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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
           Perspectives
    • 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
           Mediators
    • 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
           Sleep
    • 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
       
  • 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
           Trial
    • 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
       
  • 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
       
  • 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
       
  • 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
       
  • Puerarin Exerts an Antiinflammatory Effect by Inhibiting NF‐kB and
           MAPK Activation in Staphylococcus aureus‐Induced Mastitis
    • Abstract: Mastitis is defined as the inflammation of the mammary gland. There is generally no effective treatment for mastitis in animals. Puerarin, extracted from Radix puerariae, has been proven to possess many biological activities. The present study aims to reveal the potential mechanism that is responsible for the antiinflammatory action of puerarin in Staphylococcus aureus (S. aureus)‐induced mastitis in mice. Histopathological changes showed that puerarin ameliorated the inflammatory injury induced by S. aureus. Quantitative real‐time polymerase chain reaction and ELISA analysis indicated that puerarin not only suppressed the production of pro‐inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6 but also promoted the secretion of IL‐10. Toll‐like receptor 2 (TLR2) is important in the immune defense against S. aureus infection. Research in molecular biology has shown that the expression of TLR2 was inhibited with administration of puerarin. Further studies were performed on NF‐kB and mitogen‐activated protein kinase signaling pathways using western blot. The results demonstrated that puerarin suppressed phosphorylated IkBα, p65, p38, extracellular signal‐regulated kinase 1and 2 (ERK), and c‐Jun N‐terminal kinase (JNK) in a dose‐dependent manner. All of the results suggested that puerarin may be a potential therapy for treating mastitis. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Methanol Extract of Bitter Melon Alleviates UVB‐Induced MMPs
           Expression via MAP Kinase and AP‐1 Signaling in Human Dermal
           Fibroblasts in vitro
    • Abstract: Ultraviolet (UV) irradiation leads to photo‐damage of the skin, which in turn induces expression of matrix metalloproteinases (MMPs) and reduces type I procollagen. Bitter melon (Momordica charantia L.) has been widely used as a traditional medicine. In this study, we tested the photo‐protective effects of methanol extracts of bitter melon pulp (BM) and the mechanism of these effects in normal human dermal fibroblasts (NHDFs). The effects of BM were investigated by measuring the levels of MMP‐1, ‐3 and ‐9, and type I procollagen following UVB irradiation. We found that BM alleviates UVB‐induced MMP‐1, ‐3 and ‐9 expression at 100 µg/mL (down to 52.0%, 73.5%, and 55.6%, respectively). However, cells treated with 100 µg/mL BM had weakly stimulated type I procollagen expression (up to 130.0%). Moreover, treatment with BM significantly reduced UVB‐induced extracellular signal‐regulated kinase (ERK), Jun N‐terminal kinase (JNK), and p38 phosphorylation, which resulted in decreasing UVB‐induced phosphorylation of c‐Fos and c‐Jun. Therefore, our results suggest that BM is a potential agent for regulating skin photoaging. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Therapeutic Potential of Essential Oils Focusing on Diterpenes
    • Abstract: Among all plant derivates, essential oils (EOs) have gained the attention of many scientists. Diterpenes, a family of components present in some EO, are becoming a milestone in the EOs world. The goal of this review is to describe a scenario of diterpenes taking into health‐consumption deportment. Previous studies revealed that diterpenes have antioxidant, antimicrobial, antiviral, antiprotozoal, cytotoxic, anticancer, antigenotoxic, antimutagenic, chemopreventive, antiinflammatory, antinociceptive, immunostimulatory, organoprotective, antidiabetic, lipid‐lowering, antiallergic, antiplatelet, antithrombotic, and antitoxin activities. In conclusion, diterpenes may be an immense featuring concern in pharmaceutical consumption from a drug discovery point of view. Copyright © 2016 John Wiley & Sons, Ltd. Dimethayllyl‐pyrophosphate (DAPP) is the ultimate product of the pyryvate‐glyceraldehyde‐3‐P and 2‐acetyl‐Co‐A pathways, as it can reversibly turn to isopentenyl‐pyrophosphate (IPP) moiety. These two then undergoing a head‐tail condensation in the presence of geranyl‐pyrophosphate (GPP) synthase form GPP. Upon a step‐wise addition of further IPPs, they ultimately form diterpenes.
       
