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Pacific Economic Review     Hybrid Journal   (Followers: 2, SJR: 0.785, h-index: 16)
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Phycological Research     Hybrid Journal   (Followers: 2)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.788, h-index: 67)
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Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (Followers: 1, SJR: 1.275, h-index: 27)
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Phytochemical Analysis     Hybrid Journal   (Followers: 1, SJR: 0.703, h-index: 39)
Phytotherapy Research     Hybrid Journal   (SJR: 0.718, h-index: 65)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 2, SJR: 1.86, h-index: 63)
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Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.124, h-index: 34)
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POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 6, SJR: 0.147, h-index: 1)
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Political Psychology     Hybrid Journal   (Followers: 15, SJR: 1.126, h-index: 40)
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Population and Development Review     Hybrid Journal   (Followers: 3, SJR: 2.084, h-index: 50)
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Practical Diabetes     Hybrid Journal   (Followers: 3)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 0.958, h-index: 64)
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Preventive Cardiology     Hybrid Journal   (Followers: 3)
Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 26)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (Followers: 2, SJR: 0.268, h-index: 14)
Process Safety Progress     Hybrid Journal   (Followers: 2, SJR: 0.366, h-index: 20)
Production and Operations Management     Hybrid Journal   (Followers: 4, SJR: 2.479, h-index: 57)
Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)

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Journal Cover Phytotherapy Research
   Journal TOC RSS feeds Export to Zotero 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  [1604 journals]   [SJR: 0.718]   [H-I: 65]
  • Effect of Ginger (Zingiber officinale) on Heavy Menstrual Bleeding: A
           Placebo‐Controlled, Randomized Clinical Trial
    • Authors: Farzaneh Kashefi; Marjan Khajehei, Mohammad Alavinia, Ebrahim Golmakani, Javad Asili
      Pages: n/a - n/a
      Abstract: Objective: A wide range of herbal plants have been reported to treat various gynecological problems of women. This study was set out to investigate the effect of ginger (Zingiber officinale) on heavy menstrual bleeding (HMB) in high school girls. Methods: Ninety‐two young women who experienced HMB and met the inclusion criteria were recruited in this study. Participants were evaluated for six consecutive menstrual cycles. During 3 assessment cycles, their HMB was confirmed by Pictorial Blood Assessment Chart. They were then randomly allocated to two study groups to receive either ginger or placebo capsules. The participants filled in the same chart during three intervention cycles. Results: The level of menstrual blood loss dramatically declined during the three intervention cycles in ginger‐receiving group. The decrease of blood loss in ginger‐receiving group was significantly more remarkable than that of participants receiving placebo (p 
      PubDate: 2014-10-08T22:32:11.515402-05:
      DOI: 10.1002/ptr.5235
  • Effect of Curcumin on Hepatic Antioxidant Enzymes Activities and Gene
           Expressions in Rats Intoxicated with Aflatoxin B1
    • Authors: S. M. El‐Bahr
      Abstract: Twenty‐eight rats were examined in a 5‐week experiment to investigate the effect of curcumin on gene expression and activities of hepatic antioxidant enzymes in rats intoxicated with aflatoxin B1 (AFB1). The rats were divided into four groups. Rats in 1–4 groups served as control, oral curcumin treated (15 mg/kg body weight), single i.p. dose of AFB1 (3 mg/kg body weight) and combination of single i.p. dose of AFB1 with oral curcumin treated, respectively. AFB1 Liver damage and oxidative stress were evident in untreated AFB1‐intoxicated rats as indicated by a significant elevation in hepatic transaminases, elevation in lipid peroxide biomarkers (thiobarbituric acid reactive substances; TBARS), reduction of reduced glutathione (GSH) concentration, reduction in the activities of antioxidant enzymes namely catalase (CAT), total superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione‐S‐transferase (GST) and down‐regulation of gene expression of these antioxidant enzymes compared to control. Liver sections of rats intoxicated with AFB1 showed a disrupted lobular architecture, scattered necrotic cells and biliary proliferation. Administration of curcumin with AFB1 resulted in amelioration of AFB1‐induced effects compared to untreated AFB1‐intoxicated rats via an up‐regulation of antioxidant enzyme gene expression, activation of the expressed genes and increase in the availability of GSH. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-07T23:07:17.05011-05:0
      DOI: 10.1002/ptr.5239
  • Isoflavones Extracted from Chickpea Cicer arietinum L. Sprouts Induce
           Mitochondria‐Dependent Apoptosis in Human Breast Cancer Cells
    • Authors: Hua Chen; Hai‐Rong Ma, Yan‐Hua Gao, Xue Zhang, Madina Habasi, Rui Hu, Haji Akber Aisa
      Abstract: Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation‐7 (MCF‐7). 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays showed that ICS (10–60 µg/mL) significantly inhibited the proliferation of both cell lines in a time‐dependent and dose‐dependent fashion. Wright‐Giemsa staining as well as annexin V‐fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose‐dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis‐promoting gene Bcl‐2‐associated X protein and decreased the expression of the antiapoptotic gene Bcl‐2. Western blot analysis showed that treatment of SKBr3 and MCF‐7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose‐dependent manner. Flow cytometry assays using the fluorescent probe 3,3′‐dihexyloxacarbocyanine iodide showed a dose‐dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose‐dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-06T23:17:00.423925-05:
      DOI: 10.1002/ptr.5241
  • Pentacyclic Triterpenoids from Spikes of Prunella vulgaris L. Inhibit
           Glycogen Phosphorylase and Improve Insulin Sensitivity in 3T3‐L1
    • Authors: Qian Yu; Jin Qi, Lu Wang, Shou‐Jin Liu, Bo‐Yang Yu
      Pages: n/a - n/a
      Abstract: Phytochemical investigation of methanol extract from the spikes of Prunella vulgaris L. led to the isolation of two new pentacyclic triterpenoid glycosides Vulgasides I (1) and II (2) along with 13 known compounds (3–15). Their structures were established on the basis of nuclear magnetic resonance (1D and 2D) and mass spectroscopic data analysis. All the isolated compounds were screened for glycogen phosphorylase inhibitory activity and also evaluated for their effect on insulin sensitivity in 3T3‐L1 adipocytes. Two new compounds (1, 2) did not demonstrate the glycogen phosphorylase inhibitory activity, but other compounds (3–11) exhibited varying degrees of glycogen phosphorylase inhibitory activity with IC50 values in the range from 30.69 to 68.85 μM. Compounds 3, 6, 7, 11, and 13 demonstrated markedly increased insulin‐mediated glucose consumption in 3T3‐L1 adipocytes. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-03T00:58:30.604692-05:
      DOI: 10.1002/ptr.5228
  • Modulation of Cox‐1, 5‐, 12‐ and 15‐Lox by Popular
           Herbal Remedies Used in Southern Italy Against Psoriasis and Other Skin
    • Authors: Ammar Bader; Francesca Martini, Guillermo R. Schinella, Jose L. Rios, Jose M. Prieto
      Pages: n/a - n/a
      Abstract: Acanthus mollis (Acanthaceae), Achillea ligustica, Artemisia arborescens and Inula viscosa (Asteraceae) are used in Southern Italy against psoriasis and other skin diseases that occur with an imbalanced production of eicosanoids. We here assessed their in vitro effects upon 5‐, 12‐, 15‐LOX and COX‐1 enzymes as well as NFκB activation in intact cells as their possible therapeutic targets. All methanol crude extracts inhibited both 5‐LOX and COX‐1 activities under 200 µg/mL, without significant effects on the 12‐LOX pathway or any relevant in vitro free radical scavenging activity. NFκB activation was prevented by all extracts but A. mollis. Interestingly, A. ligustica, A. arborescens and A. mollis increased the biosynthesis of 15(S)‐HETE, an anti‐inflammatory eicosanoid. A. ligustica (IC50 = 49.5 µg/mL) was superior to Silybum marianum (IC50 = 147.8 µg/mL), which we used as antipsoriatic herbal medicine of reference. Its n‐hexane, dichloromethane and ethyl acetate fractions had also inhibitory effects on the LTB4 biosynthesis (IC50s = 9.6, 20.3 and 68 µg/mL, respectively) evidencing that the apolar extracts of A. ligustica are promising active herbal ingredients for future phytotherapeutical products targeting psoriasis. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2014-10-03T00:16:07.513125-05:
      DOI: 10.1002/ptr.5234
  • A Review of the Receptor Binding and Pharmacological Effects of
    • Authors: Sidney J. Stohs; Michael J. Hartman
      Pages: n/a - n/a
      Abstract: N‐methyltyramine (NMT) is a protoalkaloid isolated from various plant species. It is assumed that NMT is an adrenergic agonist with pharmacological properties similar to other structurally related biogenic amines. Current research studies indicate that NMT is an α‐adrenoreceptor antagonist, and exhibits modest inhibitory (antagonistic) activity with respect to the breakdown of fats (lipolysis). Furthermore, NMT has been shown to enhance appetite and digestion of foods through its stimulatory effects on gastrin and pancreatic secretions. As a consequence, NMT is not an ingredient that should be used in dietary supplements designed to promote weight loss. It may result in an increase in perceived energy by promoting appetite and the digestion and absorption of nutrients while inhibiting the breakdown to fats to energy. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-10-02T00:10:05.106774-05:
      DOI: 10.1002/ptr.5231
  • In vitro Combinatory Antimicrobial Effect of Plumbagin with Oxacillin and
           Tetracycline against Staphylococcus aureus
    • Authors: Johana Rondevaldova; Pavel Novy, Ladislav Kokoska
      Pages: n/a - n/a
      Abstract: Plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone), a bicyclic naphthoquinone naturally distributed among Plumbago species, has been reported to have antimicrobial activity against a wide range of microorganisms. In this study, plumbagin was examined for its combinatory antimicrobial effect with tetracycline or oxacillin against nine strains of Staphylococcus aureus, including its methicillin‐ and multidrug‐resistant strains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated according to the sum of fractional inhibitory concentration (ΣFIC) indices. Additive interactions were obtained for both combinations against most of the strains tested. Synergy was obtained for combination with oxacillin against two out of seven strains (ΣFIC range 0.273–0.281), both were methicillin resistant. Our results proved plumbagin as a compound suitable for anti‐Staphylococcal combinatory testing. Moreover, to the best of our knowledge, this is the first report of plumbagin synergy with oxacillin against S. aureus strains, including its resistant forms. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-30T05:26:18.705046-05:
      DOI: 10.1002/ptr.5237
  • Extracts from Calendula officinalis Offer in Vitro Protection Against H2O2
           Induced Oxidative Stress Cell Killing of Human Skin Cells
    • Authors: Abdullah M. Alnuqaydan; Claire E. Lenehan, Rachel R. Hughes, Barbara J. Sanderson
      Pages: n/a - n/a
      Abstract: The in vitro safety and antioxidant potential of Calendula officinalis flower head extracts was investigated. The effect of different concentrations (0.125, 0.5, 1.0, 2.0 and 5.0% (v/v)) of Calendula extracts on human skin cells HaCaT in vitro was explored. Doses of 1.0% (v/v) (0.88 mg dry weight/mL) or less showed no toxicity. Cells were also exposed to the Calendula extracts for either 4, 24 or 48 h before being exposed to an oxidative insult (hydrogen peroxide H2O2) for 1 h. Using the MTT cytotoxicity assay, it was observed that two independent extracts of C. officinalis gave time‐dependent and concentration‐dependent H2O2 protection against induced oxidative stress in vitro using human skin cells. Pre‐incubation with the Calendula extracts for 24 and 48 h increased survival relative to the population without extract by 20% and 40% respectively following oxidative challenge. The antioxidant potential of the Calendula extracts was confirmed using a complimentary chemical technique, the DPPH● assay. Calendula extracts exhibited free radical scavenging abilities. This study demonstrates that Calendula flower extracts contain bioactive and free radical scavenging compounds that significantly protect against oxidative stress in a human skin cell culture model. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-30T02:19:11.404107-05:
