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Physik in unserer Zeit     Hybrid Journal   (Followers: 1)
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Population and Development Review     Hybrid Journal   (Followers: 4, SJR: 2.686, h-index: 56)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.836, h-index: 33)
Poverty & Public Policy     Hybrid Journal   (Followers: 13)
Practical Diabetes     Hybrid Journal   (Followers: 6, SJR: 0.175, h-index: 3)
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Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 1.262, h-index: 69)
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Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)
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Progress in Photovoltaics: Research & Applications     Hybrid Journal   (Followers: 7, SJR: 4.314, h-index: 74)
Progress in Structural Engineering and Materials     Hybrid Journal   (Followers: 5)
Project Management J.     Hybrid Journal   (Followers: 30, SJR: 0.497, h-index: 8)
Propellants, Explosives, Pyrotechnics     Hybrid Journal   (Followers: 212, SJR: 0.765, h-index: 37)
Protein Science     Hybrid Journal   (Followers: 26, SJR: 2.013, h-index: 132)

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Journal Cover   Phytotherapy Research
  [SJR: 0.82]   [H-I: 76]   [1 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
   Published by John Wiley and Sons Homepage  [1597 journals]
  • Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and
           their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T
           Lymphocyte (Jurkat) Cells via the Activation of c‐Jun
           n‐terminal Kinase Phosphorylation
    • Abstract: Infrared‐guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C. concolor. The structures of these compounds were elucidated by one‐dimensional and two‐dimensional nuclear magnetic resonance techniques, as well as high‐resolution mass spectrometry. The purified and characterized compounds were subjected to cytotoxicity assay. The sesquiterpene lactones desoxyjanerin and rhaserolide showed significant cytotoxic activities against five different cancer cell lines and the normal human embryonic kidney cell line. Rhaserolide was chosen to evaluate the possible mechanism of action. Western blot analysis revealed that rhaserolide could induce apoptosis in Jurkat cells via the activation of c‐Jun n‐terminal kinase phosphorylation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-19T00:07:17.871705-05:
      DOI: 10.1002/ptr.5519
  • Protocatechuic Acid Restores Vascular Responses in Rats With Chronic
           Diabetes Induced by Streptozotocin
    • Authors: Yoswaris Semaming; Upa Kukongviriyapan, Bunkerd Kongyingyoes, Wipawee Thukhammee, Patchareewan Pannangpetch
      Abstract: Oxidative stress has been shown to play an important role in development of vascular dysfunction in diabetes. Protocatechuic acid (PCA) has been reported to exert antioxidant and anti‐hyperglycemic activities. Diabetes was induced in male Sprague–Dawley rats by a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The rats were maintained in a state of hyperglycemia for 12 weeks. Then, PCA (50 or 100 mg/kg/day) was administered orally or insulin (4 U/kg/day) was subcutaneous injected to the rats for 6 weeks. Blood pressure, vascular responses to vasoactive agents, vascular superoxide production, blood glucose, insulin, malondialdehyde, nitric oxide and antioxidant enzymes were examined. The diabetic rats showed weight loss, insulin deficiency, hyperglycemia, increased oxidative stress, decreased plasma nitric oxide, elevated blood pressure, increased vascular response to phenylephrine and decreased vascular responses to acetylcholine and sodium nitroprusside. PCA significantly decreased blood glucose and oxidative stress, and increased plasma nitric oxide in diabetic rats. Interestingly, PCA treatment restored blood pressure and vascular reactivity, and antioxidant enzyme activity diabetic rats. This study provides the first evidence of the efficacy of PCA in restoring the vascular reactivity of diabetic rats. The mechanism of action may be associated with an alleviation of oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-17T05:32:04.875039-05:
      DOI: 10.1002/ptr.5520
  • Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve
           Growth Factor‐Mediated Signaling
    • Abstract: The flower bud of Zingiber mioga Roscoe, known as ‘myoga’ or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal‐regulated kinases and cAMP response element‐binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-13T00:59:52.083213-05:
      DOI: 10.1002/ptr.5511
  • Nobiletin, a Polymethoxylated Flavone, Inhibits Glioma Cell Growth and
           Migration via Arresting Cell Cycle and Suppressing MAPK and Akt Pathways
    • Abstract: Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3',4'‐hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20–100 µm) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI‐annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin‐dependent kinase 2, cyclin‐dependent kinase 4, and E2 promoter‐binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen‐activated protein kinases, including p38, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen‐activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-12T00:10:30.557429-05:
      DOI: 10.1002/ptr.5517
  • Picrorhiza kurroa Inhibits Experimental Arthritis Through Inhibition of
           Pro‐inflammatory Cytokines, Angiogenesis and MMPs
    • Authors: Rohit Kumar; Yogendra Kumar Gupta, Surender Singh, S. Arunraja
      Abstract: The present study investigates the anti‐arthritic activity of Picrorhiza kurroa (PK), on formaldehyde and adjuvant‐induced arthritis (AIA) in rat. Administration of Picrorhiza kurroa rhizome extract (PKRE) significantly inhibited joint inflammation in both animal models. In AIA‐induced arthritic rat, treatment with PKRE considerably decreased synovial expression of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor receptor‐1 (TNF‐R1) and vascular endothelial growth factor as compared with control. The anti‐arthritic activity was found to be well substantiated with significant suppression of oxidative and inflammatory markers as there was decreased malonaldehyde, Nitric oxide, tumor necrosis factor alpha levels accompanied with increased glutathione and superoxide dismutase, catalase activities. Additionally, PKRE significantly inhibited the expression of degrading enzymes, matrix metalloproteinases‐3 and matrix metalloproteinases‐9 in AIA‐induced arthritic rat. Histopathology of paw tissue displayed decreased inflammatory cell infiltration as compared with control. Taken together, these results demonstrated the anti‐arthritic activity of PKRE against experimental arthritis, and the underlying mechanism behind this efficacy might be mediated by inhibition of inflammatory mediators and angiogenesis, improvement of the synovium redox status and decreased expression of matrix metalloproteinases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-11T04:48:17.149394-05:
      DOI: 10.1002/ptr.5509
  • Apoptotic Effect of Sanggenol L via Caspase Activation and Inhibition of
           NF‐κB Signaling in Ovarian Cancer Cells
    • Abstract: In the present study, the underlying apoptotic mechanism of sanggenol L was elucidated in ovarian cancer cells. Sanggenol L showed cytotoxic and antiproliferative effect in A2780, SKOV‐3, and OVCAR‐3 ovarian cancer cells in a concentration‐dependent fashion. Consistently, sanggenol L increased sub‐G1 phase population and early and late apoptotic portion in ovarian cancer cells. Also, sanggenol L activated caspase9/3, suppressed the phosphorylation of IκBα and p65 NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells), attenuated the expression of Cyclin D1, and cleaved poly(adenosine diphosphate ribose ‐ribose) polymerase in SKOV‐3, A2780, and OVCAR‐3 cells. Furthermore, sanggenol L blocked nuclear translocation of NF‐κB and also attenuated the expression of NF‐κB related genes such as c‐Myc, Cyclin D1, and Bcl‐XL, Bcl‐2, in lipopolysaccharide‐treated SKOV‐3 cells. Overall, our findings for the first time suggest that sanggenol L induces apoptosis via caspase activation and inhibition of NF‐κB/IκBα phosphorylation as a potent chemotherapeutic agent for ovarian cancers. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-11T04:09:00.481543-05:
      DOI: 10.1002/ptr.5505
  • Nanotechnology in Phytotherapy: Antiinflammatory Effect of a
           Nanostructured Thymol Gel from Lippia sidoides in Acute Periodontitis in
    • Abstract: Lippia sidoides Cham (Verbenaceae) is largely distributed in the northeastern region of Brazil. It is popularly known as ‘Alecrim‐pimenta’. Recent studies have shown that some species of Lippia have interesting pharmacological activities. This study aimed to evaluate the effect of a nanostructured thymol gel (TG) 1.2 mg/g on acute phase of ligature‐induced periodontitis model [acute periodontal disease (APD)] in rats. APD was induced in 24 Wistar rats subjected to ligature placement on left molars in maxillae. Animals were treated with TG, immediately after APD induction. Saline‐based gel was utilized as negative control and diethylammonium diclofenac gel 10 mg/g was used as positive control. Animals were randomly assigned into the groups. The periodontium and the surrounding gingiva were examined at histopathology, as well as the neutrophil influx into the gingiva was assayed using myeloperoxidase activity levels by ELISA method. TG treatment reduced tissue lesion at histopathology coupled to decreased myeloperoxidase activity production in gingival tissue when compared with the saline gel control group (p 
      PubDate: 2015-11-10T02:36:32.684566-05:
      DOI: 10.1002/ptr.5516
  • Identification and Characterization of Baicalin as a Phosphodiesterase 4
    • Abstract: Asthma is a chronic inflammatory disease of lung airways, and pharmacological inhibitors of cyclic adenosine monophosphate‐specific phosphodiesterase 4 (PDE4) have been considered as therapeutics for the treatment of asthma. However, development of PDE4 inhibitors in clinical trials has been hampered because of the severe side effects of non‐selective PDE4 inhibitors. Here, screening of a plant extract library in conjunction with dereplication technology led to identification of baicalin as a new type of PDE4‐selective inhibitor. We demonstrated that while rolipram inhibited the enzyme activity of a range of PDE4 subtypes in in vitro enzyme assays, baicalin selectively inhibited the enzyme activity of PDE4A and 4B. In addition, baicalin suppressed lipopolysaccharide‐induced TNF‐α expression in macrophage where PDE4B plays a key role in lipopolysaccharide‐induced signaling. Furthermore, baicalin treatment in an animal model of allergic asthma reduced inflammatory cell infiltration and TNF‐α levels in bronchoalveolar lavage fluids, indicating that the antiinflammatory effects of baicalin in vivo are attributable, in part, to its ability to inhibit PDE4. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-09T02:00:39.190425-05:
      DOI: 10.1002/ptr.5515
  • Gymnemic Acid Stimulates In Vitro Splenic Lymphocyte Proliferation
    • Authors: Vineet Kumar Singh; Padmanabh Dwivedi, B. R. Chaudhary, Ramesh Singh
      Abstract: Gymnemic acid is a mixture of triterpenoid saponins of oleanane class, isolated from Gymnema sylvestre Wild R.Br (family: Asclepidaceae), an herbal plant used in traditional medicine to treat diabetes. Effect of gymnemic acid (0.1–20 µg/mL) on in vitro mitogen (concanavalin A and lipopolysaccharide)‐induced splenic lymphocyte proliferation was studied using rat as model. Significant (p 