  • Non‐alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids
    • Abstract: Non‐alcoholic fatty liver disease (NAFLD) has been known as the hepatic feature of metabolic syndrome. Extra fat depots, especially in visceral areas, develop insulin resistance as a result of mild oxidation and inflammation. Insulin resistance induces lipolysis and releases free fatty acids into the circulation, where they are transported to the liver. In the liver, free fatty acids are converted to triglycerides and accumulate, causing simple steatosis that, if left untreated, can lead to steatohepatitis, and subsequently liver necrosis and cirrhosis.Flavonoids, a group of plant compounds with incredible biological characteristics, have shown advantages in pathological conditions. Beneficial effects of flavonoids against NAFLD and its related disorders have been observed in both animal and human studies. Various mechanisms have been found for their protection. Flavonoids prevent hepatosteatosis by increasing fatty acid oxidation in the liver. They can also reduce caloric intake and decrease body weight and fat deposition in visceral tissues. Flavonoids are unique antioxidants that exert their beneficial effects through inhibition of nuclear factor κB, thereby attenuating release of inflammatory cytokines, which are triggers of insulin resistance. Finally, flavonoids have shown to increase adiponectin, improve insulin sensitivity and glucose tolerance, correct dyslipidemia, and reduce blood pressure in patients with NAFLD. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • A Pharmacological Review of Bioactive Constituents of Paeonia lactiflora
           Pallas and Paeonia veitchii Lynch
    • Abstract: The roots of two peony species, Paeonia lactiflora Pallas and Paeonia veitchii Lynch are routinely referred to as either chishao (赤芍) or baishao (白芍). This paper reviews the botanical origins and traditional medicinal usage of each species, as well as pharmacological like activity of their constituents. A search of herbal pharmacological encyclopaedia, PubChem and PubMed databases identified their known constituents. The biological data for these constituents were evaluated and classified according to pharmacological‐like activity, with emphasis on compounds of greatest concentration and bioavailability. It was found that P. lactiflora and P. veitchii have some common compounds; however, their phytochemical bioavailability varies. Furthermore, a larger number of compounds have been identified in P. lactiflora. These have greater potential for antiinflammatory, antiviral, antibacterial and antioxidant therapeutic activity compared with P. veitchii. However, evidence indicates both species are similarly indicated for antiviral and glycaemic activity. Major compounds of each are classified as flavonoids, hydrolysable tannins (polyphenols) and monoterpene glycosides. The evidence suggests both species, when administered in entire botanical form, have an excellent safety profile; however, constituent toxicity risk evidence is limited, requiring further investigation. Although experiments show many compounds have biological activity, further investigation of their therapeutic potential is needed. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Effect of crocin on aged rat kidney through inhibition of oxidative stress
           and proinflammatory state
    • Abstract: This study evaluated whether crocin, a bioactive component of saffron, has a protective effect on kidney through reducing the oxidative stress and inflammatory response in aged rats. In this study the changes in activities of antioxidant enzymes, lipid peroxidation, glutathione (GSH) levels and the expression of pro‐inflammatory cytokines in the serum and renal tissue were evaluated by ELISA and RT‐PCR, respectively. The middle and aged rats were given intraperitoneal injections of crocin (10, 20, 30 mg/kg/day) for 4 weeks. After 4 weeks, animals were anesthetized with diethyl ether. The kidney samples were taken for biochemical analysis. The results revealed the aging was associated with a significant decrease in the activities of antioxidant enzymes, and GSH content with increase in lipid peroxidation level in kidney of the aged rats (p 
       
  • Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects
           with Prediabetes: A Proof‐of‐concept, Randomized,
           Double‐blind, Placebo‐controlled Clinical Trial
    • Abstract: Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12‐week, randomized, double‐blind, placebo‐controlled trial. Forty‐four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low‐dose RO extract (LRE; n = 14), or high‐dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75‐g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (−28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p 
       
  • Efficacy of a Nasal Spray from Citrus limon and Cydonia oblonga for the
           Treatment of Hay Fever Symptoms—A Randomized, Placebo Controlled
           Cross‐Over Study
    • Abstract: Nasal spray from lemon and quince (LQNS) is used to treat hay fever symptoms and has been shown to inhibit histamine release from mast cells in vitro. Forty‐three patients with grass pollen allergy (GPA) were randomized to be treated either with placebo or LQNS for one week, respectively, in a cross‐over study. At baseline and after the respective treatments patients were provoked with grass pollen allergen. Outcome parameters were nasal flow measured with rhinomanometry (primary), a nasal symptom score, histamine in the nasal mucus and tolerability. In the per protocol population absolute inspiratory nasal flow 10 and 20 min after provocation was higher with LQNS compared to placebo (−37 ± 87 mL/s; p = 0.027 and −44 ± 85 mL/s; p = 0.022). The nasal symptom score showed a trend (3.3 ± 1.8 in the placebo and 2.8 ± 1.5 in the LQNS group; p = 0.070) in favor of LQNS; the histamine concentration was not significantly different between the groups. Tolerability of both, LQNS and placebo, was rated as very good. LQNS seems to have an anti‐allergic effect in patients with GPA. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Phytochemical and Pharmacological Investigations on Nymphoides indica Leaf
           Extracts
    • Abstract: Nymphoides indica (L.) Kuntze (Menyanthaceae) is traditionally used in the Indian subcontinent. However, scientific data reporting its constituents are poor. This study aimed at evaluating its phytochemical constituents and various biological activities. Phytochemical investigations of the extracts and fractions resulted in the isolation of 5 lipophilic compounds, i.e. azelaic (nonanedioic) acid (1) and 4‐methyl‐heptanedioic acid (3), hexadecanoic (2) and stearic acid (5) and the fatty alcohol hexadecanol (4); 3 seco‐iridoids, i.e. 7‐epiexaltoside (6), 6″,7″‐dihydro‐7‐epiexaltoside (7) and menthiafolin (8); 3 flavonoids, i.e. 3,7‐di‐O‐methylquercetin‐4′‐O‐β‐glucoside (9), 3‐O‐methylquercetin‐7‐O‐β‐glucoside (10) and 3,7‐di‐O‐methylquercetin (11); scopoletin (12) and ferulic acid (13); and the monoterpenoids foliamenthoic acid (14) and 6,7‐dihydrofoliamenthoic acid methyl ester (15). Compounds 1–5 showed moderate antimicrobial activities, whereas compound 9 presented mild antiprotozoal activities against Trypanosoma brucei (IC50 8 μM), Leishmania infantum (IC50 32 μM) and Trypanosoma cruzi (IC50 30 μM). Antiglycation activity was shown by compounds 7 (IC50 0.36 mM), 10 (IC50 0.42 mM) and 15 (IC50 0.61 mM). Finally α‐glucosidase inhibition was shown by compounds 7, 9, 11 and 13–15. It could be concluded that N. indica leaf extracts possess mild to moderate antimicrobial, antiprotozoal, antioxidant and antidiabetic activities. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • An Insight into a Blockbuster Phytomedicine; Marrubium vulgare L. Herb.
           More of a Myth than a Reality'
    • Abstract: Aerial parts and the root of Marrubium vulgare L. (white horehound) have been traditionally used in Europe and in southern and eastern Mediterranean countries. During colonization, the plant was introduced in America to great levels of popularity because of the simplicity of its growing; it was especially popular in Mexico and Brazil, where it has been known as ‘maromba’, ‘marroio’ or ‘marroio‐branco’. Ethnopharmacological uses of M. vulgare include treating respiratory diseases such as acute or chronic bronchitis, colds and asthma. The plant is also used in cases where there is a lack of appetite or dyspepsia and for diagnosed type II diabetes. It has even been used for antihypertensive therapy. For decades, scientists have carried out extensive research trying to explain these and other pharmacologic actions. It is time to systematize and critically analyse the quality of results found to date. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Cytotoxicity Effects and Apoptosis Induction by Bisbenzylisoquinoline
           Alkaloids from Triclisia subcordata
    • Abstract: Triclisia subcordata Oliv (Menispermeaceae) is a medicinal plant traditionally used for the treatment of various diseases in West Africa. The ethanol extract of T. subcordata and its fractions were screened for in vitro anti‐ovarian cancer activities using the Sulforhodamine B assay. The crude alkaloids showed the strongest activity in cell growth assays on Ovcar‐8 and A2780 cell lines (IC50 
       
  • Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell
           Damage in Early Rheumatoid Arthritis Patients—A Pilot Study
    • Abstract: The effects of co‐administration of dry olive leaf extract (DOLE) with standard methotrexate (MTX) therapy on the parameters of cell damage and inflammation in patients with early and long‐term rheumatoid arthritis (RA) were evaluated at baseline, 3 and 6 weeks. Patients were assigned to groups: the early phase RA group on MTX monotherapy (E MTX), and the two RA groups that received co‐treatment with DOLE and MTX: early (E MTX + DOLE) and long‐term phase patients (L‐t MTX+ DOLE). Baseline values indicated increased parameters of cell damage and disruption of redox balance in all groups. After three weeks the E MTX + DOLE group maintained high catalase activity, exhibited decrease of lipid peroxidation and protein damage indicators—thiols and nitrites, while levels of DNA damage and pro‐inflammatory interleukin‐6 were significantly reduced. In E MTX group catalase activity remained unaltered while significant lipid peroxidation and DNA damage reductions were seen only after six weeks. L‐t MTX + DOLE group showed only modest alterations of cell damage parameters during six weeks. Combined administration of DOLE with MTX contributes to faster reduction of cell damage, restores oxidative balance and improves interleukin‐6 suppression during high disease activity in early phase RA, but not in long term patients. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Nimbolide Inhibits Nuclear Factor‐КB Pathway in Intestinal
           Epithelial Cells and Macrophages and Alleviates Experimental Colitis in
           Mice
    • Abstract: Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor‐kappa B (NF‐κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin‐10‐deficient (IL‐10−/−) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor‐α (TNF‐α) or lipopolysaccharide. Dextran sulfate sodium‐induced acute colitis model and chronic colitis model in IL‐10−/− mice were used for in vivo experiments. Nimbolide significantly suppressed the expression of inflammatory cytokines (IL‐6, IL‐8, IL‐12, and TNF‐α) and inhibited the phosphorylation of IκBα and the DNA‐binding affinity of NF‐κB in IECs and macrophages. Nimbolide ameliorated weight loss, colon shortening, disease activity index score, and histologic scores in dextran sulfate sodium colitis. It also improved histopathologic scores in the chronic colitis of IL‐10−/− mice. Staining for phosphorylated IκBα was significantly decreased in the colon tissue after treatment with nimbolide in both models. Nimbolide inhibits NF‐κB signaling in IECs and macrophages and ameliorates experimental colitis in mice. These results suggest nimbolide could be a potentially new treatment for inflammatory bowel disease. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Treatment of Non‐alcoholic Fatty Liver Disease with Curcumin: A
           Randomized Placebo‐controlled Trial
    • Abstract: Non‐alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double‐blind placebo‐controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70‐mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow‐up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low‐density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof‐of‐concept trial suggested improvement of different features of NAFLD after a short‐term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.
       
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    • Abstract: No abstract is available for this article.
       
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    • Abstract: No abstract is available for this article.
       
  • An Hydroalcoholic Chamomile Extract Modulates Inflammatory and Immune
           Response in HT29 Cells and Isolated Rat Colon
    • Abstract: Inflammatory bowel diseases (IBDs) are chronic disorders characterized by disruption and ulceration of the colonic mucosa or of any part of the digestive tract (Crohn's disease). Antioxidant/anti‐inflammatory herbal extract supplementation could represent an innovative approach to contrast IBDs. Clinical trials demonstrated the efficacy of natural formulas, containing chamomile, in patients with gastrointestinal disorders. This is consistent, albeit in part, with the antioxidant and anti‐inflammatory properties of chamomile. The aim of the present study was to explore the possible protective role of a chamomile extract, on human colorectal adenocarcinoma HT29 cell, and rat colon specimens treated with lipopolysaccharide (LPS) to induce an inflammatory stimulus, a well established model of acute ulcerative colitis. In this context, the activities of different biomarkers of inflammation and lipid peroxidation such as ROS, myeloperoxidase (MPO), serotonin (5‐HT), prostaglandin (PG)E2, 8‐iso‐prostaglandin (8‐iso‐PG)F2α, NF‐kB, tumor necrosis factor (TNF)α and interleukin (IL)‐6 were assessed. We found that chamomile extract was as effective as sulfasalazine (2 mg/ml) in reducing the production of MPO, 5‐HT, IL‐6, NF‐kB, TNFα, PGE2 and 8‐iso‐PGF2α, after inflammatory stimulus. The observed modulatory effects support a rationale use of chamomile supplementation as a promising pharmacological tool for the prevention and management of ulcerative colitis in humans. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Prooxidant Activity of Polyphenols, Flavonoids, Anthocyanins and
           Carotenoids: Updated Review of Mechanisms and Catalyzing Metals
    • Abstract: Natural antioxidants, including polyphenols, flavonoids, anthocyanins and carotenoids, play an important role in the treatment and prevention of a large number of diseases. However, studies indicate that natural antioxidants can act as prooxidants, which produce free radicals and cause DNA damage and mutagenesis. The prooxidant activity is typically catalyzed by metals, particularly transition metals such as Fe and Cu, present in biological systems. In this article, we aim to review new in vitro and in vivo evidence of the prooxidant activity of phenolics, flavonoids, anthocyanins and carotenoids. We highlight the role of catalyzing metals, including transition metals, non‐transition metals and metalloids, in the prooxidant activity of natural antioxidants. Prooxidant structure–activity relationships of simple phenolics, flavonoids and anthocyanins and the role of cellular antioxidant defense, including endogenous antioxidant compounds and antioxidant enzymes, are also addressed in this review. In addition, we discuss the question, With respect to in vitro evidence of the prooxidant activity of antioxidants, can we translate this activity into biological systems and the human body'
       