      DOI: 10.1002/ptr.5236
  • Effect of Hypericum perforatum L. Extract on Insulin Resistance and Lipid
           Metabolic Disorder in High‐Fat‐Diet Induced Obese Mice
    • Authors: Jin‐ying Tian; Rong‐ya Tao, Xiao‐lin Zhang, Qian Liu, Yi‐bo He, Ya‐lun Su, Teng‐fei Ji, Fei Ye
      Pages: n/a - n/a
      Abstract: Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin‐layer chromatography, ultraviolet, high‐performance liquid chromatography (HPLC), and HPLC‐mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic–euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-29T23:55:41.874995-05:
      DOI: 10.1002/ptr.5230
  • Anticancer Activities of Selected Species of North American Lichen
    • Authors: Gajendra Shrestha; Atif M. El‐Naggar, Larry L. St. Clair, Kim L. O'Neill
      Abstract: Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0/G1 stage, and caused apoptosis in a dose‐dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-24T22:52:13.559669-05:
      DOI: 10.1002/ptr.5233
  • Anti‐Inflammatory and Antinociceptive Activity of Urera aurantiaca
    • Authors: R. Riedel; C. Marrassini, C. Anesini, S. Gorzalczany
      Abstract: Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti‐inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti‐inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan‐induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose‐dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis 3‐ethylbenzothiazoline 6‐sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-24T22:08:29.020127-05:
      DOI: 10.1002/ptr.5226
  • Alhagi: A Plant Genus Rich in Bioactives for Pharmaceuticals
    • Authors: Gulzar Muhammad; Muhammad Ajaz Hussain, Farooq Anwar, Muhammad Ashraf, Anwarul‐Hassan Gilani
      Abstract: Alhagi, a plant genus from family Fabaceae, is widely distributed in many countries of Asia, Australia and Europe. Commonly known as camel thorn, Alhagi has many species famous for feed and folk medicinal uses. Different species of Alhagi such as Alhagi pseudalhagi, A. graecorum, A. sparsifolia, A. kirgisorum, A. maurorum, A. camelorum and A. persarum have been explored for their antioxidant potential and nutritive value along with various medicinal properties. A wide array of pharmacologically active secondary metabolites such as flavonoids, alkaloids (alhacidin and alhacin), steroids, pseudalhagin A, phospholipids and polysaccharides have been reported from different parts of Alhagi species. A broad range of biological activities such as antioxidant, cardiovascular, anti‐ulcer, hepatoprotective, antispasmodic, antidiarrheal, antinociceptive, antipyretic, anti‐inflammatory, anti‐rheumatic, antibacterial and antifungal have been ascribed to different parts of Alhagi. In addition, Alhagi plants are also valued as a rich source of digestible protein and important minerals. This review focuses on the medicinal applications and detailed profile of high‐value bioactive phytochemicals along with pharmacological attributes and therapeutic potential of these multi‐purpose plants. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-24T21:52:47.057306-05:
      DOI: 10.1002/ptr.5222
  • A Novel Diterpene Skeleton: Identification of a Highly Aromatic, Cytotoxic
           and Antioxidant
           5‐Methyl‐10‐demethyl‐abietane‐type Diterpene
           from Premna serratifolia
    • Authors: Solomon Habtemariam; George K. Varghese
      Abstract: Premna serratifolia Linn. (syn: . P. corymbosa (Burm. f.) Merr., P. integrifolia L. and P. obtusifolia R. Br.) is a member of the Verbenaceae family that is extensively used in the Ayurvedic system of medicine in India. As part of our continuous pharmacological and phytochemical studies on medicinal plants, we have screened the methanolic extracts of leaves, root bark (RB) and root wood of P. serratifolia for cytotoxic activity against two cancer cell lines: SHSY‐5Y neuroblastoma and B16 melanoma cells. The RB extract that showed promising activity was fractionated using solvents of increasing polarity followed by a combination of Sephadex LH‐20 column and Combiflash chromatography as well as HPLC to afford the active principle. Comprehensive spectroscopic analysis including 1D and 2D NMR (COSY, HMQC, HMBC, NOESY) and MS analysis revealed the identity of the isolated compound as 11,12,16‐trihydroxy‐2‐oxo‐5‐methyl‐10‐demethyl‐abieta‐1[10],6,8,11,13‐pentene that appears to be a novel compound based on a new diterpene skeleton. The cytotoxic activity of the isolated compound was 21 and 23 times higher than the crude extract against the SHSY‐5Y and B16 cells, respectively. The novel compound also possesses in vitro antioxidant effects as evidenced by the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging effect where an IC50 value of 20.4 ± 1.3 μM was obtained. In comparison, the positive control, caffeic acid, showed an IC50 value of 14.4 ± 1.6 μM. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-22T23:47:30.765105-05:
      DOI: 10.1002/ptr.5229
  • Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter
           pylori Based on Inhibition of Urease
    • Authors: Xiao‐Dan Yu; Jian‐Hui Xie, Yong‐Hong Wang, Yu‐Cui Li, Zhi‐Zhun Mo, Yi‐Feng Zheng, Ji‐Yan Su, Ye‐er Liang, Jin‐Zhi Liang, Zi‐Ren Su, Ping Huang
      Abstract: The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H. pylori and jack bean in concentration‐dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver‐Burk plots indicated that the type of inhibition was non‐competitive against H. pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA‐inactivated urease assay showed DL‐dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H. pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H. pylori infection. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-22T02:48:39.479258-05:
      DOI: 10.1002/ptr.5227
  • Modulating Potential of L‐Sulforaphane in the Expression of
           Cytochrome P450 to Identify Potential Targets for Breast Cancer
           Chemoprevention and Therapy Using Breast Cell Lines
    • Authors: Barbara Licznerska; Hanna Szaefer, Iwona Matuszak, Marek Murias, Wanda Baer‐Dubowska
      Abstract: The L‐sulforaphane (SFN) component of broccoli sprout showed anticancer activity in several preclinical studies including breast cancer. Estrogens are considered major risk factors in breast carcinogenesis. The aim of this study was to evaluate the effect of SFN on the expression of cytochrome P450 involved in the estrogen metabolism in breast cancer cell lines MCF7 and MDA‐MB‐231 and in non‐tumorigenic MCF10A cell line. The expression of CYP19, CYP1A1, 1A2, 1B1 was determined at the transcript and protein levels. There were found some remarkable differences in the effect of SFN at a dose of 5 µmol/L on CYP19 expression: in ER(+) MCF7 significant reduction, in ER(−) MDA‐MB‐231 an increased expression and unchanged expression in MCF10A cell line. The effect of SFN on CYPs (1A1, 1A2, 1B1) involved in estrogen catabolism was to a lesser extent dependent on breast cell line. The slightly reduced CYP1A1 protein level was observed in all cell lines tested. An increased level of CYP1A2 and decreased level of CYP1B1 expression were found in MCF10A. These results indicate that the naturally occurring L isomer of SFN may affect the expression of P450s involved in estrogen metabolism. This effect may contribute to the anticancer activity of SFN in breast tissue. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-19T01:17:05.011063-05:
      DOI: 10.1002/ptr.5232
  • Phloroglucinols from Anti‐Microbial Deposit‐Resins of
           Australian Stingless Bees (Tetragonula carbonaria)
    • Authors: C. Flavia Massaro; Thomas J. Smyth, W. Franklin Smyth, Tim Heard, Sara D. Leonhardt, Mohammad Katouli, Helen M. Wallace, Peter Brooks
      Abstract: Stingless bees accumulate deposits of plant resins that are mixed with beeswax to produce propolis. Previous studies have reported anti‐microbial constituents of stingless bee (Tetragonula carbonaria) propolis from East Australia, but several components remained to be characterized. In the search of natural products yet unreported for Australian propolis, four bee deposit‐resins of T. carbonaria bees were analysed by gas and liquid chromatography mass spectrometry with accurate mass measurements. Ethanolic extracts of the deposit‐resins were tested in vitro against Staphylococcus aureus ATCC 25983 and Pseudomonas aeruginosa ATCC 27853 by the agar diffusion method. Phloroglucinols, flavonoids and isoprenoids were identified in samples. The crude extracts showed strong anti‐staphylococcal effects but were less active against the Gram‐negative bacterium. The diagnostic data enabled the identification of markers that can be used for profiling other Australian propolis sources and to target the isolation of bioactive phloroglucinols in future studies against antibiotic resistant S. aureus strains. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-18T00:23:10.854374-05:
      DOI: 10.1002/ptr.5225
  • Expression of BDNF and TH mRNA in the Brain Following Inhaled
           Administration of α‐Pinene
    • Authors: Hikaru Kasuya; Narumi Okada, Mika Kubohara, Tadaaki Satou, Yoshinori Masuo, Kazuo Koike
      Abstract: Essential oils are mainly administered by inhalation. Administration by inhalation is considered to occur through two pathways, neurological transfer and pharmacological transfer. However, the relationship between the two routes is not clear. To clarify this relationship, we administered α‐pinene, which has an anxiolytic‐like effect, to mice. Emotional behavior and accumulation and expression of relevant mRNAs in the brain (brain‐derived neurotrophic factor (BDNF); tyrosine hydroxylase (TH)) were examined following inhaled administration of α‐pinene (10 μL/L air for 60 or 90 min). To evaluate the anxiolytic‐like effect, the elevated plus maze (EPM) test was used. Inhalation of α‐pinene for 60 min produced a significant increase in the total distance traveled in the EPM test compared with control (water). The concentration of α‐pinene in the brain after 60 min of inhalation was significantly increased compared with that after 90 min of inhalation. The expression of BDNF mRNA in the olfactory bulb and in the hippocampus was almost the same after 60 min of inhalation compared to that after 90 min of inhalation. The expression of TH mRNA in the midbrain after 60 min of inhalation was significantly increased compared with that of the control. Thus, an increase in α‐pinene in the brain induces an increase in TH mRNA expression and increases locomotor activity. The anxiolytic‐like effect may be related to both neurological transfer and pharmacological transfer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-17T02:46:32.332697-05:
      DOI: 10.1002/ptr.5224
  • The Standardized BHH10 Extract, a Combination of Astragalus membranaceus,
           Cinnamomum cassia, and Phellodendron amurense, Reverses Bone Mass and
           Metabolism in a Rat Model of Postmenopausal Osteoporosis
    • Authors: Jeong‐Eun Huh; Soo‐Jeong Kim, Jung‐Won Kang, Dong‐Woo Nam, Do‐Young Choi, Dong‐Suk Park, Jae‐Dong Lee
      Abstract: Jasin‐hwan‐gagambang (BHH10), a modified prescription of Jasin‐hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)‐induced rats. Sprague–Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17β‐estradiol (E2). BHH10 treatment significantly inhibited OVX‐induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low‐density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C‐telopeptide type 1 collagen, and bone morphogenetic protein‐2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10‐treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN‐treated or E2‐treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2014-09-17T02:33:17.413168-05:
      DOI: 10.1002/ptr.5218
  • Modulation of Radiation‐Induced Alterations in Oxidative Stress and
           Cytokine Expression in Lung Tissue by Panax Ginseng Extract
    • Authors: Seong Soon Jang; Hyeong Geug Kim, Jong Min Han, Jin Seok Lee, Min Kyung Choi, Gil Ja Huh, Chang Gue Son
      Abstract: We investigated the modulating effect of Panax ginseng extract (PGE) on radiation‐induced lung injury (RILI) by measuring early changes in oxidative stress levels, cytokine expression, and the histopathology of mouse lung tissue treated with high dose of X‐ray radiation. The mice were pretreated with 25, 50, and 100‐mg/kg doses of PGE orally for four consecutive days, and their thoraces were then exposed to 15‐Gy X‐ray radiation 1 h after the last administration of PGE on day 4. The pretreatments with 50 and 100 mg/kg PGE led to significant reductions in the elevation of lipid peroxidation levels at 2 and 10 days, respectively, after irradiation. The mice pretreated with PGE exhibited dose‐dependent reductions in the irradiation‐induced production of tumor necrosis factor α and transforming growth factor β1 cytokines 10 days after irradiation, with these reductions nearly reaching the control levels after the 100‐mg/kg dose. Furthermore, together with providing significant protection against reductions in catalase activity and glutathione content, pretreatment with 100 mg/kg PGE resulted in a marked attenuation of the severity of inflammatory changes in lung tissue 10 days after irradiation. A high pretreatment dose of PGE may be a useful pharmacological approach for protection against RILI. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-15T01:25:54.24004-05:0