      PubDate: 2015-11-09T00:50:52.353953-05:
      DOI: 10.1002/ptr.5514
  • Protolichesterinic Acid, Isolated from the Lichen Cetraria islandica,
           Reduces LRRC8A Expression and Volume‐Sensitive Release of Organic
           Osmolytes in Human Lung Epithelial Cancer Cells
    • Authors: Unnur Arna Thorsteinsdottir; Margret Thorsteinsdottir, Ian Henry Lambert
      Abstract: We have tested the effect of protolichesterinic acid (PA) on the activity of the volume‐sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine‐rich‐repeat‐channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 µg/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 → 200 mOsm) by 60%. C75 (20 µg/mL, 24 h), a γ‐lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 µg/mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to γ‐lactone's inhibitory action. 5‐Lipoxygenase (5‐LO) activity is essential for swelling‐induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5‐HETE/LTB4) under hypotonic conditions, excluding that PA mediated inhibition of VSOAC involves 5‐LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 μM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3‐, 1.5‐ and 3.3‐fold increase in the expression of LRRC8A, Bax (regulator of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro‐apoptotic drug in A549 cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-09T00:45:13.591104-05:
      DOI: 10.1002/ptr.5507
  • Harmine Hydrochloride Triggers G2 Phase Arrest and Apoptosis in
           MGC‐803 Cells and SMMC‐7721 Cells by Upregulating p21,
           Activating Caspase‐8/Bid, and Downregulating ERK/Bad Pathway
    • Abstract: This study aimed to investigate the effects of harmine hydrochloride (HMH) on digestive tumor cells in vitro and its molecular mechanism. MTT assays showed that HMH inhibited the proliferation of some human cancer cell lines and had no obvious inhibitory effects on human LO2 cells. Flow cytometry assays showed that HMH trigged G2 phase arrest in MGC‐803 cells and SMMC‐7721 cells, while the expression of cyclin A, cyclin B, p21, Myt1, and p‐cdc2 (Tyr15) was upregulated. Flow cytometry assays also showed that the percentages of apoptotic cells were increased, the mitochondrial transmembrane potential (ΔΨm) decreased, and the cleavage of caspase‐9, caspase‐3, and poly (Adenosine diphosphate ribose) polymerase (PARP) were observed, the expression of Bad increased, phospho‐Bad (S112) decreased, pro‐caspase‐8 was cleaved, and Bid (22 kDa) was cleaved. The expression of p‐ERK decreased in both cells. In conclusion, these results demonstrated that HMH upregulates the expression of p21, activates Myt1 and inhibits cdc2 by phospho‐cdc2 (Y15), and triggers G2 phase arrest in both MGC‐803 cells and SMMC‐7721 cells. It can also activate the mitochondria‐related cell apoptosis pathway through the caspase‐8/Bid pathway, inhibiting the ERK/Bad pathway and promoting apoptosis in both of these two cell types. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-09T00:41:26.162607-05:
      DOI: 10.1002/ptr.5497
  • The Effect of Verbascoside in Neuropathic Pain Induced by Chronic
           Constriction Injury in Rats
    • Authors: Bahareh Amin; Ehsan Poureshagh, Hossein Hosseinzadeh
      Abstract: We examined the effects of verbascoside in rats subjected to chronic constriction injury (CCI). Verbascoside (50, 100, and 200 mg/kg, i.p.), was administered from the day of surgery for 14 days. Spinal cord levels of apoptotic factors and glia markers were quantified on days 3, 7, and 14 post‐CCI. Oxidative stress markers were assessed on days 7 and 14. CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post‐CCI. A significant increase in the levels of Iba (a marker of microglia activation) and Bax (a proapoptotic factor) was observed on day 3. Iba remained high on day 7. In contrast, there were no differences in glial fibrillary acidic protein contents between sham and CCI animals. Malondialdehyde increased and reduced glutathione decreased on day 14. Verbascoside significantly attenuated behavioral changes associated with neuropathy. Bax decreased, while Bcl‐2 was increased by verbascoside on day 3. Verbascoside also reduced Iba protein on days 3 and 7. The results support evidence that microglial activation, apoptotic factors, and oxidative stress may have a pivotal role in the neuropathic pain pathogenesis. It is suggested that antinociceptive effects elicited by verbascoside might be through the inhibition of microglia activation, apoptotic pathways, and antioxidant properties. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-05T04:08:45.75353-05:0
      DOI: 10.1002/ptr.5512
  • Bioactive Phenylpropanoids, Phenolic Acid and Phytosterol from Landolphia
           owariensis P. Beauv Stringy Seed Pulp
    • Authors: Tochukwu J. N. Okonkwo; Patience O. Osadebe, Peter Proksch
      Abstract: Landolphia owariensis P. Beauv is economically important for latex/rubber and folklore medicine. Its stringy seed pulp is freely eaten by humans and animals. Thus, L. owariensis stringy seed pulp was extracted serially with hexane and acetone to isolate and characterize its active pharmaceutical ingredients. Solvent/solvent partition and chromatographic separations afforded four bioactive compounds, (E)‐3‐(3,4‐Dihydroxylcinnamoyl)quinic acid [(E)‐Chlorogenic acid], I; (E)‐3‐(3,4‐Dihydroxylcinnamoyl)quinic acid methyl ester [(E)‐Chlorogenic acid methyl ester], II; 3,4‐Dihydroxylbenzoic acid, (Protocatechuic acid), III; and 22,23‐Dihydrostigmaster‐3β‐ol (3β–Sitosterol) (IV). Structures of I, II and III were assigned by combinations of high‐performance liquid chromatography‐ultraviolet‐visible spectroscopy, 1D and 2D nuclear magnetic resonance spectroscopy, high‐performance liquid chromatography–mass spectrometry and reference to published literatures, while compound IV was identified by chemical methods and gas chromatography–mass spectrometry. The phenylpropanoids and phenolic acid (compounds I, II and III) are notable standard antioxidants with confirmed hepatic‐protective activity and other exciting biological activities. Compound IV has been reported to possess anti‐inflammatory activity, anti‐colon cancer action and a cholesterol‐lowering effect. The described compounds are important medicinal constituents of L. owariensis stringy seed pulp, and this is the first major report on the phytochemistry of L. owariensis P. Beauv. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-05T03:32:44.878391-05:
      DOI: 10.1002/ptr.5503
  • Artepillin C and Other Herbal PAK1‐blockers: Effects on Hair Cell
           Proliferation and Related PAK1‐dependent Biological Function in Cell
    • Authors: Binh Cao Quan Nguyen; Nozomi Taira, Hiroshi Maruta, Shinkichi Tawata
      Abstract: PAK1 (RAC/CDC42‐activated kinase 1) is the major oncogenic kinase, and a number of herbal PAK1‐blockers such as propolis and curcumin have been shown to be anti‐oncogenic and anti‐melanogenic as well as anti‐alopecia (promoting hair growth). Previously, we found several distinct PAK1‐inhibitors in Okinawa plants including Alpinia zerumbet (alpinia). Thus, here, we tested the effects of these herbal compounds and their derivatives on the growth of cancer or normal hair cells, and melanogenesis in cell culture of A549 lung cancer, hair follicle dermal papilla cell, and B16F10 melanoma. Among these herbal PAK1‐inhibitors, cucurbitacin I from bitter melon (Goya) turned out to be the most potent to inhibit the growth of human lung cancer cells with the IC50 around 140 nM and to promote the growth of hair cells with the effective dose around 10 nM. Hispidin, a metabolite of 5,6‐dehydrokawain from alpinia, inhibited the growth of cancer cells with the IC50 of 25 μM as does artepillin C, the major anti‐cancer ingredient in Brazilian green propolis. Mimosine tetrapeptides (MFWY, MFYY, and MFFY) and hispidin derivatives (H1–3) also exhibited a strong anti‐cancer activity with the IC50 ranging from 16 to 30 μM. Mimosine tetrapeptides and hispidin derivatives strongly suppressed the melanogenesis in melanoma cells. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-04T23:32:20.272592-05:
      DOI: 10.1002/ptr.5510
  • Strong Specific Inhibition of UDP‐glucuronosyltransferase 2B7 by
           Atractylenolide I and III
    • Abstract: Drug‐metabolizing enzymes inhibition‐based drug–drug interaction remains to be the key limiting factor for the research and development of efficient herbal components to become clinical drugs. The present study aims to determine the inhibition of uridine 5′‐diphospho‐glucuronosyltransferases (UGTs) isoforms by two important efficient herbal ingredients isolated from Atractylodes macrocephala Koidz, atractylenolide I and III. In vitro recombinant UGTs‐catalysed glucuronidation of 4‐methylumbelliferone was used to determine the inhibition capability and kinetics of atractylenolide I and III towards UGT2B7, and in silico docking method was employed to explain the possible mechanism. Atractylenolide I and III exhibited specific inhibition towards UGT2B7, with negligible influence towards other UGT isoforms. Atractylenolide I exerted stronger inhibition potential than atractylenolide III towards UGT2B7, which is attributed to the different hydrogen bonds and hydrophobic interactions. Inhibition kinetic analysis was performed for the inhibition of atractylenolide I towards UGT2B7. Inhibition kinetic determination showed that atractylenolide I competitively inhibited UGT2B7, and inhibition kinetic parameter (Ki) was calculated to be 6.4 μM. In combination of the maximum plasma concentration of atractylenolide I after oral administration of 50 mg/kg atractylenolide I, the area under the plasma concentration‐time curve ration AUCi/AUC was calculated to be 1.17, indicating the highly possible drug–drug interaction between atractylenolide I and drugs mainly undergoing UGT2B7‐catalysed metabolism. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-04T23:01:39.755914-05:
      DOI: 10.1002/ptr.5496
  • Structural Elements and Cough Suppressing Activity of Polysaccharides from
           Zingiber officinale Rhizome
    • Authors: K. Bera; G. Nosalova, V. Sivova, B. Ray
      Abstract: Zingiber officinale is used for the management of fever, bronchial asthma and cough for thousands of years. While the link to a particular indication has been established in human, the active principle of the formulation remains unknown. Herein, we have investigated a water extracted polysaccharides (WEP) containing fraction from its rhizome. Utilizing a traditional aqueous extraction protocol and using chemical, chromatographic and spectroscopic methods a fraction containing a branched glucan and polygalaturonan in a ratio of 59:1 was characterized. This glucan, which has a molecular mass of 36 kDa, is made up of terminal‐, (1,4)‐ and (1,4,6)‐linked α‐Glcp residues. Oral administration of WEP in doses of 25 and 50 mg/kg body weight significantly inhibited the number of citric acid‐induced cough efforts in guinea pigs. It does not alter the specific airway smooth muscle reactivity significantly. Thus, traditional aqueous extraction method provides molecular entities, which induces antitussive activity without addiction. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-02T01:48:21.657979-05:
      DOI: 10.1002/ptr.5508
  • Treatment of Mild Gastrointestinal Disorders with a Herbal Combination:
           Results of a Non‐interventional Study with Gastritol® Liquid
    • Authors: Tankred Wegener; Edgar Heimueller