  • Oxidative Inactivation of Liver Mitochondria in High Fructose
           Diet‐Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin
           Treatment
    • Abstract: Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome‐induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra‐peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe2+ ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Antenatal Saireito (TJ‐114) Can Improve Pulmonary Hypoplasia and
           Pulmonary Vascular Remodeling in Nitrofen‐Induced Congenital
           Diaphragmatic Hernia
    • Abstract: Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ‐114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague‐Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p 
       
  • Chemistry, Pharmacology and Health Benefits of Anthocyanins
    • Abstract: Anthocyanins are naturally occurring molecules belonging to the flavonoid class characterized by the presence of chromophores. Apart from their well‐known antioxidant activity, they show a wide variety of health‐promoting properties for human health, ranging from cytoprotective, antimicrobial and antitumour activities to neuroprotective, anti‐obesity and lipidomic potential, properties for which anthocyanins have been prescribed as medicines in several countries for thousands of years. Despite this, these phytochemicals have received less attention than other flavonoids, and there is still a gap in the literature, particularly regarding pharmacological and toxicological aspects. Moreover, epidemiological evidence suggests a direct correlation between anthocyanin intake and a lower incidence of chronic and degenerative diseases. In light of this, the aim of this review is to cover the current literature on anthocyanins, their biological in vitro and in vivo effects and their potential therapeutic applications, as well as their bioavailability and pharmacokinetics, all of which are essential to gain a better understanding of their biological effectiveness and potential toxicity.
       
  • The Prokinetic, Laxative, and Antidiarrheal Effects of Morus nigra:
           
    • Abstract: Morus nigra Linn. (black mulberry) is used in gastrointestinal ailments. This study demonstrates gut modulatory properties of M. nigra. The prokinetic, laxative, and antidiarrheal activities of M. nigra were assessed in mice, while isolated rabbit jejunum and guinea‐pig ileum were used to explore insight into mechanism(s). At 30 and 70 mg/kg, the crude extract of M. nigra (Mn.Cr) exhibited atropine‐sensitive prokinetic and laxative effects, similar to carbachol (CCh). While at higher doses (100, 300, and 500 mg/kg), Mn.Cr offered protection against castor oil‐induced diarrhea. In rabbit jejunum, Mn.Cr and its chloroform fraction inhibited CCh‐induced contractions more potently compared with high K+ (80 mm). Conversely, petroleum fraction was more potent against high‐K+‐induced contractions. At 0.01 mg/mL, Mn.Cr caused a parallel shift in acetylcholine concentration–response curves (CRCs) followed by a non‐parallel shift at 0.03 mg/mL, similar to dicyclomine. At further tested concentrations, Mn.Cr (0.1 and 0.3 mg/mL) and petroleum fraction suppressed Ca2+ CRCs, similar to verapamil. In guinea‐pig ileum, Mn.Cr, its aqueous and ethyl acetate fractions exhibited atropine‐sensitive gut stimulant activity along with additional uncharacterized excitatory response in the aqueous fraction only. These results suggest that black mulberry possesses prokinetic, laxative, and antidiarrheal effects, putatively mediated through cholinomimetic, antimuscarinic, and Ca2+ antagonist mechanisms, respectively. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Attenuation of Adhesion, Biofilm Formation and Quorum Sensing of
           Campylobacter jejuni by Euodia ruticarpa
    • Abstract: Thermophilic campylobacters are a major cause of bacterial food‐borne diarrhoeal disease. Adherence and biofilm formation are key elements of Campylobacter jejuni persistence in unfavourable environmental conditions. The phytochemical analysis of Euodia ruticarpa fruit ethanol solution extract (EREE) indicated that the major compounds were evodiamine (1), rutaecarpine (2) and evocarpine (9). E. ruticarpa fruit ethanol solution extract, compounds 1 and 2 as well as a mixture of quinolinone alkaloids with 41.7% of 9 were tested for antibacterial, antibiofilm and antiquorum sensing activities against C. jejuni. Minimal inhibitory concentrations varied from 64 to 1024 µg/mL. A mutant strain that lacks the functional gene coding for the CmeB efflux pump protein was the most susceptible. Interestingly, in addition to the wild‐type (NCTC 11168) and cmeB mutant, also a mutant that lacks autoinducer‐2 production (luxS) was able to adhere (1 h) and to produce a biofilm (24, 48 and 72 h). The subinhibitory concentrations of all preparations at least partly inhibited C. jejuni adhesion and biofilm formation with the most visible effect of the quinolinone alkaloid fraction. Using a Vibrio harveyi luminescence assay, the inhibition of autoinducer‐2 production was observed in the wild‐type and cmeB mutant after 48 h with the most visible effect of EREE and its fraction Q. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • The Chemistry and Biological Activities of Mimosine: A Review
    • Abstract: Mimosine [β‐[N‐(3‐hydroxy‐4‐oxypyridyl)]‐α‐aminopropionic acid] is a non‐protein amino acid found in the members of Mimosoideae family. There are a considerable number of reports available on the chemistry, methods for estimation, biosynthesis, regulation, and degradation of this secondary metabolite. On the other hand, over the past years of active research, mimosine has been found to have various biological activities such as anti‐cancer, antiinflammation, anti‐fibrosis, anti‐influenza, anti‐virus, herbicidal and insecticidal activities, and others. Mimosine is a leading compound of interest for use in the development of RAC/CDC42‐activated kinase 1 (PAK1)‐specific inhibitors for the treatment of various diseases/disorders, because PAK1 is not essential for the growth of normal cells. Interestingly, the new roles of mimosine in malignant glioma treatment, regenerative dentistry, and phytoremediation are being emerged. These identified properties indicate an exciting future for this amino acid. The present review is focused on the chemistry and recognized biological activities of mimosine in an attempt to draw a link between these two characteristics. Copyright © 2016 John Wiley & Sons, Ltd. Mimosine has been evolved as a multi‐functional compound. Mimosine has been found as a leading compound for development of protein‐activated kinase 1 inhibitors. The new evidences to explain why mimosine is implicated in regenerative dentistry, periodontal regeneration, oral surgery, and phytoremediation. The review is to bridge the gaps between the chemistry and recognized biological activities of mimosine.
       
