First page: 187
      Abstract: Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones. Their diverse biological activities are ascribed to their different structures. Saponins have long been recognized as key ingredients in traditional Chinese medicine. Accumulated evidence suggests that saponins have significant neuroprotective effects on attenuation of central nervous system disorders, such as stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, our understanding of the mechanisms underlying the observed effects remains incomplete. Based on recently reported data from basic and clinical studies, this review highlights the proposed mechanisms of their neuroprotective function including antioxidant, modulation of neurotransmitters, anti‐apoptosis, anti‐inflammation, attenuating Ca2+ influx, modulating neurotrophic factors, inhibiting tau phosphorylation, and regeneration of neural networks. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-19T02:04:19.507263-05:
      DOI: 10.1002/ptr.5246
  • Modulation of Radiation‐Induced Alterations in Oxidative Stress and
           Cytokine Expression in Lung Tissue by Panax Ginseng Extract
    • Authors: Seong Soon Jang; Hyeong Geug Kim, Jong Min Han, Jin Seok Lee, Min Kyung Choi, Gil Ja Huh, Chang Gue Son
      First page: 201
      Abstract: We investigated the modulating effect of Panax ginseng extract (PGE) on radiation‐induced lung injury (RILI) by measuring early changes in oxidative stress levels, cytokine expression, and the histopathology of mouse lung tissue treated with high dose of X‐ray radiation. The mice were pretreated with 25, 50, and 100‐mg/kg doses of PGE orally for four consecutive days, and their thoraces were then exposed to 15‐Gy X‐ray radiation 1 h after the last administration of PGE on day 4. The pretreatments with 50 and 100 mg/kg PGE led to significant reductions in the elevation of lipid peroxidation levels at 2 and 10 days, respectively, after irradiation. The mice pretreated with PGE exhibited dose‐dependent reductions in the irradiation‐induced production of tumor necrosis factor α and transforming growth factor β1 cytokines 10 days after irradiation, with these reductions nearly reaching the control levels after the 100‐mg/kg dose. Furthermore, together with providing significant protection against reductions in catalase activity and glutathione content, pretreatment with 100 mg/kg PGE resulted in a marked attenuation of the severity of inflammatory changes in lung tissue 10 days after irradiation. A high pretreatment dose of PGE may be a useful pharmacological approach for protection against RILI. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-15T01:25:54.24004-05:0
      DOI: 10.1002/ptr.5223
  • Isoflavones Extracted from Chickpea Cicer arietinum L. Sprouts Induce
           Mitochondria‐Dependent Apoptosis in Human Breast Cancer Cells
    • Authors: Hua Chen; Hai‐Rong Ma, Yan‐Hua Gao, Xue Zhang, Madina Habasi, Rui Hu, Haji Akber Aisa
      First page: 210
      Abstract: Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation‐7 (MCF‐7). 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays showed that ICS (10–60 µg/mL) significantly inhibited the proliferation of both cell lines in a time‐dependent and dose‐dependent fashion. Wright‐Giemsa staining as well as annexin V‐fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose‐dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis‐promoting gene Bcl‐2‐associated X protein and decreased the expression of the antiapoptotic gene Bcl‐2. Western blot analysis showed that treatment of SKBr3 and MCF‐7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose‐dependent manner. Flow cytometry assays using the fluorescent probe 3,3′‐dihexyloxacarbocyanine iodide showed a dose‐dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose‐dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-06T23:17:00.423925-05:
      DOI: 10.1002/ptr.5241
  • Mechanisms of improvement of intestinal transport of baicalin and puerarin
           by extracts of Radix Angelicae Dahuricae
    • Authors: Xin‐Li Liang; Jing Zhang, Guo‐Wei Zhao, Zhe Li, Yun Luo, Zheng‐Gen Liao, Dong‐Mei Yan