      Abstract: A combination of extracts from chamomile, silverweed, licorice, angelica, blessed thistle and wormwood, Gastritol® Liquid, is registered for the use of indigestion and gastrointestinal spasmodic complaints. To gain data on the experience in practice, a non‐interventional open study was conducted in ambulatory patients including diabetics which were treated for 2 weeks. The efficacy of treatment was assessed by medical examination and evaluation of typical symptoms by patients. A total of 149 patients was enrolled, 90 without and 59 with diabetes. The treatment led to relevant improvements in all symptoms in both study groups. The most notable improvements were seen for the symptoms vomiting (−66.7%; diabetics: −63.9%) and retching (−52.2%; diabetics: −53.6%). An overall improvement was rated by about 90% in both study groups. In seven patients adverse events had been reported (5 times temporary nausea after intake, one time gastric spasm and one time oral burning sensation), all of them of mild nature. The global tolerability was assessed as good or very good in more than 80% by practitioners and patients. Under the conditions of this open study method Gastritol® Liquid had been shown to be safe and effective in the treatment of mild gastrointestinal disorders, including diabetic patients. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-02T01:23:39.688723-05:
      DOI: 10.1002/ptr.5502
  • Antimicrobial Assessment of Resins from Calophyllum Antillanum and
           Calophyllum Inophyllum
    • Abstract: The Calophyllum genus is well‐known for its antimicrobial and cytotoxic activities, and therefore, we analyzed these biological activities for resins of Calophyllum antillanum and Calophyllum inophyllum growing in Cuba. C. antillanum resins showed a potent activity against Plasmodium falciparum (IC50 = 0.3 ± 0.1 µg/mL), while its cytotoxicity against MRC‐5 cells was much lower (IC50 = 21.6 ± 1.1 µg/mL). In contrary, the resin of C. inophyllum showed an unspecific activity. The presence of apetalic acid, isoapetalic acid, calolongic acid, pinetoric acid I, pinetoric acid II, isocalolongic acid, pinetoric acid III, and isopinetoric acid III in C. antillanum resins was also confirmed. These results demonstrated for the first time the potential activity of C. antillanum resins against P. falciparum. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-30T05:14:23.3258-05:00
      DOI: 10.1002/ptr.5506
  • Ex Vivo and In Situ Evaluation of ‘Dispelling‐Wind’
           Chinese Medicine Herb–Drugs on Intestinal Absorption of Chlorogenic
    • Authors: Lixiang Zhai; Jun Shi, Weitong Xu, Michael Heinrich, Jianying Wang, Wenji Deng
      Abstract: This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used ‘dispelling‐wind’ TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P‐gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the Papp and Ka of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P‐gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-30T04:29:51.34442-05:0
      DOI: 10.1002/ptr.5492
  • Hypercholesterolemia and Ecto‐enzymes of Purinergic System: Effects
           of Paullinia cupana
    • Abstract: Hypercholesterolemia is a metabolic disorder characterized by high levels of low‐density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto‐nucleoside triphosphate diphosphohydrolase (E‐NTPDase) and ecto‐adenosine deaminase activity in lymphocytes of rats with diet‐induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto‐adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low‐density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-30T03:17:33.640382-05:
      DOI: 10.1002/ptr.5499
  • Modulation of Multidrug Resistance Protein 2 Efflux in the Cisplatin
           Resistance Human Ovarian Carcinoma Cells A2780/RCIS by Sesquiterpene
    • Authors: Jamal Kasaian; Fatemeh Mosaffa, Javad Behravan, Milena Masullo, Sonia Piacente, Mehrdad Iranshahi
      Abstract: Recent in vitro studies showed that sesquiterpene coumarins (SCs) can be used as chemosensitizers. In this study, 14 SCs were isolated and purified from roots of four Ferula species and their structures were elucidated by spectroscopic methods. The purified SCs were evaluated for multidrug resistance (MDR) reversal properties in A2780/RCIS cells (cisplatin‐resistant derivatives of the human ovarian carcinoma cell line A2780P). Among the tested compounds, mogoltacin, mogoltadone, farnesiferol A, farnesiferol B, farnesiferol C, lehmferin, conferdione, and samarcandin showed significant MDR reversing effects. The combination of nontoxic concentrations of SCs (20 μM) with cisplatin enhanced cisplatin cytotoxicity on A2780/RCIS cells significantly. Flow cytometric efflux assay confirmed that the intracellular accumulation of 5‐carboxyfluorescein diacetate (5‐CFDA) was significantly increased in A2780/RCIS cells when treated with SCs. Our findings revealed that conferdione and samarcandin possessed the highest inhibitory effects on multidrug resistance‐associated protein 2 pump efflux, and therefore, these compounds could be considered as lead scaffolds for further structure modifications. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-27T04:39:03.913262-05:
      DOI: 10.1002/ptr.5504
  • The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and
           Other Mood Symptoms
    • Authors: Mark Cropley; Adrian P. Banks, Julia Boyle
      Abstract: This trial evaluated the impact of a Rhodiola rosea L. extract on self‐reported anxiety, stress, cognition, and other mood symptoms. Eighty mildly anxious participants were randomized into two different groups of either Rhodiola rosea L (2 × 200 mg dose Vitano®, 1 tablet taken before breakfast and 1tablet before lunch) or a control condition (no treatment). Self‐report measures and cognitive tests were completed at four testing sessions over a period of 14 days. Relative to the controls, the experimental group demonstrated a significant reduction in self‐reported, anxiety, stress, anger, confusion and depression at 14 days and a significant improvements in total mood. No relevant differences in cognitive performance between the groups were observed. Rhodiola rosea L (Vitano®) presented a favourable safety tolerability profile. Although this was a non‐placebo controlled trial, it is unlikely that the findings were the result of placebo effects as changes appeared gradual and were specific to certain psychological measures. However, we cannot determine a causal relationship; further investigations are recommended to support the effects of Rhodiola rosea L. extract on stress related symptoms. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-27T03:58:07.519286-05:
      DOI: 10.1002/ptr.5486
  • Inhibitory Activities of Thai Medicinal Plants with Promising Activities
           Against Malaria and Cholangiocarcinoma on Human Cytochrome P450
    • Abstract: Malaria and cholangiocarcinoma remain important public health problems in tropical countries including Southeast Asian nations. Newly developed chemotherapeutic and plant‐derived drugs are urgently required for the control of both diseases. The aim of the present study was to investigate the propensity to inhibit cytochrome P450‐mediated hepatic metabolism (CYP1A2, CYP2C19, CYP2D6 and CYP3A4) of the crude ethanolic extract of eight Thai medicinal plants with promising activities against malaria and cholangiocarcinoma, using human liver microsomes in vitro. Piper chaba Linn. (PC) and Atractylodes lancea (thung.) DC. (AL) exhibited the most potent inhibitory activities on CYP1A2‐mediated phenacetin O‐deethylation with mean IC50 of 0.04 and 0.36 µg/mL, respectively. Plumbago indica Linn. (PI) and Dioscorea membranacea Pierre. (DM) potently inhibited CYP2C19‐mediated omeprazole 5‐hydroxylation (mean IC50 4.71 and 6.92 µg/mL, respectively). DM, Dracaena loureiri Gagnep. (DL) and PI showed the highest inhibitory activities on dextromethorphan O‐demethylation (mean IC50 2.93–9.57 µg/mL). PC, DM, DL and PI exhibited the most potent inhibitory activities on CYP3A4‐mediated nifedipine oxidation (mean IC50 1.54–6.43 µg/mL). Clinical relevance of the inhibitory potential of DM, PC and PI is of concern for the further development of these plants for the treatment of malaria and/or cholangiocarcinoma. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-22T02:33:51.168667-05:
      DOI: 10.1002/ptr.5485
  • Badiranji Buya Keli, a Traditional Uyghur Medicine, Induces Vasodilation
           in Rat Artery: Signaling Mediated by Nitric Oxide Production in
           Endothelial Cells
    • Authors: A. Miernisha; Cathy W. C. Bi, Lily K. W. Cheng, J. G. Xing, J. Liu, M. Maiwulanjiang, H. A. Aisa, Tina T. X. Dong, Huangquan Lin, Y. Huang, Karl W. K. Tsim
      Abstract: Badiranji Buya Keli (BBK) is a traditional Uyghur medicine derived from Dracocephalum Moldavica Herba (DMH, the aerial part of Dracocephalum moldavica L.). BBK has been widely used in treating cardiovascular and cerebrovascular diseases. Here, the quality control of BBK was established by using HPLC analysis of rosmarinic acid and tilianin. After chemical standardization, the biological effects of BBK was tested. First, BBK inhibited platelet aggregation of rabbit plasma. Second, BBK induced vasodilation in rat aortic ring, and this effect was partially mediated by nitric oxide (NO) production in endothelial cells. Third, BBK induced NO production in cultured human umbilical vein endothelial cells (HUVECs). In HUVECs, the phosphorylation of endothelial NO synthase (eNOS) was markedly increased after application of BBK. Pre‐treatment with the eNOS blocker Nω‐nitro‐l‐arginine methyl ester hydrochloride could abolish BBK‐induced NO production and eNOS phosphorylation. Taken together, these results suggest that BBK could exert beneficial effects in cardiovascular system, which may provide parts of molecular explanation to account for its traditional usage in Uyghur medicine. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-21T03:12:34.536519-05:
      DOI: 10.1002/ptr.5494
  • Aconitum Alkaloid Poisoning Because of Contamination of Herbs by Aconite
    • Authors: Thomas Y. K. Chan
      Abstract: Aconitum alkaloid poisoning can occur after drinking decoction and soup made from non‐toxic herbs contaminated by aconite roots. In the present review, the main objective is to describe the clinical features, investigations and possible sources of contamination. A combination of neurological, gastrointestinal and cardiovascular signs and symptoms was seen. Ventricular tachyarrhythmias could occur in 18% of subjects. Yunaconitine and crassicauline A, mainly found in certain aconite roots from Southwest China, are most commonly involved. Herbal residues and unused herbs should first be inspected for gross contamination. On‐site inspection at the retailer should exclude accidental mix‐up or cross‐contamination when handling aconite roots. Samples of prescribed herbs are examined for gross contamination and analysed for the presence of Aconitum alkaloids. Samples of the implicated herb are also collected from the wholesaler for investigation. If post‐import contamination is unlikely, the regulatory authorities of the exporting countries should be notified for follow‐up actions. It is a challenging task to work out how non‐toxic herbs become contaminated by aconite roots. The source control with good agricultural and collection practices and quality assurance must be enhanced. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-19T22:39:49.484049-05:
      DOI: 10.1002/ptr.5495
  • Ginkgo biloba Extract (EGb 761®) Inhibits Glutamate‐induced