      DOI: 10.1002/ptr.5223
  • Chemical Composition and Antimicrobial Activity of the Essential Oil of
           Apricot Seed
    • Authors: Hyun‐hee Lee; Jeong‐Hyun Ahn, Ae‐Ran Kwon, Eun Sook Lee, Jin‐Hwan Kwak, Yu‐Hong Min
      Abstract: In traditional oriental medicine, apricot (Prunus armeniaca L.) seed has been used to treat skin diseases such as furuncle, acne vulgaris and dandruff, as well as coughing, asthma and constipation. This study describes the phytochemical profile and antimicrobial potential of the essential oil obtained from apricot seeds (Armeniacae Semen). The essential oil isolated by hydrodistillation was analysed by gas chromatography–mass spectroscopy. Benzaldehyde (90.6%), mandelonitrile (5.2%) and benzoic acid (4.1%) were identified. Disc diffusion, agar dilution and gaseous contact methods were performed to determine the antimicrobial activity against 16 bacteria and two yeast species. The minimum inhibitory concentrations ranged from 250 to 4000, 500 to 2000 and 250 to 1000 µg/mL for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The minimum inhibitory doses by gaseous contact ranged from 12.5 to 50, 12.5 to 50 and 3.13 to 12.5 mg/L air for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The essential oil exhibited a variable degree of antimicrobial activity against a range of bacteria and yeasts tested. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-15T00:59:17.065597-05:
      DOI: 10.1002/ptr.5219
  • Tolerance of Phellodendron amurense Bark Extract (Nexrutine®) in
           Patients with Human Prostate Cancer
    • Authors: Gregory P. Swanson; William E. Jones, Chul S. Ha, Carol A. Jenkins, Addanki Pratap Kumar, Joseph Basler
      Abstract: Phellodendron amurense bark extract (Nexrutine®) has shown a favorable effect on prostate cancer in vivo and in vitro. We evaluated its tolerance in patients undergoing surgery or radiation for prostate cancer. Patients received Nexrutine® orally (500 mg tid) either 1 to 2 months preoperatively or 1 to 2 months prior to and with radiation therapy. Common Terminology Criteria for Adverse Events were used to measure tolerance. In total, 21 patients (9 surgery and 12 radiation) underwent treatment. During the Nexrutine® alone component, there were two transient grade 3 toxicities (hypokalemia and urinary incontinence). There was no grade 4 toxicity. For the combined Nexrutine® and radiation component, no additional patients suffered a grade 3 toxicity. All the toxicities were transient. By the end of the neoadjuvant treatment, 81% of the patients had a decline in prostate‐specific antigen. This is the first report of patients with prostate cancer being treated with P. amurense bark extract, and it was very well tolerated. Toxicities were minimal and self‐limited. This compound can be safely used in further evaluation of a treatment effect on cancer. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-09T21:36:29.73631-05:0
      DOI: 10.1002/ptr.5221
  • Evaluation of Inhibitory Effects of Caffeic acid and Quercetin on Human
           Liver Cytochrome P450 Activities
    • Authors: Himanshu Rastogi; Snehasis Jana
      Abstract: When herbal drugs and conventional allopathic drugs are used together, they can interact in our body which can lead to the potential for herb–drug interactions. This work was conducted to evaluate the herb–drug interaction potential of caffeic acid and quercetin mediated by cytochrome P450 (CYP) inhibition. Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of caffeic acid and quercetin. IC50, Ki values, and the types of inhibition were determined. Both caffeic acid and quercetin were potent competitive inhibitors of CYP1A2 (Ki = 1.16 and 0.93 μM, respectively) and CYP2C9 (Ki = 0.95 and 1.67 μM, respectively). Caffeic acid was a potent competitive inhibitor of CYP2D6 (Ki = 1.10 μM) and a weak inhibitor of CYP2C19 and CYP3A4 (IC50 > 100 μM). Quercetin was a potent competitive inhibitor of CYP 2C19 and CYP3A4 (Ki = 1.74 and 4.12 μM, respectively) and a moderate competitive inhibitor of CYP2D6 (Ki = 18.72 μM). These findings might be helpful for safe and effective use of polyphenols in clinical practice. Our data indicated that it is necessary to study the in vivo interactions between drugs and pharmaceuticals with dietary polyphenols. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-08T01:38:07.903895-05:
      DOI: 10.1002/ptr.5220
  • Anti‐Proliferative Properties of Kahweol in Oral Squamous Cancer
           Through the Regulation Specificity Protein 1
    • Authors: Jung‐Il Chae; Young‐Joo Jeon, Jung‐Hyun Shim
      Abstract: Kahweol, the coffee‐specific deterpene, has been shown to have potential anti‐cancer effects against several cancers. However, the molecular mechanisms underlying the anti‐cancer activity of kahweol have not yet established. In this study, we investigated whether kahweol could show anti‐cancer effects on oral squamous cell lines (OSCCs), HN22 and HSC4. We conducted an 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxy‐phenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay, 4′‐6‐diamidino2‐phenylindole (DAPI) staining, propidium iodide staining, immunocytochemistry, and Western blot analysis for the characterization of kahweol and the underlying signaling pathway. We determined that kahweol‐treated cells showed significantly decreased cell viability and increased nuclear condensation and an increased sub‐G1 population in OSCCs. Interestingly, suppression of the transcription factor specificity protein 1 (Sp1) was followed by induced apoptosis by kahweol in a dose‐dependent manner. In addition, kahweol modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and anti‐apoptotic proteins, resulting in apoptosis. Taken together, results from these findings suggest that kahweol may be a potential anti‐cancer drug candidate to induce apoptotic cell death through downregulation of Sp1 in OSCCs. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-09-08T01:30:43.228251-05:
      DOI: 10.1002/ptr.5217
  • Evaluation of Hemostatic and Anti‐inflammatory Activities of
           Extracts from Different Lagochilus Species in Experimental Animals:
           Comparison of Different Extractives and Sources
    • Authors: Ying Jiao; Pei‐Hua Chen, Ai‐Zhen Xiong, Zheng‐Tao Wang, Karl Wah‐Keung Tsim, Gui‐Xin Chou, Hong Xu
      Abstract: Different members of Lagochilus genus have been used in folkloric medicine to treat hemorrhages and inflammation. However, only a few species of them have received scientific attention supporting their efficacy. Here, the hemostatic and antiinflammatory activities of five Lagochilus species were determined and compared by using in vivo assays. The results showed that the extracts of Lagochilus lanatonodus and Lagochilus diacanthophyllus showed better hemostatic activities among five species. The high doses of L. lanatonodus extracts were able to shorten the values of thrombin time, activated partial thromboplastin time and prothrombin time in a rat model. Moreover, the extracts of L. lanatonodus and L. diacanthophyllus showed strong inhibitory effects on the acute phase of inflammation in both xylene‐induced ear edema mouse model and carrageenan‐induced paw edema rat model. In parallel, the treatment of these extracts modulated the expressions of those inflammatory parameters, that is, nitric oxide, prostaglandin E2, inducible nitric oxide synthase, malondialdehyde and superoxide dismutase. L. lanatonodus and L. diacanthophyllus showed better hemostatic and antiinflammatory activities in several test models: these results therefore supported the folkloric utilization. L. lanatonodus was found to be the most active Lagochilus species. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-29T23:39:58.93252-05:0
      DOI: 10.1002/ptr.5216
  • Cancer Patients at Risk of Herb/Food Supplement–Drug Interactions: A
           Systematic Review
    • Authors: Saud M. Alsanad; Elizabeth M. Williamson, Rachel L. Howard
      Abstract: Herbal medicines and dietary supplements are commonly taken by patients with cancer, leading to concern over interactions with conventional medicines. A literature search was carried out to identify published studies exploring supplement use by patients with a cancer diagnosis. A total of 818 articles were retrieved using the key words, but only 41 are judged to be relevant based on title. Following the review of the abstracts, ten papers were considered to be potentially relevant, but of these, only two met the selection criteria, and three additional papers were identified from published reviews. Of 806 patients surveyed, 433 (53.7%) were reported to be taking combinations of supplements and drugs, and 167 incidents of risk were identified, affecting 60 patients (13.9%). The interactions identified were mainly theoretical and not supported by clinical data. No studies reported any adverse events associated with these combinations; most did not record the actual drug combinations taken, and the risk potential of some supplements appears to have been over‐estimated. More effort should be made to investigate supplement use in this vulnerable patient group, based on sound evidence of plausible interaction, not only to avoid harm but also to provide reassurance where appropriate if the patient wishes to take a particular supplement. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-26T06:09:30.043259-05:
      DOI: 10.1002/ptr.5213
  • The Protective Effects of Rhodiola crenulata Extracts on Drosophila
           melanogaster Gut Immunity Induced by Bacteria and SDS Toxicity
    • Authors: Caixia Zhu; Fachun Guan, Chao Wang, Li Hua Jin
      Abstract: The aim of this study was to observe the effect of the Rhodiola crenulata extracts on gut immunity of Drosophila melanogaster. Wild‐type flies fed standard cornmeal–yeast medium were used as controls. Experimental groups were supplemented with 2.5% R. crenulata aqueous extracts in standard medium. Survival rate was determined by feeding pathogenic microorganisms and toxic compounds. The levels of reactive oxygen species and dead cells were detected by dihydroethidium and 7‐amino‐actinomycin D staining, respectively. The expression of antimicrobial peptides was evaluated by quantitative polymerase chain reaction, and morphological change of the intestine was imaged by an Axioskop 2 plus microscope. The results demonstrate that R. crenulata increased the survival rates of adult flies and expression of antimicrobial peptide genes after pathogen or toxic compound ingestion. Moreover, decreased levels of reactive oxygen species and epithelial cell death were associated with results in improved intestinal morphology. The pharmacological action of R. crenulata from Tibet was greater than that from Sichuan. These results indicate that the R. crenulata extracts from Tibet had better pharmacological effect on D. melanogaster gut immunity after ingestion of pathogens and toxic compounds. These results may provide the pharmacological basis for prevention of inflammatory diseases of the intestine. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-22T04:34:08.631529-05:
      DOI: 10.1002/ptr.5215
  • Effects of Supplementation with Heracleum persicum Fruit Extract on Serum
           Lipids in Patients Undergoing Coronary Angiography: A Pilot Trial
    • Authors: Yahya Dadjo; Yunes Panahi, Bahram Pishgoo, Amirhossein Sahebkar, Hamidreza Taghipour, Ahmad Akbari, Shahram Parvin
      Abstract: Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the Iranian traditional medicine and also a safe and common dietary spice. The present pilot study aimed to investigate the impact of supplementation with H. persicum fruits on serum lipid concentrations in a group of patients with minimal coronary artery disease. Subjects who were diagnosed with  0.05). However, serum triglycerides levels were reduced after H. persicum extract supplementation in a borderline significant manner (p = 0.063). Short‐term supplementation with H. persicum fruit extract might be used as an adjunctive treatment for patients with hypertriglyceridemia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-19T06:11:39.153698-05:
      DOI: 10.1002/ptr.5214
  • Effect of Kuwanon G Isolated from the Root Bark of Morus alba on
           Ovalbumin‐induced Allergic Response in a Mouse Model of Asthma
    • Authors: Hyo Won Jung; Seok Yong Kang, Jong Seong Kang, A Ryun Kim, Eun‐Rhan Woo, Yong‐Ki Park
