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Journal Cover Phytotherapy Research
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   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
   Published by John Wiley and Sons Homepage  [1598 journals]
  • Antiinflammatory, Antioxidant, and Immunomodulatory Effects of Crocus
           sativus L. and its Main Constituents
    • Authors: Mohammad Hossein Boskabady; Tahereh Farkhondeh
      Abstract: Crocus sativus L. (C. sativus), commonly known as saffron, is used as a food additive, preservative, and medicinal herb. Traditionally, it has been used as an alternative treatment for different diseases. C. sativus' medicinal effects are related to its major constituents like crocins, crocetin, and safranal. According to the literature, C. sativus and its constituents could be considered as an effective treatment for neurodegenerative disorders, coronary artery diseases, asthma, bronchitis, colds, fever, diabetes, and so on. Recently, numerous studies have reported such medicinal properties and found that the underlying mechanisms of action may be mediated by antioxidant, inflammatory, and immunomodulatory effects. C. sativus enhances the antioxidant capacity and acts as a free radical scavenger. As an antiinflammatory and immunomodulatory agent, it modulates inflammatory mediators, humoral immunity, and cell‐mediated immunity responses. This review highlights in vitro and animal findings regarding antiinflammatory, antioxidant, and immunomodulatory effects of C. sativus and its constituents. Present review found that the C. sativus and its main constituents such as safranal, crocins, and crocetin could be effective against various diseases because of their antioxidant, anti‐inflammation, and immunomodulatory effects. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-21T04:36:29.323968-05:
      DOI: 10.1002/ptr.5622
  • Dietary Phenolic Acids of Macrotyloma uniflorum (Horse Gram) Protect the
           Rat Heart Against Isoproterenol‐Induced Myocardial Infarction
    • Authors: Vandana Panda; Ankit Laddha, Mukesh Nandave, Sudhamani Srinath
      Abstract: The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p‐coumaric acid and ferulic acid) in isoproterenol (ISO)‐induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO‐elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C‐reactive protein and malondialdehyde and a restoration of the levels of the ISO‐depleted marker enzymes, reduced glutathione and the antioxidant enzymes—superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO‐altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO‐challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-19T04:41:39.964578-05:
      DOI: 10.1002/ptr.5620
  • Polyphenolic Compounds and Antioxidant Activity of Cold‐Pressed Seed
           Oil from Finola Cultivar of Cannabis sativa L.
    • Authors: Antonella Smeriglio; Enza M. Galati, Maria T. Monforte, Francesco Lanuzza, Valeria D'Angelo, Clara Circosta
      Abstract: The aim of this study was to characterize the polyphenolic compounds and antioxidant activity of cold‐pressed seed oil from Finola cultivar of industrial hemp (Cannabis sativa L.). Several methodologies have been employed to evaluate the in vitro antioxidant activity of Finola hempseed oil (FHSO) and both lipophilic (LF) and hydrophilic fractions (HF). The qualitative and quantitative composition of the phenolic fraction of FHSO was performed by HPLC analyses. From the results is evident that FHSO has high antioxidative activity, as measured by DPPH radical (146.76 mmol of TE/100 g oil), inhibited β‐carotene bleaching, quenched a chemically generated peroxyl radical in vitro and showed high ferrous ion chelating activity. Reactivity towards 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) radical cation and ferric‐reducing antioxidant power values were 695.2 µmol of TE/100g oil and 3690.6 µmol of TE/100 g oil respectively. FHSO contains a significant amount of phenolic compounds of which 2780.4 mg of quercetin equivalent/100 g of total flavonoids. The whole oil showed higher antioxidant activity compared with LF and HF. Our findings indicate that the significant antioxidant properties shown from Finola seed oil might generally depend on the phenolic compounds, especially flavonoids, such as flavanones, flavonols, flavanols and isoflavones.
      PubDate: 2016-04-14T00:35:38.974856-05:
      DOI: 10.1002/ptr.5623
  • Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and
    • Authors: Gulshan Bansal; Nancy Suthar, Jasmeen Kaur, Astha Jain
      Abstract: Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (−80 to 100 °C), humidity (0–100%) and duration (a few hours–36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-13T02:56:45.76183-05:0
      DOI: 10.1002/ptr.5618
  • Scope of Hydrolysable Tannins as Possible Antimicrobial Agent
    • Authors: Sanmuga Priya Ekambaram; Senthamil Selvan Perumal, Ajay Balakrishnan
      Abstract: Hydrolysable tannins (HTs) are secondary metabolites from plants, which are roughly classified into gallotannins and ellagitannins having gallic acid and ellagic acid residues respectively attached to the hydroxyl group of glucose by ester linkage. The presence of hexahydroxydiphenoyl and nonahydroxyterphenoyl moieties is considered to render antimicrobial property to HTs. HTs also show considerable synergy with antibiotics. Nevertheless, they have low pharmacokinetic property. The present review presents the scope of HTs as future antimicrobial agent. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-07T21:50:37.163823-05:
      DOI: 10.1002/ptr.5616
  • Medicinal Plants with Antiplatelet Activity
    • Authors: Mohammed El Haouari; Juan A. Rosado
      Abstract: Blood platelets play an essential role in the hemostasis and wound‐healing processes. However, platelet hyperactivity is associated to the development and the complications of several cardiovascular diseases. In this sense, the search for potent and safer antiplatelet agents is of great interest. This article provides an overview of experimental studies performed on medicinal plants with antiplatelet activity available through literature with particular emphasis on the bioactive constituents, the parts used, and the various platelet signaling pathways modulated by medicinal plants. From this review, it was suggested that medicinal plants with antiplatelet activity mainly belong to the family of Asteraceae, Rutaceae, Fabaceae, Lamiaceae, Zygophyllaceae, Rhamnaceae, Liliaceae, and Zingiberaceae. The antiplatelet effect is attributed to the presence of bioactive compounds such as polyphenols, flavonoids, coumarins, terpenoids, and other substances which correct platelet abnormalities by interfering with different platelet signalization pathways including inhibition of the ADP pathway, suppression of TXA2 formation, reduction of intracellular Ca2+ mobilization, and phosphoinositide breakdown, among others. The identification and/or structure modification of the plant constituents and the understanding of their action mechanisms will be helpful in the development of new antiplatelet agents based on medicinal plants which could contribute to the prevention of thromboembolic‐related disorders by inhibiting platelet aggregation. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-06T22:25:45.073211-05:
      DOI: 10.1002/ptr.5619
  • Anti‐Nociceptive Effect of Resveratrol During Inflammatory
           Hyperalgesia via Differential Regulation of pro‐Inflammatory
    • Authors: Ajeet Kumar Singh; Manjula Vinayak
      Abstract: Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti‐hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c‐Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL‐1β, TNF‐α and IL‐6 as well as inflammatory enzymes COX‐2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX‐2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti‐nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-06T00:16:04.503159-05:
      DOI: 10.1002/ptr.5624
  • In vitro Effect of Mouthrinse Containing Essential Oils on Proliferation
           and Migration of Gingival Epithelial Cells
    • Authors: Kouki Yoshikawa; Jin Sekino, Kentaro Imamura, Koki Ota, Daichi Kita, Atsushi Saito
      Abstract: We aimed to investigate in vitro the effects of mouthrinses containing essential oils (EOs) on proliferation and migration of gingival epithelial cells. Human gingival epithelial cells were treated with predetermined dilutions of commercially available EO mouthrinses with or without ethanol and a mouthrinse containing cetyl pyridinium chloride (CPC) for 60 s. Cell proliferation was evaluated using WST‐1 assay. Cell migration was assessed using a wound closure model. Within 10 s of exposure to EO mouthrinse without ethanol, the epithelial cells became aberrant and shrank. No statistically significant difference in cell migration or proliferation was observed among cells pretreated by the EO mouthrinse with ethanol, CPC mouthrinse and control (phosphate buffered saline). In contrast, the EO mouthrinse without ethanol significantly reduced cell proliferation (p 
      PubDate: 2016-04-05T03:21:12.780655-05:
      DOI: 10.1002/ptr.5613
  • Depressant Effects of Salvia divinorum Involve Disruption of Physiological
    • Abstract: Although Salvia divinorum is traditionally known as a ‘mind‐altering’ or psychoactive herb used, among others things, as a tranquilizer, this property has not been validated with regard to its efficacy and safety. The objective of this study is to provide evidence for the sedative effects of S. divinorum and discriminate the nature of the responsible constituents by examining different experimental models. A battery of tests, including the open‐field, hole‐board, exploration cylinder, plus‐maze and sodium pentobarbital‐induced hypnosis potentiation, were used in mice after administration of non‐polar, medium polar and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic analysis in rats receiving an active medium polar extract (10 and 100 mg/kg) containing salvinorins was also assessed to study the effects of this plant on sleep architecture. All tested extracts produced significant sedative‐like responses, although those of the medium polar extract were more pronounced in mice. The sedative effect of this latter extract, which contains a mixture of salvinorins, caused fragmented sleep architecture in rats by diminishing rapid eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg. Our results provide evidence that S. divinorum exhibits sedative‐like depressant properties that alter physiological sleep architecture. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-01T01:25:32.0483-05:00
      DOI: 10.1002/ptr.5617
  • Polyphenol‐Rich Fraction from Larrea divaricata and its Main
           Flavonoid Quercetin‐3‐Methyl Ether Induce Apoptosis in
           Lymphoma Cells Through Nitrosative Stress