  • Effects of Turmeric (Curcuma longa) on Skin Health: A Systematic Review of
           the Clinical Evidence
    • Abstract: Turmeric (Curcuma longa), a commonly used spice throughout the world, has been shown to exhibit antiinflammatory, antimicrobial, antioxidant, and anti‐neoplastic properties. Growing evidence shows that an active component of turmeric, curcumin, may be used medically to treat a variety of dermatologic diseases. This systematic review was conducted to examine the evidence for the use of both topical and ingested turmeric/curcumin to modulate skin health and function. The PubMed and Embase databases were systematically searched for clinical studies involving humans that examined the relationship between products containing turmeric, curcumin, and skin health. A total of 234 articles were uncovered, and a total of 18 studies met inclusion criteria. Nine studies evaluated the effects of ingestion, eight studies evaluated the effects of topical, and one study evaluated the effects of both ingested and topical application of turmeric/curcumin. Skin conditions examined include acne, alopecia, atopic dermatitis, facial photoaging, oral lichen planus, pruritus, psoriasis, radiodermatitis, and vitiligo. Ten studies noted statistically significant improvement in skin disease severity in the turmeric/curcumin treatment groups compared with control groups. Overall, there is early evidence that turmeric/curcumin products and supplements, both oral and topical, may provide therapeutic benefits for skin health. However, currently published studies are limited and further studies will be essential to better evaluate efficacy and the mechanisms involved.
       
  • Plumbagin, a Plant‐Derived Compound, Exhibits Antifungal Combinatory
           Effect with Amphotericin B against Candida albicans Clinical Isolates and
           Anti‐hepatitis C Virus Activity
    • Abstract: Plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone), the major active constituent of Plumbago indica L., has been shown to be effective against a wide range of infectious microbes. In this study, plumbagin has been evaluated in vitro for its antifungal combinatory effect with amphotericin B against Candida albicans (C. albicans) clinical isolates and anti‐hepatitis C virus (HCV) activity. Antifungal activity was determined by broth microdilution method, and combinatory effect was evaluated by checkerboard assay according to ΣFIC indices, while cytotoxicity was determined by MTT assay. Anti‐HCV activity was determined in infected Huh7.5 cells using quantitative real‐time reverse transcription PCR, and cytotoxicity was evaluated by MTT assay. Plumbagin exerted inhibitory effect against all C. albicans strains with minimum inhibitory concentration values ranging from 7.41 to 11.24 µg/mL. The additive effect of plumbagin when combined with amphotericin B at concentrations of (0.12, 0.13 and 0.19, 1.81 µg/mL, respectively) was obtained against five of seven strains tested with ΣFIC ranging from 0.62 to 0.91. In addition, plumbagin was found to be used safely for topical application when combined with amphotericin B at concentrations corresponding to the additive effect. Plumbagin exerted anti‐HCV activity compared with that of telaprevir with IC50 values of 0.57 and 0.01 μM/L, respectively, and selectivity indices SI = 53.7 and SI = 2127, respectively. Our results present plumbagin as a potential therapeutic agent in the treatment of C. albicans and HCV infections. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Anti‐infective potential of Citrus bergamia Risso et Poiteau
           (bergamot) derivatives: a systematic review
    • Abstract: Infectious diseases remain among the leading causes of morbidity and mortality worldwide, mainly because of the increase of resistance to chemotherapeutic drugs. Nature is the major source of anti‐infective drugs and could represent a font of medicines that may help overcome antibiotic resistance. Recently, the potential antimicrobial effect of certain plant extracts has attracted attention within the scientific community as alternatives to synthetic drugs. Here, we present a systematic review on the anti‐infective properties of bergamot derivatives that highlight the activity of bergamot essential oil against bacteria, mycetes and larvae, as well as the anti‐Helicobacter pylori effect of bergamot juice and the antimicrobial properties of extracts from bergamot peel. Findings presented herein could be used to develop novel and alternative preventive and therapeutic strategies aimed to overcome antibiotic resistance.
       
  • Therapeutic Potential of Polyphenols from Epilobium Angustifolium
           (Fireweed)
    • Abstract: Epilobium angustifolium is a medicinal plant used around the world in traditional medicine for the treatment of many disorders and ailments. Experimental studies have demonstrated that Epilobium extracts possess a broad range of pharmacological and therapeutic effects, including antioxidant, anti‐proliferative, anti‐inflammatory, antibacterial, and anti‐aging properties. Flavonoids and ellagitannins, such as oenothein B, are among the compounds considered to be the primary biologically active components in Epilobium extracts. In this review, we focus on the biological properties and the potential clinical usefulness of oenothein B, flavonoids, and other polyphenols derived from E. angustifolium. Understanding the biochemical properties and therapeutic effects of polyphenols present in E. angustifolium extracts will benefit further development of therapeutic treatments from this plant. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Systematic Review of Adverse Effects from Herbal Drugs Reported in
           Randomized Controlled Trials
    • Abstract: Herbal drugs have become a popular form of healthcare, raising concerns about their safety. This study aimed to characterize the adverse effects of herbal drugs through a systematic review of results reported in randomized controlled trials (RCTs). Using eight electronic databases including PubMed, the Cochrane library and six Korean medical databases, the frequency of reported toxicity was recorded based on drug composition and indication. Among 4957 potentially relevant articles, 242 papers comprised of 244 studies met our inclusion criteria; these included 111 studies of a single herb and 133 of multiple herbs. These studies accounted for a total 15 441 participants (male = 5590; female = 9851; 7383 for single and 8058 for multiple herb studies). There were 480 cases (3.1%) of adverse events (344 for single, 136 for multiple herb studies; p 
       