      First page: 220
      Abstract: Radix Angelicae Dahuricae is the dried root of Angelicae Dahurica (Fisch.ex Hoffm.) Hook.f. var.formosana (Boiss.) Shan et Yuan (Fam.Umbelliferae). The total coumarins (Cou) and volatile oil (VO) were main active components that drived from Radix Angelicae Dahuricae. Our previous studies have shown that Cou and VO could increase intestinal absorption for transmucosal drug delivery with unknown mechanism. The aim of this study was to investigate the molecular mechanism of Radix Angelicae Dahuricae for improving drug intestinal transport. Caco‐2 cell model was used to study the effect of Radix Angelicae Dahurica on transepithelial electrical resistance. Western blot was used to study its effect on the expression of the actin and ZO‐1, tight junction proteins. The effect of Radix Angelicae Dahurica on the expression of P‐gp protein was investigated using flow cytometry. VO (0.036–2.88 μL/mL) and Cou (0.027–0.54 mg/mL) caused a reversible, time‐ and dose‐dependent decrease in transepithelial electrical resistance. VO and/or Cou could inhibit the expression of the tight junction protein, ZO‐1 and actin. VO and/or Cou also could inhibit the expression of P‐gp. These data suggested that Radix Angelicae Dahurica increased cell permeability by affecting the expression of actin, ZO‐1 or P‐gp, opening the tight junction or inhibiting the efflux induced by P‐gp. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-14T02:21:24.293505-05:
      DOI: 10.1002/ptr.5242
  • Potent Effects of the Total Saponins from Dioscorea nipponica Makino
           Against Streptozotocin‐Induced Type 2 Diabetes Mellitus in Rats
    • Authors: Hao Yu; Lingli Zheng, Lina Xu, Lianhong Yin, Yuan Lin, Hua Li, Kexin Liu, Jinyong Peng
      First page: 228
      Abstract: The aim of the present paper was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against type 2 diabetes mellitus. Streptozotocin (STZ) with high‐fat diet induced type 2 diabetes mellitus (T2DM) rats were treated with TSDN. Some biochemical parameters, target proteins and genes were investigated. The results showed that TSDN decreased the levels of food/water intake, fasting blood glucose and serum lipid parameters, ameliorated oral glucose and insulin tolerance test levels, markedly increased body weight and serum insulin, reduced excess free radicals and affected ossification and renal protection. Histopathological examination indicated that TSDN increased liver glycogen, decreased the production of lipid vacuoles and lightened liver damage. Further investigation showed that TSDN down‐regulated the protein expressions of NF‐κB, GRP78, ATF6, eIF2 and the levels of MAPK phosphorylation and up‐regulated the protein expressions of IRS‐1, GLUT‐4, p‐Akt and p‐AMPK. In addition, TSDN obviously decreased the gene expressions of TNF‐a, IL‐6, PEPCK, G6Pase, GSK‐3β and GSK‐3β activity, and increased the gene expressions of PFK, PK and GK activity. These findings show the anti‐diabetic activity of total saponins from D. nipponica Makino, which should be developed as a new potent drug for treatment of diabetes mellitus in future. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-16T20:23:21.963912-05:
      DOI: 10.1002/ptr.5243
  • Formula Optimization of the Jiashitang Scar Removal Ointment and
           Antiinflammatory Compounds Screening by NF‐κB
           Bioactivity‐guided Dual‐luciferase Reporter Assay System
    • Authors: Jie Gao; Jin Tao, Nannan Zhang, Yanjie Liu, Min Jiang, Yuanyuan Hou, Qian Wang, Gang Bai
      First page: 241