           Up‐regulation of Tissue Plasminogen Activator Through Inhibition of
           c‐Fos Translocation in Rat Primary Cortical Neurons
    • Abstract: EGb 761®, a standardized extract of Ginkgo biloba leaves, has antioxidant and antiinflammatory properties in experimental models of neurodegenerative disorders such as stroke and Alzheimer's disease. Tissue plasminogen activator (tPA) acts a neuromodulator and plays a crucial role in the manifestation of neurotoxicity leading to exaggerated neuronal cell death in neurological insult conditions. In this study, we investigated the effects of EGb 761 on the basal and glutamate‐induced activity and expression of tPA in rat primary cortical neurons. Under basal condition, EGb 761 inhibited both secreted and cellular tPA activities, without altering tPA mRNA level, as modulated by the activation of p38. Compared with basal condition, EGb 761 inhibited the glutamate‐induced up‐regulation of tPA mRNA resulting in the normalization of overt tPA activity and expression. c‐Fos is a component of AP‐1, which plays a critical role in the modulation of tPA expression. Interestingly, EGb 761 inhibited c‐Fos nuclear translocation without affecting c‐Fos expression in glutamate‐induced rat primary cortical neurons. These results demonstrated that EGb 761 can modulate tPA activity under basal and glutamate‐stimulated conditions by both translational and transcriptional mechanisms. Thus, EGb 761 could be a potential and effective therapeutic strategy in tPA‐excessive neurotoxic conditions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-19T00:33:10.443934-05:
      DOI: 10.1002/ptr.5500
  • Camellia sinensis Mediated Enhancement of Humoral Immunity to Particulate
           and Non‐particulate Antigens
    • Authors: Adnan Khan; Nafisa Hassan Ali, Viviana Santercole, Bianca Paglietti, Salvatore Rubino, Shahana Urooj Kazmi, Amber Farooqui
      Abstract: The most common drinking beverage in large portion of the world is Camellia sinensis (green tea). In the present study, we evaluated the adjuvant effect of green tea and tea polyphenols to particulate and non‐particulate antigens. BALB/c mice were immunized with particulate and non‐particulate antigens. Modulation of immunoglobulin‐secreting splenocytes, IgG‐mediated and IgM‐mediated immunity, was evaluated by hemolytic plaque assay and enzyme‐linked immunosorbent assay, respectively. Dose‐dependent response of tea polyphenols was also assayed. Phenolic content was measured in crude preparations of green tea. We observed a stimulatory effect of green tea preparations on humoral immune response mediated by the increased number of antibody‐secreted cells in spleen. A significant increase in IgM‐mediated and IgG‐mediated immune response to non‐particulate antigen was also observed in green tea‐treated animals. A dose‐dependent adjuvant effect was seen in the case of tea polyphenols for a longer period of time compared with crude tea preparations. This study indicates polyphenols as major constituents responsible for the enhanced and sustained adjuvant activity of green tea. We suggest that tea polyphenols might be considered for real‐life evaluation during adjuvant‐mediated vaccination trial programs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-18T23:04:50.687121-05:
      DOI: 10.1002/ptr.5498
  • Effects of Resveratrol on Receptor for Advanced Glycation End Products
           (RAGE) Expression and Oxidative Stress in the Liver of Rats with Type 2
    • Authors: Mohammad Khazaei; Jamshid Karimi, Nasrin Sheikh, Mohammad Taghi Goodarzi, Massoud Saidijam, Iraj Khodadadi, Heresh Moridi
      Abstract: Incidence of diabetes mellitus is dramatically growing in the world. Oxidative stress, advanced glycation end products (AGEs) and receptor for AGE (RAGE) play key role in the pathogenesis of diabetes. Little is known about resveratrol effects on the liver. We hypothesize that resveratrol may exert a hepatoprotective effect in diabetic rats. Male rats with diabetes were treated with or without resveratrol at 1, 5 and 10 mg/kg body weight for 30 days. Total AGEs and malondialdehyde (MDA) levels in liver tissues were determined by spectrofluorimetric methods. Total antioxidant capacity and total oxidant contents in the liver and glucose in plasma were measured by a colorimetric assay. Expression of RAGE was assayed in liver of all animals using quantitative polymerase chain reaction. In liver tissue extract of resveratrol‐treated rats with diabetes, MDA levels, total oxidant, plasma glucose and expression of RAGE were significantly reduced compared to the untreated group. Moreover, total antioxidant levels were significantly increased in treated rats. There was no significant difference in AGE contents among all groups. These results revealed that resveratrol had beneficial effects on the liver by extenuating oxidative stress and down regulation of RAGE expression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-14T22:27:07.46448-05:0
      DOI: 10.1002/ptr.5501
  • Betanin‐Enriched Red Beetroot (Beta vulgaris L.) Extract Induces
           Apoptosis and Autophagic Cell Death in MCF‐7 Cells
    • Abstract: Recent studies have pointed out the preventive role of beetroot extracts against cancers and their cytotoxic activity on cancer cells. Among many different natural compounds, these extracts contained betanin and its stereoisomer isobetanin, which belongs to the betalain group of highly bioavailable antioxidants. However, a precise identification of the molecules responsible for this tumor‐inhibitory effect was still required. We isolated a betanin/isobetanin concentrate from fresh beetroots, corresponding to the highest purified betanin extract used for studying anticancer activities of these molecules. The cytotoxicity of this betanin‐enriched extract was then characterized on cancer and normal cells and we highlighted the death signalling pathways involved. Betanin/isobetanin concentrate significantly decreased cancer cell proliferation and viability. Particularly in MCF‐7‐treated cells, the expressions of apoptosis‐related proteins (Bad, TRAILR4, FAS, p53) were strongly increased and the mitochondrial membrane potential was altered, demonstrating the involvement of both intrinsic and extrinsic apoptotic pathways. Autophagosome vesicles in MCF‐7‐treated cells were observed, also suggesting autophagic cell death upon betanin/isobetanin treatment. Importantly, the betanin‐enriched extract had no obvious effect towards normal cell lines. Our data bring new insight to consider the betanin/isobetanin mix as therapeutic anticancer compound, alone or in combination with classical chemotherapeutic drugs, especially in functional p53 tumors. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-14T06:35:33.550718-05:
      DOI: 10.1002/ptr.5491
  • Photoprotective Activity of Vulpinic and Gyrophoric Acids Toward
           Ultraviolet B‐Induced Damage in Human Keratinocytes
    • Abstract: Vulpinic and gyrophoric acids are known as ultraviolet filters for natural lichen populations because of their chemical structures. However, to the best of our knowledge, there has been no reference to their cosmetic potential for skin protection against ultraviolet B (UVB)‐induced damage and, consequently, we propose to highlight their photoprotective profiles in human keratinocytes (HaCaT). Therefore, vulpinic acid and gyrophoric acid were isolated from acetone extracts of Letharia vulpina and Xanthoparmelia pokornyi, respectively. Their photoprotective activities on irradiated HaCaT cells and destructive effects on non‐irradiated HaCaT cells were compared through in vitro experimentation: 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and lactate dehydrogenase assays, 4′,6‐diamino‐2‐phenylindole and tetramethylrhodamine B isothiocyanate‐phalloidin staining protocols. Both of the lichen substances effectively prevented cytotoxic, apoptotic and cytoskeleton alterative activities of 2.5 J/cm2 UVB in a dose‐dependent manner. Moreover, vulpinic and gyrophoric acids showed no toxic, apoptotic or cytoskeleton alterative effects on non‐irradiated HaCaT cells, except at high doses (≥400 μM) of gyrophoric acid. The findings suggest that vulpinic and gyrophoric acids can be promising cosmetic ingredients to photo‐protect human skin cells and should therefore be further investigated by in vitro and in vivo multiple bioassays. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-14T02:30:55.233577-05:
      DOI: 10.1002/ptr.5493
  • Anti‐inflammatory Activity of Constituents Isolated from Aerial Part
           of Angelica acutiloba Kitagawa
    • Authors: Takuhiro Uto; Nguyen Huu Tung, Risa Taniyama, Tosihide Miyanowaki, Osamu Morinaga, Yukihiro Shoyama
      Abstract: Recently, the resources of medicinal plants have been exhausting. The root of Angelica acutiloba is one of the most important ingredients in Japanese Kampo medicine for the treatment of gynecological diseases. In our search for alternative medicinal plant resources of the root of A. acutiloba, we found that its aerial part has the anti‐inflammatory potency as well as the root. Phytochemical investigation of the aerial part resulted in the isolation of four compounds including a new dimeric phthalide, namely tokiaerialide (2), along with Z‐ligustilide (1), falcarindiol (3), and bergaptol (4). Next, we investigated the in vitro anti‐inflammatory activity of 1–4 in lipopolysaccharide‐stimulated RAW264 macrophages. Among the isolated compounds, 1 exhibited the most potent inhibition against lipopolysaccharide‐induced production of prostaglandin E2, nitric oxide, and pro‐inflammatory cytokines (interleukin‐6 and tumor necrosis factor‐α). Compounds 3 and 4 also inhibited all inflammatory mediators, but their inhibitory abilities were weaker than those of 1. Furthermore, 1, 3, and 4 strongly also induced heme oxygenase‐1. These results suggest that 1, 3, and 4 potentially exert anti‐inflammatory activity, and the aerial part of A. acutiloba may be considered to be a useful medicinal resource for inflammatory diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-14T02:01:53.516593-05:
      DOI: 10.1002/ptr.5490
  • Pharmacological Effects of Glycyrrhiza spp. and Its Bioactive
           Constituents: Update and Review
    • Abstract: The roots and rhizomes of various species of the perennial herb licorice (Glycyrrhiza) are used in traditional medicine for the treatment of several diseases. In experimental and clinical studies, licorice has been shown to have several pharmacological properties including antiinflammatory, antiviral, antimicrobial, antioxidative, antidiabetic, antiasthma, and anticancer activities as well as immunomodulatory, gastroprotective, hepatoprotective, neuroprotective, and cardioprotective effects. In recent years, several of the biochemical, molecular, and cellular mechanisms of licorice and its active components have also been demonstrated in experimental studies. In this review, we summarized the new phytochemical, pharmacological, and toxicological data from recent experimental and clinical studies of licorice and its bioactive constituents after our previous published review. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-13T22:57:56.760876-05:
      DOI: 10.1002/ptr.5487
  • A Systemic Review on Aloe arborescens Pharmacological Profile: Biological
           Activities and Pilot Clinical Trials
    • Abstract: Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-13T05:57:24.051354-05:
      DOI: 10.1002/ptr.5483
  • Camphor Induces Proliferative and Anti‐senescence Activities in
           Human Primary Dermal Fibroblasts and Inhibits UV‐Induced Wrinkle