    • Abstract: Larrea divaricata is a plant with antiproliferative principles. We have previously identified the flavonoid quercetin‐3‐methyl ether (Q‐3‐ME) in an ethyl acetate fraction (EA). Both the extract and Q‐3‐ME were found to be effective against the EL‐4 T lymphoma cell line. However, the mechanism underlying the inhibition of tumor cell proliferation remains to be elucidated. In this work, we analyzed the role of nitric oxide (NO) in the induction of apoptosis mediated by Q‐3‐ME and EA. Both treatments were able to induce apoptosis in a concentration‐dependent and time‐dependent manner. The western blot analysis revealed a sequential activation of caspases‐9 and 3, followed by poly‐(ADP‐ribose)‐polymerase cleavage. EA and Q‐3‐ME lowered the mitochondrial membrane potential, showing the activation of the intrinsic pathway of apoptosis. Q‐3‐ME and EA increased NO production and inducible NO synthase expression in tumor cells. The involvement of NO in cell death was confirmed by the nitric oxide synthases inhibitor L‐NAME. In addition, EA and Q‐3‐ME induced a cell cycle arrest in G0/G1 phase. These drugs did not affect normal cell viability. This data suggested that EA and Q‐3‐ME induce an increase in NO production that would lead to the cell cycle arrest and the activation of the intrinsic pathway of apoptosis. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-04-01T00:45:40.6043-05:00
      DOI: 10.1002/ptr.5615
  • Embelin Inhibits Invasion and Migration of MDA‐MB‐231 Breast
           Cancer Cells by Suppression of CXC Chemokine Receptor 4, Matrix
    • Abstract: Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant. Recent scientific evidence shows that EB induces apoptosis and inhibits migration and invasion in highly metastatic human breast cancer cells. However, the exact mechanisms of EB in tumor metastasis and invasion have not been fully elucidated. Here, we investigated the underlying mechanisms of antimetastatic activities of EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4) as well as matrix metalloproteinase (MMP)‐9/2 expression and upregulated the tissue inhibitor of metalloproteinase 1 expression in MDA‐MB‐231 cells under noncytotoxic concentrations but not in MCF‐7 cells. Additionally, EB inhibited the CXC motif chemokine ligand 12 induced invasion and migration activities of MDA‐MB‐231 cells. A detailed study of underlying mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by the downregulation of mRNA expression and suppression of nuclear factor‐kappa B (NF‐κB) activation. It further reduced the binding of NF‐κB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker proteins (neural cadherin and vimentin) and concurrently upregulated epithelial markers (epithelial cadherin and occludin). Overall, these findings suggest that EB can abrogate breast cancer cell invasion and metastasis by suppression of CXCR4, MMP‐9/2 expressions, and inhibition of epithelial–mesenchymal transition and thus may have a great potential to suppress metastasis of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-31T01:05:36.556883-05:
      DOI: 10.1002/ptr.5612
  • Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of
           Soluble Epoxide Hydrolase Enzyme
    • Authors: Sumanta Kumar Goswami; Mohammed Naseeruddin Inamdar, Shekhar M. Dethe, Giligar M. Gururaj, Rohitash Jamwal, Anirban Bhaskar, Deepak Mundkinajeddu, Amit Agarwal
      Abstract: Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile erection; therefore, sEH could be useful for management of erectile dysfunction. Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for their sEH inhibition potential. Fifteen extracts showed >50% inhibition when screened at 50 µg/mL in sEH inhibition assay. Methanolic extract of Moringa oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 ± 0.1 µg/mL and was selected for in vitro studies on isolated rat corpus cavernosum smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats. Rats were divided into five groups, each containing six animals and treated orally with either water, vehicle (1% Tween‐20), MEMO (45 and 90 mg/kg/day for 21 days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of female rats were used, and the effect of MEMO and sildenafil was compared with that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth muscle at 0.1–100 µg/mL in vitro and significantly increased (p 
      PubDate: 2016-03-28T20:40:30.370818-05:
      DOI: 10.1002/ptr.5614
  • Diterpenes: Advances in Neurobiological Drug Research
    • Abstract: A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action‐wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro‐protection, anti‐epileptic, anxiolytic, anti‐Alzheimer's disease, anti‐Parkinson's disease, anti‐cerebral ischemia, anti‐neuropathic pain, anti‐neuro‐inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-28T20:20:33.908818-05:
      DOI: 10.1002/ptr.5609
  • Sakuranetin Induces Melanogenesis in B16BL6 Melanoma Cells through
           Inhibition of ERK and PI3K/AKT Signaling Pathways
    • Authors: Riadh Drira; Kazuichi Sakamoto
      Abstract: Sakuranetin (Sak) is considered one of the most important flavanone phytoalexins in regard to antimicrobial activity, and accumulation, in the rice plant. The current study determined that Sak strongly stimulates melanogenesis in B16BL6 melanoma cells in a dose‐dependent manner. This flavonoid upregulates the expression of microphthalmia transcription factor (MITF) and reaches its maximum after 24 h. In addition, Sak was found to increase in vitro tyrosinase (Tyr) activity, along with time‐dependent upregulation of Tyr, tyrosinase‐related protein 1 (TRP1), and tyrosinase‐related protein 2 (TRP2). Sakuranetin also decreased the proliferation rate in these cells without directly affecting their viability, as revealed by MTT and trypan blue assays. Further, Sak was shown to inhibit phosphorylation and activation of ERK1/2 from 12 h, without significantly affecting p38 and JNK phosphorylation. Sakuranetin was also found to inhibit the phosphorylation of AKT at threonine 308 and serine 473 and leads to activation of GSK3β via decreased phosphorylation at serine 9. Taken together, these results demonstrate that Sak stimulates melanogenesis in B16 melanoma cells via inhibition of ERK1/2 and PI3K/AKT signaling pathways, which lead to upregulation of Tyr, TRP1, and TRP2. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-22T00:45:34.590471-05:
      DOI: 10.1002/ptr.5606
  • Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid
           and Carnitine‐containing Compound in Prostate and Hair Follicle
           Cell‐based Assays
    • Authors: Li Chen; Jiaolong Wang, Glen Mouser, Yan Chun Li, Geno Marcovici
      Abstract: Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age‐dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5‐alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down‐regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-17T22:55:30.269344-05:
      DOI: 10.1002/ptr.5611
  • Dual Inhibition of Ca+2 Influx and Phosphodiesterase Enzyme Provides
           Scientific Base for the Medicinal Use of Chrozophora prostrata Dalz. in
           Respiratory Disorders
    • Abstract: The crude ethanolic extract of Chrozophora prostrata (Cp.Cr) was tested using in vivo and ex vivo assays for its possible bronchodilatory effects in order to validate its medicinal use in respiratory disorders, like asthma and cough. Cp.Cr exhibited dose‐dependent inhibition of carbachol (CCh)‐induced bronchospasm in anesthetized rats, similar to aminophylline. When tested on guinea‐pig tracheal preparations, Cp.Cr caused relaxation of both CCh (1 μM) and high K+ (80 mM)‐induced contractions with comparable potencies, similar to papaverine, a dual inhibitor of phosphodiesterse (PDE) and Ca+2 influx. Pre‐treatment of the tracheal tissues with Cp.Cr resulted in potentiation of the inhibitory effect of isoprenaline on CCh‐induced contractions, like that caused by papaverine indicative of PDE inhibitory activity, which was confirmed when Cp.Cr concentration dependently (1 and 3 mg/mL) increased intracellular cAMP levels of the tracheal preparations, like papaverine. Cp.Cr shifted concentrationresponse curves of Ca+2 constructed in guinea‐pig tracheal preparation towards right with suppression of the maximum response, similar to both verapamil and papaverine. These data indicate bronchodilator activity of Chrozophora prostrata mediated possibly through dual inhibition of PDE and Ca+2 influx, thus, showing therapeutic potential in asthma with effect enhancing and side‐effect neutralizing potential Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-17T01:05:36.113772-05:
      DOI: 10.1002/ptr.5610
  • Impact of Tetrahydropalmatine on the Pharmacokinetics of Probe Drugs for
           CYP1A2, 2D6 and 3A Isoenzymes in Beagle Dogs
    • Authors: Yong Zhao; Aihua Liang, Yushi Zhang, Chunying Li, Yan Yi, Odd Georg Nilsen
      Abstract: Tetrahydropalmatine (Tet) exhibit multiple pharmacological activities and is used frequently by clinical practitioners. In this study, we evaluate the in vivo effects of single and repeated oral Tet administrations on CYP1A2, 2D6 and 3A activities in six beagle dogs in a randomized, controlled, open‐label, crossover study. A cocktail approach, with dosages of the probe drugs caffeine (3.0 mg/kg), metoprolol (2.33 mg/kg) and midazolam (0.45 mg/kg), was used to measure cytochrome P450 (CYP) metabolic activities. The cocktail was administered orally as a single dose (12 mg/kg) 1 day prior to and 4 days after repeated oral Tet administrations (12 mg/kg three times daily). The probe drugs and their metabolites in plasma were quantified simultaneously by a validated HPLC technique, and non‐compartmental parameters were used to evaluate metabolic variables for assessment of CYP inhibition or induction. Tet had no or minor impact on the pharmacokinetics and metabolism of the probe drugs caffeine and metoprolol, CYP1A2 and CYP2D6 substrates, respectively. However, Tet increased AUC0–24 h and decreased AUCratio(0–24 h) (1‐hydroxymidazolam/midazolam ratio) for midazolam statistically significant, both in single or multiple dosing of Tet, with up to 39 or 57% increase for AUC0–24 h and 29% or 22 decrease for AUCratio(0–24 h), respectively, in line with previous in vitro findings for its CYP3A4 inhibition. The extensive use of Tet and herbal medicines containing Tet makes Tet a candidate for further evaluation of CYP3A‐mediated herb–drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-17T00:50:55.205974-05:
      DOI: 10.1002/ptr.5608
  • A Systematic Review on the Health Effects of Plums (Prunus domestica and
           Prunus salicina)
    • Authors: Ezinne O. Igwe; Karen E. Charlton
      Abstract: In recent times, plums have been described as foods with health‐promoting properties. Research on the health effects of plum continue to show promising results on its antiinflammatory, antioxidant and memory‐improving characteristics. The increased interest in plum research has been attributed to its high phenolic content, mostly the anthocyanins, which are known to be natural antioxidants. A systematic review of literature was carried out to summarize the available evidence on the impact of plums (Prunus species; domestica and salicina) on disease risk factors and health outcomes. A number of databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for relevant studies on plum health effects in vitro, animal studies and clinical trials. A total of 73 relevant peer‐reviewed journal articles were included in this review. The level of evidence remains low. Of the 25 human studies, 6 were confirmatory studies of moderate quality, while 19 were exploratory. Plums have been shown to possess antioxidant and antiallergic properties, and consumption is associated with improved cognitive function, bone health parameters and cardiovascular risk factors. Most of the human trials used the dried version of plums rather than fresh fruit, thus limiting translation to dietary messages of the positioning of plums in a healthy diet. Evidence on the health effect of plums has not been extensively studied, and the available evidence needs further confirmation. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-16T00:05:28.731312-05:
      DOI: 10.1002/ptr.5581
  • Evaluation of the Biological Activity of Opuntia ficus indica as a
           Tissue‐ and Estrogen Receptor Subtype‐Selective Modulator
    • Abstract: Phytoestrogens are selective estrogen receptor modulators (SERMs) with potential for use in hormone replacement therapy (HRT) to relieve peri/postmenopausal symptoms. This study was aimed at elucidating the molecular mechanisms underlying the SERM properties of the extract of Korean‐grown Opuntia ficus‐indica (KOFI). The KOFI extract induced estrogen response element (ERE)‐driven transcription in breast and endometrial cancer cell lines and the expression of endogenous estrogen‐responsive genes in breast cancer cells. The flavonoid content of different KOFI preparations affected ERE‐luciferase activities, implying that the flavonoid composition likely mediated the estrogenic activities in cells. Oral administration of KOFI decreased the weight gain and levels of both serum glucose and triglyceride in ovariectomized (OVX) rats. Finally, KOFI had an inhibitory effect on the 17β‐estradiol‐induced proliferation of the endometrial epithelium in OVX rats. Our data demonstrate that KOFI exhibited SERM activity with no uterotrophic side effects. Therefore, KOFI alone or in combination with other botanical supplements, vitamins, or minerals may be an effective and safe alternative active ingredient to HRTs, for the management of postmenopausal symptoms. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-14T22:20:32.559024-05:
      DOI: 10.1002/ptr.5602
  • Biological Properties and Therapeutic Applications of Propolis
    • Abstract: Propolis is a resinous material collected by bees from bud and exudates of the plants, mixed with bee enzymes, pollen and wax. In this review, the biological properties of propolis and some therapeutic applications are discussed. The same biological activities have been investigated until today, using samples from different geographic regions. Thus, the study of the biological properties of a given sample should always be associated with its chemical composition and botanical source, representing a particular sample of a given geographic area, exploring its biological potential and the role of its constituents. Efforts have been carried out to explain propolis' mechanisms of action in vivo and in vitro, but the majority of propolis' targets and actions are still unclear. The number of formulations containing propolis and patents have increased, although propolis extracts have been used deliberately with different recommendations, not always mentioning the chemical composition, vegetal source and the methods of extraction. Clinical studies will help to obtain criterious recommendations in view of the expected outcomes. Further investigation should explore the effects of common compounds found in the samples from all over the world in an attempt to standardize the research on propolis and to obtain new drugs. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-14T07:29:37.38422-05:0
      DOI: 10.1002/ptr.5605
  • Slimming and Appetite‐Suppressing Effects of Caraway Aqueous Extract
           as a Natural Therapy in Physically Active Women
    • Authors: Mahnaz Kazemipoor; Sareena Hamzah, Majid Hajifaraji, Che Wan Jasimah Bt Wan Mohamed Radzi, Geoffrey A. Cordell
      Abstract: Following the current ‘Globesity’ trend, there is an increasing demand for alternative natural therapies for weight management. Numerous phytoconstituents reduce body weight through suppressing appetite and reducing food intake. Caraway (Carum carvi L.) is one of the medicinal plants that is traditionally used for weight loss. In this study, the appetite‐suppressing effects of caraway aqueous extract (CAE) on 70 aerobically trained, overweight, and obese women were examined in a triple‐blind, placebo‐controlled, clinical study. Subjects were randomly allocated into placebo and experimental groups and consumed either 30 mL/day of CAE or placebo without changing their diet or physical activity over a period of 90 days. Calorie and macronutrient intake and anthropometric indices were measured before and after the intervention. In addition, appetite changes were assessed through a visual analog scale and an ad libitum pizza test. After the intervention, the results showed a significant reduction in appetite levels and carbohydrate intake of the experimental group compared with the placebo group. All of the anthropometric indices were reduced significantly in CAE compared with placebo group (p 
      PubDate: 2016-03-14T07:21:50.512703-05:
      DOI: 10.1002/ptr.5603
  • Molecular Signaling Pathways Behind the Biological Effects of Salvia
           Species Diterpenes in Neuropharmacology and Cardiology
    • Authors: M. Akaberi; M. Iranshahi, S. Mehri
      Abstract: The genus Salvia, from the Lamiaceae family, has diverse biological properties that are primarily attributable to their diterpene contents. There is no comprehensive review on the molecular signaling pathways of these active components. In this review, we investigated the molecular targets of bioactive Salvia diterpenes responsible for the treatment of nervous and cardiovascular diseases. The effects on different pathways, including apoptosis signaling, oxidative stress phenomena, the accumulation of amyloid beta plaques, and tau phosphorylation, have all been considered to be mechanisms of the anti‐Alzheimer properties of Salvia diterpenes. Additionally, effects on the benzodiazepine and kappa opioid receptors and neuroprotective effects are noted as neuropharmacological properties of Salvia diterpenes, including tanshinone IIA, salvinorin A, cryptotanshinone, and miltirone. Tanshinone IIA, as the primary diterpene of Salvia miltiorrhiza, has beneficial activities in heart diseases because of its ability to scavenge free radicals and its effects on transcription factors, such as nuclear transcription factor‐kappa B (NF‐κB) and the mitogen‐activated protein kinases (MAPKs). Additionally, tanshinone IIA has also been proposed to have cardioprotective properties including antiarrhythmic activities and effects on myocardial infarction. With respect to the potential therapeutic effects of Salvia diterpenes, comprehensive clinical trials are warranted to evaluate these valuable molecules as lead compounds. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-14T07:16:55.515449-05:
      DOI: 10.1002/ptr.5599
  • Diarylheptanoids Rich Fraction of Alnus nepalensis Attenuates Malaria
           Pathogenesis: In‐vitro and In‐vivo Study
    • Authors: Archana Saxena; Deepti Yadav, Shilpa Mohanty, Harveer Singh Cheema, Madan M. Gupta, Mahendra P. Darokar, Dnyaneshwar U. Bawankule
      Abstract: Diarylheptanoids from Alnus nepalensis leaves have been reported for promising activity against filariasis, a mosquito‐borne disease, and this has prompted us to investigate its anti‐malarial and safety profile using in‐vitro and in‐vivo bioassays. A. nepalensis leaf extracts were tested in‐vitro against chloroquine‐sensitive Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. Among all, the chloroform extract (ANC) has shown promising anti‐plasmodial activity (IC50 8.06 ± 0.26 µg/mL). HPLC analysis of ANC showed the presence of diarylheptanoids. Efficacy and safety of ANC were further validated in in‐vivo system using Plasmodium berghei‐induced malaria model and acute oral toxicity in mice. Malaria was induced by intra‐peritoneal injection of P. berghei infected red blood cells to the female Balb/c mice. ANC was administered orally at doses of 100 and 300 mg/kg/day following Peter's 4 day suppression test. Oral administration of ANC showed significant reduction of parasitaemia and increase in mean survival time. It also attributed to inhibition of the parasite induced pro‐inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle‐treated infected mice. In‐vivo safety evaluation study revealed that ANC is non‐toxic at higher concentration. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-11T04:06:12.80731-05:0
      DOI: 10.1002/ptr.5596
  • Efficacy of a Standardized Extract of Prunus mume in Liver Protection and
           Redox Homeostasis: A Randomized, Double‐Blind,
           Placebo‐Controlled Study
    • Abstract: The antioxidant, anti‐inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double‐blind, placebo‐controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3‐month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty‐five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma‐glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine‐glycine, oxidized cysteine (intracellular pro‐oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation‐based diseases. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-08T04:06:23.149221-05:
      DOI: 10.1002/ptr.5597
  • Ginger for Prevention of Antituberculosis‐induced Gastrointestinal
           Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical
    • Authors: Zahra Emrani; Esphandiar Shojaei, Hossein Khalili
      Abstract: In this study, the potential benefits of ginger in preventing antituberculosis drug‐induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)® or placebo one‐half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug‐induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug‐induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug‐induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug‐induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug‐induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-07T04:37:32.932454-05:
      DOI: 10.1002/ptr.5607
  • Adverse Effects of Plant Food Supplements and Plants Consumed as Food:
           Results from the Poisons Centres‐Based PlantLIBRA Study
    • Abstract: Plant food supplements (PFS) are products of increasing popularity and wide‐spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres‐based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro‐intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS‐related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-07T04:28:35.389528-05:
      DOI: 10.1002/ptr.5604
  • Cardiovascular Safety of Oral p‐Synephrine (Bitter Orange) in
           Healthy Subjects: A Randomized Placebo‐Controlled Cross‐over
           Clinical Trial
    • Authors: Mohd Shara; Sidney J. Stohs, Tareq L. Mukattash
      Abstract: Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p‐synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance. p‐Synephrine is also present in juices and foods derived from a variety of Citrus species. Questions exist regarding the safety of p‐synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49‐mg p‐synephrine) given to 18 healthy subjects (nine men and nine women) in a double‐blinded, placebo‐controlled cross‐over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4 , 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, and p‐synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control or p‐synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in the p‐synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants. p‐Synephrine does not act as a stimulant at the dose used.
