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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  [1597 journals]
  • Effects of Ginkgo Biloba Extract EGb‐761 on Neuropathic Pain in Mice:
           Involvement of Opioid System
    • Abstract: Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb‐761 is extracted from leaves of Ginkgo biloba and has analgesia and anti‐inflammatory properties. This study aimed to examine the effect of EGb‐761 on chronic constriction injury (CCI)‐induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb‐761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu‐opioid receptor expression were measured. Results showed that EGb‐761 attenuated thermal hyperalgesia and mechanical allodynia dose‐dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb‐761 treatment significantly decreased pro‐inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb‐761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb‐761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb‐761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb‐761‐induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-25T04:21:40.643989-05:
      DOI: 10.1002/ptr.5685
  • Bacopa monnieri‐Induced Protective Autophagy Inhibits
           Benzo[a]pyrene‐Mediated Apoptosis
    • Authors: Durgesh Nandini Das; Prajna Paramita Naik, Aditi Nayak, Prashanta Kumar Panda, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
      Abstract: Benzo[a]pyrene (B[a]P) is capable of inducing oxidative stress and cellular injuries leading to cell death and associates with a significant risk of cancer development. Prevention of B[a]P‐induced cellular toxicity with herbal compound through regulation of mitochondrial oxidative stress might protect cell death and have therapeutic benefit to human health. In this study, we demonstrated the cytoprotective role of Bacopa monnieri (BM) against B[a]P‐induced apoptosis through autophagy induction. Pretreatment with BM rescued the reduction in cell viability in B[a]P‐treated human keratinocytes (HaCaT) cells indicating the cytoprotective potential of BM against B[a]P. Moreover, BM was found to inhibit B[a]P‐mediated reactive oxygen species (ROS)‐induced apoptosis activation in HaCaT cells. Furthermore, BM was found to preserve mitochondrial membrane potential and inhibited release of cytochrome c in B[a]P‐treated HaCaT cells. Bacopa monnieri induced protective autophagy; we knocked down Beclin‐1, and data showed that BM was unable to protect from B[a]P‐induced mitochondrial ROS‐mediated apoptosis in Beclin‐1‐deficient HaCaT cells. Moreover, we established that B[a]P‐induced damaged mitochondria were found to colocalize and degraded within autolysosomes in order to protect HaCaT cells from mitochondrial injury. In conclusion, B[a]P‐induced apoptosis was rescued by BM treatment and provided cytoprotection through Beclin‐1‐dependent autophagy activation. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-19T03:05:30.026777-05:
      DOI: 10.1002/ptr.5682
  • The Water Fraction of Calendula officinalis Hydroethanol Extract
           Stimulates In Vitro and In Vivo Proliferation of Dermal Fibroblasts in
           Wound Healing
    • Authors: Manikarna Dinda; Swagata Mazumdar, Saurabh Das, Durba Ganguly, Uma B Dasgupta, Ananya Dutta, Kuladip Jana, Parimal Karmakar
      Abstract: The active fraction and/or compounds of Calendula officinalis responsible for wound healing are not known yet. In this work we studied the molecular target of C. officinalis hydroethanol extract (CEE) and its active fraction (water fraction of hydroethanol extract, WCEE) on primary human dermal fibroblasts (HDF). In vivo, CEE or WCEE were topically applied on excisional wounds of BALB/c mice and the rate of wound contraction and immunohistological studies were carried out. We found that CEE and only its WCEE significantly stimulated the proliferation as well as the migration of HDF cells. Also they up‐regulate the expression of connective tissue growth factor (CTGF) and α‐smooth muscle actin (α‐SMA) in vitro. In vivo, CEE or WCEE treated mice groups showed faster wound healing and increased expression of CTGF and α‐SMA compared to placebo control group. The increased expression of both the proteins during granulation phase of wound repair demonstrated the potential role of C. officinalis in wound healing. In addition, HPLC‐ESI MS analysis of the active water fraction revealed the presence of two major compounds, rutin and quercetin‐3‐O‐glucoside. Thus, our results showed that C. officinalis potentiated wound healing by stimulating the expression of CTGF and α‐SMA and further we identified active compounds. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-18T00:23:03.974563-05:
      DOI: 10.1002/ptr.5678
  • Chinese Herbal Medicine for Mild Cognitive Impairment: A Systematic Review
           and Meta‐Analysis of Cognitive Outcomes
    • Authors: Lin Dong; Brian H May, Mei Feng, Anna J Hyde, Hsiewe Ying Tan, Xinfeng Guo, Anthony Lin Zhang, Chuanjian Lu, Charlie Changli Xue
      Abstract: Mild cognitive impairment (MCI) is a condition that may be prodromal to the development of dementia. There remain, as yet, no approved pharmaceutical interventions for MCI. Chinese herbal medicines (CHMs) have a long history of use for cognitive impairments and some plant ingredients have shown neuroprotective actions in experimental studies. This review assesses the current clinical evidence from controlled clinical trials for the effects of CHMs on cognitive outcomes as measured by Mini‐mental state examination (MMSE) or Alzheimer's Disease Assessment Scale‐Cognitive subscale (ADAS‐Cog). Fifty one studies (4026 participants) were included. These compared CHM with placebo, supportive care, pharmaceutical treatment or combined CHM with a pharmaceutical in an integrative setting. For the eight randomised controlled trials (RCTs) of comparisons with placebo, MMSE was significantly higher in the CHM groups (MD 1.56 [0.78, 2.34] I2 = 85%, n = 503), similarly for eight RCTs of comparisons with supportive care (MD 1.77 [1.33, 2.21] I2 = 0%, n = 555). Benefits were also evident in comparisons with some pharmaceuticals and with integrative treatment. The small size of most studies and methodological weaknesses mean that these results should be interpreted with caution. Further studies employing rigorous methods are required to investigate the potential benefits of these CHMs for MCI. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-14T23:05:27.009143-05:
      DOI: 10.1002/ptr.5679
  • Pharmacological Effects of Capparis spinosa L.