      Abstract: Inflammation plays a role in scar formation; therefore, decreasing inflammation benefits scar removal. Jiashitang scar removal ointment (JST) is a commercially available traditional Chinese medicinal formulation. It is composed of extracts from Carthamus tinctorius L. (Car), Rheum officinale Baill. (Rhe), Salvia miltiorrhiza Beg. (Sal), and Panax notoginseng (Burk.) F. H. Chen (Pan), which are all herbs with potent antiinflammatory activities. Our aims are to optimize the formula of JST and to elucidate its antiinflammatory active components. Response surface methodology was applied to optimize proportions of the four herb extracts. The antiinflammatory effects were evaluated using in vitro and in vivo models. To screen for active components in this formula, a bioactivity‐based ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry analysis was performed. After optimization, the antiinflammatory effects of the new formula were significantly superior to the original one. Screening identified 13 active ingredients: a series of saffiomin, emodin, salvianolic acid, tanshinone, and triterpenoid saponin derivatives. These active ingredients were predicted to exert nuclear factor‐κB inhibiting effects through MAPK, PI3K/AKT, and NIK‐IKK pathways. In conclusion, the original formula was successfully optimized with more potent antiinflammatory activity. These methods can be applied to researches of other formulas. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-02T23:56:37.642371-05:
      DOI: 10.1002/ptr.5244
  • Inhibitory Effects of French Pine Bark Extract, Pycnogenol®, on
           Alveolar Bone Resorption and on the Osteoclast Differentiation
    • Authors: Hideki Sugimoto; Kiyoko Watanabe, Toshizo Toyama, Shun‐suke Takahashi, Shuta Sugiyama, Masaichi‐Chang‐il Lee, Nobushiro Hamada
      First page: 251
      Abstract: Pycnogenol® (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non‐infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate‐resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1–100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-21T22:42:47.726099-05:
      DOI: 10.1002/ptr.5245
  • Effect of Ginkgo Biloba Extract on Lipopolysaccharide‐induced
           Anhedonic Depressive‐like Behavior in Male Rats
    • Authors: Kuei‐Ying Yeh; Sing‐Siang Shou, Yi‐Xuan Lin, Chao‐Cin Chen, Chen‐Yen Chiang, Chien‐Yu Yeh
      First page: 260
      Abstract: The peripheral administration of lipopolysaccharide (LPS) induces depressive‐like behavior. Anhedonia is a core symptom of depression, defined as a loss of the capacity to experience pleasure. The present study used the sucrose preference test to investigate the influence of Ginkgo biloba extract (EGb 761) on LPS‐induced anhedonia in male rats. The animals were randomly divided into four groups: (I) vehicle + saline, (II) vehicle + LPS, (III) EGb 761 + saline, and (IV) EGb 761 + LPS. Saline or LPS (100 µg/kg) was administered intraperitoneally 2 h before the sucrose preference test. Sucrose consumption was recorded 2, 4, 6, 13, and 24 h after 100 µg/kg of LPS or saline injection in the dark phase of the light/dark cycle. Dopamine and serotonin levels in the nucleus accumbens were measured. Our results indicated that the vehicle + LPS group exhibited a significant decrease in sucrose intake compared with the vehicle + saline group. The EGb 761 + LPS group showed more sucrose and food consumption than the vehicle + LPS group. Additionally, compared with the EGb 761 + LPS group, the vehicle + LPS group had less dopamine levels in the nucleus accumbens. Treatment with EGb 761 had no effect on water intake. Our results suggest that EGb 761 may be useful for reducing anhedonic depressive‐like behavior. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons, Ltd.
      PubDate: 2014-10-24T04:33:27.020913-05:
      DOI: 10.1002/ptr.5247
  • Gallic Acid Exhibits Risks of Inducing Muscular Hemorrhagic Liposis and
           Cerebral Hemorrhage—Its Action Mechanism and Preventive Strategy
    • Authors: Chiu‐Lan Hsieh; Chien‐Hong Lin, Hui‐Er Wang, Chiung‐Chi Peng, Robert Y. Peng
      First page: 267