      PubDate: 2016-03-07T03:30:44.283875-05:
      DOI: 10.1002/ptr.5590
  • Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates
           VEGF Signaling in Caco‐2 Human Colon Carcinoma Cell Line Through a
           Selective PPAR‐α‐Dependent Inhibition of Akt/mTOR Pathway
    • Authors: Giovanni Sarnelli; Stefano Gigli, Elena Capoccia, Teresa Iuvone, Carla Cirillo, Luisa Seguella, Nicola Nobile, Alessandra D'Alessandro, Marcella Pesce, Luca Steardo, Rosario Cuomo, Giuseppe Esposito
      Abstract: Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco‐2 cell line. Caco‐2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator‐activated receptor‐a (PPAR‐α) or PPAR‐γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration‐dependent decrease of Caco‐2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration‐dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of phospho‐mTOR and of p‐p70S6K were observed as compared with untreated cells. PPAR‐α, but not PPAR‐γ antagonist, reverted all effects of PEA. PEA is able to decrease cell proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the specific inhibition of the AkT/mTOR axis, through the activation of PPAR‐α pathway. If supported by in vivo models, our data pave the way to PEA co‐administration to the current chemotherapeutic regimens for colon carcinoma.
      PubDate: 2016-03-01T02:41:28.666841-05:
      DOI: 10.1002/ptr.5601
  • Antioxidant and Physicochemical Properties of Hydrogen
           Peroxide‐Treated Sugar Beet Dietary Fibre
    • Abstract: The aim of the present work was to examine if hydrogen peroxide treatment of sugar beet fibre that aimed at improving its physicochemical properties would impair its antioxidant potential. Three different sugar beet fibres were obtained from sugar beet – non‐treated fibre (NTF) from sugar beet cossettes extracted with sulphurous acid, treated fibre (TF) from NTF treated with hydrogen peroxide in alkaline solution and commercially available Fibrex®. The antioxidant activity of extractable and non‐extractable fibre fractions in ethanol/water mixture (80:20, v/v) of three fibre samples was estimated. Non‐extractable fractions obtained after alkaline treatment of investigated fibres were much higher in phenolic compounds and possessed higher antioxidant potential than extractable fractions. Ferulic acid was proven to be the dominant phenolic acid. Regarding both extractable and non‐extractable fractions, Fibrex® had the highest antioxidant activity in chemical tests, while NTF was superior in comparison with TF. Based on the results of Caco‐2 cells‐based test, all non‐extractable fractions possessed potential for reactive oxygen species inhibition. Regarding the extractable fractions, only the TF manifested this effect.Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-01T01:58:27.274623-05:
      DOI: 10.1002/ptr.5598
  • Polygonum aviculare L. and its active compounds, quercitrin hydrate,
           caffeic acid, and rutin, activate the Wnt/β‐catenin pathway and
           induce cutaneous wound healing
    • Abstract: Polygonum aviculare L. is a member of the Polygonaceae family of plants, which has been known for its antioxidant and anti‐obesity effects. However, the wound healing function of P. aviculare extract has not been assessed. In this study, we identified a novel property of P. aviculare extract as a Wnt/β‐catenin pathway activator based on a screen of 350 plant extracts using HEK293‐TOP cells retaining the Wnt/β‐catenin signaling reporter gene. P. aviculare extract accelerated the migration of HaCaT keratinocytes without showing significant cytotoxicity. Moreover, P. aviculare extract efficiently re‐epithelized wounds generated on mice. Additionally, ingredients of P. aviculare extract, such as quercitrin hydrate, caffeic acid, and rutin, also accelerated the motility of HaCaT keratinocytes with the activation of Wnt/β‐catenin signaling. Therefore, based on our findings, P. aviculare extract and its active ingredients could be potential therapeutic agents for wound healing. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-03-01T01:41:27.061395-05:
      DOI: 10.1002/ptr.5593
  • Neurotherapeutic Effects of Pueraria mirifica Extract in Early‐ and
           Late‐Stage Cognitive Impaired Rats
    • Authors: Kanya Anukulthanakorn; Ishwar S. Parhar, Sukanya Jaroenporn, Takashi Kitahashi, Gen Watanbe, Suchinda Malaivijitnond
      Abstract: We determined the neurotherapeutic effects of Pueraria mirifica extract (PME) and pure puerarin (PU) in comparison with 17β‐estradiol (E2) in early‐ and late‐stage cognitive impaired rats. Rats were ovariectomized (OVX), kept for 2 and 4 months to induce early‐ and late‐stage cognitive impairment, respectively, and divided into four groups that were treated daily with (i) distilled water, (ii) 100 mg/kg of PME, (iii) 7 mg/kg of PU, and (iv) 80 µg/kg of E2 for 4 months. The estrogen deficiency symptoms of OVX rats were abrogated by treatment with E2 or PME, but not by treatment with PU. The mRNA level of genes associated with amyloid production (App and Bace1) and hyperphosphorylated Tau (Tau4) were upregulated together with the level of impaired cognition in the 2‐ and 4‐month OVX rats. Treatment with E2 reduced the level of cognitive impairment more than that with PME and PU, and 2‐month OVX rats were more responsive than 4‐month OVX rats. All treatments down‐regulated the Bace1 mRNA level in 2‐month OVX rats, while PU and PME also decreased the App mRNA level in 2‐ and 4‐month OVX rats, respectively. Only PU suppressed Tau4 expression in 2‐month OVX rats. Thus, PME and PU elicit neurotherapeutic effects in different pathways, and earlier treatment is optimal. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-25T00:13:50.172003-05:
      DOI: 10.1002/ptr.5595
  • Effect of Subgingivally Delivered 10% Emblica officinalis Gel as an
           Adjunct to Scaling and Root Planing in the Treatment of Chronic
           Periodontitis – A Randomized Placebo‐controlled Clinical Trial
    • Authors: Shilpa Grover; Shikha Tewari, Rajinder K Sharma, Gajendra Singh, Aparna Yadav, Satish C Naula
      Abstract: Emblica officinalis fruit possesses varied medicinal properties including cytoprotective antimicrobial, antioxidant, antiresorptive and antiinflammatory activity. The present study aimed to investigate the effect of subgingival application of indigenously prepared E. officinalis (Amla) sustained‐release gel adjunctive to scaling and root planing (SRP) on chronic periodontitis. Forty‐six patients (528 sites) were randomly assigned to control group (23;264): SRP +placebo gel and test group (23;264): SRP + 10% E. officinalis gel application. Periodontal parameters: plaque index, gingival index, probing pocket depth (PPD), clinical attachment level (CAL) and modified sulcus bleeding index (mSBI) were assessed at baseline, 2 and 3‐month post‐therapy. Forty patients (470 sites) completed the trial. When test and control sites were compared, significantly more reduction in mean PPD, mSBI, number of sites with PPD = 5–6 mm, PPD ≥ 7 mm, CAL ≥ 6 mm and greater CAL gain were achieved in test sites at 2‐ and 3‐month post‐therapy (p 
      PubDate: 2016-02-24T00:44:29.261308-05:
      DOI: 10.1002/ptr.5600
  • Integrative Medicine for Relief of Nausea and Vomiting in the Treatment of
           Colorectal Cancer Using Oxaliplatin‐Based Chemotherapy: A Systematic
           Review and Meta‐Analysis
    • Authors: Meng hua Chen; Brian H. May, Iris W. Zhou, Anthony L. Zhang, Charlie C. Xue
      Abstract: The management of chemotherapy‐induced nausea and vomiting (CINV) remains an issue in the treatment of colorectal cancer using oxaliplatin‐based regimens. Certain traditional plant‐based medicines (TMs) have histories of use for nausea and vomiting and have been integrated with conventional therapies for CINV. To assess the effectiveness of integrative management of CINV, meta‐analysis was conducted of 27 randomised controlled studies (1843 participants) published from 2005 to 2013. The oxaliplatin plus TM groups showed significantly reduced CINV (risk ratio 0.65 [0.59, 0.71], I2 = 28%) compared with oxaliplatin controls, with or without the addition of conventional anti‐emetics. Further sensitivity analyses based on the ingredients of the TMs identified six plants (Atractylodes macrocephala, Poria cocos, Coix lacryma‐jobi, Astragalus membranaceus, Glycyrrhiza uralensis and Panax ginseng) that were associated with significant reductions in CINV without important heterogeneity. Experimental studies of these six plants have reported inhibitory effects on nausea and vomiting (or its animal equivalent), regulation of gastrointestinal motility, gastroprotective effects and antioxidant actions, which may at least partially explain the effects identified in the meta‐analyses of the clinical trial results. These plants warrant further clinical research as potential additions to chemotherapy regimens in patients whose CINV is not sufficiently well controlled by conventional therapies. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-23T03:02:10.198368-05:
      DOI: 10.1002/ptr.5586
  • Anti‐stress Activity of Ocimum sanctum: Possible Effects on
           Hypothalamic–Pituitary–Adrenal Axis
    • Authors: Edwin Jothie Richard; Ramanaiah Illuri, Bharathi Bethapudi, Senthilkumar Anandhakumar, Anirban Bhaskar, Chandrasekaran Chinampudur Velusami, Deepak Mundkinajeddu, Amit Agarwal