    • Authors: Seyed Fazel Nabavi; Filippo Maggi, Maria Daglia, Solomon Habtemariam, Luca Rastrelli, Seyed Mohammad Nabavi
      Abstract: Medicinal plants have been known as one of the most important therapeutic agents since ancient times. During the last two decades, much attention has been paid to the health‐promoting effects of edible medicinal plants, because of multiple beneficial effects and negligible adverse effects. Capparis spinosa L. is one of the most common medicinal plants, used widely in different parts of the world to treat numerous human diseases. This paper aims to critically review the available scientific literature regarding the health‐promoting effects of C. spinosa, its traditional uses, cultivation protocols and phytochemical constituents. Recently, a wide range of evidence has shown that this plant possesses different biological effects, including antioxidant, anticancer and antibacterial effects. Phytochemical analysis shows that C. spinosa has high quantities of bioactive constituents, including polyphenolic compounds, which are responsible for its health‐promoting effects, although many of these substances are present in low concentrations and significant changes in their content occur during processing. In addition, there is negligible scientific evidence regarding any adverse effects. Different health promotion activities, as well as tremendous diversity of active constituents, make C. spinosa a good candidate for discovering new drugs. However these findings are still in its infancy and future experimental and clinical studies are needed. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-13T02:41:06.524886-05:
      DOI: 10.1002/ptr.5684
  • Fucoxanthin Suppresses Lipid Accumulation and ROS Production During
           Differentiation in 3T3‐L1 Adipocytes
    • Abstract: Fucoxanthin, a pigment from the chloroplasts of marine brown algae, has a number of effects against obesity, diabetes, inflammation and cancer and provides cerebrovascular protection. In this study, we investigated the inhibitory effects of fucoxanthin on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis. Treatment with fucoxanthin suppresses protein levels of the adipogenic transcription factors CCAAT/enhancer‐binding protein alpha C/EBPα and peroxisome proliferator‐activated receptor‐γ and of their target protein, fatty acid binding protein 4. Lipogenesis‐related enzymes, such as diglyceride acyltransferase 1 and lysophosphatidic acid acyltransferase‐θ, were downregulated by fucoxanthin. The ROS‐producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and the NADPH‐generating enzyme glucose‐6‐phosphate dehydrogenase also decreased following fucoxanthin treatment. The adipokine adiponectin and the ROS‐scavenging enzymes superoxide dismutase 2, glutathione reductase and catalase were dose‐dependently increased by fucoxanthin. Furthermore, lipolysis‐related enzymes and superoxide dismutase 1 were slightly decreased, because of the suppression of lipid‐generating factors and the cytosolic enzyme NOX4. To confirm these results, we investigated lipid accumulation and ROS production in zebrafish, where fucoxanthin suppressed lipid and triglyceride accumulation, as well as ROS production. Our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic and lipogenic factors and ROS‐regulating enzymes. We provide evidence that fucoxanthin suppresses protein levels of the adipogenic transcription factors and lipogenesis‐associated enzymes in 3T3‐L1. The reactive oxygen species (ROS) producing enzyme NOX4 and the nicotinamide adenine dinucleotide phosphate‐generating enzyme glucose‐6‐phosphate dehydrogenase is also decreased in 3T3‐L1 treated with fucoxanthin. Moreover, fucoxanthin inhibits the accumulation of intracellular lipid and the production of ROS in high‐fat diet‐induced obese zebrafish model. Therefore, our data suggest that fucoxanthin inhibits lipid accumulation and ROS production by controlling adipogenic factors and ROS‐regulating enzymes in vitro and in vivo.
      PubDate: 2016-07-13T01:40:42.111458-05:
      DOI: 10.1002/ptr.5683
  • A Novel Extract of Fenugreek Husk (FenuSMART™) Alleviates Postmenopausal
           Symptoms and Helps to Establish the Hormonal Balance: A Randomized,
           Double‐Blind, Placebo‐Controlled Study
    • Authors: S. Shamshad Begum; H. K. Jayalakshmi, H. G. Vidyavathi, G. Gopakumar, Issac Abin, Maliakel Balu, K. Geetha, S. V. Suresha, M. Vasundhara, I. M. Krishnakumar
      Abstract: Despite the widespread use of hormone replacement therapy, various reports on its side effects have generated an increasing interest in the development of safe natural agents for the management of postmenopausal discomforts. The present randomized, double‐blinded, placebo‐controlled study investigated the effect of 90‐day supplementation of a standardized extract of fenugreek (Trigonella foenum‐graecum) (FenuSMART™), at a dose of 1000 mg/day, on plasma estrogens and postmenopausal discomforts. Eighty‐eight women having moderate to severe postmenopausal discomforts and poor quality of life (as evidenced from the scores of Greene Climacteric Scale, short form SF‐36® and structured medical interview) were randomized either to extract‐treated (n = 44) or placebo (n = 44) groups. There was a significant (p 
      PubDate: 2016-07-13T01:20:33.41771-05:0
      DOI: 10.1002/ptr.5680
  • Herbal Medicines in Idiopathic Heavy Menstrual Bleeding: A Systematic
    • Abstract: Idiopathic heavy menstrual bleeding (HMB; IHMB) is a common gynecological problem with no pelvic pathology or general bleeding disorder. Herbal remedies are commonly used to treat HMB. This systematic review aimed to assess the effectiveness and safety of herbal preparations for the treatment of IHMB. MEDLINE, Ovid, and the Cochrane Central Register of Controlled Trials were searched from inception to 23 August 2015. Only randomized controlled trials were considered. Three randomized controlled trials were included in this systematic review. Different herbal preparations were used in the included trials. In two studies, Ginger capsules and myrtle fruit syrup significantly reduced the menstrual duration and blood loss compared with placebo based on the pictorial blood loss assessment chart score (p 
      PubDate: 2016-07-10T22:05:22.095835-05:
      DOI: 10.1002/ptr.5675
  • Astragaloside I Stimulates Osteoblast Differentiation Through the
           Wnt/β‐catenin Signaling Pathway
    • Authors: Xun Cheng; Biaofang Wei, Lijuan Sun, Xiaofang Hu, Jichao Liang, Yong Chen