      Pages: n/a - n/a
      Abstract: The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)‐induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA‐specific IgE and Th2 cytokines (IL‐4, IL‐5, and IL‐13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA‐specific IgE and IL‐4, IL‐5, and IL‐13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-13T06:05:25.635971-05:
      DOI: 10.1002/ptr.5191
  • Alkali‐Soluble Polysaccharide, Isolated from Lentinus edodes,
           Induces Apoptosis and G2/M Cell Cycle Arrest in H22 Cells Through
           Microtubule Depolymerization
    • Authors: Ru‐xu You; Jin‐yu Liu, Shi‐jun Li, Liu Wang, Kai‐ping Wang, Yu Zhang
      Pages: n/a - n/a
      Abstract: The aim of the study was to evaluate the pro‐apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN‐induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca2+. In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN‐induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti‐tumour effect of LTN. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-11T06:28:19.018762-05:
      DOI: 10.1002/ptr.5209
  • Antiinflammatory Properties of the Stem‐bark of Anopyxis klaineana
           and its Major Constituent, Methyl Angolensate
    • Authors: Evelyn A. Mireku; Abraham Y. Mensah, Merlin L. K. Mensah, Derek A. Tocher, Solomon Habtemariam
      Pages: n/a - n/a
      Abstract: Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West African folkloric medicines that has never been investigated for its pharmacological effects or phytochemical constituents. In the present study, the antiinflammatory properties of the stem‐bark extracts were evaluated using the carrageenan‐induced paw oedema model in chicks. The petroleum ether, ethyl acetate and methanol extracts all showed a time and dose‐dependent antiinflammatory effect over the 5‐h observation period. Phytochemical analysis of the most active extract (methanol extract) yielded the principal constituent that was identified as methyl angolensate through extensive spectroscopic and X‐ray analysis studies. Although slightly less potent (ED50, 4.05 ± 0.0034 mg/kg, orally) than the positive control, diclofenac (ED50, 2.49 ± 0.023, intraperitoneally n = 5), this first ever compound isolated from A. klaineana showed promising antiinflammatory activity that may account to some of the reported medicinal uses of the plant. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-11T05:59:44.307133-05:
      DOI: 10.1002/ptr.5212
  • Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and
           Hairless Mice
    • Authors: Eunson Hwang; Sang‐Yong Park, Hyun Ji Lee, Tae Youp Lee, Zheng‐wang Sun, Tae Hoo Yi
      Abstract: Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin‐6, and MMP‐1 were significantly suppressed, and type I procollagen expression was stimulated in UVB‐irradiated and GA‐treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP‐1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor‐β1. Our data indicate that GA is a potential candidate for the prevention of UVB‐induced premature skin aging. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-08T01:33:04.742814-05:
      DOI: 10.1002/ptr.5198
  • Eugenia punicifolia (Kunth) DC. as an Adjuvant Treatment for Type‐2
           Diabetes Mellitus: A non‐Controlled, Pilot Study
    • Authors: Débora Simone Sales; Fabio Carmona, Bruna Cestari Azevedo, Silvia Helena Taleb‐Contini, Ana Carolina Duó Bartolomeu, Fernando B. Honorato, Edson Z. Martinez, Ana Maria Soares Pereira
      Abstract: Type‐2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type‐2 DM. Fifteen patients were enrolled in a pilot, non‐controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid‐stimulating hormone, C‐reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin‐3‐O‐rhamnoside, quercetin‐3‐O‐galactoside, quercetin‐3‐O‐xyloside, quercetin‐3‐O‐rhamnoside, kaempferol‐3‐O‐rhamnoside, phytol, gallic acid, and trans‐caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type‐2 DM and deserve further investigation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-06T07:40:47.985891-05:
      DOI: 10.1002/ptr.5206
  • Lipid‐Lowering Effects of Curcumin in Patients with Metabolic
           Syndrome: A Randomized, Double‐Blind, Placebo‐Controlled Trial
    • Authors: Yi‐Sun Yang; Ying‐Fang Su, Hui‐Wen Yang, Yu‐Hsien Lee, Janet I. Chou, Kwo‐Chang Ueng
      Abstract: Human studies of curcumin extract on lipid‐lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty‐five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high‐density lipoprotein cholesterol (HDL‐C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p 
      PubDate: 2014-08-06T07:35:50.344871-05:
      DOI: 10.1002/ptr.5197
  • Effects of Smilaxchinoside A and Smilaxchinoside C, Two Steroidal
           Glycosides from Smilax riparia, on Hyperuricemia in a Mouse Model
    • Authors: Xiao‐Hui Wu; Chong‐Zhi Wang, Jun Zhang, Shu‐Qing Wang, Lide Han, Yan‐Wen Zhang, Chun‐Su Yuan
      Abstract: The roots and rhizomes of Smilax riparia, called ‘Niu‐Wei‐Cai’ in traditional Chinese medicine, are believed to be effective in treating the symptoms of gout. However, the active constituents and their uricosuric mechanisms are unknown. In this study, we isolated two steroidal glycosides, named smilaxchinoside A and smilaxchinoside C, from the total saponins obtained from the ethanol extract of the roots of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We observed that these two steroidal glycosides possess potent uricosuric activities, and the observed effects accompanied the reduction of renal mURAT1 and the inhibition of xanthine oxidase, which contribute to the enhancement of uric acid excretion and the reduction of hyperuricemia‐induced renal dysfunction. Smilaxchinoside A and smilaxchinoside C may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-06T00:13:47.100955-05:
      DOI: 10.1002/ptr.5207
  • Investigation of the Efficacy of Adjunctive Therapy with
           Bioavailability‐Boosted Curcuminoids in Major Depressive Disorder
    • Authors: Yunes Panahi; Roghayeh Badeli, Nima Karami, Amirhossein Sahebkar
      Abstract: Current medications have limited efficacy in controlling the symptoms of major depressive disorder (MDD), and are associated with several adverse events on long‐term use. Curcuminoids are extremely safe and multifunctional phytopharmaceuticals that have been shown to alleviate depressive symptoms in a variety of experimental models. The present study aimed to investigate the efficacy of curcuminoids as an add‐on to standard antidepressants in patients with MDD. One hundred and eleven subjects were assigned to standard antidepressive therapy plus curcuminoids–piperine combination (1000–10 mg/day; n = 61) or standard antidepressive therapy alone (n = 50) for a period of 6 weeks. Efficacy measures were changes in the psychological status on the basis of the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI‐II). The BDI‐II and HADS total and subscale scores were reduced by the end of trial in both study groups. There were significantly greater reductions in total HADS score and subscales of anxiety and depression in the curcuminoids versus control group (p 
      PubDate: 2014-08-04T06:26:29.744501-05:
      DOI: 10.1002/ptr.5211
  • Effects of Five Ayurvedic Herbs on Locomotor Behaviour in a Drosophila
           melanogaster Parkinson's Disease Model
    • Authors: R. L. M. Jansen; B. Brogan, A. J. Whitworth, E. J. Okello
      Abstract: Current conventional treatments for Parkinson's disease (PD) are aimed at symptom management, as there is currently no known cure or treatment that can slow down its progression. Ayurveda, the ancient medical system of India, uses a combination of herbs to combat the disease. Herbs commonly used for this purpose are Zandopa (containing Mucuna pruriens), Withania somnifera, Centella asiatica, Sida cordifolia and Bacopa monnieri. In this study, these herbs were tested for their potential ability to improve climbing ability of a fruit fly (Drosophila melanogaster) PD model based on loss of function of phosphatase and tensin‐induced putative kinase 1 (PINK1). Fruit flies were cultured on food containing individual herbs or herbal formulations, a combination of all five herbs, levodopa (positive control) or no treatment (negative control). Tests were performed in both PINK1 mutant flies and healthy wild‐type (WT) flies. A significant improvement in climbing ability was observed in flies treated with B. monnieri compared with untreated PINK1 mutant flies. However, a significant decrease in climbing ability was observed in WT flies for the same herb. Centella asiatica also significantly decreased climbing ability in WT flies. No significant effects were observed with any of the other herbs in either PINK1 or WT flies compared with untreated flies. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-04T06:01:37.095359-05:
      DOI: 10.1002/ptr.5199
  • The Protective Effects of a Polyphenol‐Enriched Protein Powder on
           Exercise‐Induced Susceptibility to Virus Infection
    • Authors: Maryam Ahmed; Dru A. Henson, Matthew C. Sanderson, David C. Nieman, Nicholas D. Gillitt, Mary Ann Lila
      Abstract: Prolonged and intensive exercise induces transient immunosuppression and is associated with an increased risk and severity of infections. The goal of this study was to characterize the antiviral and antibacterial properties of the bioactive metabolites of a blueberry–green tea‐polyphenol soy protein complex (PSPC) in the serum of supplemented subjects during a 3‐day intensified training period. Long‐distance runners, randomly divided into two groups, ingested 40 g/day PSPC or placebo (soy protein and colorings) for 17 days, with a 3‐day running period inserted at day 14. Blood serum samples were collected pre‐14 days and post‐14 days supplementation, and immediately and 14 h after the third day of running. The post‐exercise serum from both groups significantly promoted the growth of Escherichia coli and Staphylococcus aureus in culture by 20–70%, but returned to normal levels following recovery. Furthermore, the serum from subjects ingesting PSPC did not display antibacterial properties at any time point. In contrast, there was a significant difference in the ability of serum from PSPC‐supplemented versus placebo‐supplemented athletes to protect cells in culture from killing by vesicular stomatitis virus following strenuous exercise. In addition, the serum of subjects who ingested PSPC significantly delayed an exercise‐induced increase in virus replication. These results indicate that polyphenol complexes containing blueberry and green tea have the potential to protect athletes from virus infections following rigorous exercise. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T03:21:43.671858-05:
      DOI: 10.1002/ptr.5208
  • Involvement of Cerebral Nervous System Areas and Cytokines on
           Antihyperalgesic and Anti‐Inflammatory Activities of Kielmeyera
           rugosa Choisy (Calophyllaceae) in Rodents
    • Authors: M.S. Melo; R.G. Brito, P.L. Santos, P.C.L. Nogueira, V.R.S. Moraes, M.C.P. Matos, J.N.S. Ferro, E.O. Barreto, W. Lucca Junior, M.A. Botelho, L.J. Quintans Junior
      Abstract: Kielmeyera rugosa is a medicinal plant known in Northeastern Brazil as ‘pau‐santo’, and it is used in the treatment of several tropical diseases such as malaria, schistosomiasis, and leishmaniasis. We evaluated antihyperalgesic and anti‐inflammatory activities of methanol stem extract of K. rugosa (MEKR) in mice. The mechanical hyperalgesia induced by carrageenan and tumor necrosis factor‐alpha (TNF‐α), prostaglandin E2, and dopamine were assessed. We also investigated the anti‐inflammatory effect of MEKR on carrageenan‐induced pleurisy and paw edema. Ninety minutes after the treatment, the animals were submitted to an imunofluorescence for Fos protein. MEKR (100, 200, and 400 mg/kg; p.o.) inhibited the development of mechanical hypernociception and edema. MEKR significantly decreased TNF‐α and interleukin 1β levels in pleural lavage and suppressed the recruitment of leukocytes. MEKR (1, 10, and 100 mg/mL) did not produce cytotoxicity, determined using the methyl‐thiazolyl‐tetrazolium assay in vitro. The locomotor activity was not affected. MEKR activated significantly the bulb olfactory, piriform cortex, and periaqueductal gray of the central nervous system. Our results provide first time evidence to propose that MEKR attenuates mechanical hyperalgesia and inflammation, in part, through an activation of central nervous system areas, mainly the periaqueductal gray and piriform cortex areas. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T01:46:38.761566-05:
      DOI: 10.1002/ptr.5205
  • Effects of Eucommia ulmoides Extract on Longitudinal Bone Growth Rate in
           Adolescent Female Rats
    • Authors: Ji Young Kim; Jeong‐Il Lee, MiKyung Song, Donghun Lee, Jungbin Song, Soo Young Kim, Juyeon Park, Ho‐Young Choi, Hocheol Kim