  • Review of the Pharmacological Effects of Vitis vinifera (Grape) and its
           Bioactive Constituents: An Update
    • Abstract: Vitis vinifera fruit (grape) contains various phenolic compounds, flavonoids and stilbenes. In recent years, active constituents found in the fruits, seeds, stems, skin and pomaces of grapes have been identified and some have been studied. In this review, we summarize the active constituents of different parts of V. vinifera and their pharmacological effects including skin protection, antioxidant, antibacterial, anticancer, antiinflammatory and antidiabetic activities, as well as hepatoprotective, cardioprotective and neuroprotective effects in experimental studies published after our 2009 review. Clinical and toxicity studies have also been examined. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Anti‐Proliferation Effects of Garlic (Allium sativum L.) on the
           Progression of Benign Prostatic Hyperplasia
    • Abstract: Benign prostatic hyperplasia (BPH) is a urologic disease that affects most of men over the age 50. But until now there is no such perfect cure without side effects. Because of diverse adverse effects, it is desirable to develop effective and long term‐safety‐herbal medicines to inhibit the progress of BPH. In spite of garlic's large use and a wide spectrum of studies, including anti‐hyperlipidemic, cardio‐protective, and anti‐inflammatory activities, there was none to prove efficacy for BPH. In this study, we evaluated the efficacy of garlic to prove its suppressing effects on BPH. Garlic administration decreased relative prostate weight ratio, suppressed mRNA expression level of AR, DHT serum levels, and the growth of prostatic tissue in BPH‐induced rats. Moreover, garlic administration decreased the levels of inflammatory proteins, iNOS, and COX‐2 in prostatic tissue. Further investigation showed that garlic induced accumulation of death‐inducing signal complex and activation of AMPK and decreased the levels of anti‐apoptotic proteins, such as Bcl‐2, Bcl‐xL, and survivin. These results suggest that garlic may have suppressing effects on BPH and it has great potential to be developed as treatment for BPH. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics
    • Abstract: Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long‐term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Brain‐derived Neurotrophic Factor Signaling Mediates the
           Antidepressant‐like Effect of the Total Flavonoids of Alpiniae
           Oxyphyllae Fructus in Chronic Unpredictable Mild Stress Mice
    • Abstract: The present study verified the antidepressant‐like effects of the total flavonoids of Alpinia oxyphylla Miq. (AOF) using the chronic unpredictable mild stresses paradigm and explored the mechanism that underlies antidepressant‐like effects of AOF in mice. Previous research has shown that tropomyosin‐related kinase B (TrkB) receptor‐mediated extracellular regulated protein kinases (ERK) signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether AOF improved depression‐like behaviors by increasing activity of ERK pathways mediated by TrkB. Results showed that AOF significantly reduced the immobility time in the forced swimming test and increased the sucrose preference in sucrose preference test. In addition, decreased phosphorylated cyclic adenosine monophosphate response element‐binding protein (pCREB)/CREB, pERK/ERK, and pTrkB/TrkB levels in the hippocampus induced by chronic unpredictable mild stresses were reversed by intragastric administration of AOF. Results suggested that AOF increased pCREB/CREB, pERK/ERK, and pTrkB/TrkB levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 2 weeks), before the intragastric administration of AOF. This resulted in an absence of antidepressant‐like effects, as well as no activation of pERK/pCREB/BDNF signaling pathways. Results demonstrated that AOF might exert antidepressant‐like effects by targeting TrkB receptor‐mediated pERK/pCREB/BDNF signal systems, which could help to identify the AOF receptor. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Potential Signaling Pathways Involved in the Clinical Application of
           Oxymatrine
    • Abstract: Oxymatrine, an alkaloid component extracted from the roots of Sophora species, has been shown to have antiinflammatory, antifibrosis, and antitumor effects and the ability to protect against myocardial damage, etc. The potential signaling pathways involved in the clinical application of oxymatrine might include the TGF‐β/Smad, toll‐like receptor 4/nuclear factor kappa‐light‐chain‐enhancer of activated B cells, toll‐like receptor9/TRAF6, Janus kinase/signal transduction and activator of transcription, phosphatidylinositol‐3 kinase/Akt, delta‐opioid receptor‐arrestinl‐Bcl‐2, CD40, epidermal growth factor receptor, nuclear factor erythroid‐2‐related factor 2/heme oxygenase‐1 signaling pathways, and dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine metabolism pathway. In this review, we summarize the recent investigations of the signaling pathways related to oxymatrine to provide clues and references for further studies on its clinical application. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • The Effects of Pycnogenol® as Add‐on Drug to Metformin Therapy
           in Diabetic Rats
    • Abstract: The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio‐protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add‐on drug to metformin therapy in streptozotocin (STZ)‐induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin‐dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy.
       