      Abstract: The present study investigated anti‐stress potential of Ocimum sanctum in chronic variable stress (CVS) paradigm. Further, the possible mechanism of anti‐stress was explored in vitro using cell and cell‐free assays. Rats were administered O. sanctum followed by CVS regimen for a period of 16 days. On days 4, 8, 12, and 16, body weight and immobility time in forced swim test were measured. In addition, the possible inhibitory effect of O. sanctum and ursolic acid on cortisol release and CRHR1 receptor activity were studied in cell‐based assays, while inhibitory effects on 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) and catechol‐O‐methyltransferase (COMT) were studied in cell‐free assays. CVS group demonstrated less body weight gain and higher immobility time than O. sanctum administered groups, while oral administration of O. sanctum significantly increased body weight gain and decreased the immobility time. Further, O. sanctum and its constituents inhibited cortisol release and exhibited a significant CRHR1 receptor antagonist activity. Also, they had specific inhibitory activity towards 11β‐HSD1 and COMT activity. Thus, O. sanctum was found to be effective in the management of stress effects, and anti‐stress activity could be due to inhibition of cortisol release, blocking CRHR1 receptor, and inhibiting 11β‐HSD1 and COMT activities. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-22T01:39:35.459218-05:
      DOI: 10.1002/ptr.5584
  • Cinnamaldehydes in Cancer Chemotherapy
    • Abstract: Cinnamaldehyde and cinnamaldehyde‐derived compounds are candidates for the development of anticancer drugs that have received extensive research attention. In this review, we summarize recent findings detailing the positive and negative aspects of cinnamaldehyde and its derivatives as potential anticancer drug candidates. Furthermore, we describe the in vivo pharmacokinetics and metabolism of cinnamaldehydes. The oxidative and antioxidative properties of cinnamaldehydes, which contribute to their potential in chemotherapy, have also been discussed. Moreover, the mechanism(s) by which cinnamaldehydes induce apoptosis in cancer cells have been explored. In addition, evidence of the regulatory effects of cinnamaldehydes on cancer cell invasion and metastasis has been described. Finally, the application of cinnamaldehydes in treating various types of cancer, including breast, prostate, and colon cancers, has been discussed in detail. The effects of cinnamaldehydes on leukemia, hepatocellular carcinoma, and oral cancer have been summarized briefly. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-18T06:32:01.118136-05:
      DOI: 10.1002/ptr.5592
  • Effect of Embelin Against Lipopolysaccharide‐induced Sickness
           Behaviour in Mice
    • Authors: Ashique Shaikh; Shivsharan B. Dhadde, Sharanbasappa Durg, V. P. Veerapur, S. Badami, B. S. Thippeswamy, Jagadevappa S. Patil
      Abstract: Sickness behaviour is a coordinated set of adaptive behavioural changes that develop in ill individuals during the course of an infection. It is relevant to understanding depression and some aspects of the suffering that in cancer. Embelin has been reported to possess antiinflammatory, neuroprotective and anxiolytic assets and has been shown to inhibit nuclear factor κB pathway and cytokine production. The present study was undertaken to investigate the effect of embelin isolated from Embelia ribes Burm in lipopolysaccharide (LPS)‐induced sickness behaviour in mice. Adult male Swiss albino mice were pre‐treated with embelin (10 and 20 mg/kg, p.o.) or dexamethasone (1 mg/kg, i.p.) for 3 days and then challenged with LPS (400 µg/kg, i.p.). At different time intervals of post‐LPS challenge, sickness behaviour was evaluated in the animals by battery of behavioural tests (plus maze, open field, light–dark box, forced swim, social behaviour assessment, sucrose preference and food and water intake). Levels of oxidative stress makers (reduced glutathione and lipid peroxidation) in mice brain were also analysed. LPS induced behavioural alterations, anhedonia and anorexia, in mice. Pre‐treatment with embelin attenuated behavioural changes induced by LPS. In addition, embelin prevented anhedonia, anorexia and ameliorated brain oxidative stress markers. The experimental outcomes of the present study demonstrated protective effect of embelin in LPS‐induced sickness behaviour in mice. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-18T05:47:03.882947-05:
      DOI: 10.1002/ptr.5585
  • Sisymbrium Officinale (L.) Scop. and its Polyphenolic Fractions Inhibit
           the Mutagenicity of Tert‐Butylhydroperoxide in Escherichia Coli
           WP2uvrAR Strain
    • Authors: Antonella Di Sotto; Silvia Di Giacomo, Chiara Toniolo, Marcello Nicoletti, Gabriela Mazzanti
      Abstract: One Sisymbrium officinale (L.) Scop. aqueous dry extract (SOE) and its polyphenolic fractions (Fb, Fc, Fd and Fe) were evaluated for their ability to inhibit the oxidative mutagenicity of tert‐butylhydroperoxide in the Ames test. The possible involvement of desmutagenic and/or bioantimutagenic mechanisms was evaluated by applying a three‐time based protocol (pre‐treatment, co‐treatment and post‐treatment). Furthermore, some protective antioxidant mechanisms were investigated. The total polyphenol and flavonol amount was also determined, and the fingerprint was outlined by high‐performance thin‐layer chromatography and densitometry. SOE, Fb and Fe exhibited strong antimutagenicity against tert‐butylhydroperoxide in all treatment protocols, this suggesting the involvement of both desmutagenic and bioantimutagenic mechanisms. These samples also showed antioxidant properties, including neutralization of the superoxide anion, lipid peroxidation inhibition and chelation and reduction of iron. Fb and Fe were rich in polyphenols and flavonols, so suggesting a possible role of these compounds in the antimutagenicity. Taking into account that oxidative stress is responsible for the damage of various environmental toxicants, particularly tobacco smoke, present results can support the traditional use of hedge mustard by smokers to restore the vocal cord function affected by the oxidative damage and suggest a possible application of SOE and its fractions as food supplements. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-18T00:44:25.374827-05:
      DOI: 10.1002/ptr.5588
  • A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and
           Drug Interactions of Herbal Remedies
    • Abstract: Systematic reviews and meta‐analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta‐analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy‐induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb–drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-17T00:38:54.219517-05:
      DOI: 10.1002/ptr.5591
  • Biological Activities of Oleanolic Acid Derivatives from Calendula
           officinalis Seeds
    • Authors: Ahmed Zaki; Ahmed Ashour, Amira Mira, Asuka Kishikawa, Toshinori Nakagawa, Qinchang Zhu, Kuniyoshi Shimizu
      Abstract: Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28‐O‐β‐D‐glucopyranosyl‐oleanolic acid 3‐O‐β‐D–glucopyranosyl (1→3)‐β‐D‐glucopyranosiduronic acid (CS1) and oleanolic acid 3‐O‐β‐D–glucopyranosyl (1→3)‐β‐D‐glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro‐2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF‐Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro‐2A cells and increased cell viability against H2O2. These activities (melanin biosynthesis stimulatory and protective effect against H2O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-16T23:57:59.209306-05:
      DOI: 10.1002/ptr.5589
  • Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect
           of Berberine in Zucker Diabetic Fatty Rats Using Uplc‐ESI‐Hdms
    • Abstract: The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti‐diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra‐performance liquid chromatography/electrospray ionization synapt high‐definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as ‘differentiating metabolites’ with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near‐normal state. These results suggested that the anti‐diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5′‐monophosphate‐activated protein kinase. Our work not only provides a better understanding of the anti‐diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-16T23:09:35.159029-05:
      DOI: 10.1002/ptr.5587
  • Herbal Medicine Offered as an Initiative Therapeutic Option for the
           Management of Hepatocellular Carcinoma
    • Abstract: Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/β‐catenin, Hedgehog, Notch, and Hippo–YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi‐level, multi‐target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-15T22:51:52.097473-05:
      DOI: 10.1002/ptr.5594
  • Safety and Efficacy of Banaba–Moringa oleifera–Green Coffee
           Bean Extracts and Vitamin D3 in a Sustained Release Weight Management
    • Authors: Sidney J. Stohs; Gilbert R. Kaats, Harry G. Preuss
      Abstract: This 60‐day, 30‐subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45‐measurement blood chemistry panel, an 86‐item self‐reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X‐ray absorptiometry measured fat mass (FM) and fat‐free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p 
      PubDate: 2016-02-12T10:50:59.089506-05:
      DOI: 10.1002/ptr.5577
  • A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents
    • Authors: Sidney J. Stohs; Vladimir Badmaev
      Abstract: Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non‐stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non‐stimulatory thermogenic agents include p‐synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The
      Authors Phytotherapy Research published by John Wiley & Sons Ltd.