           Formation in Mouse Skin
    • Authors: Thao Anh Tran; Manh Tin Ho, Yeon Woo Song, Moonjae Cho, Somi Kim Cho
      Abstract: Camphor ((1R)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐one), a bicyclic monoterpene, is one of the major constituents of essential oils from various herbs such as rosemary, lavender, and sage. In this study, we investigated the beneficial effects of camphor as a botanical ingredient in cosmetics. Camphor induced the proliferation of human primary dermal fibroblasts in a dose‐dependent manner via the PI3K/AKT and ERK signaling pathways. Camphor attenuated the elevation of senescence associated with β‐galactosidase (SA‐β‐gal) activity. Elastase activity decreased, while the total amount of collagen increased, in a dose‐ and time‐dependent manner in human primary dermal fibroblasts treated with camphor. Camphor induced the expression of collagen IA, collagen IIIA, collagen IVA, and elastin in human primary dermal fibroblasts. In addition, posttreatment with 26 and 52 mM camphor for 2 weeks led to a significant reduction in the expression of MMP1 but increases in the expression of collagen IA, IIIA, and elastin in mouse skin exposed to UV for 4 weeks. These posttreatments also reduced the depths of the epidermis and subcutaneous fat layer in UV‐exposed mouse skin. Taken together, these findings suggest camphor to be a potent wound healing and antiwrinkle agent with considerable potential for use in cosmeceuticals. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-13T01:01:44.822643-05:
      DOI: 10.1002/ptr.5484
  • Young Coconut Juice Supplementation Results in Greater Bone Mass and Bone
           Formation Indices in Ovariectomized Rats: A Preliminary Study
    • Authors: Yuko Morii; Hiroshi Matsushita, Akira Minami, Hiroaki Kanazawa, Takashi Suzuki, Sanan Subhadhirasakul, Kazushi Watanabe, Akihiko Wakatsuki
      Abstract: Young coconut juice (Cocos nucifera Linn.) (YCJ) has traditionally been consumed to alleviate symptoms associated with menopause by women in Southeast Asia. The aim of the present study was to determine the effects of YCJ on bone metabolism in ovariectomized rats. Female 10‐week‐old Wistar rats were randomly assigned to the following 4 groups: Baseline, Sham, Ovx, and Ovx + YCJ (n = 10 rats per group). Rats in the Baseline group were sacrificed immediately, and those in the other groups were subjected to either sham operation (Sham) or bilateral ovariectomy (Ovx and Ovx + YCJ). The Ovx + YCJ rats were administered 5×‐concentrated YCJ at a dose of 10 mL/kg body weight per day. Six weeks after surgery, the rats were sacrificed, and indices of bone mass and bone histomorphometry were measured. The bone mineral density of the left femur was significantly higher in the Ovx + YCJ group compared with the Ovx group. In addition, the Ovx + YCJ group showed significantly higher measurements for bone formation rate compared with the Ovx group. These findings suggest that YCJ supplementation has a positive effect on bone metabolism and thus represents a possible intervention to slow the bone loss observed following menopause. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-06T22:23:36.273319-05:
      DOI: 10.1002/ptr.5489
  • Can Chinese Herbal Medicine Adjunctive Therapy Improve Outcomes of Senile
           Vascular Dementia? Systematic Review with Meta‐analysis of
           Clinical Trials
    • Authors: Lingfeng Zeng; Yuanping Zou, Lingshuo Kong, Ningsheng Wang, Qi Wang, Lu Wang, Ye Cao, Kezhu Wang, Yunbo Chen, Suiqing Mi, Wei Zhao, Haitao Wu, Shuyi Cheng, Weihua Xu, Weixiong Liang
      Abstract: Many publications have reported the growing application of complementary and alternative medicine, particularly the use of Chinese herbal medicine (CHM) in combination with routine pharmacotherapy (RP) for senile vascular dementia (SVD), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM adjunctive therapy (CHMAT), which is CHM combined with RP, in the treatment of SVD. Publications in seven electronic databases were searched extensively, and 27 trials with a total of 1961 patients were included for analysis. Compared with RP alone, CHMAT significantly increased the effective rate [odds ratio (OR) 2.98, 95% confidence interval (CI) 2.30, 3.86]. In addition, CHMAT showed benefits in detailed subgroups of the Mini‐Mental State Exam (MMSE) score from time of onset to 4 weeks (WMD 3.01, 95% CI 2.15, 3.87), 8 weeks (weighted mean difference (WMD) 2.30, 95% CI 1.28, 3.32), 12 weeks (WMD 2.93, 95% CI 2.17, 3.69), and 24 weeks (WMD 3.25, 95% CI 2.61, 3.88), and in the activity of daily living scale score from time of onset to 4 weeks (WMD −4.64, 95% CI −6.12, −3.17), 8 weeks (WMD −4.30, 95% CI −6.04, −2.56), 12 weeks (WMD −3.89, 95% CI −4.68, −3.09), and 24 weeks (WMD −4.04, 95% CI −6.51, −1.57). Moreover, CHMAT had positive effects on changes in the Hasegawa dementia scale, National Institutes of Health Stroke Scale, Clinical Dementia Rating, and Montreal Cognitive Assessment scores, as well as blood fat levels (total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and apolipoprotein E), platelet aggregation rate (1‐min platelet aggregation rate, 5‐min platelet aggregation rate, and maximal platelet aggregation rate), and blood rheology (whole‐blood viscosity and hematocrit). No serious or frequently occurring adverse effects were reported. Weaknesses of methodological quality in most trials were assessed using the Cochrane risk of bias tool, while the quality level of Grades of Recommendations Assessment Development and Evaluation (GRADE) evidence classification indicated ‘very low’. This systematic review suggests that CHM as an adjunctive therapy can improve cognitive impairment and enhance immediate response and quality of life in SVD patients. However, because of limitations of methodological quality in the included studies, further research of rigorous design is needed. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-06T22:04:40.265025-05:
      DOI: 10.1002/ptr.5481
  • Flavonoids of Korean Citrus aurantium L. Induce Apoptosis via Intrinsic
           Pathway in Human Hepatoblastoma HepG2 Cells
    • Abstract: Korean Citrus aurantium L. has long been used as a medicinal herb for its anti‐inflammatory, antioxidant, and anticancer properties. The present study investigates the anticancer role of flavonoids extracted from C. aurantium on human hepatoblastoma cell, HepG2. The Citrus flavonoids inhibit the proliferation of HepG2 cells in a dose‐dependent manner. This result was consistent with the in vivo xenograft results. Apoptosis was detected by cell morphology, cell cycle analysis, and immunoblot. Flavonoids decreased the level of pAkt and other downstream targets of phosphoinositide‐3‐kinase/Akt pathway – P‐4EBP1 and P‐p70S6K. The expressions of cleaved caspase 3, Bax, and Bak were increased, while those of Bcl‐2 and Bcl‐xL were decreased with an increase in the expression of Bax/Bcl‐xL ratio in treated cells. Loss of mitochondrial membrane potential was also observed in flavonoid‐treated HepG2 cells. It was also observed that the P‐p38 protein level was increased both dose and time dependently in flavonoid‐treated cells. Collectively, these results suggest that flavonoid extracted from Citrus inhibits HepG2 cell proliferation by inducing apoptosis via an intrinsic pathway. These findings suggest that flavonoids extracted from C. aurantium L. are potential chemotherapeutic agents against liver cancer. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-06T01:32:29.890415-05:
      DOI: 10.1002/ptr.5488
  • Anti‐Arthritic and Antiinflammatory Effects of the Traditional
           Uighur Formula Kursi Caper In Vivo
    • Authors: Zulfiye Talat; Xirali Tursun, Lufeng Cheng, Ailati Mijiti, Haji Akber Aisa
      Abstract: Kursi Caper (KC) is a Uighur medicine based on caper which is widely used to treat arthritis and rheumatism, and preliminary studies in our laboratory showed that this traditional formula may possess potent antiinflammatory effects. This study confirms the antiinflammatory effect of KC in the adjuvant induced arthritis (AIA) model, the carrageenan and cotton‐pellet induced granuloma rat models, and further investigates in vivo the mechanism of action by measuring relevant indicators of anti‐arthritic activity. KC showed significant and dose‐dependent anti‐arthritic and antiinflammatory effects, demonstrated by reduced paw edema and arthritic scores in all animal models. Histopathological examination showed that KC reduced levels of synovial inflammatory factors in AIA rats. The overproduction of TNF‐α and IL‐1β was attenuated, and CAT, MDA and SOD levels were restored to normal in KC‐treated rats. KC also significantly reduced LPS‐induced proliferation of B lymphocytes and ConA induced proliferation of T lymphocytes in a dose‐dependent manner. Flow cytometry showed that the high dose KC‐treated group had a significantly decreased frequency of Th17 cells. This study indicates that KC can significantly attenuate arthritis and inflammation in rats by decreasing the levels of inflammatory cytokines, regulating oxidative stress, reducing lymphocyte proliferation and decreasing Th17. This supports the traditional use of KC as a potential modern therapeutic agent for the treatment of arthritis and related conditions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-04T22:17:28.73124-05:0
      DOI: 10.1002/ptr.5479
  • Effects of Cyanidin‐3‐O‐glucoside on Synthetic and
           Metabolic Activity of Ethanol Stimulated Human Pancreatic Stellate Cells
    • Authors: Vaidotas Cesna; Rasa Baniene, Aurelija Maziukiene, Kristina Kmieliute, Sonata Trumbeckaite, Linas Venclauskas, Giedrius Barauskas, Antanas Gulbinas
      Abstract: Activated pancreatic stellate cells (PSC) play a major role in the development of chronic pancreatitis. Flavonoids (C‐3‐O‐G) theoretically may have potential to suppress activated PSC. The aim of our study was to determine the ability of C‐3‐O‐G to invert synthetic and metabolic activity of alcohol stimulated human pancreatic stellate cells (hPSC). In the present study we demonstrate that treatment with C‐3‐O‐G decreased proliferation rate of ethanol activated hPSC by 51%. Synthesis of extracellular matrix proteins in activated hPSC was markedly inhibited, as shown by reduced levels of collagen I and fibronectin expression. The decrease of secretion of fibronectin by 33% and in collagen I‐25% in ethanol activated and C‐3‐O‐G treated hPSC was observed. Moreover, treatment of ethanol activated hPSC with C‐3‐O‐G resulted in the decrease of oxygen consumption rate by 44% and reduced levels of ATP synthesis (i.e. energy production) by 41%. Hence, the effects of C‐3‐O‐G on ethanol activated hPSC may provide new insights for the use of anthocyanins as anti‐fibrogenic agents in treatment and/or prevention of pancreatic fibrosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-01T03:55:49.034791-05:
      DOI: 10.1002/ptr.5476
  • Dammarenediol‐II Prevents VEGF‐Mediated Microvascular
           Permeability in Diabetic Mice