      Abstract: Astragaloside I (As‐I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As‐I‐induced osteogenic effects and its underlying mechanism were studied in MC3T3‐E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose‐dependent manner by As‐I. To clarify the mechanisms involved in this process, the effect of As‐I on the key osteogenic‐related genes was investigated. We found that As‐I stimulated the expression of β‐catenin and Runx2 in MC3T3‐E1 cells, which play central roles in the Wnt/β‐catenin signaling pathway, suggesting that As‐I could promote osteoblastic differentiation by regulating the Wnt/β‐catenin signaling pathway. Moreover, the osteogenic effect of As‐I could be inhibited by DKK‐1, which is the classical inhibitor of Wnt/β‐catenin‐signaling pathway. Furthermore, As‐I also increased BMP‐2, BGP and OPG/RANKL expression, which are also activated by Wnt/β‐catenin signaling pathway. Taken together, our findings show that As‐I stimulates osteoblast differentiation through the Wnt/β‐catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As‐I for pharmaceutical and medicinal applications such as treating bone disease. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-10T21:55:31.318051-05:
      DOI: 10.1002/ptr.5674
  • Drug Resistance Reversal Potential of Isoliquiritigenin and Liquiritigenin
           Isolated from Glycyrrhiza glabra Against Methicillin‐Resistant
           Staphylococcus aureus (MRSA)
    • Authors: Rashmi Gaur; Vivek Kumar Gupta, Pooja Singh, Anirban Pal, Mahendra Padurang Darokar, Rajendra Singh Bhakuni
      Abstract: Isoliquiritigenin (ISL) and liquiritigenin (LTG) are structurally related flavonoids found in a variety of plants. Discovery of novel antimicrobial combinations for combating methicillin‐resistant Staphylococcus aureus (MRSA) infections is of vital importance in the post‐antibiotic era. The present study was taken to explore the in vitro and in vivo combination effect of LTG and ISL with β‐lactam antibiotics (penicillin, ampicillin and oxacillin) against mec A‐containing strains of MRSA. Minimum inhibitory concentration (MIC) of both LTG and ISL exhibited significant anti‐MRSA activity (50–100 µg/mL) against clinical isolates of MRSA. The result of in vitro combination study showed that ISL significantly reduced MIC of β‐lactam antibiotics up to 16‐folds [∑ fractional inhibitory concentration (FIC) 0.312–0.5], while LTG reduced up to 8‐folds (∑FIC 0.372–0.5). Time kill kinetics at graded MIC combinations (ISL/LTG + β‐lactam) indicated 3.27–9.79‐fold and 2.59–3.48‐fold reduction in the growth of clinical isolates of S. aureus respectively. In S. aureus‐infected Swiss albino mice model, combination of ISL with oxacillin significantly (p 
      PubDate: 2016-07-08T01:10:31.050095-05:
      DOI: 10.1002/ptr.5677
  • Two Alkaloids from Bulbs of Lycoris sanguinea MAXIM. Suppress PEPCK
           Expression by Inhibiting the Phosphorylation of CREB
    • Authors: Young Sook Yun; Miki Tajima, Shigeru Takahashi, Yuji Takahashi, Mariko Umemura, Haruo Nakano, Hyun Sun Park, Hideshi Inoue
      Abstract: In the fasting state, gluconeogenesis is upregulated by glucagon. Glucagon stimulates cyclic adenosine monophosphate production, which induces the expression of key enzymes for gluconeogenesis, such as cytosolic phosphoenolpyruvate carboxykinase (PEPCK‐C), which are involved in gluconeogenesis through the protein kinase A/cAMP response element‐binding protein (CREB) pathway. Using a luciferase reporter gene assay, a methanol extract of the bulbs of Lycoris sanguinea MAXIM. var. kiushiana Makino was found to suppress cAMP‐enhanced PEPCK‐C promoter activity. In addition, two alkaloids, lycoricidine and lycoricidinol, in the extract were identified as active constituents. In forskolin‐stimulated human hepatoma cells, these alkaloids suppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated CREB and PEPCK mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress PEPCK‐C expression by inhibiting the phosphorylation of CREB and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. Lycoricidine and lycoricidinol, from methanol extract of Lycoris sanguineas uppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated cAMP response element‐binding protein and phosphoenolpyruvate carboxykinase mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress cytosolic phosphoenolpyruvate carboxykinase expression by inhibiting the phosphorylation of cAMP response element‐binding protein and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes.
      PubDate: 2016-07-08T01:10:23.881811-05:
      DOI: 10.1002/ptr.5676
  • Natural Products as Mechanism‐based Anticancer Agents: Sp
           Transcription Factors as Targets
    • Authors: Stephen Safe; Ravi Kasiappan
      Abstract: Naturally occurring anticancer agents and their derivatives act on multiple pathways to inhibit carcinogenesis and their inhibition of migration, invasion, growth, survival, and metastasis is associated with downregulation of genes associated with these responses. Several phytochemical‐derived anticancer drugs including curcumin, betulinic acid, phenethylisothiocyanate and celastrol, and many others induce reactive oxygen species, and their effects on gene regulation show some overlap in various cancer cell lines. We hypothesize that reactive oxygen species‐inducing anticancer agents and many other natural products target a common pathway in cancer cells, which initially involves downregulation of specificity protein 1 (Sp1), Sp3, and Sp4, which are highly expressed in tumors/cell lines derived from solid tumors. This hypothesis is supported by several published reports showing that a large number of phytochemical‐derived anticancer agents downregulate Sp1, Sp3, Sp4, and pro‐oncogenic Sp‐regulated genes involved in cell growth (cyclin D1 and growth factor receptors), survival (bcl‐2 and survivin), angiogenesis and migration (MMP‐9, vascular endothelial growth factor and its receptors), and inflammation (NF‐kB). The contribution of this pathway to the anticancer activity of drugs such as curcumin, celastrol, betulinic acid, and phenethylisothiocyanate must be determined in order to optimize clinical applications of drug combinations containing these compounds. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-07T00:00:32.706912-05:
      DOI: 10.1002/ptr.5669
  • The Mechanisms of Pharmacological Activities of Ophiocordyceps sinensis
    • Abstract: The entomopathogenic fungus Ophiocordyceps sinensis, formerly known as Cordyceps sinensis, has long been used as a traditional Chinese medicine for the treatment of many illnesses. In recent years its usage has increased dramatically because of the improvement of people's living standard and the emphasis on health. Such demands have resulted in over‐harvesting of this fungus in the wild. Fortunately, scientists have demonstrated that artificially cultured and fermented mycelial products of O. sinensis have similar pharmacological activities to wild O. sinensis. The availability of laboratory cultures will likely to further expand its usage for the treatment of various illnesses. In this review, we summarize recent results on the pharmacological activities of the components of O. sinensis and their putative mechanisms of actions. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-03T22:15:39.274007-05:
      DOI: 10.1002/ptr.5673
  • The Suppressive Effects of the Petroleum Ether Fraction from Atractylodes
           lancea (Thunb.) DC. On a Collagen‐Induced Arthritis Model
    • Authors: Renping Liu; Enwei Tao, Shuwen Yu, Bo Liu, Lingman Dai, Liangyu Yu, Yifeng Xiong, Ruijun Fu, Lang Lei, Xiaoping Lai
      Abstract: In Chinese traditional medicine, the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) is used extensively for the treatment of several diseases such as rheumatic diseases, but its actions on rheumatoid arthritis have not been clarified. The purpose of this article was to investigate the pharmacological effect of an A. lancea rhizome extract on collagen‐induced arthritis (CIA) in rats. The CIA model was induced by the injection of bovine type II collagen. The rats were orally administered the petroleum ether (PE) fraction of the A. lancea rhizome (0.82 and 1.64 mg/kg), methotrexate (0.3 mg/kg body weight), or a vehicle from day 7 to day 15 after the model was established. The histological examination and radiological observation showed that the PE fraction significantly reduced the inflammatory responses and collagen loss in the joints of the rats with CIA. The PE fraction inhibited the production of tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐17, and IL‐6 in the sera. Moreover, the treatment with the PE fraction in vivo was able to reduce the level of Beclin 1 protein in the synovial tissue of the rats. These results highlight the antiarthritic potential of the PE fraction of the A. lancea rhizome and provide further evidence of the involvement of Beclin 1 inhibition in the effects of the PE fraction of the A. lancea rhizome. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-03T22:00:45.478915-05:
      DOI: 10.1002/ptr.5671
  • The Impact of Cocoa Flavanols on Cardiovascular Health
    • Abstract: The aim of the study was to review the effect of cocoa flavanols on cardiovascular health, with emphasis on the doses ingested, and to analyze a range of cocoa products for content of these compounds. PubMed was searched from 2010 to locate systematic reviews (SR) on clinical effects of chocolate consumption. Thirteen SRs were identified and reviewed, and provided strong evidence that dark chocolate did not reduce blood pressure. The evidence was however strong for an association with increased flow‐mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Our analysis showed that cocoa products with around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure in specific individuals and/or if consumed over longer periods. Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, around 100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin) would need to be consumed. Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-01T01:05:34.664033-05:
      DOI: 10.1002/ptr.5665
  • Cytotoxicity of the Roots of Trillium govanianum Against Breast (MCF7),
           Liver (HepG2), Lung (A549) and Urinary Bladder (EJ138) Carcinoma Cells
    • Abstract: Trillium govanianum Wall. (Melanthiaceae alt. Trilliaceae), commonly known as ‘nag chhatri’ or ‘teen patra’, is a native species of the Himalayas. It is used in various traditional medicines containing both steroids and sex hormones. In folk medicine, the rhizomes of T. govanianum are used to treat boils, dysentery, inflammation, menstrual and sexual disorders, as an antiseptic and in wound healing. With the only exception of the recent report on the isolation of a new steroidal saponin, govanoside A, together with three known steroidal compounds with antifungal property from this plant, there has been no systematic pharmacological and phytochemical work performed on T. govanianum. This paper reports, for the first time, on the cytotoxicity of the methanol extract of the roots of T. govanianum and its solid‐phase extraction (SPE) fractions against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549) and urinary bladder (EJ138), using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazoliumbromide cytotoxicity assay and liquid chromatography and electrospray ionization quadrupole time‐of‐flight mass spectrometry analysis of the SPE fractions. The methanol extract and all SPE fractions exhibited considerable levels of cytotoxicity against all cell lines, with the IC50 values ranging between 5 and 16 µg/mL. Like other Trillium species, presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography mass spectrometry data. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-01T00:33:46.384019-05:
      DOI: 10.1002/ptr.5672
  • Long‐term Treatment with Hesperidin Improves Endothelium‐dependent
           Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The
           Involvement of NO‐synthase and Kv Channels
    • Abstract: Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO‐synthase and Kv channels. The 15‐week‐old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO‐synthase with l‐NNA and Kv channels with 4‐AP. Hesperidin had no effect on blood pressure. Endothelium‐dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l‐NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of Kv channels significantly reduced endothelium‐dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium‐dependent vasodilation during hypertension, possibly through the enhancement of Kv channels function. Copyright © 2016 John Wiley & Sons, Ltd.
      PubDate: 2016-07-01T00:20:31.691955-05:
      DOI: 10.1002/ptr.5670
  • Puerarin Exerts an Antiinflammatory Effect by Inhibiting NF‐kB and MAPK
           Activation in Staphylococcus aureus‐Induced Mastitis
    • Authors: Haichong Wu; Gan Zhao, Kangfeng Jiang, Xiuying Chen, Zhe Zhu, Changwei Qiu, Ganzhen Deng
      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.
      PubDate: 2016-06-23T00:10:42.68498-05:0
      DOI: 10.1002/ptr.5666
  • 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.
      PubDate: 2016-06-22T23:50:29.20477-05:0
      DOI: 10.1002/ptr.5656
  • Non‐alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids
    • Authors: Masoumeh Akhlaghi
      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.
      PubDate: 2016-06-16T03:40:44.275079-05:
      DOI: 10.1002/ptr.5667
  • 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.
      PubDate: 2016-06-16T01:00:38.071206-05:
      DOI: 10.1002/ptr.5652
  • 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.