      Abstract: Gallic acid (3,4,5‐trihydroxybenzoic acid) (GA) occurs in many plants. The adverse effects of GA are seldom cited. GA (6–14 μM) provoked the hemorrhagic liposis of the cervical muscles and intracranial hemorrhage. The cause of these pathological events and the method for prevention are still lacking. Using the chicken embryo model and some selected nutraceutics such as folate, glutathione (GSH), N‐acetylcysteine, and vitamin E (Vit E), we carried out this study. Results revealed that the action mechanism of GA involved (i) inducing hypoxia with upregulated gene hif‐1α and downregulated ratio vegf‐r2/vegf‐a, leading to dys‐vascularization and myopathy; (ii) impairing cytochrome c oxidase; (iii) stimulating creatine kinase and lactate dehydrogenase release; (iv) eliciting carnitine accumulation and liposis via downregulating gene CPT1; (v) suppressing superoxide dismutase and stimulating NO, H2O2, and malondialdehyde; and (vi) depleting erythrocytic and tissue GSH, resulting in hemorrhage. When both Vit E and GSH were applied to the day 1 chicks, a better alleviation effect was revealed. Conclusively, GA potentially exhibits adverse effect by eliciting hemorrhagic liposis of cervical muscles and cerebral hemorrhage. Supplementation with GSH, Vit E, and N‐acetylcysteine is able to ameliorate these adverse effects, warranting the importance of restricting the clinical phytotherapeutic doses of GA and related compounds. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-17T22:37:45.44128-05:0
      DOI: 10.1002/ptr.5249
  • Soyasaponins Aa and Ab Exert an Anti‐Obesity Effect in 3T3‐L1
           Adipocytes Through Downregulation of PPARγ
    • Authors: Seung Hwan Yang; Eun‐Kyung Ahn, Jung A Lee, Tai‐Sun Shin, Chigen Tsukamoto, Joo‐won Suh, Itabashi Mei, Gyuhwa Chung
      First page: 281
      Abstract: Saponins are a diverse group of biologically functional products in plants. Soyasaponins are usually glycosylated, which give rise to a wide diversity of structures and functions. In this study, we investigated the effects and molecular mechanism of soyasaponins Aa and Ab in regulating adipocyte differentiation and expression of adipogenic marker genes in 3T3‐L1 adipocytes. Soyasaponins Aa and Ab dose‐dependently inhibited the accumulation of lipids and the expression of adiponectin, adipocyte determination and differentiation factor 1/sterol regulatory element binding protein 1c, adipocyte fatty acid‐binding protein 2, fatty acid synthase, and resistin in 3T3‐L1 adipocytes. In addition, soyasaponins Aa and Ab suppressed the transcriptional activity of peroxisome proliferator‐activated receptor γ (PPARγ) in HEK 293T cells. Furthermore, we confirmed that the expression of PPARγ and of CCAAT‐enhancer‐binding protein α (C/EBPα) was suppressed at both the mRNA and protein levels in 3T3‐L1 adipocytes by treatment with soyasaponins Aa and Ab. Taken together, these findings indicate that soyasaponin Aa and Ab markedly inhibit adipocyte differentiation and expression of various adipogenic marker genes through the downregulation of the adipogenesis‐related transcription factors PPARγ and C/EBPα in 3T3‐L1 adipocytes. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-04T01:33:11.684082-05:
      DOI: 10.1002/ptr.5252
  • Garlic (Allium sativum) Stimulates Lipopolysaccharide‐induced Tumor
           Necrosis Factor‐alpha Production from J774A.1 Murine Macrophages
    • Authors: Jessica Sung; Youssef Harfouche, Melissa De La Cruz, Martha P. Zamora, Yan Liu, James A. Rego, Nancy E. Buckley
      First page: 288
      Abstract: Garlic (Allium sativum) is known to have many beneficial attributes such as antimicrobial, antiatherosclerotic, antitumorigenetic, and immunomodulatory properties. In the present study, we investigated the effects of an aqueous garlic extract on macrophage cytokine production by challenging the macrophage J774A.1 cell line with the garlic extract in the absence or presence of lipopolysaccharide (LPS) under different conditions. The effect of allicin, the major component of crushed garlic, was also investigated. Using enzyme‐linked immunosorbent assay and reverse transcriptase‐quantitative polymerase chain reaction, it was found that garlic and synthetic allicin greatly stimulated tumor necrosis factor‐alpha (TNF‐α) production in macrophages treated with LPS. The TNF‐α secretion levels peaked earlier and were sustained for a longer time in cells treated with garlic and LPS compared with cells treated with LPS alone. Garlic acted in a time‐dependent manner. We suggest that garlic, at least partially via its allicin component, acts downstream from LPS to stimulate macrophage TNF‐α secretion. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons, Ltd.