      Abstract: Eucommia ulmoides is one of the popular tonic herbs for the treatment of low back pain and bone fracture and is used in Korean medicine to reinforce muscles and bones. This study was performed to investigate the effects of E. ulmoides extract on longitudinal bone growth rate, growth plate height, and the expressions of bone morphogenetic protein 2 (BMP‐2) and insulin‐like growth factor 1 (IGF‐1) in adolescent female rats. In two groups, we administered a twice‐daily dosage of E. ulmoides extract (at 30 and 100 mg/kg, respectively) per os over 4 days, and in a control group, we administered vehicle only under the same conditions. Longitudinal bone growth rate in newly synthesized bone was observed using tetracycline labeling. Chondrocyte proliferation in the growth plate was observed using cresyl violet dye. In addition, we analyzed the expressions of BMP‐2 and IGF‐1 using immunohistochemistry. Eucommia ulmoides extract significantly increased longitudinal bone growth rate and growth plate height in adolescent female rats. In the immunohistochemical study, E. ulmoides markedly increased BMP‐2 and IGF‐1 expressions in the proliferative and hypertrophic zones. In conclusion, E. ulmoides increased longitudinal bone growth rate by promoting chondrogenesis in the growth plate and the levels of BMP‐2 and IGF‐1. Eucommia ulmoides could be helpful for increasing bone growth in children who have growth retardation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T00:34:35.834751-05:
      DOI: 10.1002/ptr.5195
  • Apple Polyphenol Extracts Protect Against Aspirin‐induced Gastric
           Mucosal Damage in Rats
    • Authors: Gunaranjan Paturi; Christine A. Butts, Kerry L. Bentley‐Hewitt, Tony K. McGhie, Zaid S. Saleh, Andrew McLeod
      Abstract: The protective role of two apple polyphenol extracts, Douglas‐FB (FB) and Douglas‐EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague–Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10‐day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10−2 m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10‐day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-28T06:20:14.25098-05:0
      DOI: 10.1002/ptr.5210
  • Phytochemistry and Antileishmanial Activity of the Leaf Latex of Aloe
           calidophila Reynolds
    • Authors: Fetene Abeje; Daniel Bisrat, Asrat Hailu, Kaleab Asres
      Abstract: Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC50 values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, 1H NMR, and 13C NMR spectral data. The isolated compounds showed strong antileishmanial activity with IC50 values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC50 = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost‐effective antileishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-28T05:29:48.454181-05:
      DOI: 10.1002/ptr.5204
  • A Chemically Standardized Extract of Ziziphus jujuba Fruit (Jujube)
           Stimulates Expressions of Neurotrophic Factors and Anti‐oxidant
           Enzymes in Cultured Astrocytes
    • Authors: Jianping Chen; Artemis L. Yan, Kelly Y. C. Lam, Candy T. W. Lam, Ning Li, Ping Yao, Aizhen Xiong, Tina T. X. Dong, Karl W. K. Tsim
      Abstract: The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as a health supplement worldwide. To study the role of jujube in brain benefits, the expression of neurotrophic factors and anti‐oxidant enzymes in the jujube‐treated cultured astrocytes was determined. Application of a chemical standardized water extract of jujube in cultured astrocytes for 24 h stimulated the expressions of nerve growth factor, brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor in a concentration‐dependent manner. The pre‐treatment with H89, a protein kinase A inhibitor, attenuated the jujube‐induced expression of neurotrophic factors. In parallel, the treatment of jujube water extract induced the transcriptional expressions of the enzymes responsible for anti‐oxidation, i.e. NAD(P)H: quinine oxidoreductase 1, glutamate‐cysteine ligase catalytic subunit, glutamate‐cysteine ligase modifier subunit and glutathione S‐transferase, in a concentration‐dependent manner. These results proposed the benefits of jujube in regulating expressions of neurotrophic factors and anti‐oxidant enzymes in cultured astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-28T05:21:06.635852-05:
      DOI: 10.1002/ptr.5202
  • Anti‐inflammatory Effects of Ginsenosides Rg5, Rz1, and Rk1:
           Inhibition of TNF‐α‐induced NF‐κB,
           COX‐2, and iNOS transcriptional expression
    • Authors: Sang Myung Lee
      Abstract: In the course of this experiment on the anti‐inflammatory effect of ginsenosides, protopanaxdiol ginsenosides have shown inhibition activities in inflammatory responses: NF‐κB, COX‐2, and iNOS were induced by TNF‐α. The responses of this experiment were evaluated by NF‐κB‐luciferase assay and RT‐PCR experiment of COX‐2 and iNOS genes. The NF‐κB expressions were inhibited by ginsenosides Rd, Rg5, Rz1, and Rk1 in a dose‐dependent manner. The IC50 values were 3.47, 0.61, 0.63, and 0.75 μM, respectively. Particularly, ginsenosides Rg5, Rz1, and Rk1 as converted ginsenosides from primary protopanaxdiol ginsenosidess significantly inhibited COX‐2 and iNOS gene expression. These inhibition levels were similar to sulfasalazine as reference material. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-20T23:19:11.100975-05:
      DOI: 10.1002/ptr.5203
  • Antiinflammatory, Antioxidant, and Immunological Effects of Carum copticum
           L. and Some of Its Constituents
    • Authors: Azam Alavinezhad; Mohammad Hossein Boskabady
      Abstract: Carum copticum L. has been used traditionally for its various therapeutic effects. The plant contains various components such as thymol and carvacrol. Different therapeutic effects such as antifungal, antioxidant, antibacterial, antiparasitic, and antilipidemic were described for the plant and its constituents. Therefore, antiinflammatory, antioxidant, and immunological effects of C. copticum and its constituents, thymol and carvacrol, were discussed in the present review. Previous studies have shown potent antiinflammatory, antioxidant, and immunological effects for C. copticum and its constituents, thymol and carvacrol. Therefore, the plant and its constituents have therapeutic values in several inflammatory and immunological disorders as well as in the oxidative stress conditions. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-20T22:11:24.051702-05:
      DOI: 10.1002/ptr.5200
  • Evaluation of the Effect of Curcumin Capsules on Glyburide Therapy in
           Patients with Type‐2 Diabetes Mellitus
    • Authors: Prasad Neerati; Raju Devde, Anil Kumar Gangi
      Abstract: This study aimed to assess the possible beneficial effects of curcumin capsules as lipid‐lowering effects and as a permeability glycoprotein (P‐gp) inhibitor on the pharmacokinetics and pharmacodynamics of glyburide and as a P‐gp substrate with glyburide in patients with type‐2 diabetes mellitus. Open‐label, randomized control trial was carried out for 11 days on eight type‐2 diabetic patients on glyburide therapy. On the first day of the study, following the administration of 5 mg of glyburide, blood samples were collected from the patients at various time intervals ranging from 0.5 to 24 h. Blood sampling was repeated on the 11th day of the study, after treating the patients with curcumin for ten consecutive days. Glyburide concentrations changed at the second hour, Cmax was unchanged, the glucose levels were decreased, Area Under first Movement Curre (AUMC) was increased, and no patient has experienced the hypoglycaemia. The low‐density lipoprotein, very‐low‐density lipoprotein and triglycerides were decreased significantly, and the high‐density lipoprotein content increased. The co‐administration of curcumin capsules with glyburide may be beneficial to the patients in better glycaemic control. The lipid lowering and antidiabetic properties of the curcumin show as a potential future drug molecule. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-17T02:42:15.002799-05:
      DOI: 10.1002/ptr.5201
  • A Pilot Study on the Effectiveness of a Rose Hip Shell Powder in Patients
           Suffering from Chronic Musculoskeletal Pain
    • Authors: S. Chrubasik‐Hausmann; C. Chrubasik, E. Neumann, U. Müller‐Ladner
      Abstract: We carried out a 3‐month preliminary investigation on the effectiveness of a rose hip shell powder and its mechanism of action. Of 52 patients suffering from acute exacerbations of low back pain (n = 39) or knee pain (n = 13), 29 had participated earlier in the pilot study with the pseudofruit powder Litozin®. After assessing the baseline values, patients were offered up to 20 g of a rose hip shell powder per day. Patients were encouraged to adjust the daily dose upwards or downwards according to their symptoms for the period of 3 months. The examination for possible effectiveness was by intention‐to‐treat analysis with last observation carried forward. There was no difference in any generic or disease‐specific outcome variables between the patients consuming the rose hip shell powder and those consuming the pseudofruit powder Litozin® in the previous surveillance study. A human protein array system and fractions from the rose powders were used to study their effect on cytokine expression in vitro. The data indicate that lipophilic rose hip fractions from the shell and the pseudofruit inhibit cytokine expression and that the shell powder may be the better starting material for a future rose hip extract prepared with a lipophilic solvent. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-17T02:39:23.665587-05:
      DOI: 10.1002/ptr.5192
  • Turmeric Toxicity in A431 Epidermoid Cancer Cells Associates with
           Autophagy Degradation of Anti‐apoptotic and Anti‐autophagic
           p53 Mutant
    • Authors: Visa Thongrakard; Rossella Titone, Carlo Follo, Federica Morani, Apichart Suksamrarn, Tewin Tencomnao, Ciro Isidoro
      Abstract: The keratinocyte‐derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin‐mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small‐interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric‐treated or Curcumin‐treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-11T03:04:18.620637-05:
      DOI: 10.1002/ptr.5196
  • Review on Liver Inflammation and Antiinflammatory Activity of Andrographis
           paniculata for Hepatoprotection
    • Authors: Lee Suan Chua
      Abstract: Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-10T03:56:53.450811-05:
      DOI: 10.1002/ptr.5193
  • The Isolation of Antiprotozoal Compounds from Libyan Propolis
    • Authors: Weam Siheri; John O. Igoli, Alexander I. Gray, Ticiano G. Nasciemento, Tong Zhang, James Fearnley, Carol J. Clements, Katharine C. Carter, John Carruthers, RuAngelie Edrada‐Ebel, David G. Watson
      Abstract: Propolis is increasingly being explored as a source of biologically active compounds. Until now, there has been no study of Libyan propolis. Two samples were collected in North East Libya and tested for their activity against Trypanosoma brucei. Extracts from both samples had quite high activity. One of the samples was fractionated and yielded a number of active fractions. Three of the active fractions contained single compounds, which were found to be 13‐epitorulosal, acetyl‐13‐epi‐cupressic acid and 13‐epi‐cupressic acid, which have been described before in Mediterranean propolis. Two of the compounds had a minimum inhibitory concentration value of 1.56 µg/mL against T. brucei. The active fractions were also tested against macrophages infected with Leishmania donovani, and again moderate to strong activity was observed with the compounds having IC50 values in the range 5.1–21.9 µg/mL. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-09T05:30:23.791192-05:
      DOI: 10.1002/ptr.5194
  • Gelidium elegans, an Edible Red Seaweed, and Hesperidin Inhibit Lipid
           Accumulation and Production of Reactive Oxygen Species and Reactive
           Nitrogen Species in 3T3‐L1 and RAW264.7 Cells
    • Authors: Hui‐Jeon Jeon; Min‐Jung Seo, Hyeon‐Son Choi, Ok‐Hwan Lee, Boo‐Yong Lee
      Abstract: Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3‐L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose‐dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator‐activated receptor gamma and CCAAT/enhancer‐binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide‐induced nitric oxide production was significantly reduced in G. elegans extract‐treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator‐activated receptor gamma, CCAAT/enhancer‐binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-15T21:57:27.017879-05:
      DOI: 10.1002/ptr.5186
  • Autophagy Activation and Antiviral Activity by a Licorice Triterpene
    • Authors: Samuela Laconi; Maria A. Madeddu, Raffaello Pompei