      PubDate: 2016-06-10T02:35:26.487951-05:
      DOI: 10.1002/ptr.5649
  • Phytochemical and Pharmacological Investigations on Nymphoides indica Leaf
    • Authors: Adnan Amin; Emmy Tuenter, Vassiliki Exarchou, Atul Upadhyay, Paul Cos, Louis Maes, Sandra Apers, Luc Pieters
      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.
      PubDate: 2016-06-10T01:41:55.848659-05:
      DOI: 10.1002/ptr.5663
  • 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 
      PubDate: 2016-06-09T03:27:04.349038-05:
      DOI: 10.1002/ptr.5664
  • 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 
      PubDate: 2016-06-09T02:42:39.563578-05:
      DOI: 10.1002/ptr.5638
  • A Pharmacological Review of Bioactive Constituents of Paeonia lactiflora
           Pallas and Paeonia veitchii Lynch
    • Authors: Shefton Parker; Brian May, Claire Zhang, Anthony Lin Zhang, Chuanjian Lu, Charlie Changli Xue
      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.
      PubDate: 2016-06-09T01:30:39.877702-05:
      DOI: 10.1002/ptr.5653
  • 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.
      PubDate: 2016-06-08T02:41:18.570787-05:
      DOI: 10.1002/ptr.5661
  • 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 
      PubDate: 2016-06-08T02:12:13.21705-05:0
      DOI: 10.1002/ptr.5660
  • Treatment of Non‐alcoholic Fatty Liver Disease with Curcumin: A
           Randomized Placebo‐controlled Trial
    • Authors: Sepideh Rahmani; Sedigheh Asgary, Gholamreza Askari, Mahtab Keshvari, Mahdi Hatamipour, Awat Feizi, Amirhossein Sahebkar
      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.
      PubDate: 2016-06-08T01:55:32.1084-05:00
      DOI: 10.1002/ptr.5659
  • Nimbolide Inhibits Nuclear Factor‐КB Pathway in Intestinal Epithelial
           Cells and Macrophages and Alleviates Experimental Colitis in Mice
    • Authors: Ji Yeon Seo; Changhyun Lee, Sung Wook Hwang, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
      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.
      PubDate: 2016-06-08T01:33:10.135206-05:
      DOI: 10.1002/ptr.5657
  • 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.
      PubDate: 2016-06-07T01:48:43.397825-05:
      DOI: 10.1002/ptr.5662
  • Oxidative Inactivation of Liver Mitochondria in High Fructose
           Diet‐Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin
    • Authors: Rajarshi Sil; Abhay Sankar Chakraborti
      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.
      PubDate: 2016-06-03T03:55:46.172032-05:
      DOI: 10.1002/ptr.5654
  • Prooxidant Activity of Polyphenols, Flavonoids, Anthocyanins and
           Carotenoids: Updated Review of Mechanisms and Catalyzing Metals
    • Authors: Samira Eghbaliferiz; Mehrdad Iranshahi
      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'
      PubDate: 2016-05-30T21:45:45.352016-05:
      DOI: 10.1002/ptr.5643
  • An Hydroalcoholic Chamomile Extract Modulates Inflammatory and Immune
           Response in HT29 Cells and Isolated Rat Colon
    • Authors: Luigi Menghini; Claudio Ferrante, Lidia Leporini, Lucia Recinella, Annalisa Chiavaroli, Sheila Leone, Giorgio Pintore, Michele Vacca, Giustino Orlando, Luigi Brunetti
      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.
      PubDate: 2016-05-30T00:05:49.572116-05:
      DOI: 10.1002/ptr.5655
  • 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.
      PubDate: 2016-05-27T01:35:46.479774-05:
      DOI: 10.1002/ptr.5658
  • 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.
      PubDate: 2016-05-27T01:20:34.448534-05:
      DOI: 10.1002/ptr.5641
  • Chemistry, Pharmacology and Health Benefits of Anthocyanins
    • Authors: Antonella Smeriglio; Davide Barreca, Ersilia Bellocco, Domenico Trombetta
      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.
      PubDate: 2016-05-25T02:45:36.050978-05:
      DOI: 10.1002/ptr.5642
  • Antenatal Saireito (TJ‐114) Can Improve Pulmonary Hypoplasia and
           Pulmonary Vascular Remodeling in Nitrofen‐Induced Congenital
           Diaphragmatic Hernia
    • Authors: Shima Hirako; Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Tomoko Nakano, Kenji Imai, Hua Li, Shinya Toyokuni, Fumitaka Kikkawa
      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 
      PubDate: 2016-05-25T02:25:50.763762-05:
      DOI: 10.1002/ptr.5645
  • Anti‐infective potential of Citrus bergamia Risso et Poiteau (bergamot)
           derivatives: a systematic review
    • Authors: Santa Cirmi; Carlo Bisignano, Giuseppina Mandalari, Michele Navarra
      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.
      PubDate: 2016-05-24T02:15:42.993636-05:
      DOI: 10.1002/ptr.5646
  • Therapeutic Potential of Polyphenols from Epilobium Angustifolium
    • Authors: Igor A. Schepetkin; Andrew G. Ramstead, Liliya N. Kirpotina, Jovanka M. Voyich, Mark A. Jutila, Mark T. Quinn
      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.
      PubDate: 2016-05-24T01:10:59.406761-05:
      DOI: 10.1002/ptr.5648
  • 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.
      PubDate: 2016-05-24T00:20:28.927259-05:
      DOI: 10.1002/ptr.5650
  • Effects of Turmeric (Curcuma longa) on Skin Health: A Systematic Review of
           the Clinical Evidence
    • Authors: Alexandra R. Vaughn; Amy Branum, Raja K. Sivamani
      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.
      PubDate: 2016-05-23T04:26:12.582937-05:
      DOI: 10.1002/ptr.5640
  • The Chemistry and Biological Activities of Mimosine: A Review
    • Authors: Binh Cao Quan Nguyen; Shinkichi Tawata
      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.
      PubDate: 2016-05-23T04:15:55.885526-05:
      DOI: 10.1002/ptr.5636
  • 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.
      PubDate: 2016-05-18T05:31:13.411335-05:
      DOI: 10.1002/ptr.5651
  • Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics
    • Authors: Xiaoxv Dong; Jing Fu, Xingbin Yin, Sali Cao, Xuechun Li, Longfei Lin, , Jian Ni
      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.