      PubDate: 2014-11-04T01:47:24.615789-05:
      DOI: 10.1002/ptr.5253
  • Mangiferin Attenuates Renal Fibrosis Through Down‐Regulation of
           Osteopontin in Diabetic Rats
    • Authors: Xia Zhu; Ya‐Qin Cheng, Lei Du, Yu Li, Fan Zhang, Hao Guo, Yao‐Wu Liu, Xiao‐Xing Yin
      First page: 295
      Abstract: This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason‐stained positive area of glomeruli, protein expression of type IV collagen, and α‐smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF‐кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF‐кB. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-07T02:43:44.689591-05:
      DOI: 10.1002/ptr.5254
  • Hypoglycaemic Activity of Culinary Pleurotus ostreatus and P. cystidiosus
           Mushrooms in Healthy Volunteers and Type 2 Diabetic Patients on Diet
           Control and the Possible Mechanisms of Action
    • Authors: W. J. A. Banukie N. Jayasuriya; Chandanie A. Wanigatunge, Gita H. Fernando, D. Thusitha U. Abeytunga, T. Sugandhika Suresh
      First page: 303
      Abstract: This study determined the oral hypoglycaemic effect of suspensions of freeze dried and powdered (SFDP) Pleurotus ostreatus (P.o) and Pleurotus cystidiosus (P.c), using healthy human volunteers and Type 2 diabetic patients on diet control at a dose of 50 mg/kg/body weight, followed by a glucose load. The possible hypoglycaemic mechanisms were evaluated using rats, by examining intestinal glucose absorption and serum levels of insulin, glucokinase (GK) and glycogen synthase kinase (GSK). The P.o and P.c showed a significant reduction (P 
      PubDate: 2014-11-08T01:45:44.113335-05:
      DOI: 10.1002/ptr.5255
  • A Combination of Glucosyl Hesperidin and Caffeine Exhibits an
           Anti‐obesity Effect by Inhibition of Hepatic Lipogenesis in Mice
    • Authors: Tatsuya Ohara; Koutarou Muroyama, Yoshihiro Yamamoto, Shinji Murosaki
      First page: 310
      Abstract: To develop an anti‐obesity agent, we examined the combination effect of glucosyl hesperidin (G‐hesperidin) and caffeine on obesity in mice. High‐fat diet‐induced obese KK mice were fed a low‐fat diet with or without G‐hesperidin, caffeine, or their combination for 2 weeks. Decreases in body weight and significantly lower adipose tissue weight were observed in the combination‐fed mice but not in the G‐hesperidin‐fed or caffeine‐fed mice. DNA microarray analysis of mouse liver suggested that the feeding of G‐hesperidin + caffeine was associated with lower lipogenesis. Therefore, we examined the anti‐lipogenic effect of G‐hesperidin + caffeine in fasted–refed KK mice. Hepatic triglyceride levels were significantly lower in the mice fed G‐hesperidin + caffeine during the refeeding period but not in the mice fed each alone. In addition, hepatic expressions of genes related to lipogenesis, such as sterol regulatory element‐binding protein‐1c or fatty acid synthase, were significantly lower in the mice fed G‐hesperidin + caffeine compared with that in the control mice. These results suggested that G‐hesperidin + caffeine is effective for controlling obesity partly by the inhibition of hepatic lipogenesis. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-11-20T02:27:52.636435-05:
      DOI: 10.1002/ptr.5258
  • The Involvement of Serotonin in the Hypoglycemic Effects Produced by
           Administration of the Aqueous Extract of Xylaria nigripes with
           Steroid‐Induced Insulin‐Resistant Rats
    • Abstract: Xylaria nigripes (XN) is a medicinal fungus with a high‐economic value. The aim of this study was to explore the hypoglycemic effects and mechanisms of the XN aqueous extract in steroid‐induced insulin‐resistant (SIIR) rats. Significant hypoglycemic effects were observed 60 min after administration of XN aqueous extract. In normal Wistar, hypoglycemic effects were 21% (the plasma glucose level decreased from 128.6 ± 12.5 to 100.9 ± 10.7 mg/dL). In SIIR, hypoglycemic effects were 26% (the plasma glucose level decreased from 177.6 ± 12.5 to 133.3 ± 29.7 mg/dL) rats refer to their baseline. The signaling proteins for insulin‐receptor substrate‐1 and glucose transporter‐4 increased 0.51‐fold and 1.12‐fold, respectively, as determined by Western blotting; the increase in the proteins was 13% and 9%, respectively, as determined by immunohistochemistry. The serotonin antagonist, α‐p‐chlorophenylalanine, effectively blocked the hypoglycemic effects and increased the signaling protein levels. After XN administration, none of the animals showed significant changes in plasma‐free fatty acids in 60 min. In summary, the XN extract may have hypoglycemic effects in normal Wistar and SIIR rats that may have a serotonin‐related hypoglycemic effect and enhance insulin sensitivity in the SIIR rats. Copyright © 2015 John Wiley & Sons, Ltd.
  • Anti‐HIV‐1 Integrase Activity and Molecular Docking Study of
           Compounds from Caesalpinia  sappan L.