      Abstract: The triterpene glycyrrhizic acid (GRA), the main product from the Glycyrrhiza glabra medicinal plant, is known for its antiinflammatory and antimicrobial activity. In this work, GRA was studied for its ability to induce the autophagic process activator Beclin 1 in epithelial cells and to observe how this property could influence its antiviral activity. After 24 h of treatment, GRA induced a Beclin 1 production that was more than twofold higher than that produced by rapamycin, used as a reference compound. When the compounds were added to HeLa cells together with the viruses, GRA demonstrated a strong antiherpes simplex virus type 1 (HSV1) activity, whereas rapamycin had no activity. However, if the compounds were added to the cells 24 h before the viruses, GRA induced the production of an even higher amount of Beclin 1 and showed an improved antiviral effect; under these conditions, rapamycin was also able to exert a significant anti‐HSV1 activity. In conclusion, GRA is a strong inducer of the autophagy activator Beclin 1, which establishes a resistance state to HSV1 replication. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T19:32:09.58923-05:0
      DOI: 10.1002/ptr.5189
  • A Review of the Pharmacological Effects of Piceatannol on Cardiovascular
    • Authors: Yee‐Ling Tang; Shun‐Wan Chan
      Abstract: The incidence of cardiovascular diseases (CVDs) is high in both developed and developing countries. It has a high global rate of mortality and causes heavy social burden. Drugs are available for managing or treating CVDs and its complications. Consumption of dietary supplements or functional foods for reducing the risk of CVDs has also gained wide recognition by the general public. Piceatannol, an analog and metabolite of resveratrol, is a natural stilbene commonly found in the skin of grapes and wine. Piceatannol is believed to be a potent compound with certain cardiovascular therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, and angiogenesis. It also has vasorelaxation and antioxidant activities. A comprehensive review of piceatannol concludes that piceatannol has the potential to be developed into health products for the cardiovascular system to help modern society reduce the high CVD incidence. However, further investigations are warranted in order to increase the bioavailability and understand the biological mechanisms and safety of using piceatannol. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T19:31:38.361145-05:
      DOI: 10.1002/ptr.5185
  • Anxiolytic‐Like Effect of Illicium verum Fruit Oil,
           trans‐Anethole and Related Compounds in Mice
    • Authors: Michiyo Miyagawa; Tadaaki Satou, Chihiro Yukimune, Ayumi Ishibashi, Haruna Seimiya, Hideo Yamada, Toshio Hasegawa, Kazuo Koike
      Abstract: The fruit of Illicium verum Hook. f. (star anise) is used by many as a spice. The fragrance of I. verum fruit is characteristically anise‐like. In this study, hexane‐extracted I. verum fruit oil (IVO), trans‐anethole as the main component, and related compounds (propiophenone, 4′‐methoxy‐propiophenone, trans‐β‐methylstyrene) were analyzed in order to clarify the emotional effect of inhaling the fragrance of I. verum fruit. As a result, although 4 μL/L air IVO did not exhibit an anxiolytic‐like effect, 1 μL/L air trans‐anethole exhibited a significant effect (p 
      PubDate: 2014-06-11T19:21:50.92941-05:0
      DOI: 10.1002/ptr.5190
  • Modulating Effects of Pycnogenol® on Oxidative Stress and DNA Damage
           Induced by Sepsis in Rats
    • Authors: Gökçe Taner; Sevtap Ayd��n, Merve Bacanl��, Zehra Sar��göl, Tolga Şahin, A. Ahmet Başaran, Nurşen Başaran
      Abstract: The aim of this study was to evaluate the protective effects of Pycnogenol® (Pyc), a complex plant extract from the bark of French maritime pine, on oxidative stress parameters (superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and total glutathione (GSH) and malondialdehyde (MDA) levels), an inflammatory cytokine (tumor necrosis factor alpha (TNF‐α) level) and also DNA damage in Wistar albino rats. Rats were treated with 100 mg/kg intraperitonally Pyc following the induction of sepsis by cecal ligation and puncture. The decreases in MDA levels and increases in GSH levels, and SOD and GPx activities were observed in the livers and kidneys of Pyc‐treated septic rats. Plasma TNF‐α level was found to be decreased in the Pyc‐treated septic rats. In the lymphocytes, kidney, and liver tissue cells of the sepsis‐induced rats, Pyc treatment significantly decreased the DNA damage and oxidative base damage using standard alkaline assay and formamidopyrimidine DNA glycosylase‐modified comet assay, respectively. In conclusion, Pyc treatment might have a role in the prevention of sepsis‐induced oxidative damage not only by decreasing DNA damage but also increasing the antioxidant status and DNA repair capacity in rats. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-11T07:30:52.528985-05:
      DOI: 10.1002/ptr.5184
  • Black Tea Extract and its Thearubigins Relieve the
           Sildenafil‐Induced Delayed Gut Motility in Mice: A Possible Role of
           Nitric Oxide
    • Authors: Hussam A. S. Murad; Hossam M. Abdallah
      Abstract: In this study we hypothesize that a standardized black tea aqueous extract (BTE) and thearubigins, its main polyphenolic pigments, will improve sildenafil‐induced delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty groups of mice (n = 8) were given a phenol red meal, and three sets of experiments were performed. In the first and second sets, effects of different concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in combinations, on GE and SIT were measured. In the third set, influence of nω‐Nitro‐l‐arginine methyl ester hydrochloride (l‐NAME) pretreatment on effects of these treatments was tested.Black tea extract (3% and 4.5%) and thearubigins (50 and 60 mg/kg) dose‐dependently increased GE and SIT, whereas BTE 6% and thearubigins 70 mg/kg did not affect them. Sildenafil dose‐dependently reduced both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l‐NAME with sildenafil (5 mg/kg) reversed its motility‐delaying effects. Pretreatment with l‐NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% + sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a standardized BTE and its thearubigins improve the sildenafil‐induced delayed gut motility in mice. This improvement was partially blocked by l‐NAME suggesting a possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be considered a reliever therapy for the sildenafil‐induced dyspepsia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-03T20:03:23.448158-05:
      DOI: 10.1002/ptr.5183
  • Sulforaphane Suppresses LPS‐Induced or TPA‐Induced
           Downregulation of PDCD4 in RAW 264.7 Cells
    • Authors: Jong‐Ho Cho; Young‐Woo Kim, Young‐Sam Keum
      Abstract: Sulforaphane is a natural chemopreventive isothiocyanate and abundantly found in various cruciferous vegetables. Although chemopreventive activity of sulforaphane is well documented, the detailed biochemical mechanism(s), underlying how it regulates the protein translation process to antagonize pro‐inflammatory responses are largely unclear. In the present study, we show that lipopolysaccharide (LPS) or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) treatment reduces cellular levels of PDCD4, and this event is mediated by affecting both transcription and proteolysis in RAW 264.7 cells. We show that LPS‐mediated or TPA‐mediated PDCD4 downregulation is catalyzed by the activation of intracellular Akt1 or S6K1 kinases and that sulforaphane suppresses LPS‐induced or TPA‐induced Akt1 or S6K1 activation, thereby resulting in the attenuation of PDCD4 downregulation in RAW 264.7 cells. We propose that sulforaphane suppression of PDCD4 downregulation serves as a novel molecular mechanism to control proliferation in response to pro‐inflammatory signals. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-06-03T20:02:40.855852-05:
      DOI: 10.1002/ptr.5171
  • Anticancer Activities of Essential Oils Constituents and Synergy with
           Conventional Therapies: A Review
    • Authors: Jean‐François Lesgards; Nicolas Baldovini, Nicolas Vidal, Sylvia Pietri
      First page: 1423
      Abstract: Many studies have shown that a large number of terpenoids and aromatic compounds contained in essential oils have significant anticancer activities, both on cell lines and on tumors in animals. The activity of these constituents is related to the activation of cell death (apoptosis) induced by the caspases proteins in cancer cells, with minor modifications of healthy cells. Many phenomena seem to occur, among which are as follows: overexpression and regulation of liver detoxification enzymes, changes in the membrane potential of cancer cells and mitochondria, production of free radicals in cancer cells, inhibition of angiogenesis, and modification of tumor‐inducing genes. These active essential oil constituents appear to act synergistically with conventional chemotherapy and radiotherapy, and some clinical studies in humans are beginning to be realized. In this review, we discuss about the antitumoral activity of 13 essential oil components selected among the most studied in the literature, with a focus on their possible mode of action. We also report current data on the anticancer properties of several total essential oils. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-15T23:12:35.724949-05:
      DOI: 10.1002/ptr.5165
  • Stimulative Effect of Ginsenosides Rg5:Rk1 on Murine Osteoblastic
           MC3T3‐E1 Cells
    • Authors: Muhammad Hanif Siddiqi; Muhammad Zubair Siddiqi, Sungeun Ahn, Sera Kang, Yeon‐Ju Kim, Karpagam Veerappan, Dong‐Uk Yang, Deok‐Chun Yang
      First page: 1447
      Abstract: Panax ginseng C.A. Meyer (P. ginseng), hereafter referred to as P. ginseng, is known to exert a wide range of pharmacological effects both in vitro and in vivo; however, few studies have investigated the effects of ginseng on bone metabolism. We therefore investigated the potential antiosteoporotic properties of ginseng on the growth and differentiation of murine MC3T3‐E1 cells. Rg5:Rk1 is a mixture of protopanaxadiol‐type ginsenosides, isolated from fresh P. ginseng root, via a repetitive steaming and drying process. In this study, we examined the stimulatory effects of Rg5:Rk1 on the differentiation and mineralization of MC3T3‐E1 cells. Undifferentiated cells were treated with a range of concentrations of Rg5:Rk1 (1–50 µg/mL), and cell viability was measured with the 3‐(4,5‐dimethyl‐thiazol‐2yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Treatment with Rg5:Rk1 significantly increased cell viability in a dose‐dependent manner. To investigate the possible mechanisms by which Rg5:Rk1 affects the early differentiation phase of MC3T3‐E1 cells, the cells were treated with Rg5:Rk1 for 14–24 days before assessing the levels of multiple osteoblastic markers. The markers examined included alkaline phosphatase (ALP) activity type I collagen content (Coll‐I), calcium deposition (by Alizarin Red S staining), extracellular mRNA expression of bone morphogenetic protein‐2 (BMP‐2), and the level of Runt‐related transcription factor 2 (Runx2). Rg5:Rk1 treatment also increased the activities of proteins associated with osteoblast growth and differentiation in a dose‐dependent manner. Overall, we found that the Rg5:Rk1 mixture of ginsenosides improved the osteoblastic function of MC3T3‐E1 cells by increasing their proliferative capacity. This improvement is due to the action of Rg5:Rk1 on BMP‐2, which is mediated by Runx2‐dependent pathways. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-03-19T00:22:30.033955-05:
      DOI: 10.1002/ptr.5146
  • Preliminary Safety Evaluation and Biochemical Efficacy of a Carum carvi
           Extract: Results from a Randomized, Triple‐Blind, and
           Placebo‐Controlled Clinical Trial
    • Authors: Mahnaz Kazemipoor; Che Wan Jasimah Bt Wan Mohamed Radzi, Majid Hajifaraji, Geoffrey A. Cordell
      First page: 1456
      Abstract: Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple‐blind, placebo‐controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25‐item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p 
      PubDate: 2014-03-17T19:39:43.268819-05:
      DOI: 10.1002/ptr.5147
  • Adjuvant Therapy with Bioavailability‐Boosted Curcuminoids
           Suppresses Systemic Inflammation and Improves Quality of Life in Patients
           with Solid Tumors: A Randomized Double‐Blind
           Placebo‐Controlled Trial
    • Authors: Yunes Panahi; Alireza Saadat, Fatemeh Beiraghdar, Amirhossein Sahebkar
      First page: 1461