      PubDate: 2016-05-18T05:01:09.138399-05:
      DOI: 10.1002/ptr.5631
  • A review of Neuropharmacology Effects of Nigella sativa and Its Main
           Component, Thymoquinone
    • Authors: Soheila Javidi; Bibi Marjan Razavi, Hossein Hosseinzadeh
      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.
      PubDate: 2016-05-11T22:47:33.098535-05:
      DOI: 10.1002/ptr.5634
  • The Effects of Pycnogenol® as Add‐on Drug to Metformin Therapy
           in Diabetic Rats
    • Authors: Stanislava Jankyova; Dominika Rubintova, Lenka Janosikova, Peter Panek, Tatiana Foltanova, Eva Kralova
      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.
      PubDate: 2016-05-11T22:35:27.472642-05:
      DOI: 10.1002/ptr.5639
  • Acetonic Extract from the Feijoa sellowiana Berg. Fruit Exerts Antioxidant
           Properties and Modulates Disaccharidases Activities in Human Intestinal
           Epithelial Cells
    • Authors: Fabio Turco; Ilaria Palumbo, Paolo Andreozzi, Giovanni Sarnelli, Francesca De Ruberto, Giuseppe Esposito, Adriana Basile, Rosario Cuomo
      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.
      PubDate: 2016-05-10T23:37:24.987-05:00
      DOI: 10.1002/ptr.5629
  • Flaxseed Supplementation in Metabolic Syndrome Management: A Pilot
           Randomized, Open‐labeled, Controlled Study
    • Authors: Zahra Yari; Mehran Rahimlou, Hossein Poustchi, Azita Hekmatdoost
      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 
      PubDate: 2016-05-06T00:40:24.633265-05:
      DOI: 10.1002/ptr.5635
  • (‐)‐Hydroxycitric Acid Nourishes Protein Synthesis via Altering
           Metabolic Directions of Amino Acids in Male Rats
    • Authors: Ningning Han; Longlong Li, Mengling Peng, Haitian Ma
      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.
      PubDate: 2016-05-04T01:56:05.827972-05:
      DOI: 10.1002/ptr.5630
  • Inhibitory Effects of the Standardized Extract of Phyllanthus amarus on
           Cellular and Humoral Immune Responses in Balb/C Mice
    • Authors: Menaga Ilangkovan; Ibrahim Jantan, Mohamed Ahmed Mesaik, Syed Nasir Abbas Bukhari
      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.
      PubDate: 2016-05-03T03:06:48.441358-05:
      DOI: 10.1002/ptr.5633
  • 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
  • Ramalin Isolated from Ramalina Terebrata Attenuates Atopic
           Dermatitis‐like Skin Lesions in Balb/c Mice and Cutaneous Immune
           Responses in Keratinocytes and Mast Cells
    • Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease that involves eczematous skin lesions with pruritic erythematous papules. In this study, we investigated the mitigating effects of ramalin, a component of the Antarctic lichen Ramalina terebrata against AD in vivo and in vitro. Oral administration of ramalin lessened scratching behaviors and significantly reduced both serum immunoglobulin E and IL‐4 levels, and mRNA levels of IL‐4 and IL‐10 in AD‐induced Balb/c mice. In vitro, treatment with ramalin produced significantly less inflammatory chemokines and cytokines, including TARC, MCP‐1, RANTES, and IL‐8 in TNF‐α‐stimulated HaCaT cells. In addition, ramalin inhibited the activation of nuclear factor‐kappa B as well as the phosphorylation of mitogen‐activated protein kinases (MAPK). Furthermore, ramalin treatment resulted in decreased production of β‐hexosaminidase and proinflammatory cytokines IL‐4, IL‐6, and TNF‐α in 2,4 dinitrophenyl‐human serum albumin‐stimulated RBL‐2H3 cells through blocking MAPK signaling pathways. The results suggest that ramalin modulates the production of immune mediators by inhibiting the nuclear factor‐kappa B and MAPK signaling pathways. Taken together, ramalin effectively attenuated the development of AD and promoted the mitigating effects on Th2 cell‐mediated immune responses and the production of inflammatory mediators in mast cells and keratinocytes. Thus, ramalin may be a potential therapeutic agent for AD. Copyright © 2016 John Wiley & Sons, Ltd.
  • Effect of Oral Silymarin Administration on Prevention of Radiotherapy
           Induced Mucositis: A Randomized, Double‐Blinded, Placebo‐Controlled
           Clinical Trial
    • Abstract: Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty‐seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute–Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p 
  • Cinnamaldehyde, Carvacrol and Organic Acids Affect Gene Expression of
           Selected Oxidative Stress and Inflammation Markers in IPEC‐J2 Cells
           Exposed to Salmonella typhimurium
    • Abstract: Essential oils and organic acids are used as feed additives to improve health status and reduce colonization with pathogens. Although bactericidal in vitro, concentrations achieved in the animal gut are probably not lethal to pathogens. The aim of this study was to investigate the effects of cinnamaldehyde, carvacrol and cinnamic, lactic and propionic acids on the ability of Salmonella typhimurium ATCC 14028 (ST) to invade intestinal epithelial cells (IPEC‐J2) and on the expression levels of immune related genes in the cells. The minimum inhibitory concentration (MIC) and non‐inhibitory concentration (NIC) were determined and influence on the invasion capacity of ST was investigated. The structure of fimbriae and flagella was analysed by electron microscopy, and expression levels of HSP70, IkBa, IL‐8 and IL‐10 in the IPEC‐J2 cells were carried out by q‐PCR. Cinnamaldehyde, carvacrol and cinnamic and propionic acids inhibited ST invasion but not cell viability, bacterial viability and motility or the development of flagella. Propionic acid and cinnamaldehyde in combination with cinnamic acid caused structural impairment of fimbriae. Cinnamaldehyde up‐regulated expression of HSP70 irrespective of the presence of organic acids or ST; exposure to carvacrol induced HSP70 only in the presence of propionic acid and ST. © 2016 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
  • Folic Acid and Grape Seed Extract Prevent Azathioprine‐induced Fetal
           Malformations and Renal Toxicity in Rats
    • Abstract: Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co‐administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co‐treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co‐administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA‐induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA‐induced oxidative renal damages. Copyright © 2016 John Wiley & Sons, Ltd.
  • Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during
           Alcohol Consumption: A Randomized, Double‐Blind, Placebo‐Controlled,
           Crossover Study
    • Abstract: Traditionally, licorice has been used to treat liver problems. Glycyrrhizin, the primary active compound, has been shown to suppress elevations in liver enzymes that occur when the liver becomes diseased or damaged. This randomized, double‐blind, placebo‐controlled, crossover study evaluated the hepatoprotective effects of a proprietary glycyrrhizin product during alcohol consumption. Twelve healthy individuals (six male and six female subjects) in a clinic setting consumed vodka nightly for 12 days with the glycyrrhizin product or placebo (blank control), achieving a blood alcohol level of 0.12%. Liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), and alkaline phosphatase and serum reduced glutathione were measured at overnight visits 1, 6, and 12. In the alcohol only group, AST, ALT, and GGT significantly increased from baseline (overnight visit 1) to overnight visit 12. In the active group, no statistically significant increases were observed for AST, ALT, and GGT, while alkaline phosphatase significantly decreased and plasma glutathione decreased relative to the alcohol control group. These results suggest that consumption of the proprietary glycyrrhizin study product during alcohol consumption may support improved liver health compared with drinking alcohol alone. Copyright © 2016 John Wiley & Sons, Ltd.
  • Overview of Oroxylin A: A Promising Flavonoid Compound
    • Abstract: Oroxylin A is one of the main active components extracted from Scutellariae radix. It has been proved that oroxylin A possesses a broad spectrum of pharmacological functions, including anti‐cancer, antiinflammation, neuroprotective, anti‐coagulation and so on. The pharmacological activity of oroxylin A has been studied in vitro and on animal models, which reflected its promising potency in disease treatment. This review aims to recapitulate the pharmacological function and the molecular mechanisms of oroxylin A, as well as its sources, extraction, synthesis and toxicity study. These data confirmed the therapeutic potential of oroxylin A and provided reference for further development. Copyright © 2016 John Wiley & Sons, Ltd.
  • Effect of the Capsicoside G‐rich Fraction from Pepper (Capsicum annuum
           L.) Seeds on High‐fat Diet‐induced Obesity in Mice
    • Abstract: Obesity is one of the most common metabolic syndromes and is a major threat to human health worldwide. Given the size of this problem, there is growing interest in natural agents that may decrease obesity. In this study, we investigated the anti‐obesity effect of a capsicoside G‐rich fraction (CRF; 13.35% capsicoside G) isolated from pepper seeds in diet‐induced obese mice. C57BL/6J mice were fed either a normal diet or a high‐fat diet (HFD), with or without CRF (HFD + CRF; 10 and 100 mg/kg body weight). The body weight and food efficiency ratio of mice fed HFD + CRF were lower in comparison to that of mice fed only an HFD. Epididymal adipose tissue weight and adipocyte hypertrophy were significantly lower in HFD + CRF mice than in HFD mice. The fat deposition in the liver of mice fed HFD + CRF was lower compared to that of mice fed only an HFD. CRF significantly reversed the HFD‐induced elevation of the expression of key adipocyte differentiation regulators, including peroxisome proliferator‐activated receptor γ, CCAAT/enhancer‐binding protein α, sterol regulatory element binding protein 1c, and their target genes. These results suggest that CRF could be used as dietary therapy for the prevention of obesity and obesity‐related metabolic diseases. Copyright © 2016 John Wiley & Sons, Ltd.
  • Inulin‐Type Oligosaccharides Extracted from Yacon Produce
           Antidepressant‐Like Effects in Behavioral Models of Depression
    • Abstract: Yacon (Smallanthus sonchifolius), a traditional food in the Andean diet, is attracting global attention for its medicinal properties, which are mainly because of its high content of non‐digestible oligosaccharides. The purpose of this study is to evaluate the antidepressant‐like effects of inulin‐type oligosaccharides extracted from yacon (YOs) in behavioral models of depression. Behavioral despair models in mice including the tail suspension test (TST) and the forced swimming test (FST) were used to determine the effects of acute YOs administration. The locomotor activity was also explored to eliminate any false‐positive activity. In addition, to further investigate the antidepressant‐like effects of subchronic YOs administration, the learned helplessness (LH) paradigm in rats was performed. The results demonstrated that YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reduced the immobility time in the mouse TST and FST in a U‐shaped, dose‐dependent manner, and showed no stimulatory effect on the locomotor activity. Furthermore, subchronic YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reversed the escape deficits in LH rats, including an increased number of escape failures and prolonged escape latency. These findings suggest that the inulin‐type oligosaccharides extracted from yacon may be a prospective natural source for antidepressants. Copyright © 2016 John Wiley & Sons, Ltd.
  • Berberis Vulgaris and Berberine: An Update Review
    • Abstract: Berberine is an isoquinoline alkaloid present in several plants, including Coptis sp. and Berberis sp. Berberine is a customary component in Chinese medicine, and is characterized by a diversity of pharmacological effects. An extensive search in electronic databases (PubMed, Scopus, Ovid, Wiley, ProQuest, ISI, and Science Direct) were used to identify the pharmacological and clinical studies on Berberis vulgaris and berberine, during 2008 to 2015, using ‘berberine’ and ‘Berberis vulgaris’ as search words. We found more than 1200 new article studying the properties and clinical uses of berberine and B. vulgaris, for treating tumor, diabetes, cardiovascular disease, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. In this article, we have updated the pharmacological effects of B. vulgaris and its active constituent, berberine. Copyright © 2016 John Wiley & Sons, Ltd.