    • Abstract: Caesalpinia sappan L. (Caesalpiniaceae) has been traditionally used as blood tonic, expectorant, and astringent by boiling with water. Searching for HIV‐1 integrase (IN) inhibitors from this plant is a promising approach. The EtOH extract of C. sappan and its isolated compounds were tested for their anti‐HIV‐1 IN effect using the multiplate integration assay, and the active compounds were determined for their mechanisms by molecular docking technique. Extraction from the heartwoods and roots of C. sappan led to the isolation of nine compounds. Among the compounds tested, sappanchalcone (2) displayed the strongest effect against HIV‐1 IN with an IC50 value of 2.3 μM followed by protosappanin A (9, IC50 = 12.6 μM). Structure‐activity relationships of compounds from C. sappan were found, in which the vicinal hydroxyl moiety were essential for anti‐HIV‐1 IN effect of compounds 2 and 9 by binding with the amino acid residues Gln148 and Thr66 in the core domain of the HIV‐ 1 IN enzyme, respectively. Copyright © 2015 John Wiley & Sons, Ltd.
  • Protective Effects of Turbinaria ornata and Padina pavonia against
           Azoxymethane‐Induced Colon Carcinogenesis through Modulation of PPAR
           Gamma, NF‐κB and Oxidative Stress
    • Abstract: The aim of this study was to investigate the antiproliferative and protective effects of the brown seaweeds, Turbinaria ornata and Padina pavonia, against azoxymethane (AOM)‐induced colon carcinogenesis in mice. Both algal extracts showed anti‐proliferative effects on the human carcinoma cell line HCT‐116 in vitro, with T. ornata demonstrating a more potent effect. Male albino Swiss mice received intraperitoneal injections of AOM (10 mg/kg) once a week for two consecutive weeks and 100 mg/kg of either T. ornata or P. pavonia extracts. AOM‐induced mice exhibited alterations in the histological structure of the colon, elevated lipid peroxidation and nitric oxide, declined glutathione content and reduced activity of superoxide dismutase and glutathione peroxidase. In addition, AOM induced downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and p53 mRNA expression, with concomitant upregulation of nuclear factor‐kappa B (NF‐κB) in colon tissue. Administration of either algal extract markedly alleviated the recorded alterations. In conclusion, the current study suggests that T. ornata and P. pavonia, through their antioxidant and anti‐inflammatory effects, are able to attenuate colon inflammation by downregulating NF‐κB expression. Furthermore, the protective effects of both algae against AOM‐initiated carcinogenesis were attributed, at least in part, to their ability to upregulate colonic PPARγ and p53 expression. Copyright © 2015 John Wiley & Sons, Ltd.
  • The Effect of Zataria multiflora and its Constituent, Carvacrol, on
           Tracheal Responsiveness and Lung Pathology in Guinea Pig Model of COPD
    • Abstract: The effects of Zataria multiflora (Z. multiflora) and its constituent, carvacrol, in guinea pigs model of chronic obstructive pulmonary disease (COPD) were examined. Animals were divided into control, COPD, COPD + drinking water containing three concentrations of extract of Z. multiflora (0.4, 0.8 and 1.6 mg/ml), COPD + drinking water containing three concentrations of carvacrol (60, 120 and 240 µg/ml) and COPD + dexamethasone (50 µg/ml). COPD was induced by exposing animals to cigarette smoke for 3 months. Emphysema as a pathological change of the lung and tracheal responsiveness were measured (n = 5 for control and COPD groups and n = 6 for another groups). Tracheal responsiveness (p 
  • Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl
           Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells
    • Abstract: Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose‐dependent manner. To identify the active components, a bioassay‐guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down‐regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase‐3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3‐related diseases, including cancer and inflammation. Copyright © 2015 John Wiley & Sons, Ltd.
  • Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and
           Centella asiatica in Human Liver Microsomes
    • Abstract: Withania somnifera is commonly used as a rejuvenator, whereas Centella asiatica is well known for its anxiolytic and nootropic effects. The present study aims at investigating the effect of crude extracts and principal phytoconstituents of both the medicinal plants with CYP3A4 and CYP2D6 enzyme activity in human liver microsomes (HLM). Phytoconstituents were quantified in the crude extracts of both the medicinal plants using reverse phase HPLC. Crude extracts and phytoconstituents of W. somnifera showed no significant interaction with both CYP3A4 and CYP2D6 enzymes in HLM. Of the crude extracts of C. asiatica screened in vitro, methanolic extract showed potent noncompetitive inhibition of only CYP3A4 enzyme (Ki—64.36 ± 1.82 µg/mL), whereas ethanol solution extract showed potent noncompetitive inhibition of only CYP2D6 enzyme (Ki—36.3 ± 0.44 µg/mL). The flavonoids, quercetin, and kaempferol showed potent (IC50 values less than 100 μM) inhibition of CYP3A4 activity, whereas quercetin alone showed potent inhibition of CYP2D6 activity in HLM. Because methanolic extract of C. asiatica showed a relatively high percentage content of quercetin and kaempferol than ethanol solution extract, the inhibitory effect of methanolic extract on CYP3A4 enzyme activity could be attributed to the flavonoids. Thus, co‐administration of the alcoholic extracts of C. asiatica with drugs that are substrates of CYP3A4 and CYP2D6 enzymes may lead to undesirable herb‐drug interactions in humans. Copyright © 2015 John Wiley & Sons, Ltd.