      PubDate: 2016-02-09T02:40:57.995156-05:
      DOI: 10.1002/ptr.5583
  • Activation of Cellular Immunity in Herpes Simplex Virus Type
           1‐Infected Mice by the Oral Administration of Aqueous Extract of
           Moringa oleifera Lam. Leaves
    • Authors: Masahiko Kurokawa; Ashish Wadhwani, Hisahiro Kai, Muneaki Hidaka, Hiroki Yoshida, Chihiro Sugita, Wataru Watanabe, Koji Matsuno, Akinori Hagiwara
      Abstract: Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti‐herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV‐1) infection model. AqMOL (300 mg/kg) was administered orally to HSV‐1‐infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed‐type hypersensitivity (DTH) reaction to inactivated HSV‐1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)‐γ production by HSV‐1 antigen from splenocytes of HSV‐1‐infected mice at 4 days post‐infection. AqMOL administration was effective in elevating the ratio of CD11b+ and CD49b+ subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV‐1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-27T01:42:29.585383-05:
      DOI: 10.1002/ptr.5580
  • Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and
           Affects Neurotransmission in Rats
    • Abstract: Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long‐term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4‐week‐old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose‐dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd. Administration of Passiflora incarnata extract in dose‐dependent manner reduces stress and improves spatial memory in young male Wistar rats. In biochemical examination the depletion of hippocampal glutamic acid, cortical serotonin and noradrenaline content along with an increase in their metabolites level and turnover were found.
      PubDate: 2016-01-27T01:16:56.785785-05:
      DOI: 10.1002/ptr.5578
  • Hydroxy‐Safflower Yellow A inhibits the TNFR1‐Mediated
           Classical NF‐κB Pathway by Inducing Shedding of TNFR1
    • Authors: Haifang Wang; Jinlian Liu, Yuejin Yang, Qingwen Cao, Xueping Huo, Shuhui Ma, Jun Hu, Fredrick M. Pavalko, Qinshe Liu
      Abstract: Hydroxy‐safflower yellow A (HSYA) is the major active component of safflower, a traditional Asia herbal medicine well known for its cardiovascular protective activities. The purpose of this study was to investigate the effect of HSYA on TNF‐α‐induced inflammatory responses in arterial endothelial cells (AECs) and to explore the mechanisms involved. The results showed that HSYA suppressed the up‐regulation of ICAM‐1 expression in TNF‐α‐stimulated AECs in a dose‐dependent manner. High concentration (120 μM) HSYA significantly inhibited the TNF‐α‐induced adhesion of RAW264.7 cells to AECs. HSYA blocked the TNFR1‐mediated phosphorylation and degradation of IκBα and also prevented the nuclear translocation of NF‐κB p65. Moreover, HSYA reduced the cell surface level of TNFR1 and increased the content of sTNFR1 in the culture media. TNF‐α processing inhibitor‐0 (TAPI‐0) prevented the HSYA inhibition of TNFR1‐induced IκBα degradation, implying the occurrence of TNFR1 shedding. Furthermore, HSYA induced phosphorylation of TNF‐α converting enzyme (TACE) at threonine 735, which is thought to be required for its activation. Conclusively, HSYA suppressed TNF‐α‐induced inflammatory responses in AECs, at least in part by inhibiting the TNFR1‐mediated classical NF‐κB pathway. TACE‐mediated TNFR1 shedding can be involved in this effect. Our study provides new evidence for the antiinflammatory and anti‐atherosclerotic effects of HSYA. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-25T01:38:58.904693-05:
      DOI: 10.1002/ptr.5579
  • Ginkgo Biloba Extract Attenuates Oxidative Stress and Apoptosis in Mouse
           Cochlear Neural Stem Cells
    • Authors: Congpin Wang; Bin Wang
      Abstract: In the organ or Corti, oxidative stress could result in damage to the hearing, and neural stem cells (NSCs) hold great therapeutic potential in treating hearing loss. Ginkgo biloba extract (GBE) has been widely shown to exhibit anti‐oxidative and anti‐apoptotic effects in treatments of neural damage and disorder. Using hydrogen peroxide to induced oxidative stress as a model, we investigated the anti‐oxidative role of GBE in isolated mouse cochlear NSCs. GBE treatment was found to significantly promote viability of NSCs, by markedly attenuating hydrogen peroxide induced oxidative stress. In addition, this anti‐oxidative function of GBE was also able to prevent mitochondrial depolarization and subsequent apoptosis. Moreover, the anti‐apoptotic role of GBE was mediated by antagonizing the intrinsic mitochondrial apoptotic pathway, where GBE could reverse the changes in key intrinsic apoptosis pathway factors including Bcl‐2, Bax, and Caspase‐3. Our data provided the first report on the beneficial role of GBE in protecting cochlear NSCs, by attenuating oxidative stress triggered intrinsic apoptosis, therefore supporting the potential therapeutic value of GBE in preventing oxidative stress‐related hearing loss. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-22T01:45:27.913373-05:
      DOI: 10.1002/ptr.5572
  • Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile
           of Luteolin‐7‐O‐glucoside Isolated from Trifolium
           alexandrinum L. in Ovariectomized Rats
    • Abstract: Luteolin‐7‐O‐glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin‐7‐O‐glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone‐specific alkaline phosphatase, plasma osteocalsin, type I procollagen N‐terminal, and C‐telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-11T04:23:00.103876-05:
      DOI: 10.1002/ptr.5564
  • Issue Information
    • First page: 518
      Abstract: No abstract is available for this article.
      PubDate: 2016-04-05T01:59:32.677346-05:
      DOI: 10.1002/ptr.5457
  • Effects of Plants on Osteogenic Differentiation and Mineralization of
           Periodontal Ligament Cells: A Systematic Review
    • First page: 519
      Abstract: This systematic review aimed to evaluate the effects of plants on osteogenic differentiation and mineralization of human periodontal ligament cells. The included studies were selected using five different electronic databases. The reference list of the included studies was crosschecked, and a partial gray literature search was undertaken using Google Scholar and ProQuest. The methodology of the selected studies was evaluated using GRADE. After a two‐step selection process, eight studies were identified. Six different types of plants were reported in the selected studies, which were Morinda citrifolia, Aloe vera, Fructus cnidii, Zanthoxylum schinifolium, Centella asiatica, and Epimedium species. They included five types of isolated plant components: acemannan, osthole, hesperetin, asiaticoside, and icariin. In addition, some active substances of these components were identified as polysaccharides, coumarins, flavonoids, and triterpenes. The studies demonstrated the potential effects of plants on osteogenic differentiation, cell proliferation, mineral deposition, and gene and protein expression. Four studies showed that periodontal ligament cells induce mineral deposition after plant treatment. Although there are few studies on the subject, current evidence suggests that plants are potentially useful for the treatment of periodontal diseases. However, further investigations are required to confirm the promising effect of these plants in regenerative treatments. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-29T00:50:03.882262-05:
      DOI: 10.1002/ptr.5568
  • Rhodiola rosea L. and Alzheimer's Disease: From Farm to Pharmacy
    • Authors: Seyed Fazel Nabavi; Nady Braidy, Ilkay Erdogan Orhan, Arash Badiee, Maria Daglia, Seyed Mohammad Nabavi
      First page: 532
      Abstract: Rhodiola rosea L. (roseroot) is a common member of the family Crassulaceae, known as one of the most important popular medicinal plants in the northern region of Europe. The roots of R. rosea possess a wide range of pharmacological activities such as antioxidant, antiinflammatory, anticancer, cardioprotective, and neuroprotective effects that are because of the presence of different phytochemicals such as phenols and flavonoids. In addition, the presence of salidroside, rosavins, and p‐tyrosol are responsible for its beneficial effects for the treatment of on depression, fatigue, and cognitive dysfunction. A plethora of studies report that R. rosea has potent neuroprotective effects through the suppression of oxidative stress, neuroinflammation, and excitotoxicity in brain tissues and antagonism of oncogenic p21‐activated kinase. However, to our knowledge, no review articles have been published addressing the neuroprotective effects of R. rosea. Therefore, the present article aims at critically reviewing the available literature on the beneficial effects of R. rosea on as a therapeutic strategy for the treatment of Alzheimer's disease and other neurodegenerative diseases where oxidative stress plays a major role in disease development and progression. We also discuss the cultivation, phytochemistry, clinical impacts, and adverse effects of R. rosea to provide a broader insight on the therapeutic potential for this plant. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-11T04:41:28.49689-05:0
      DOI: 10.1002/ptr.5569
  • Grapes (Vitis vinifera) as a Potential Candidate for the Therapy of the
           Metabolic Syndrome
    • Authors: Maryam Akaberi; Hosein Hosseinzadeh
      First page: 540