    • Abstract: Diabetic retinopathy is a major diabetic complication predominantly caused by vascular endothelial growth factor (VEGF)‐induced vascular permeability in the retina; however, treatments targeting glycemic control have not been successful. Here, we investigated the protective effect of dammarenediol‐II, a precursor of triterpenoid saponin biosynthesis, on VEGF‐induced vascular leakage using human umbilical vein endothelial cells (HUVECs) and diabetic mice. We overproduced the compound in transgenic tobacco expressing Panax ginseng dammarenediol‐II synthase gene and purified using column chromatography. Analysis of the purified compound using a gas chromatography–mass spectrometry system revealed identical retention time and fragmentation pattern to those of authentic standard dammarenediol‐II. Dammarenediol‐II inhibited VEGF‐induced intracellular reactive oxygen species generation, but it had no effect on the levels of intracellular Ca2+ in HUVECs. We also found that dammarenediol‐II inhibited VEGF‐induced stress fiber formation and vascular endothelial‐cadherin disruption, both of which play critical roles in modulating endothelial permeability. Notably, microvascular leakage in the retina of diabetic mice was successfully inhibited by intravitreal dammarenediol‐II injection. Our results suggest that the natural drug dammarenediol‐II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-24T07:11:46.583813-05:
      DOI: 10.1002/ptr.5480
  • Multiple ABC Transporters Efflux Baicalin
    • Abstract: Baicalein, the aglycone formed by hydrolysis of baicalin in the intestine, is well absorbed by passive diffusion but subjected to extensive intestinal glucuronidation. Efflux of baicalin, the low passive permeability glucuronide of baicalein from enterocytes, likely depends on a carrier‐mediated transport. The present study was designed to explore potential drug–herb interaction by investigating the inhibitory effect of baicalin on the transport of reporter substrates by transporters and to identify the transporters responsible for the efflux of baicalin from enterocytes and hepatocytes. The interaction of baicalin with specific ABC transporters was studied using membranes from cells overexpressing human BCRP, MDR1, MRP2, MRP3 and MRP4. Baicalin was tested for its potential to inhibit vesicular transport by these transporters. The transport of baicalin by the selected transporters was also investigated. Transport by BCRP, MRP3 and MRP4 was inhibited by baicalin with an IC50 of 3.41 ± 1.83 μM, 14.01 ± 2.51 μM and 14.39 ± 5.69 μM respectively. Inhibition of MDR1 (IC50 = 94.84 ± 31.10 μM) and MRP2 (IC50 = 210.13 ± 110.49 μM) was less potent. MRP2 and BCRP are the apical transporters of baicalin that may mediate luminal efflux in enterocytes and biliary efflux in hepatocytes. The basolateral efflux of baicalin is likely mediated by MRP3 and MRP4 both in enterocytes and hepatocytes. Via inhibition of transport by ABC transporters, baicalin could interfere with the absorption and disposition of drugs. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-24T06:49:07.346595-05:
      DOI: 10.1002/ptr.5477
  • The Amoebicidal Effect of Ergosterol Peroxide Isolated from Pleurotus
    • Abstract: Dysentery is an inflammation of the intestine caused by the protozoan parasite Entamoeba histolytica and is a recurrent health problem affecting millions of people worldwide. Because of the magnitude of this disease, finding novel strategies for treatment that does not affect human cells is necessary. Ergosterol peroxide is a sterol particularly known as a major cytotoxic agent with a wide spectrum of biological activities produced by edible and medicinal mushrooms. The aim of this report is to evaluate the amoebicidal activity of ergosterol peroxide (5α, 8α‐epidioxy‐22E‐ergosta‐6,22‐dien‐3β‐ol isolated from 5α, 8α‐epidioxy‐22E‐ergosta‐6,22‐dien‐3β‐ol) (Jacq.) P. Kumm. f. sp. Florida. Our results show that ergosterol peroxide produced a strong cytotoxic effect against amoebic growth. The inhibitory concentration IC50 of ergosterol peroxide was evaluated. The interaction between E. histolytica and ergosterol peroxide in vitro resulted in strong amoebicidal activity (IC50 = 4.23 nM) that may be due to the oxidatory effect on the parasitic membrane. We also tested selective toxicity of ergosterol peroxide using a cell line CCL‐241, a human epithelial cell line isolated from normal human fetal intestinal tissue. To the best of our knowledge, this is the first report on the cytotoxicity of ergosterol peroxide against E. histolytica, which uncovers a new biological property of the lipidic compound isolated from Pleurotus ostreatus (Jacq.) P. Kumm. f. sp. Florida. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-22T01:49:29.38636-05:0
      DOI: 10.1002/ptr.5474
  • Standardized Prunella vulgaris var. lilacina Extract Enhances Cognitive
           Performance in Normal Naive Mice
    • Authors: Se Jin Park; Young Je Ahn, Hyung Eun Lee, Eunyoung Hong, Jong Hoon Ryu
      Abstract: Adult hippocampal neurogenesis is closely associated with neuronal plasticity, cognitive function and the etiology of neurological diseases. We previously reported that the standardized ethanolic extract of Prunella vulgaris var. lilacina (EEPV) can be used for the prevention and treatment of cognitive impairments associated with Alzheimer's disease or schizophrenia. In the present study, we investigated the effects of EEPV on cognitive ability in normal naive mice and the underlying mechanism(s) governing these effects, including adult hippocampal neurogenesis. In the passive avoidance task, sub‐chronic administration of EEPV (25 or 50 mg/kg, p.o.) for 14 days markedly induced the improvement of cognitive function in mice. In addition, sub‐chronic administration of EEPV (25 or 50 mg/kg) for 14 days significantly increased neural cell proliferation and the number of immature neurons, but not newly generated cell survival, in the hippocampal dentate gyrus. Increased ERK, Akt and GSK‐3β phosphorylation levels in the hippocampus were also observed after such administration. Our results indicate that EEPV may enhance cognitive function via the activation of various intracellular signaling molecules and the up‐regulation of adult hippocampal neurogenesis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-17T03:47:38.588031-05:
      DOI: 10.1002/ptr.5449
  • Mechanisms of Vasorelaxation Induced by Hexahydrocurcuminin Isolated Rat
           Thoracic Aorta
    • Authors: Aida Moohammadaree; Chatchawan Changtam, Piyawadee Wicha, Apichart Suksamrarn, Jiraporn Tocharus, Chainarong Tocharus
      Abstract: This study was designed to examine the vasorelaxant effects of hexahydrocurcumin (HHC), one of the major natural metabolites of curcumin from Curcuma longa, on rat isolated aortic rings, and the underlying mechanisms. Isometric tension of the aortic rings was recorded using organ bath system. HHC (1 nM to 1 mM) relaxed the endothelium‐intact aortic rings pre‐contracted with PE and KCl in a concentration‐dependent manner. Removal of the endothelium did not alter the effect of HHC‐induced relaxation. In Ca2+‐free Krebs solution, HHC significantly inhibited the CaCl2‐induced contraction in high K+ depolarized rings and suppressed the transient contraction induced by PE and caffeine in a concentration‐dependent manner. HHC was also observed to relax phobal‐12‐myristate‐13‐acetate (PMA), an activator of protein kinase C (PKC), precontracted aortic rings in a concentration‐dependent manner with EC50 values equivalent to 93.36 ± 1.03 μM. In addition, pre‐incubation with propranolol (a β‐adrenergic receptor blocker) significantly attenuated the HHC‐induced vasorelaxation. These results suggest that the vasorelaxant effect of HHC is mediated by the endothelium‐independent pathway, probably because of the inhibition of extracellular Ca2+ influx through voltage‐operated Ca2+ channels and receptor‐operated Ca2+ channels, the inhibition of Ca2+mobilization from intracellular stores, as well as inhibition of PKC‐mediated Ca2+‐independent contraction. Moreover, HHC produces vasorelaxant effects probably by stimulating the β‐adrenergic receptor. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-11T02:17:43.208581-05:
      DOI: 10.1002/ptr.5448
  • Recent trends in preclinical drug–drug interaction studies of
           flavonoids — Review of case studies, issues and
    • Authors: Nuggehally R. Srinivas
      Abstract: Because of health benefits that are manifested across various disease areas, the consumption of herbal products and/or health supplements containing different kinds of flavonoids has been on the rise. While the drug–drug interaction potential between flavonoids and co‐ingested drugs still remain an issue, opportunities exist for the combination of flavonoids with suitable anti‐cancer drugs to enhance the bioavailability of anti‐cancer drugs and thereby reduce the dose size of the anti‐cancer drugs and improve its therapeutic index. In recent years, scores of flavonoids have undergone preclinical investigation with variety of drugs encompassing therapeutic areas such as oncology (etoposide, doxorubicin, paclitaxel, tamoxifen etc.), immunosuppression (cyclosporine) and hypertension (losartan, felodipine, nitrendipine etc.). The review provides examples of the recent trends in the preclinical investigation of 14 flavonoids (morin, quercetin, silibinin, kaempferol etc.) with various co‐administered drugs. The relevance of combination of flavonoids with anti‐cancer drugs and a framework to help design the in vitro and in vivo preclinical studies to gain better mechanistic insights are discussed. Also, concise discussions on the various physiological factors that contribute for the reduced bioavailability of flavonoids along with the significant challenges in the data interpretation are provided. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-06T22:38:05.672496-05:
      DOI: 10.1002/ptr.5447
  • Effect of Trimeric Myricetin Rhamnoside (TMR) in Carrageenan‐induced
           Inflammation and Caecal Ligation and Puncture‐induced Lung Oxidative
           Stress in Mice
    • Authors: Najeeb Latief; Shikha Anand, Madhu Cholenahalli Lingaraju, Venkanna Balaganur, Nitya Nand Pathak, Jaspreet Kalra, Dinesh Kumar, Brijesh K Bhadoria, Surendra Kumar Tandan
      Abstract: The Eugenia jambolana is used in folklore medicine. Leaves of E. jambolana contain flavonoids as their active constituents which possess in vitro antiinflammatory, antioxidant and the antimicrobial activity. The aim of the present study was to investigate the antiinflammatory and antioxidant effects of a flavonoid glucoside, trimeric myricetin rhamnoside (TMR) isolated from leaves of E. jambolana. TMR was studied for antiinflammatory activity in carrageenan‐induced hind paw oedema and antioxidant activity in lung by caecal ligation and puncture (CLP)‐induced sepsis in mice. Results of the present study indicated that TMR significantly attenuated the oedema, myeloperoxidase (MPO), cytokines and prostaglandin levels in the paw after 5 h of carrageenan injection as compared to vehicle control. It also reduced the lung MPO, lipid peroxides, and serum nitrite plus nitrate levels and increased lung reduced glutathione levels 20 h of CLP as compared to vehicle control. Thus the results of this study concluded that the TMR appears to have potential benefits in diseases that are mediated by both inflammation and oxidative stress and support the pharmacological basis of use of E. jambolana plant as traditional herbal medicine for the treatment of inflammatory diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-06T22:30:59.282409-05:
      DOI: 10.1002/ptr.5446
  • Evaluation of the Wound Healing Properties of Hancornia speciosa Leaves