  • Acetonic Extract from the Feijoa sellowiana Berg. Fruit Exerts Antioxidant
           Properties and Modulates Disaccharidases Activities in Human Intestinal
           Epithelial Cells
    • Abstract: Feijoa sellowiana fruit has been shown to possess various biological activities, such as anti‐bacterial and anti‐cancer properties, in a variety of cellular models, but its activity on human intestinal epithelial cells has never been tested. The purpose of this study was to investigate the effects of the acetonic extract of F. sellowiana fruits on the viability, membrane peroxidation, disaccharidases activities and proliferation of in vitro models of human intestinal epithelial cells. To obtain this goal, Caco‐2 and HT‐29 cells were exposed to the acetonic extract for 24 h. Cell proliferation, viability, lactase and sucrase‐isomaltase activity and H2O2‐induced membrane lipid peroxidation were tested. We found that, compared to control conditions, the acetonic extract significantly increased lactase and sucrase‐isomaltase activity in Caco‐2, but not HT‐29, cells, decreased proliferation, had no effects on viability and restored lipid peroxidation in both cell models. This study suggests that the acetonic extract improves lactase and sucrase‐isomaltase activity, inhibits cell proliferation, have no cytotoxic effects and prevent lipid peroxidation of intestinal epithelial cells. These effects may be exploited in case of disaccharidases deficit and also as an adjuvant treatment of diseases related to oxidative stress. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • A review of Neuropharmacology Effects of Nigella sativa and Its Main
           Component, Thymoquinone
    • Abstract: Neuropharmacology is the scientific study of drug effect on nervous system. In the last few years, different natural plants and their active constituents have been used in neurological therapy. The availability, lower price, and less toxic effects of herbal medicines compared with synthetic agents make them as simple and excellent choice in the treatment of nervous diseases. Nigella sativa, which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. In traditional and modern medicines several beneficial properties have been attributed to N. sativa and its main component, thymoquinone (TQ). In this review, various studies in scientific databases regarding the neuropharmacological aspects of N. sativa and TQ have been introduced. Results of these studies showed that N. sativa and TQ have several properties including anticonvulsant, antidepressant, anxiolytic, anti‐ischemic, analgesic, antipsychotic, and memory enhancer. Furthermore, its protective effects against neurodegenerative diseases such as Alzheimer, Parkinson and multiple sclerosis have been discussed. Although there are many studies indicating the beneficial actions of this plant in nervous system, the number of research projects relating to the human reports is rare. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Flaxseed Supplementation in Metabolic Syndrome Management: A Pilot
           Randomized, Open‐labeled, Controlled Study
    • Abstract: The aim of this study was to evaluate the efficacy of flaxseed supplementation plus lifestyle modification in comparison with lifestyle modification alone in the management of metabolic syndrome (MetS). A randomized controlled clinical trial was conducted on 44 patients with MetS. Participants were assigned to receive either the lifestyle advice and 30‐g brown milled flaxseed daily or only the lifestyle advice as the control group. The percentage of individuals with MetS decreased from baseline by 50% and 82% in the control and intervention group, respectively. The reversion rate of central obesity was higher in the flaxseed group (36%) than control group (13%). Moreover, greater reduction in insulin resistance was observed in flaxseed group in comparison with control group (p 
       
  • Polyphenols from Artemisia annua L Inhibit Adhesion and EMT of Highly
           Metastatic Breast Cancer Cells MDA‐MB‐231
    • Abstract: Recent evidence suggests that polyphenolic compounds from plants have anti‐invasion and anti‐metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti‐metastatic effects of pKAL on the highly metastatic MDA‐MB‐231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial‐mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA‐MB‐231 cells in a dose‐dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA‐MB‐231 cells to ECs through reducing vascular cell adhesion molecule‐1 expression of MDA‐MB‐231 and ECs, but not intracellular adhesion molecule‐1 at the concentrations where pKAL did not influence the cell viability of either MDA‐MB‐231 cells nor EC. Further, pKAL inhibited tumor necrosis factor‐activated MDA‐MB‐231 breast cancer cell invasion through inhibition of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule‐1 and invasion through suppression of EMT. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Dietary Supplementation of Ginger and Turmeric Rhizomes Modulates
           Platelets Ectonucleotidase and Adenosine Deaminase Activities in
           Normotensive and Hypertensive Rats
    • Abstract: Hypertension is associated with platelet alterations that could contribute to the development of cardiovascular complications. Several studies have reported antiplatelet aggregation properties of ginger (Zingiber officinale) and turmeric (Curcuma longa) with limited scientific basis. Hence, this study assessed the effect of dietary supplementation of these rhizomes on platelet ectonucleotidase and adenosine deaminase (ADA) activities in Nω‐nitro‐l‐arginine methyl ester hydrochloride (l‐NAME) induced hypertensive rats. Animals were divided into seven groups (n = 10): normotensive control rats; induced (l‐NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre‐treatment, the animals were induced with hypertension by oral administration of l‐NAME (40 mg/kg/day). The results revealed a significant (p 
       
  • Bioavailability of Bioactive Molecules from Olive Leaf Extracts and its
           Functional Value
    • Abstract: Olive leaves are an important low‐cost source of bioactive compounds. The present study aimed to examine the effect of in vitro digestibility of an olive leaf aqueous extract so as to prove the availability of its phenolic compounds as well as its antioxidant, antimicrobial, and anticancer activity after a simulated digestion process. The total phenolic content was significantly higher in the pure lyophilized extract. Phenolic compounds, however, decreased by 60% and 90% in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), respectively. Regarding antioxidant activity, it was reduced by 10% and 50% after gastric and intestinal digestion, respectively; despite this fact, high antioxidant capacity was found in both SGF and SIF. Moreover, the olive leaf extract showed an unusual combined antimicrobial action at low concentration, which suggested their great potential as nutraceuticals, particularly as a source of phenolic compounds. Finally, olive leaf extracts produced a general dose‐dependent cytotoxic effect against U937 cells. To sum up, these findings suggest that the olive leaf aqueous extract maintains its beneficial properties after a simulated digestion process, and therefore its regular consumption could be helpful in the management and the prevention of oxidative stress‐related chronic disease, bacterial infection, or even cancer.
       