  • Corosolic Acid Exhibits Anti‐angiogenic and
           Anti‐lymphangiogenic Effects on In Vitro Endothelial Cells and on an
           In Vivo CT‐26 Colon Carcinoma Animal Model
    • Abstract: We describe the anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid, a pentacyclic triterpenoid isolated from Cornus kousa Burg. A mouse colon carcinoma CT‐26 animal model was employed to determine the in vivo anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid. Corosolic acid induced apoptosis in CT‐26 cells, mediated by the activation of caspase‐3. In addition, it reduced the final tumor volume and the blood and lymphatic vessel densities of tumors, indicating that it suppresses in vivo angiogenesis and lymphangiogenesis. Corosolic acid inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells. In addition, corosolic acid decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin‐1. Pretreatment with corosolic acid decreased the phosphorylation of focal adhesion kinase (FAK) and ERK1/2, suggesting that corosolic acid contains anti‐angiogenic activity that can suppress FAK signaling induced by angiopoietin‐1. Copyright © 2015 John Wiley & Sons, Ltd.
  • Apoptotic Effects of the Extracts of Cordyceps militaris via Erk
           Phosphorylation in a Renal Cell Carcinoma Cell Line
    • Abstract: Cordyceps militaris (CM) is gaining attention as a traditional medicinal food, but its molecular biological mechanisms for anti‐cancer activity are not identified or clarified. We aimed to elucidate the synthesizing apoptotic effects of CM extracts and to determine the biological effects of CM extract against cordycepin alone in a renal cell carcinoma (RCC) cell line. CM extract showed higher effects of growth inhibition, apoptotic effect, and cell cycle arrest than cordycepin alone. Moreover, CM extract activated extracellular signal‐regulated kinase (Erk) highly more than cordycepin alone. We suggest that cordycepin and CM extract induced apoptosis via the activation of Erk dominantly and AMP‐activated protein kinase slightly; CM extract has more potent effects on apoptotic effects associated with Erk activation than cordycepin alone. Copyright © 2015 John Wiley & Sons, Ltd.
  • Natural Sesquiterpene Lactones Enhance Oxacillin and Gentamicin
           Effectiveness Against Pathogenic Bacteria Without Antibacterial Effects on
           Beneficial Lactobacilli
    • Abstract: This is a report on the synergistic interactions (SIs) between melampolide‐type sesquiterpene lactones 1–8 from Acanthospermum hispidum DC., and oxacillin or gentamicin, against four pathogenic strains of Staphylococcus aureus and Enterococcus faecalis; two of them were multi‐resistant strains obtained from chronic infectious processes. Our results showed that all associations of 1–8 with antibiotics (ATBs) are more effective than pure ATBs to control pathogenic strains of S. aureus and E. faecalis. The most relevant SIs were observed when the major lactone of A. hispidum, acanthospermal B [5], was combined with gentamicin (protein synthesis inhibitor) against an ex vivo culture of methicillin‐resistant S. aureus SAR 1, displaying a significant MIC reduction in 5 (312.5 to 78.1 µg/mL), and gentamicin (120 µg/mL to 3 µg/mL). Compound 4 improved the antibiotic potency of oxacillin (cell wall synthesis inhibitor) against ampicillin‐resistant E. faecalis (60 µg/mL to 1.5 µg/mL). It is important to remark that three beneficial lactobacilli were resistant to 1–8 and their mixtures with gentamicin or oxacillin in effective concentrations against pathogenic bacteria. Synergism between ATBs and phytochemicals is a therapeutically helpful concept to improve ATB efficacy and prevent resistance. The present results show that selective SIs occur between melampolides and gentamicin or oxacillin, and open a new field of research. Copyright © 2015 John Wiley & Sons, Ltd.
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2014