      Abstract: Metabolic syndrome is associated with several disorders, including hypertension, diabetes, hyperlipidemia as well as cardiovascular diseases and stroke. Plant‐derived polyphenols, compounds found in numerous plant species, play an important role as potential treatments for components of metabolic syndrome. Studies have provided evidence for protective effects of various polyphenol‐rich foods against metabolic syndrome. Fruits, vegetables, cereals, nuts, and berries are rich in polyphenolic compounds. Grapes (Vitis vinifera), especially grape seeds, stand out as rich sources of polyphenol potent antioxidants and have been reported helpful for inhibiting the risk factors involved in the metabolic syndrome such as hyperlipidemia, hyperglycemia, and hypertension. There are also many studies about gastroprotective, hepatoprotective, and anti‐obesity effects of grape polyphenolic compounds especially proanthocyanidins in the literature. The present study investigates the protective effects of grape seeds in metabolic syndrome. The results of this study show that grape polyphenols have significant effects on the level of blood glucose, lipid profile, blood pressure, as well as beneficial activities in liver and heart with various mechanisms. In addition, the pharmacokinetics of grape polyphenols is discussed. More detailed mechanistic investigations and phytochemical studies for finding the exact bioactive component(s) and molecular signaling pathways are suggested. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-22T01:15:33.097834-05:
      DOI: 10.1002/ptr.5570
  • Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration,
           Invasion, and In Vivo Invasive Growth Through Targeting C‐Met
    • Authors: Hassan Y. Ebrahim; Heba E. Elsayed, Mohamed M. Mohyeldin, Mohamed R. Akl, Joydeep Bhattacharjee, Susan Egbert, Khalid A. El Sayed
      First page: 557
      Abstract: Breast cancer is a major health problem affecting the female population worldwide. The triple‐negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto‐oncogenic receptor tyrosine kinase c‐Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c‐Met is proposed as a promising candidate target for the control of TNBCs. Lichens‐derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen‐derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer‐guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone‐derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA‐MB‐231 cell proliferation, migration, and invasion, with minimal toxicity to non‐tumorigenic MCF‐10A mammary epithelial cells. Molecular modeling, Z'‐LYTE biochemical kinase assay and Western blot analysis identified c‐Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA‐MB‐231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen‐derived natural products are promising resources to discover novel c‐Met inhibitors useful to control TNBCs. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-06T22:59:19.593075-05:
      DOI: 10.1002/ptr.5551
  • Ginkgetin Blocks Constitutive STAT3 Activation and Induces Apoptosis
           through Induction of SHP‐1 and PTEN Tyrosine Phosphatases
    • First page: 567
      Abstract: Ginkgetin, a biflavone from Ginkgo biloba leaves, is known to exhibit antiinflammatory, antifungal, neuroprotective, and antitumor activities, but its precise mechanism of action has not been fully elucidated. Because the aberrant activation of STAT3 has been linked with regulation of inflammation, proliferation, invasion, and metastasis of tumors, we hypothesized that ginkgetin modulates the activation of STAT3 in tumor cells. We found that ginkgetin clearly suppressed constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK1 and c‐Src kinases and nuclear translocation of STAT3 on both A549 and FaDu cells. Treatment with sodium pervanadate reversed the ginkgetin‐induced down‐modulation of STAT3, thereby indicating a critical role for a PTP. We also found that ginkgetin strongly induced the expression of the SHP‐1 and PTEN proteins and its mRNAs. Further, deletion of SHP‐1 and PTEN genes by siRNA suppressed the induction of SHP‐1 and PTEN, and reversed the inhibition of STAT3 activation. Ginkgetin induced apoptosis as characterized by an increased accumulation of cells in subG1 phase, positive Annexin V binding, loss of mitochondrial membrane potential, down‐regulation of STAT3‐regulated gene products, and cleavage of PARP. Overall, ginkgetin abrogates STAT3 signaling pathway through induction of SHP‐1 and PTEN proteins, thus attenuating STAT3 phosphorylation and tumorigenesis. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-12T01:20:51.69485-05:0
      DOI: 10.1002/ptr.5557
  • Hydroxysafflor Yellow A Attenuates Bleomycin‐induced Pulmonary
           Fibrosis in Mice
    • Authors: Ming Jin; Yan Wu, Lin Wang, Baoxia Zang, Li Tan
      First page: 577
      Abstract: Hydroxysafflor yellow A (HSYA) is an active component of Carthamus tinctorius L., and we want to investigate whether HSYA attenuates pulmonary fibrosis induced by bleomycin (BLM) in mice. The mice received a BLM via oropharyngeal aspiration, and HSYA was intraperitoneally injected. Arterial blood gas analysis was performed. Morphological changes and hydroxyproline content were measured. mRNA expression of transforming growth factor‐β1 (TGF‐β1), connective tissue growth factor, α‐smooth muscle actin (α‐SMA), and collagen I was measured by real‐time polymerase chain reaction. α‐SMA‐positive cells in lung tissues were detected by immunohistochemical staining. A549 cell was cultured, and morphological changes were observed after TGF‐β1 and HSYA treatment. mRNA expression was detected by real‐time polymerase chain reaction. Phosphorylation of Smad3 was evaluated by western blotting. HSYA decreased the lung consolidation area and collagen deposition in mice with pulmonary fibrosis. The blood gas changes due to BLM were attenuated by HSYA. HSYA also alleviated the BLM‐induced increase of TGF‐β1, connective tissue growth factor, α‐SMA, and collagen I mRNA levels. HSYA treatment inhibited the increase of α‐SMA expression, Smad3 phosphorylation, the morphological changes in lung tissue. HSYA inhibits Smad3 phosphorylation and elevated expression of collagen I mRNA in epithelial–mesenchymal transition induced by TGF‐β1. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-18T00:56:54.561354-05:
      DOI: 10.1002/ptr.5560
  • 6‐Gingerol Mediates its Anti Tumor Activities in Human Oral and
           Cervical Cancer Cell Lines through Apoptosis and Cell Cycle Arrest
    • Authors: Vaishali Kapoor; Sadhna Aggarwal, Satya N. Das
      First page: 588
      Abstract: 6‐Gingerol, a potent nutraceutical, has been shown to have antitumor activity in different tumors, although its mechanism of action is not well understood. In this study, we evaluated antitumor activities of 6‐gingerol on human oral (SCC4, KB) and cervical cancer (HeLa) cell lines with or without wortmannin, rapamycin, and cisplatin. Tumor cell proliferation was observed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H tetrazolium, inner salt assay, cell cycle analysis by propidium iodide labeling and flow cytometry, apoptosis by Annexin‐V binding assay, and caspase activity by chemiluminescence assay. 6‐Gingerol showed dose‐dependent cytotoxicity in all three cell lines. Combinations of 6‐gingerol with wortmannin and cisplatin showed additive effects, while with rapamycin, it showed 50% cytotoxicity that was equivalent to IC50 of 6‐gingerol alone. Treatment with 6‐gingerol resulted in G2‐phase arrest in KB and HeLa cells and S‐phase arrest in SCC4 cells. 6‐Gingerol, wortmannin, and rapamycin treatment showed almost two‐fold higher expression of caspase 3 in all cell lines. The results imply that 6‐gingerol either alone or in combination with PI‐3 K inhibitor and cisplatin may provide better therapeutic effects in oral and cervical carcinoma. Thus, 6‐gingerol appears to be a safe and potent chemotherapeutic/chemopreventive compound acting through cell cycle arrest and induction of apoptosis in human oral and cervical tumor cells. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-07T21:49:08.195331-05:
      DOI: 10.1002/ptr.5561
  • c‐Jun N‐terminal Kinase‐Dependent Endoplasmic Reticulum
           Stress Pathway is Critically Involved in Arjunic Acid Induced Apoptosis in
           Non‐Small Cell Lung Cancer Cells
    • First page: 596
      Abstract: Though arjunic acid, a triterpene isolated from Terminalia arjuna, was known to have antioxidant, antiinflammatory, and cytotoxic effects, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the molecular antitumor mechanism of arjunic acid was examined in A549 and H460 non‐small cell lung cancer (NSCLC) cells. Arjunic acid exerted cytotoxicity by 3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5‐diphenyl tetrazolium bromide (MTT) assay and significantly increased sub‐G1 population in A549 and H460 cells by cell cycle analysis. Consistently, arjunic acid cleaved poly (ADP‐ribose) polymerase (PARP), activated Bax, and phosphorylation of c‐Jun N‐terminal kinases (JNK), and also attenuated the expression of pro‐caspase‐3 and Bcl‐2 in A549 and H460 cells. Furthermore, arjunic acid upregulated the expression of endoplasmic reticulum (ER) stress proteins such as IRE1 α, ATF4, p‐eIF2α, and C/EBP homologous protein (CHOP) in A549 and H460 cells. Conversely, CHOP depletion attenuated the increase of sub‐G1 population by arjunic acid, and also JNK inhibitor SP600125 blocked the cytotoxicity and upregulation of IRE1 α and CHOP induced by arjunic acid in A549 and H460 cells. Overall, our findings suggest that arjunic acid induces apoptosis in NSCLC cells via JNK mediated ER stress pathway as a potent chemotherapeutic agent for NSCLC.