      Abstract: Curcuminoids are bioactive polyphenolics with potent antiinflammatory properties. Although several lines of in vitro and preclinical evidence suggest potent anticancer effects of curcuminoids, clinical findings have not been conclusive. The present randomized double‐blind placebo‐controlled trial aimed to evaluate the efficacy of curcuminoids as adjuvant therapy in cancer patients. Eighty subjects with solid tumors who were under standard chemotherapy regimens were randomly assigned to a bioavailability‐boosted curcuminoids preparation (180 mg/day; n = 40) or matched placebo (n = 40) for a period of 8 weeks. Efficacy measures were changes in the health‐related quality of life (QoL) score (evaluated using the University of Washington index) and serum levels of a panel of mediators implicated in systemic inflammation including interleukins 6 (IL‐6) and 8 (IL‐8), TNF‐α, transforming growth factor‐β (TGFβ), high‐sensitivity C‐reactive protein (hs‐CRP), calcitonin gene‐related peptide (CGRP), substance P and monocyte chemotactic protein‐1 (MCP‐1). Curcuminoid supplementation was associated with a significantly greater improvement in QoL compared with placebo (p 
      PubDate: 2014-03-19T21:01:53.048264-05:
      DOI: 10.1002/ptr.5149
  • Triggering of p38 MAPK and JNK Signaling is Important for Oleanolic
           Acid‐Induced Apoptosis via the Mitochondrial Death Pathway in
           Hypertrophic Scar Fibroblasts
    • Authors: Jian‐Yu Chen; Lei Zhang, Hong Zhang, Li Su, Lu‐Ping Qin
      First page: 1468
      Abstract: Hypertrophic scarring is characterized by collagen overproduction and excessive deposition of extracellular matrix. No consensus arises currently about the best therapeutics to produce complete and permanent improvement of scars with few side effects. In the present study, the mechanism of oleanolic acid (OA)‐induced apoptosis in hypertrophic scar fibroblasts (HSFs) was investigated for the first time. OA activated the protein phosphorylation of p38 MAPK and JNK but not ERK. OA did not antagonize the inhibitory effects of SB203580 on p38 MAPK pathway activity but sharply enhanced JNK phosphorylation when HSFs were pretreated with SB203580. Similarly, the inhibition of JNK signal pathway activation by pretreatment with SP600125 facilitated the protein phosphorylation of p38 MAPK caused by OA. Inhibition of p38 MAPK and/or JNK by inhibitors significantly enhanced cell viability and OA only partially depressed the increased cell viability. Moreover, OA increased Bax translocation, MMP loss, mitochondrial cytochrome c and AIF release, Bax and caspase‐3 protein expression and the ratio of Bax to Bcl‐2, decreased Bcl‐2 protein expression, and elevated the mRNA expression of Apaf‐1, caspase‐9, and capase‐3. These results suggest that OA elicits apoptosis through triggering of p38 MAPK and JNK signaling and activation of the mitochondrial death pathway. OA might be a good and useful natural drug against hypertrophic scars. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-04-06T22:15:20.264968-05:
      DOI: 10.1002/ptr.5150
  • Inhibition of LPS‐Induced TNF‐α and NO Production in
           Mouse Macrophage and Inflammatory Response in Rat Animal Models by a Novel
           Ayurvedic Formulation, BV‐9238
    • Authors: Debendranath Dey; Sunetra Chaskar, Nitin Athavale, Deepa Chitre
      First page: 1479
      Abstract: Rheumatoid arthritis is a chronic crippling disease, where protein‐based tumor necrosis factor‐alpha (TNF‐α) inhibitors show significant relief, but with potentially fatal side effects. A need for a safe, oral, cost‐effective small molecule or phyto‐pharmaceutical is warranted. BV‐9238 is an Ayurvedic poly‐herbal formulation containing specialized standardized extracts of Withania somnifera, Boswellia serrata, Zingiber officinale and Curcuma longa. The anti‐inflammatory and anti‐arthritic effects of BV‐9238 were evaluated for inhibition of TNF‐α and nitric oxide (NO) production, in lipopolysaccharide‐stimulated, RAW 264.7, mouse macrophage cell line. BV‐9238 reduced TNF‐α and NO production, without any cytotoxic effects. Subsequently, the formulation was tested in adjuvant‐induced arthritis (AIA) and carrageenan‐induced paw edema (CPE) rat animal models. AIA was induced in rats by injecting Freund's complete adjuvant intra‐dermally in the paw, and BV‐9238 and controls were administered orally for 21 days. Arthritic scores in AIA study and inflamed paw volume in CPE study were significantly reduced upon treatment with BV‐9238. These results suggest that the anti‐inflammatory and anti‐arthritic effects of BV‐9238 are due to its inhibition of TNF‐α, and NO, and this formulation shows promise as an alternate therapy for inflammatory disorders where TNF‐α and NO play important roles. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-04-07T00:15:00.153855-05:
      DOI: 10.1002/ptr.5151
  • (−)‐Epigallocatechin‐3‐Gallate Ameliorates
           Photodynamic Therapy Responses in an In Vitro T Lymphocyte Model
    • Authors: Hang Qi; Naomi Abe, Beiwei Zhu, Yoshiyuki Murata, Yoshimasa Nakamura
      First page: 1486
      Abstract: (−)‐Epigallocatechin‐3‐gallate (EGCG), the most abundant polyphenolic constituent in green tea, is known as a powerful antioxidant but concomitantly possesses a prooxidant property. We investigated the effect of EGCG on phloxine B (PhB)‐induced photocytotoxicity in human T lymphocytic leukemia Jurkat cells. EGCG significantly potentiated PhB‐induced photocytotoxic effects, including the inhibition of cell proliferation, DNA fragmentation, and caspase‐3 activity induction in Jurkat cells. Catalase attenuated the enhanced cytotoxicity by EGCG, suggesting the involvement of extracellularly produced hydrogen peroxide. Indeed, EGCG significantly enhanced extracellular hydrogen peroxide formation induced by photo‐irradiated PhB. The EGCG also enhanced intracellular reactive oxygen species accumulation, c‐Jun N‐terminal kinase (JNK) phosphorylation, and interferon‐γ (IFN‐γ) gene expression, all of which are involved in PhB‐induced apoptosis. Taken together, our data suggest that EGCG is capable of potentiating photodynamic therapy responses, presumably through the intracellular oxidative stress‐sensitive JNK/IFN‐γ pathway by exogenous hydrogen peroxide formation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-04-03T22:06:30.67878-05:0
      DOI: 10.1002/ptr.5152
  • Effects of Black Raspberry on Lipid Profiles and Vascular Endothelial
           Function in Patients with Metabolic Syndrome
    • Authors: Han Saem Jeong; Soon Jun Hong, Tae‐Bum Lee, Ji‐Wung Kwon, Jong Tae Jeong, Hyung Joon Joo, Jae Hyoung Park, Chul‐Min Ahn, Cheol Woong Yu, Do‐Sun Lim
      First page: 1492
      Abstract: Black raspberry (Rubus occidentalis) has been known for its anti‐inflammatory and anti‐oxidant effects. However, short‐term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12‐week follow‐up. Lipid profiles, brachial artery flow‐mediated dilatation (baFMD), and inflammatory cytokines such as IL‐6, TNF‐α, C‐reactive protein, adiponectin, sICAM‐1, and sVCAM‐1 were measured at the baseline and at the 12‐week follow‐up. Decreases from the baseline in the total cholesterol level (−22.8 ± 30.4 mg/dL vs. −1.9 ± 31.8 mg/dL, p 
      PubDate: 2014-04-07T00:01:22.246008-05:
      DOI: 10.1002/ptr.5154
  • In Vitro and In Silico Evaluation of NF‐κB Targeted Costunolide
           Action on Estrogen Receptor‐Negative Breast Cancer Cells—A
           Comparison with Normal Breast Cells
    • Authors: Daisy Pitchai; Anita Roy, Sakhila Banu
      First page: 1499
      Abstract: Costunolide, a sesquiterpene lactone is a plant‐derived secondary metabolite found to be present in most of the pharmacologically active herbs, being the cause for their medicinal values. The present study aims to evaluate the cytotoxic effect of costunolide isolated from Costus speciosus rhizome extract on MDA‐MB‐231 cells and explore its targeted action in comparison with its action on the normal breast cells (MCF 10A). The effect of costunolide on cell viability of the cells was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide viability assay. The targeted action of the compound was analyzed comparing the effectiveness of the compound to alter the protein expression levels of NF‐κB subunits in the normal and the cancer cells using western blotting analysis. In silico studies were performed to predict the targeted interaction of costunolide with the NF‐κB subunit proteins. Costunolide inhibited the cell viability of MDA‐MB‐231 cells in a dose‐dependent manner leaving no significant change in the viability of the normal breast cells. The over expressed NF‐κB subunits – p65, 52 and 100 in the cancer cells were found to be downregulated when treated with costunolide at an effective dose of 20 and 40 μM costunolide. In silico results provided stable interactions between costunolide and the target proteins, supporting the in vitro results in addition. Thus, costunolide derived from C. speciosus plant source elevates a fresh conviction for its use in breast cancer therapy for its cytotoxic efficacy and non‐toxic nature. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-04-15T05:31:57.724644-05:
      DOI: 10.1002/ptr.5155
  • Asiatic Acid Reduces Blood Pressure by Enhancing Nitric Oxide
           Bioavailability with Modulation of eNOS and p47phox Expression in
           l‐NAME‐induced Hypertensive Rats
    • Authors: Sarawoot Bunbupha; Poungrat Pakdeechote, Upa Kukongviriyapan, Parichat Prachaney, Veerapol Kukongviriyapan
      First page: 1506
      Abstract: We investigated the effect of asiatic acid (AA) on hemodynamic status, vascular function, oxidative stress markers, endothelial nitric oxide synthase (eNOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression in Nω‐nitro‐l‐arginine methyl ester hydrochloride (l‐NAME)‐induced hypertensive rats. Male Sprague–Dawley rats treated with l‐NAME (40 mg/kg/day) in drinking water for 5 weeks showed significant increases in mean arterial pressure, heart rate, hindlimb vascular resistance, vascular dysfunction, superoxide anion (O2•−) production, and plasma malondialdehyde. Moreover, NO metabolite (NOx) levels were reduced, aortic eNOS expression was downregulated, and NADPH oxidase subunit p47phox was upregulated in hypertensive rats (p 
      PubDate: 2014-04-11T03:35:24.939759-05:
      DOI: 10.1002/ptr.5156
  • Prophylactic and Therapeutic Effects of Acanthopanax senticosus Harms
           Extract on Murine Collagen‐induced Arthritis
    • Authors: Yusuke Takahashi; Maki Tanaka, Ryosei Murai, Kageaki Kuribayashi, Daisuke Kobayashi, Nozomi Yanagihara, Naoki Watanabe
      First page: 1513
      Abstract: Evidences are accumulating that extract of Acanthopanax senticosus Harms (ASH; syn Eleutherococcus senticosus [Rupr. & Maxim.] Maxim), a shrub native to Northeastern Asia, has antiinflammatory effects. In this study, we examined prophylactic and therapeutic effects of ASH extract (ASHE) on rheumatoid arthritis using collagen‐induced arthritis (CIA) mouse model. Acanthopanax senticosus Harms extract was administered before the onset of arthritis in the prophylaxis model. In the therapeutic model, ASHE was administered after the onset of arthritis with or without anti‐TNF‐α antibody. The ASHE treatment showed efficacy before onset of CIA but there was no effect after CIA was established. The ASHE treatment delayed the onset and decreased severity of CIA. In vitro examinations showed that ASHE is an antioxidant and that ASHE suppresses TNF‐α and interleukin‐6 production in human peripheral blood mononuclear cells. The combination therapy with ASHE and anti‐TNF‐α antibody reduced the severity of arthritis compared with anti‐TNF‐α antibody alone. The present study shows that ASHE has prophylactic effect against CIA and support therapeutic effect of anti‐TNF‐α antibody. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2014-05-02T19:41:02.939731-05:
      DOI: 10.1002/ptr.5157
  • IQP‐GC‐101 Reduces Body Weight and Body Fat Mass: A
           Randomized, Double‐Blind, Placebo‐Controlled Study
    • Authors: Pee‐Win Chong; Zhi‐Ming Beah, Barbara Grube, Linda Riede
      First page: 1520
      Abstract: IQP‐GC‐101 is a patented blend of the standardized extracts of Garcinia cambogia, Camellia sinensis, unroasted Coffea arabica, and Lagerstroemia speciosa. These individual ingredients of IQP‐GC‐101 have each shown promise in promoting weight loss; however, the efficacy of the blend has not been established. This randomized, placebo‐controlled, double‐blind, parallel group study conducted over 14 weeks (including a 2‐week run‐in phase) aimed to investigate the efficacy and safety of IQP‐GC‐101 in reducing body weight and body fat mass in overweight Caucasian adults. Subjects took three IQP‐GC‐101 or placebo tablets, twice a day, 30 min before main meals. All subjects also adhered to a 500 kcal/day energy deficit diet with 30% of energy from fat. Ninety‐one overweight and mildly obese subjects (46 in the IQP‐GC‐101 group, 45 in the placebo group) completed the study. After 12‐week intervention, IQP‐GC‐101 resulted in a mean (±SD) weight loss of 2.26 ± 2.37 kg compared with 0.56 ± 2.34 kg for placebo (pU = 0.002). There was also significantly more reduction in body fat mass, waist circumference, and hip circumference in the IQP‐GC‐101 group. No serious adverse events were reported. The use of IQP‐GC‐101 has been shown to result in body weight and body fat reduction in the current study, with good tolerability. © 2014 InQpharm Group Sdn Bhd. Phytotherapy Research published by John Wiley & Sons, Ltd.