    • Abstract: The leaves of Hancornia speciosa Gomes (Apocynaceae), a medicinal species found in the Brazilian cerrado biome, are traditionally used to treat wounds and inflammatory disorders. The goal of the present study was to investigate the in vitro wound healing properties of ethanolic extract of H. speciosa leaves and its isolated compounds, using the scratch assay, and to evaluate their effects on the release of the pro‐inflammatory cytokine tumor necrosis factor (TNF‐α) by lipopolysaccharide (LPS)‐stimulated human acute monocytic (THP‐1) cells. H. speciosa ethanolic extract significantly increased (42.8% ± 5.4 at 25 µg/mL) cell migration and proliferation of fibroblasts compared with control cells, as well as the isolated compounds bornesitol (80.8% ± 5.1) and quinic acid (69.1% ± 6.2), both assayed at 50 μM. TNF‐α release by LPS‐stimulated THP‐1 cells was significantly reduced by the ethanolic extract (62.9% ± 8.2, i.e. 1791.1 ± 394.7 pg/mL) at 10 µg/mL, bornesitol (48.9% ± 0.9, i.e. 2461.6 ± 43.1 pg/mL) at 50 μM, and quinic acid (90.2% ± 3.4, i.e. 473.5 ± 164.4 pg/mL) and rutin (82.4% ± 5.6, i.e. 847.0 ± 271.8 pg/mL) at 10 μM. These results provided evidences to support the traditional use of H. speciosa leaves to treat wounds and inflammatory disorders. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-06T21:36:46.738785-05:
      DOI: 10.1002/ptr.5438
  • Anti‐carious Effects of Galla chinensis: A Systematic Review
    • Authors: Tieting Zhang; Jinpu Chu, Xuedong Zhou
      Abstract: As a natural traditional Chinese medicine, Galla chinensis has been widely used since ancient times for its astringency, stypticity, detoxification, and antibacterial activity. Our group has concentrated on the research about its potential of being an applicable anti‐caries agent. The crude extract and some other components purified from it show remarkable efficacy on anticaries, and the most likely mechanism is proposed through specific research. For the fact that crude drugs consist of numerous compounds, and their bioactivity is a result of synergistic effects and/or antagonistic effects of several compounds, it is difficult to clarify the exact mechanism and evaluate the safety and effectiveness of G. chinensis. This review article systematically summarizes previous findings from the following aspects: (1) inhibitory effect on oral bacteria; (2) the demineralization inhibition property; (3) the remineralization‐enhancing property; and (4) stability and toxicity evaluation, and thus indicates the further research direction. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-09-01T04:49:34.133234-05:
      DOI: 10.1002/ptr.5444
  • Sambucus Williamsii Hance Promotes MC3T3‐E1 Cells Proliferation and
           Differentiation via BMP‐2/Smad/p38/JNK/Runx2 Signaling Pathway
    • Authors: Bingyou Yang; Xiaoying Lin, Chunli Yang, Jinyan Tan, Wei Li, Haixue Kuang
      First page: 1692
      Abstract: The 50% ethanol elution fractions of root‐bark of Sambucus Williamsii Hance (rbSWH) evaluated the effect of proliferation and differentiation on preosteoblast MC3T3‐E1 cell, and the mechanism of actions. We found that rbSWH(30, 60, and 90 µg/mL) can enhance cell proliferation by MTT assay and promote alkaline phosphatase (ALP) and bone Gla protein (BGP) activities, type I collagen (Col‐I) synthesis, and mineralization nodule formation in primary cultured osteoblasts. The results showed that rbSWH can increase mRNA levels of BMP‐2 and Runx2 using real‐time reverse transcription‐quantitative polymerase chain reaction, whereas the BMP‐2 antagonist Noggin attenuated the increase of ALP activity induced by rbSWH, indicating that BMP‐2 expression was required for the action of rbSWH in osteoblastic. We also found that rbSWH can enhance the expressions of BMP‐2, BMPRIB, BMPRII, phosphorylation of Smad, JNK and p38, and Runx2 proteins by western blotting. In addition, pretreatment of cells with p38 inhibitor (SB203580) or JNK inhibitor (SP600125) can antagonize the elevation of BMP‐2 expression, ALP activity, and cell viability induced by rbSWH. Taken together, our results provided an evidence that rbSWH can promote MC3T3‐E1 cell proliferation and differentiation via BMP‐2/Smad/p38/JNK/Runx2 signaling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-12T03:05:29.111904-05:
      DOI: 10.1002/ptr.5482
  • Phloroglucinol Protects INS‐1 Pancreatic β‐cells Against
           Glucotoxicity‐Induced Apoptosis
    • Authors: Mi Hwa Park; Ji Sook Han
      First page: 1700
      Abstract: Decreasing numbers, and impaired function, of pancreatic β‐cells are key factors in the development of type 2 diabetes. This study was designed to investigate whether phloroglucinol protected pancreatic β‐cells against glucotoxicity‐induced apoptosis using a rat insulinoma cell line (INS‐1). High glucose treatment (30 mM) induced INS‐1 cell death; however, the level of glucose‐induced apoptosis was significantly reduced in cells treated with 100‐μM phloroglucinol. Treatment with 10–100‐μM phloroglucinol increased cell viability and decreased intracellular levels of reactive oxygen species, nitric oxide, and lipid peroxidation dose‐dependently in INS‐1 cells pretreated with high glucose. Furthermore, phloroglucinol treatment markedly reduced the protein expression of Bax, cytochrome c, and caspase 9, while increasing anti‐apoptotic Bcl‐2 protein expression. Cell death type was examined using annexin V/propidium iodide staining, revealing that phloroglucinol markedly reduced high glucose‐induced apoptosis. These results demonstrated that phloroglucinol could be useful as a potential therapeutic agent for the protection of pancreatic β‐cells against glucose‐induced apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-07T03:30:50.137997-05:
      DOI: 10.1002/ptr.5407
  • Differential Inhibition of T Lymphocyte Proliferation and Cytokine
           Synthesis by [6]‐Gingerol, [8]‐Gingerol, and
    • Authors: Megan Bernard; Suzanne J. Furlong, Melanie R. Power Coombs, David W. Hoskin
      First page: 1707
      Abstract: [6]‐Gingerol, [8]‐gingerol, and [10]‐gingerol are pungent components of fresh ginger, extracts of which inhibit various components of the inflammatory response. Because little is known regarding the effect of gingerols with different unbranched alkyl side chain lengths on the activation and effector function of T lymphocytes, we compared the effects of [6]‐gingerol, [8]‐gingerol, and [10]‐gingerol on murine T lymphocyte proliferation, expression of CD25 and CD69 activation markers, cytokine synthesis, and interleukin (IL)‐2 receptor signaling. All three gingerols inhibited DNA synthesis by T lymphocytes, as well as interferon‐γ synthesis. In contrast, only [8]‐gingerol and [10]‐gingerol inhibited CD25 and CD69 expression, and IL‐2 synthesis. None of the gingerols affected IL‐4 synthesis. Exogenous IL‐2 enhanced T lymphocyte proliferation in the presence of [6]‐gingerol but did not significantly increase T lymphocyte proliferation in the presence of [8]‐gingerol or [10]‐gingerol. In line with this finding, [8]‐gingerol and [10]‐gingerol impaired IL‐2‐induced proliferation of CTLL‐2 cells, but constitutive CD25 expression was unaffected, indicating inhibition of IL‐2 receptor signaling. In general, [10]‐gingerol and [8]‐gingerol were more potent inhibitors of T lymphocytes than [6]‐gingerol. Suppression of T lymphocyte responses by gingerols suggests that these phytochemicals may be beneficial in chronic inflammatory conditions associated with excessive or inappropriate T lymphocyte activation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:51:04.302563-05:
      DOI: 10.1002/ptr.5414
  • Dual Effects of Liquiritigenin on the Proliferation of Bone Cells:
           Promotion of Osteoblast Differentiation and Inhibition of Osteoclast
    • Authors: Kaho Uchino; Kuniaki Okamoto, Eiko Sakai, Erika Yoneshima, Mayumi Iwatake, Yutaka Fukuma, Kazuhisa Nishishita, Takayuki Tsukuba
      First page: 1714
      Abstract: Bone is constantly controlled by a balance between osteoblastic bone formation and osteoclastic bone resorption. Liquiritigenin is a plant‐derived flavonoid and has various pharmacological effects, such as antioxidative, antitumor, and antiinflammatory effects. Here, we show that liquiritigenin has dual effects on the proliferation of bone cells, regarding the promotion of osteoblast differentiation and the inhibition of osteoclast differentiation. Liquiritigenin‐treated murine osteoblastic MC3T3‐E1 cells showed an increased alkaline phosphatase activity and enhanced phosphorylation of Smad1/5 compared with untreated cells. Moreover, liquiritigenin inhibited osteoclast differentiation, its bone‐resorption activity through slightly decreased the phosphorylation of extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase, and inhibitor of nuclear factor kappa Bα; however, the phosphorylation of Akt and p38 slightly increased in bone marrow‐derived osteoclasts. The expression levels of the osteoclast marker proteins nuclear factor of activated T‐cell cytoplasmic‐1, Src, and cathepsin K diminished. These results suggest that liquiritigenin may be useful as a therapeutic and/or preventive agent for osteoporosis or inflammatory bone diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-14T08:46:57.664656-05:
      DOI: 10.1002/ptr.5416
  • Oxidative Stress Responses to Nigella sativa Oil Concurrent with a
           Low‐Calorie Diet in Obese Women: A Randomized, Double‐Blind
           Controlled Clinical Trial
    • Authors: Nazli Namazi; Reza Mahdavi, Mohammad Alizadeh, Safar Farajnia
      First page: 1722
      Abstract: The aim of the present study was to determine the effects of Nigella sativa (NS) oil concurrent with a low‐calorie diet on lipid peroxidation and oxidative status in obese women. In this double‐blind placebo‐controlled randomized clinical trial, 50 volunteer obese (body mass index = 30–35 kg/m2) women aged 25–50 years old were recruited. Participants were randomly divided into intervention (n = 25) and placebo (n = 25) groups. They received a low‐calorie diet with 3 g/day NS oil or low‐calorie diet with 3 g/day placebo for 8 weeks. Forty‐nine women (intervention group = 25; placebo group = 24) completed the trial. NS oil concurrent with a low‐calorie diet decreased weight in the NS group compared to the placebo group (−4.80 ± 1.50 vs. −1.40 ± 1.90 kg; p 
      PubDate: 2015-07-14T22:56:08.570371-05:
      DOI: 10.1002/ptr.5417
  • Extract from Ceratonia siliqua Exhibits Depigmentation Properties
    • Authors: Namrita Lall; Navneet Kishore, Saeideh Momtaz, Ahmed Hussein, Sanushka Naidoo, Mabatho Nqephe, Bridget Crampton
      First page: 1729
      Abstract: Skin hyper‐pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L‐tyrosine as a substrate and showed diphenolase activity. The extract further significantly lowered tyrosinase mRNA levels in B16‐F10 mouse melanocytes. Bioassay‐guided fractionation led to the isolation of six compounds. Compounds (−)‐epicatechin‐3‐O‐gallate, 1,2,3,6‐tetra‐O‐galloyl‐ß‐D‐glucose and gallocatechin‐3‐O‐gallate showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30 µg/mL, respectively. These compounds also exhibited L‐DOPA activities with IC50 values of >200, 150 and 200 µg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non‐irritant with irritancy potential of −34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-07-20T04:33:50.189768-05:
      DOI: 10.1002/ptr.5420
  • Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic
           Activity: From a Bioactivity‐guided Approach to Comprehensive
           Metabolite Profiling
    • First page: 1737
      Abstract: Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n‐butanol, and the remaining water fractions was evaluated in streptozotocin‐induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large‐scale untargeted metabolite profiling of methanol extract was performed via UPLC‐PDA and qTOF‐MS (ultra‐performance liquid chromatography photodiode array detection and quadrupole time‐of‐flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O‐caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-03T01:00:28.451313-05:
      DOI: 10.1002/ptr.5424
  • Distinct Responses of Cytotoxic Ganoderma lucidum Triterpenoids in Human
           Carcinoma Cells
    • Authors: Weimei Ruan; Ying Wei, David G. Popovich
      First page: 1744
      Abstract: The medicinal mushroom Ganoderma lucidum is well recognized for its effective cancer‐preventative and therapeutic properties, while specific components responsible for these anticancer effects are not well studied. Six triterpenoids that are ganolucidic acid E, lucidumol A, ganodermanontriol, 7‐oxo‐ganoderic acid Z, 15‐hydroxy‐ganoderic acid S, and ganoderic acid DM were isolated and identified from an extract of the mushroom. All compounds reduced cell growth in three human carcinoma cells (Caco‐2, HepG2, and HeLa cells) dose dependently with LC50s from 20.87 to 84.36 μM. Moreover, the six compounds induced apoptosis in HeLa cells with a maximum increase (22%) of sub‐G1 accumulations and 43.03% apoptotic cells in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (15‐hydroxy‐ganoderic acid S treatment). Apoptosis was further confirmed by annexin‐V staining. Four of the compounds also caused apoptosis in Caco‐2 cells with maximum 9.5% increase of sub‐G1 accumulations (7‐oxo‐ganoderic acid Z treatment) and maximum 29.84% apoptotic cells in TUNEL assay (ganoderic acid DM treatment). Contrarily, none of the compounds induced apoptosis in HepG2 cells. The different responses of the three cell lines following these treatments indicated that the bioactive properties of these compounds may vary from cells of different sites of origin and are likely acting under diverse regulatory mechanisms. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-21T02:08:56.7812-05:00
      DOI: 10.1002/ptr.5426
  • Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive
           Oxygen Species‐Mediated Apoptosis in Lung Cancer Cells and Decreases
           Xenograft Tumor Growth
    • First page: 1753
      Abstract: Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI‐H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl‐2 and Bcl‐xL, and upregulation of Bax, suggesting that caspase‐mediated pathways were involved in MSF‐induced apoptosis. ROS activation of the mitogen‐activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI‐H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. © 2015 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd
      PubDate: 2015-08-27T05:30:23.244004-05:
      DOI: 10.1002/ptr.5428
  • The Protective Effect of α‐Hederin, the Active Constituent of
           Nigella sativa, on Lung Inflammation and Blood Cytokines in Ovalbumin
           Sensitized Guinea Pigs
    • First page: 1761
      Abstract: In the present study, the preventive effect of two different concentrations of α‐hederin, the active constituent of Nigella sativa, on lung inflammation and blood cytokines in ovalbumin sensitized guinea pigs was examined. Forty eight male adult guinea pigs were divided into control (C), sensitized (S) and sensitized pretreated groups; with thymoquinone (S+TQ), low dose (S+LAH) and high dose of α‐hederin (S+HAH) and inhaled fluticasone propionate (S+FP). The lung histopathology and blood levels of IL‐4, IFN‐γ and IL‐17 were assessed. Compared to sensitized animals, all pathological changes improved significantly in pretreated groups (p 
      PubDate: 2015-08-21T02:19:21.605391-05:
      DOI: 10.1002/ptr.5429
  • Paeoniflorin ameliorates ANIT‐induced cholestasis by activating Nrf2
           through an PI3K/Akt‐dependent pathway in rats
    • Authors: Zhe Chen; Xiao Ma, Yun Zhu, Yanling Zhao, Jiabo Wang, Ruisheng Li, Chang Chen, Shizhang Wei, Wenjuan Jiao, Yaming Zhang, Jianyu Li, Lifu Wang, Ruilin Wang, Honghong Liu, Honghui Shen, Xiaohe Xiao
      First page: 1768
      Abstract: Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha‐naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT‐induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma‐glutamyl transpeptidase (γ‐GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT‐administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate‐cysteine ligase catalytic subunit (GCLc) and glutamate‐cysteine ligase modifier subunit (GCLm) in ANIT‐treated group. In addition, the RNA and protein expression of Akt and nuclear factor‐E2‐related factor‐2 (Nrf2) were also activated by paeoniflorin in ANIT‐induced rats. These findings indicated that paeoniflorin protected ANIT‐induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt‐dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-13T02:09:39.806322-05:
      DOI: 10.1002/ptr.5431
  • Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian
    • Authors: Mohammad A. Khanfar; Sanaa K. Bardaweel, Mohamed R. Akl, Khalid A. El Sayed
      First page: 1776
      Abstract: The established anticancer and neuroprotective properties of oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimer's disease development encouraged us to examine the possibility that oleocanthal inhibits mTOR. To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K‐γ. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3‐γ/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose‐dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA‐MB‐231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-07T03:46:17.655965-05:
      DOI: 10.1002/ptr.5434
  • Zingerone activates VMAT2 during MPP+‐induced Cell Death
    • First page: 1783
      Abstract: Parkinson's disease (PD) is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatum. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is used to produce an animal model for PD, and it is converted to 1‐methyl‐4‐phenylpyridine (MPP+) in animals. MPP+ accumulation leads to neuronal cell death. Vesicular monoamine transporter 2 (VMAT2) regulates the accumulation of monoamine neurotransmitters into synaptic vesicles and is involved in neuroprotection against neurotoxin‐induced cell death. Recently, zingerone has been reported to reduce oxidative stress and inhibit inflammation. Therefore, we examined the effect of zingerone on neuronal cell death in a PD model. In an MPP+ and MPTP‐mediated PD model, neuronal cell survival was increased by zingerone without modifying neuroinflammation or reactive oxygen species generation. Zingerone also induced ERK activation and VMAT2 expression, leading to the attenuation of MPP+‐induced neuronal cell death. Our current results suggest that zingerone has a neuroprotective effect in a PD model. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-17T22:51:47.82582-05:0
      DOI: 10.1002/ptr.5435
  • Antimicrobial Effects of Blueberry, Raspberry, and Strawberry Aqueous
           Extracts and their Effects on Virulence Gene Expression in Vibrio cholerae
    • Authors: Hazim O. Khalifa; Maki Kamimoto, Toshi Shimamoto, Tadashi Shimamoto
      First page: 1791
      Abstract: The antimicrobial effects of aqueous extracts of blueberry, raspberry, and strawberry on 13 pathogenic bacteria were evaluated. The minimum inhibitory concentrations and minimum bactericidal concentrations of the extracts were determined before and after neutralization to pH 7.03 ± 0.15. Both Gram‐positive and Gram‐negative pathogenic bacteria were selectively inhibited by the non‐neutralized berries. Blueberry was the best inhibitor, and Vibrio and Listeria were the most sensitive bacteria. After neutralization, blueberry affected only Vibrio and Listeria, whereas the antimicrobial activities of raspberry and strawberry were abolished. The total contents of phenolics, flavonoids, and proanthocyanidins in the extracts were measured with colorimetric methods and were highest in strawberry, followed by raspberry, and then blueberry. We also studied the effects of sub‐bactericidal concentrations of the three berry extracts on virulence gene expression in Vibrio cholerae. Real‐time quantitative reverse transcription–polymerase chain reaction revealed that the three berry extracts effectively repressed the transcription of the tcpA gene. Raspberry also repressed the transcription of the ctxA gene, whereas blueberry and strawberry did not. However, the three berry extracts did not affect the transcription of toxT. These results suggest that the three berry extracts exert potent antimicrobial effects and inhibit the expression of the virulence factors of V. cholerae. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-08-21T03:05:29.627726-05:
      DOI: 10.1002/ptr.5436
  • A Randomized Clinical Trial of Berberine Hydrochloride in Patients with
           Diarrhea‐Predominant Irritable Bowel Syndrome
    • Authors: Chunqiu Chen; Chunhua Tao, Zhongchen Liu, Meiling Lu, Qiuhui Pan, Lijun Zheng, Qing Li, Zhenshun Song, Jakub Fichna
      First page: 1822
      Abstract: We aimed to evaluate clinical symptoms in diarrhea predominant irritable bowel syndrome (IBS‐D) receiving berberine hydrochloride in a randomized double‐blind placebo‐controlled clinical trial. Overall, 196 patients with IBS‐D were recruited for this study; consequently, 132 patients randomized to receive daily 400 mg of berberine hydrochloride, delivered twice daily or placebo for 8 weeks followed by a 4‐week washout period. After a 2‐week run‐in period, diarrhea, abdominal pain, urgent need for defecation frequency and any adverse events were recorded daily. Prior to administration of the medication and after completing the treatment, assessment of IBS symptom scores, depression and anxiety scale scores and the IBS scale for quality of life (QOL) was carried out. The effects of berberine hydrochloride on IBS‐D, defined by a reduction of diarrhea frequency (P = 0.032), abdominal pain frequency (P 
      PubDate: 2015-09-24T06:42:15.506415-05:
      DOI: 10.1002/ptr.5475
  • Brassinin Combined with Capsaicin Enhances Apoptotic and
           Anti‐metastatic Effects in PC‐3 Human Prostate Cancer Cells
    • First page: 1828
      Abstract: Brassinin (BSN), a type of indole compound derived from cruciferous vegetables, has shown anti‐cancer effects in cells and animals. Capsaicin (CAP), an alkaloid derived from the chilli pepper, is also of interest in for its reported efficacy against various malignancies. The objective of our study was to analyze the potential synergistic anti‐tumor effects of BSN combined with CAP on prostate cancer PC‐3 cells. After treatment with BSN and CAP at various concentrations, the synergistic cytotoxic effect of PC‐3 cells was analyzed by MTT method, proliferation, apoptosis, mitochondrial membrane potential, colony formation, and Western blotting. Moreover, the inhibitory effects of BSN and CAP on the constitutive expressions of MMP‐9/2, their enzymatic activities, cellular migration, and cell invasion were also investigated. The cytotoxicity was synergistically increased in combination compared with the single drug used; moreover, proliferation, apoptosis, mitochondrial membrane potential, and colony formation were significantly suppressed and anti‐apoptotic‐, proliferative‐, and metastatic‐related proteins were clearly abolished in the combination group. Besides, constitutive MMP‐9/2 expression, their enzymatic activities, cell migration, and tumor cell invasion were inhibited, and TIMP‐1 was up‐regulated in the combination group in PC‐3 cells. Our results indicate, for the first time, that BSN and CAP in combination exert synergistic anticancer effects in prostate carcinoma. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-10-01T17:40:26.39541-05:0
      DOI: 10.1002/ptr.5478
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