      PubDate: 2016-01-20T04:12:47.098304-05:
      DOI: 10.1002/ptr.5563
  • Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating
           JNK/c‐Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in
    • First page: 604
      Abstract: Protocatechuic acid (PCA) plays a critical role in nutritional metabolism; it is a major metabolite of anthocyanins, which are flavonoids with a range of health benefits. PCA has a variety of biological activities including anti‐oxidant, antiinflammatory, anti‐apoptosis, and anti‐microbial activities. However, the pharmacological effect of PCA, especially on osteoclastogenesis, remains unknown. We examined the effect of PCA on receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation and bone resorption. PCA dose‐dependently inhibited RANKL‐induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and suppressed the bone‐resorbing activity of mature osteoclasts. At the molecular level, PCA suppressed RANKL‐induced phosphorylation of JNK among MAPKs only, without significantly affecting the early signaling pathway. PCA also suppressed RANKL‐stimulated expression of c‐Fos and nuclear factor of activated T cells c1 (NFATc1) at the mRNA and protein levels, without altering c‐Fos mRNA expression. Additionally, PCA down‐regulated the expression of downstream osteoclastogenesis‐related genes including β3‐integrin, DC‐STAMP, OC‐STAMP, Atp6v0d2, CTR, and CtsK. Mice treated with PCA efficiently recovered from lipopolysaccharide‐induced bone loss in vivo. Thus, PCA inhibits RANKL‐induced osteoclast differentiation and function by suppressing JNK signaling, c‐Fos stability, and expression of osteoclastic marker genes. These results suggest that PCA could be useful in treatment of inflammatory bone disorders. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-20T22:42:37.639078-05:
      DOI: 10.1002/ptr.5565
  • Anxiolytic Effect of Citrus aurantium L. on Patients with Chronic Myeloid
    • First page: 613
      Abstract: The bone marrow aspiration procedure is used in hematological diseases and consists of a painful, invasive procedure causing anxiety‐associated symptoms. The present study assessed the effect of Citrus aurantium L. essential oil on the treatment of anxiety, in the moment that precedes the collection of medullary material in patients with chronic myeloid leukemia (CML). Volunteers from both sexes were divided into groups receiving either the C. aurantium essential oil through inhalation, diazepam (10 mg), or the placebo. The evaluation was performed through psychometric scales [State‐Trait Anxiety Inventory (STAI)] and physiological measurements (blood pressure and cardiac and respiratory frequency). Inhalation of C. aurantium was associated with a decrease in the STAI‐S scores, suggesting an anxiolytic effect. In support of these results, a change in all the physiological measurements was observed in the group exposed to C. aurantium. In the diazepam group, only the diastolic pressure decreased, and no effect was observed in the placebo group. Therefore, the results showed that C. aurantium exhibits an anxiolytic effect and reduces the signs and symptoms associated with anxiety in patients with CML. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-20T04:29:24.712275-05:
      DOI: 10.1002/ptr.5566
  • Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics
           of Ribavirin and Its Major Metabolite in Rats
    • Authors: Sha Liao; Xueyuan Jin, Jinglai Li, Tianhong Zhang, Wenpeng Zhang, Weiguo Shi, Shiyong Fan, Xiaoying Wang, Juan Wang, Bohua Zhong, Zhenqing Zhang
      First page: 618
      Abstract: The herb‐derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (PO) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, PO), glycyrrhizin (15 mg/kg, intraperitoneal [IP]), or oxymatrine (60 mg/kg, PO). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration‐time curve (AUC0–t) and the peak plasma concentration (Cmax) of ribavirin and ribavirin base by 31.2–44.5% and 48.9–50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0–t of both ribavirin and its metabolite by 35.3–37.6% and 38.6–39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax. Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-22T01:37:44.845356-05:
      DOI: 10.1002/ptr.5567
  • Immunomodulation in Middle‐Aged Humans Via the Ingestion of
           Physta® Standardized Root Water Extract of Eurycoma longifolia
           Jack—A Randomized, Double‐Blind, Placebo‐Controlled,
           Parallel Study
    • Authors: Annie George; Naoko Suzuki, Azreena Binti Abas, Kiminori Mohri, Masanori Utsuyama, Katsuiku Hirokawa, Tsuyoshi Takara
      First page: 627
      Abstract: This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta® to modulate human immunity in a middle‐aged Japanese population. This randomized, double‐blind, placebo‐controlled, parallel study was conducted for 4 weeks. Eighty‐four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty‐three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p 
      PubDate: 2016-01-27T05:48:11.338443-05:
      DOI: 10.1002/ptr.5571
  • The Hot‐Water Extract of Smilacis Chinae Rhizome Suppresses
           2,4‐Dinitrochlorobenzene and House Dust Mite‐Induced Atopic
           Dermatitis‐Like Skin Lesions in Mice
    • First page: 636
      Abstract: Smilacis Chinae Rhizome (SCR) has been used as an oriental folk medicine for various biological activities. However, its effect on atopic dermatitis (AD) remains undetermined to date. We assessed the effect of orally administered hot‐water extract of SCR on AD‐like skin lesions in mice and its underlying mechanisms. AD‐like murine model was prepared by repeated alternate application of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4‐dinitrochlorobenzene (DNCB) for 4 weeks, topically to the ears. Daily oral administration of SCR for 3 and 4 weeks significantly reduced inflammatory ear thickening, with the effect being enhanced at the earlier start and longer period of administration. This effect was accompanied by a significant decrease in both Th2 and Th1 serum antibodies (total IgE, DFE‐specific IgE, and IgG2a). Histological analysis showed that SCR markedly decreased the epidermal/dermal ear thickening and the dermal infiltration of inflammatory cells. Furthermore, SCR suppressed DFE/DNCB‐induced expression of IL‐4, IL‐13, IL‐17, IL‐18, TSLP, and IFN‐γ genes in the ear tissue. Taken together, our observations demonstrate that chronic oral administration of SCR exerts beneficial effect in mouse AD model, suggesting that SCR has the therapeutic potential as an orally active treatment of AD by modulating both Th1 and Th2 responses. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-03T00:41:10.529253-05:
      DOI: 10.1002/ptr.5573
  • [6]‐Shogaol, a Novel Chemopreventor in
           7,12‐Dimethylbenz[a]anthracene‐induced Hamster Buccal Pouch
    • Authors: Suresh Kathiresan; Annamalai Govindhan
      First page: 646
      Abstract: Oral cancer is a major cause of morbidity and mortality in developing countries. Despite advances in chemotherapy for the cancer management, the survival rate has not yet been improved. Dietary nutrient has been receiving a lot of attention and interest in the chemotherapeutic development. [6]‐Shogaol is a major bioactive compound identified in ginger that possesses many pharmacological properties. The aim of the present study is to investigate the effect of [6]‐shogaol on 7,12‐dimethylbenz[a]anthracene‐induced hamster buccal pouch (HBP) carcinogenesis. Oral squamous cell carcinoma induced in HBP by painting with 0.5% 7,12‐dimethylbenz(a)anthracene (DMBA), thrice in a week for 16 weeks. We observed 100% tumour incidence, decreased levels of lipid peroxidation, antioxidant, and phase II detoxification enzymes (GST, GR and GSH) in DMBA‐induced hamsters. Further, enhanced activity of phase I enzymes (cytochrome p450 and b5) and over‐expression of mutant p53, Bcl‐2 and decreased expression of wild type p53 and Bax were noticed in DMBA‐induced hamsters. Our results indicated that [6]‐shogaol (10, 20 and 40 mg/kg body weight) treated with DMBA‐painted hamsters, considerably reversed tumour incidence, improved antioxidant status, phase II detoxification enzymes, and also inhibit lipid peroxidation and phase I enzymes. Moreover, [6]‐shogaol inhibits mutant p53 and Bcl‐2 expression and significantly restored normal p53, Bax levels. Thus, we concluded that [6]‐shogaol prevents DMBA‐induced HBP carcinogenesis through its antioxidant as well as modulating apoptotic signals. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-03T00:47:40.890751-05:
      DOI: 10.1002/ptr.5574
  • Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of
           Paeoniflorin Against ANIT Induced Cholestasis
    • Authors: Zhe Chen; Yun Zhu, Yanling Zhao, Xiao Ma, Ming Niu, Jiabo Wang, Haibin Su, Ruilin Wang, Jianyu Li, Liping Liu, Zhenman Wei, Qingguo Zhao, Hongge Chen, Xiaohe Xiao
      First page: 654
      Abstract: Cholestasis is a leading cause of hepatic accumulation of bile acids resulting in liver injury, fibrosis, and liver failure. Paeoniflorin displays bright prospects in liver protective effect. However, its molecular mechanism has not been well‐explored. This study was designed to assess the effects and possible mechanisms of paeoniflorin against alpha‐naphthylisothiocyanate‐induced liver injury. Ultraperformance liquid chromatography coupled with quadrupole time‐of‐flight combined with principle component analysis and partial least squares discriminant analysis were integrated to obtain differentiating metabolites for the pathways and clarify mechanisms of disease. The results indicated that paeoniflorin could remarkably downregulate serum biochemical indexes and alleviate the histological damage of liver tissue. Different expression of 14 metabolites demonstrated that paeoniflorin mainly regulated the dysfunctions of glycerophospholipid metabolism and primary bile acid biosynthesis. Moreover, several pathways such as arginine and proline metabolism, ether lipid metabolism, and arachidonic acid metabolism were also related to the efficacy. In conclusion, paeoniflorin has indicated favorable pharmacological effect on serum biochemical indexes and pathological observation on cholestatic model. And metabolomics is a promising approach to unraveling hepatoprotective effects by partially regulating the perturbed pathways, which provide insights into mechanisms of cholestasis. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-01-25T01:28:14.188382-05:
      DOI: 10.1002/ptr.5575
  • Dihydro‐Resveratrol Ameliorates Lung Injury in Rats with
           Cerulein‐Induced Acute Pancreatitis
    • First page: 663
      Abstract: Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro‐resveratrol, a prominent analog of trans‐resveratrol, against acute pancreatitis‐associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro‐inflammatory cytokines. When treated with dihydro‐resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro‐inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor‐kappaB (NF‐κB) activation was attenuated. This study is the first to report the oral administration of dihydro‐resveratrol ameliorated acute pancreatitis‐associated lung injury via an inhibitory modulation of pro‐inflammatory response, which was associated with a suppression of the NF‐κB signaling pathway.Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-01T03:41:59.316828-05:
      DOI: 10.1002/ptr.5576
  • Possible Involvement of Nitric Oxide Modulatory Mechanisms in the
           Neuroprotective Effect of Centella asiatica Against Sleep Deprivation
           Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation
    • Authors: Priyanka Chanana; Anil Kumar
      First page: 671
      Abstract: Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72‐h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF‐alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti‐anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep‐deprived 72‐h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD‐induced anxiety‐like behaviour, oxidative damage and neuroinflammation in mice. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-02-05T01:12:38.694111-05:
      DOI: 10.1002/ptr.5582
  • TOC
    • Abstract: No abstract is available for this article.
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