      PubDate: 2014-05-02T19:30:32.966362-05:
      DOI: 10.1002/ptr.5158
  • The Standardized Extract of Ziziphus jujuba Fruit (Jujube) Regulates
           Pro‐inflammatory Cytokine Expression in Cultured Murine Macrophages:
           Suppression of Lipopolysaccharide‐stimulated NF‐κB
    • Authors: Jianping Chen; Crystal Y. Q. Du, Kelly Y. C. Lam, Wendy L. Zhang, Candy T. W. Lam, Artemis L. Yan, Ping Yao, David T. W. Lau, Tina T. X. Dong, Karl W. K. Tsim
      First page: 1527
      Abstract: The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as a health supplement or herbal medicine worldwide. To study the beneficial role of jujube in regulating immune response, we investigated its roles on the expressions of pro‐inflammatory cytokines in cultured macrophages. Application of chemically standardized jujube water extract for 24 h stimulated the transcriptional expression of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α in cultured RAW 264.7 macrophages. In contrast, the pretreatment with jujube water extract suppressed the expression of IL‐1β and IL‐6, but not for TNF‐α in lipopolysaccharide (LPS)‐stimulated macrophages. The IL‐1β and IL‐6 cytokines in LPS‐induced macrophages were suppressed by jujube water extract in both mRNA and protein levels. In parallel, the inhibition of jujube water extract on the transcriptional activity of nuclear factor‐kappa B was revealed in LPS‐induced macrophages. These results verified the bidirectional immune‐modulatory roles of jujube by regulating the expressions of pro‐inflammatory cytokines in macrophages. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-07T23:25:34.611095-05:
      DOI: 10.1002/ptr.5160
  • The Effects of Galangin on a Mouse Model of Vitiligo Induced by
    • Authors: Shi‐Xia Huo; Xin‐Ming Liu, Chun‐Hui Ge, Li Gao, Xiao‐Ming Peng, Ping‐Ping Zhao, Ming Yan
      First page: 1533
      Abstract: Galangin, the main active component of Alpinia officinarum Hance, was tested in a mouse model of vitiligo induced in C57BL/6 mice by the topical application of 2 mL of 2.5% hydroquinone daily to shaved areas (2 × 2 cm) of dorsal skin for 60 days. Thirty days after the final application of hydroquinone, galangin (0.425, and 4.25 mg/kg) was administered orally for 30 days. The hair colour darkened when it grew back after treatment, and histological analysis showed that the number of melanin‐containing hair follicles had increased after treatment with all doses of galangin groups and 8‐methoxypsoralen (8‐MOP, the positive control) compared with the untreated vitiligo group (p 
      PubDate: 2014-05-13T06:23:24.582092-05:
      DOI: 10.1002/ptr.5161
  • Evaluation of Anti‐atopic Dermatitis Activity of Hypsizigus
           marmoreus Extract
    • Authors: TaeHo Kim; KiMoon Park, Hye Sun Jung, Won‐Sik Kong, DaeHoon Jeon, Seung Ho Lee
      First page: 1539
      Abstract: Hypsizigus marmoreus is an edible mushroom that is cultivated worldwide. In this study, we investigated antiinflammatory activities of H. marmoreus extract on atopic dermatitis (AD)‐like symptoms. Ethanol extract of H. marmoreus (HMEE) was administrated in powder to BALB/c mice in which AD was induced by 1‐chloro 2, 4, 6‐trinitrobenzene [picryl‐chloride, (PCL)]. The dermatitis severity score and the thickness of the epidermis were significantly decreased following daily intake of HMEE powder (1 g/kg/day) for 5 weeks compared with a PCL‐treated group. The mRNA expression of proinflammatory cytokines, such as interleukin‐1 beta (IL‐1β) and interferon‐gamma (IFN‐γ), was significantly attenuated in the dorsal skin of the HMEE‐fed mouse group compared with the PCL‐treated mouse group. In addition, in concanavalin A‐stimulated and lipopolysaccharide‐stimulated mouse splenocytes and macrophages, levels of IL‐1β and IFN‐γ production were attenuated following the addition of HMEE. Interestingly, the administration of HMEE to mouse splenocytes stimulated the production of an antiinflammatory cytokine, IL‐4. However, increases in the levels of proinflammatory cytokines and nitric oxide were attenuated by treating the mouse splenocytes, mouse macrophages, and Raw 264.7 cell line with HMEE. These results strongly suggest that HMEE exhibits anti‐AD activity via the regulation of inflammatory responses. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-19T22:02:57.230927-05:
      DOI: 10.1002/ptr.5164
  • Attachment and Penetration of Acyclovir‐resistant Herpes Simplex
           Virus are Inhibited by Melissa officinalis Extract
    • Authors: Akram Astani; Mojdeh Heidary Navid, Paul Schnitzler
      First page: 1547
      Abstract: Medicinal plants are increasingly of interest as novel source of drugs for antiherpetic agents, because herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis and the phenolic compounds caffeic acid, p‐coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV‐1) acyclovir‐sensitive and clinical isolates of acyclovir‐resistant strains in vitro. When drugs were added during the intracellular replication of HSV‐1 infected cells, no antiviral effect was observed by plaque reduction assay. However, Melissa extract interacted directly with free viral particles of two acyclovir‐resistant HSV strains at low IC50 values of 0.13 and 0.23 µg/mL and high selectivity indices of 2692 and 1522, respectively. The Melissa extract and rosmarinic acid inhibited HSV‐1 attachment to host cells in a dose‐dependent manner for acyclovir‐sensitive and acyclovir‐resistant strains. These results indicate that mainly rosmarinic acid contributed to the antiviral activity of Melissa extract. Penetration of herpes viruses into cells was inhibited by Melissa extract at 80% and 96% for drug‐sensitive and drug‐resistant viruses, respectively. Melissa extract exhibits low toxicity and affects attachment and penetration of acyclovir‐sensitive and acyclovir‐resistant HSVs in vitro. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-12T04:18:40.193941-05:
      DOI: 10.1002/ptr.5166
  • Curcumin Modulates miR‐19/PTEN/AKT/p53 Axis to Suppress Bisphenol
           A‐induced MCF‐7 Breast Cancer Cell Proliferation
    • Authors: Xiaoting Li; Wei Xie, Chunfeng Xie, Cong Huang, Jianyun Zhu, Zhaofeng Liang, Feifei Deng, Mingming Zhu, Weiwei Zhu, Rui Wu, Jieshu Wu, Shanshan Geng, Caiyun Zhong
      First page: 1553
      Abstract: Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin‐mediated protection from BPA‐associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen‐receptor‐positive MCF‐7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF‐7 cells. Meanwhile, BPA‐induced upregulation of oncogenic miR‐19a and miR‐19b, and the dysregulated expression of miR‐19‐related downstream proteins, including PTEN, p‐AKT, p‐MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR‐19 in BPA‐mediated MCF‐7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR‐19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA‐associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast‐cancer‐promoting effect as well as its target intervention. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-15T22:23:47.367651-05:
      DOI: 10.1002/ptr.5167
  • Antiinflammatory Effects and Chemical Constituents of Veronicastrum
    • Authors: Cheng‐Jian Zheng; Xue‐Hong Deng, Yu Wu, Yi‐Ping Jiang, Jian‐Yong Zhu, Lu‐Ping Qin
      First page: 1561
      Abstract: Our study aims to ascertain the antiinflammatory activity of Veronicastrum axillare and characterize the bioactive constituents. Antiinflammatory activity of the total extract and different fractions from V. axillare was investigated by employing the xylene‐induced mouse ear edema model. As a result, the ethyl acetate (EtOAc) fraction showed the highest antiinflammatory activity in vivo. From the EtOAc fraction and the inactive dichloromethane fraction, a total of five new compounds, axillasides A–C and axillactones A and B, together with four known compounds, procumboside A, buergeriside C1, indole‐3‐carboxylic acid and apigenin, were isolated and identified. Their structures were elucidated on the basis of spectroscopic analysis and by comparison of their nuclear magnetic resonance data with those reported in the literature. Procumboside A, a major constituent in EtOAc fraction, showed significant antiinflammatory activity in vivo. Further studies revealed that procumboside A was a potent COX‐2 inhibitor, significantly reducing the COX‐2 protein level in lipopolysaccharide‐stimulated RAW 264.7 macrophages. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-12T04:13:36.545606-05:
      DOI: 10.1002/ptr.5168
  • Anti‐Diabetic Properties of Rice‐Based Herbal Porridges in
           Diabetic Wistar Rats
    • Authors: Senadheera Pathirannehelage Anuruddhika Subhashinie Senadheera; Sagarika Ekanayake, Chandanie Wanigatunge
      First page: 1567
      Abstract: The present study aims to investigate anti‐hyperglycaemic, anti‐hyperlipidaemic and toxic effects of long‐term consumption of selected green leafy porridges in a streptozotocin‐induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c, C reactive protein (CRP), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p  0.05). Among the diabetic groups, lowest TC (119 ± 20.6 mg/dL) and highest HDL‐C (33 ± 6.3 mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p > 0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p 
      PubDate: 2014-05-19T22:02:47.158765-05:
      DOI: 10.1002/ptr.5169
  • Fennel and Raspberry Leaf as Possible Inhibitors of Acetaminophen
    • Authors: Astrid Jordet Langhammer; Odd Georg Nilsen
      First page: 1573
      Abstract: In addition to CYP2E1, several CYP isoenzymes, notably CYP1A2, 2D6, and 3A4, are suggested to contribute in acetaminophen oxidation and formation of the hepatotoxic metabolite N‐acetyl‐p‐benzoquinone imine (NAPQI). The in vitro CYP2E1 inhibitory potentials of fennel and raspberry leaf, herbs previously found to inhibit CYP1A2, 2D6, and 3A4 activities in vitro, were investigated. Extracts from commercially available herbal products were incubated with recombinant cDNA‐expressed human CYP2E1. A validated LC/MS/MS methodology was applied for determination of 6‐hydroxychlorzoxazone formation with disulfiram used as a positive inhibitory control. CYP2E1 IC50 inhibition constants were found to be 23 ± 4 and 27 ± 5 µg/ml for fennel and raspberry leaf, respectively, constants significantly lower than those presented in the literature for other herbal extracts. Together with previous findings, the presented in vitro data for CYP2E1 inhibition suggest that fennel and raspberry leaf have a significant potential of inhibiting all the major metabolic pathways for acetaminophen oxidation and NAPQI formation. Both herbs should be further investigated for their in vivo ability of inhibiting acetaminophen oxidation and NAPQI formation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-01-23T21:05:13.964561-05:
      DOI: 10.1002/ptr.5124
  • Biotransformation of Glucoaurantio‐Obtusin Towards
           Aurantio‐Obtusin Increases the Toxicity of Irinotecan Through
           Increased Inhibition Towards SN‐38 Glucuronidation
    • Authors: Jian Yu; Jing‐Chun Han, Ya‐Jie Gao
      First page: 1577
      Abstract: The present study aims to investigate the influence of irinotecan's toxicity by the biotransformation of glucoaurantio‐obtusin to aurantio‐obtusin. Intraperitoneal administration (i.p.) of 100 mg/kg aurantio‐obtusin significantly increased the toxicity of irinotecan, but the i.p. administration of 100 mg/kg glucoaurantio‐obtusin showed negligible influence towards irinotecan's toxicity. Furthermore, the mechanism was explained through determining the inhibition potential of glucoaurantio‐obtusin and aurantio‐obtusin towards the glucuronidation metabolism of SN‐38 that has been regarded to be the major active product responsible for the toxicity of irinotecan. The results showed that aurantio‐obtusin exhibited strong competitive inhibition towards the glucuronidation of SN‐38, but negligible inhibition potential of glucoaurantio‐obtusin towards SN‐38 glucuronidation was observed. These results showed that biotransformation of glucoaurantio‐obtusin towards aurantio‐obtusin increased the toxicity of irinotecan through increased inhibition of SN‐38 glucuronidation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-05-19T22:18:40.115134-05:
      DOI: 10.1002/ptr.5162
  • The application of metabolomics in traditional Chinese medicine opens up a
           dialogue between Chinese and Western medicine
    • 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.
  • Potent Effects of the Total Saponins from Dioscorea nipponica Makino
           Against Streptozotocin‐Induced Type 2 Diabetes Mellitus in Rats
    • 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.
  • Aqueous Extract of Rosmarinus officinalis L. Inhibits Neutrophil Influx
           and Cytokine Secretion
    • Abstract: Rosmarinus officinalis L. phenolic compounds have attracted considerable attention because of their antioxidant and antimicrobial properties, including its ability to treat inflammatory disorders. In this work, we investigated the in vivo and in vitro effects of R. officinalis aqueous extract on neutrophil trafficking from the blood into an inflamed tissue, on cell‐derived secretion of chemical mediators, and on oxidative stress. Anti‐inflammatory activity was investigated using carrageenan‐induced inflammation in the subcutaneous tissue of male Wistar rats orally treated with the R. officinalis extract (100, 200, or 400 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (prostaglandin E2 (PGE2), TNF‐α, interleukin 6 (IL‐6), leukotriene B4 (LTB4), and cytokine‐induced neutrophil chemoattractant 1 by enzyme‐linked immunosorbent assay), and the anti‐oxidative profile (super oxide dismutase (SOD), glutathione peroxidase, and thiobarbituric acid reactive substance (TBARS) spectrophotometry) were quantified in the inflamed exudate. N‐Formyl‐methionine‐leucine‐phenylalanine‐induced chemotaxis, lipopolysaccharide‐induced NO2− production (Greiss reaction), and adhesion molecule expression (flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 µg/mL). Animals orally treated with phosphate‐buffered saline and neutrophils incubated with Hank's balanced salt solution were used as control. R. officinalis extract oral treatment caused a dose‐dependent reduction in the neutrophil migration as well as decreased SOD, TBARS, LTB4, PGE2, IL‐6, and TNF‐α levels in the inflamed exudate. In vitro treatment with R. officinalis decreased neutrophil chemotaxis, NO2− production, and shedding of L‐selectin and β2 integrin expressions. Results here presented show that R. officinalis aqueous extract displays important in vivo and in vitro anti‐inflammatory actions by blocking pathways of neutrophil migration and secretion, suggesting its therapeutic application to acute inflammatory reactions. Copyright © 2014 John Wiley & Sons, Ltd.
  • Mechanisms of improvement of intestinal transport of baicalin and puerarin
           by extracts of Radix Angelicae Dahuricae
    • 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.
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