  • Inhibitory Effects of the Standardized Extract of Phyllanthus amarus on
           Cellular and Humoral Immune Responses in Balb/C Mice
    • Abstract: Phyllanthus amarus has been shown to have strong inhibitory effects on phagocytic activity of human neutrophils and on cellular immune responses in Wistar–Kyoto rats. In this study, we investigated the effects of daily treatment of standardized extract of P. amarus at 50, 100 and 200 mg/kg for 14 days in Balb/C mice by measuring the myeloperoxidase activity (MPO), nitric oxide (NO) release, macrophage phagocytosis, swelling of footpad in delayed type hypersensitivity (DTH), and serum immunoglobulins, ceruloplasmin and lysozyme levels. Qualitative and quantitative analyses of the extract using validated reversed‐phase HPLC methods identified phyllanthin, hypophyllanthin, corilagin and geraniin as the biomarkers. Significant dose‐dependent inhibitions of MPO activity and NO release were observed in treated mice. The extract also inhibited E. coli phagocytic capacity of peritoneal macrophages of treated mice and inhibited the sheep red blood cells (sRBC)‐induced swelling rate of mice paw in the DTH. There was also a significant decrease in non‐specific humoral immunity including ceruloplasmin and lysozyme levels in the extract‐fed groups as well as the release of serum level immunoglobulins. The strong inhibitory effects of the extract on the cellular and humoral immune responses suggest the potential of the plant to be developed as an effective immunosuppressive agent.
       
  • Inhibition of UDP‐Glucuronosyltransferase (UGT) Isoforms by Arctiin
           and Arctigenin
    • Abstract: Arctiin is the major pharmacological ingredient of Fructus Arctii, and arctigenin is the metabolite of arctiin formed via the catalysis of human intestinal bacteria. The present study aims to investigate the inhibition profile of arctiin and arctigenin on important phase II drug‐metabolizing enzymes UDP‐glucuronosyltransferases (UGTs), indicating the possible herb–drug interaction. In vitro screening experiment showed that 100 μM of arctiin and arctigenin inhibited the activity of UGT1A3, 1A9, 2B7, and 2B15. Homology modeling‐based in silico docking of arctiin and arctigenin into the activity cavity of UGT2B15 showed that hydrogen bonds and hydrophobic interactions contributed to the strong binding free energy of arctiin (−8.14 kcal/mol) and arctigenin (−8.43 kcal/mol) with UGT2B15. Inhibition kinetics study showed that arctiin and arctigenin exerted competitive and noncompetitive inhibition toward UGT2B15, respectively. The inhibition kinetic parameters (Ki) were calculated to be 16.0 and 76.7 μM for the inhibition of UGT2B15 by arctiin and arctigenin, respectively. Based on the plasma concentration of arctiin and arctigenin after administration of 100 mg/kg of arctiin, the [I]/Ki values were calculated to be 0.3 and 0.007 for arctiin and arctigenin, respectively. Based on the inhibition evaluation standard ([I]/Ki 
       
  • Adjuvant Treatment with Yupingfeng Formula for Recurrent Respiratory Tract
           Infections in Children: A Meta‐analysis of Randomized Controlled
           Trials
    • Abstract: This meta‐analysis aimed to evaluate the immunomodulating function of Yupingfeng Formula (YPFF) in children with recurrent respiratory tract infections (RRTIs). The PubMed, EMBASE, Cochrane Library, CNKI and WanFang databases were searched for randomized controlled trials comparing with and without YPFF for RRTIs in children. Twelve trials with 1236 patients were identified. Adjuvant treatment with YPFF significantly increased serum levels of IgA (weighted mean difference [WMD] 0.33 mg/mL; 95% confidence interval [CI] 0.20 to 0.45), IgG (WMD 1.36 mg/mL; 95% CI 1.06 to 1.65), IgM (WMD 0.16 mg/mL; 95% CI 0.02 to 0.31), and CD3+ T‐lymphocytes (WMD 10.16%; 95% CI 4.62 to 15.69) but not CD4+ T‐lymphocytes (WMD 3.16%; 95% CI −0.27 to 6.59) and CD8+ T‐lymphocytes (WMD −0.84%; 95% CI −2.50 to 0.81). YPFF also reduced the frequency of RRTIs (WMD −3.80 times; 95% CI −4.86 to −2.74) and increased total effective rates of symptom improvement (risk ratio: 1.44; 95% CI 1.19 to 1.75). Adjuvant treatment with YPFF could improve total clinical effective rate and decrease the frequency of respiratory tract infections in children with RRTIs. The beneficial effects of YPFF may be correlated to its immunomodulating action. More well‐designed trials with larger sample sizes are needed to evaluate its efficacy and safety.
       
  • (‐)‐Hydroxycitric Acid Nourishes Protein Synthesis via
           Altering Metabolic Directions of Amino Acids in Male Rats
    • Abstract: (‐)‐Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress body weight gain and fat accumulation in animals and humans. While, the underlying mechanism of (‐)‐HCA has not fully understood. Thus, this study was aimed to investigate the effects of long‐term supplement with (‐)‐HCA on body weight gain and variances of amino acid content in rats. Results showed that (‐)‐HCA treatment reduced body weight gain and increased feed conversion ratio in rats. The content of hepatic glycogen, muscle glycogen, and serum T4, T3, insulin, and Leptin were increased in (‐)‐HCA treatment groups. Protein content in liver and muscle were significantly increased in (‐)‐HCA treatment groups. Amino acid profile analysis indicated that most of amino acid contents in serum and liver, especially aromatic amino acid and branched amino acid, were higher in (‐)‐HCA treatment groups. However, most of the amino acid contents in muscle, especially aromatic amino acid and branched amino acid, were reduced in (‐)‐HCA treatment groups. These results indicated that (‐)‐HCA treatment could reduce body weight gain through promoting energy expenditure via regulation of thyroid hormone levels. In addition, (‐)‐HCA treatment could promote protein synthesis by altering the metabolic directions of amino acids.
       
 
 
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