  • Cytotoxic activity of Secondary Metabolites from Marine‐derived Fungus
           Neosartorya siamensis in Human Cancer Cells
    • Abstract: Compounds isolated from the marine sea fan‐derived fungus Neosartorya siamensis (KUFA 0017), namely, 2,4‐dihydroxy‐3‐methylacetophenon (1), chevalone C (2), nortryptoquivaline (4), tryptoquivaline H (6), tryptoquivaline F (7), fiscalin A (8), epi‐fiscalin A (9), epi‐neofiscalin A (11) and epi‐fiscalin C (13) were tested for anti‐proliferative activity by MTT assay, DNA damage induction by comet assay, and induction of cell death by nuclear condensation assay on colon HCT116, liver HepG2 and melanoma A375 cancer cell lines. Compounds 2, 4, 8, 9, 11 and 13 presented IC50 values ranging from 24 to 153 μM in the selected cell lines. Cell death was induced in HCT116 by compounds 2, 4 and 8. In HepG2, compounds 4, 8, 9 and 11 were able to induce significant cell death. This induction of cell death is possibly not related to genotoxicity because none of the compounds induced significant DNA damage. These results suggest that selected compounds present an interesting anti‐proliferative activity and cell death induction, consequently showing potential (specifically epi‐fiscalin C) as future leads for chemotherapeutic agents. Further studies on mechanisms of action should ensue. Copyright © 2016 John Wiley & Sons, Ltd.
  • Progress in the Development and Applicability of Potential Medicinal Plant
           Extract‐Conjugated Polymeric Constructs for Wound Healing and Tissue
    • Abstract: Wound, burn and tissue related diseases are the most common and devastating forms of trauma worldwide and thousands are still dying each year when they are left untreated. The traditional treatments for wound infection using medicinal plant extracts in hydrogels and ointment formulations have several disadvantages, delicate shape and dry up quickly upon exposure to air. Indeed, there is need for the development of an alternative form of dressing material for wound healing applications. Because the medicinal plant products are economical, researchers have adopted a novel approach of complexing the active components of plants with various groups of polymers to develop biodegradable fabrications. Moreover, fabricated constructs are very extremely useful as scaffold in tissue regeneration with known successes in wound healing/ dressing applications that the fabricated substitutes mimic the extracellular matrix of tissue. In this review, we give an extensive overview on scientifically evaluated bioactive molecules of medicinal plants as well as plant extract blended polymeric constructs for the possible treatment of various skin injuries. In addition, the technological challenges and future trends for recent developments of the treatments of wound infections are extensively summarized. Copyright © 2016 John Wiley & Sons, Ltd.
  • Plumbagin Enhances Tamoxifen Sensitivity and Inhibits Tumor Invasion in
           Endocrine Resistant Breast Cancer through EMT Regulation
    • Abstract: Tamoxifen is widely used as the first line drug for estrogen receptor‐positive subtype which is expressed in 70% of overall breast cancer patients. However, approximately 50% of these patients develop acquired resistance after 5 years of treatment, which is characterized by tumor recurrence and metastasis. The epithelial mesenchymal transition (EMT) is an important process in breast cancer invasion. Fundamentally, targeting the EMT represents a crucial therapeutic strategy for preventing or treating breast cancer metastasis. Plumbagin (PLB) is a natural naphthoquinone with significant anticancer effects against several types of tumor cells including breast cancer. In this study, we investigated the effect of PLB on human endocrine‐resistant breast cancer cell growth, invasion and the possible mechanisms underlying such actions. PLB exhibited potent cytotoxic activity at a micromolar concentration against endocrine‐resistant breast cancer cells. Interestingly, a fixed low concentration of PLB and tamoxifen combination resulted in an increase in growth inhibition in endocrine‐resistant cells. In addition, PLB also significantly suppressed mesenchymal biomarker expressions that govern the EMT process, resulting in attenuated metastatic capabilities. In conclusion, PLB should be developed as a pharmacological agent for the use as a single treatment or in combination for endocrine‐resistant breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
  • The Inhibition of UDP‐Glucuronosyltransferase (UGT) Isoforms by
           Praeruptorin A and B
    • Abstract: Praeruptorin A (PA) and B (PB) are two important compounds isolated from Bai‐hua Qian‐hu and have been reported to exert multiple biochemical and pharmacological activities. The present study aims to determine the inhibition of PA and PB on the activity of important phase II drug‐metabolizing enzymes uridine 5'‐diphospho‐glucuronosyltransferase (UGTs) isoforms. In vitro UGT incubation system was used to determine the inhibition potential of PA and PB on the activity of various UGT isoforms. In silico docking was performed to explain the inhibition difference between PA and PB towards the activity of UGT1A6. Inhibition behaviour was determined, and in vitro–in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (Ki) and in vivo exposure level of PA. Praeruptorin A (100 μM) exhibited the strongest inhibition on the activity of UGT1A6 and UGT2B7, with 97.8% and 90.1% activity inhibited by 100 μM of PA, respectively. In silico docking study indicates the significant contribution of hydrogen bond interaction towards the stronger inhibition of PA than PB towards UGT1A6. Praeruptorin A noncompetitively inhibited the activity of UGT1A6 and competitively inhibited the activity of UGT2B7. The inhibition kinetic parameter (Ki) of PA towards UGT1A6 and UGT2B7 was calculated to be 1.2 and 3.3 μM, respectively. The [I]/Ki value was calculated to be 15.8 and 5.8 for the inhibition of PA on UGT1A6 and UGT2B7, indicating high inhibition potential of PA towards these two UGT isoforms in vivo. Therefore, closely monitoring the interaction between PA and drugs mainly undergoing UGT1A6 or UGT2B7‐catalyzed metabolism is very necessary. Copyright © 2016 John Wiley & Sons, Ltd.
  • Flavonoids Isolated from Flowers of Lonicera japonica Thunb. Inhibit
           Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF‐α and
           IL‐β Through PI3K/Akt/NF‐kb Signaling Pathways
    • Abstract: Decoctions of the dried flowers of Lonicera japonica Thunb. (Indongcho) have been utilized in folk remedies against various inflammatory diseases, and it is reported neuroprotective effects. The cytokines release from microglia is closely linked to various chronic neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. It is still unknown whether the neuroprotective effects are associated with the antiinflammatory effects. Here, we determined whether polyphenols extracted from lyophilized Lonicera japonica Thunb. (PELJ) would inhibit inflammatory cytokines and mediators. We stimulated microglia with lipopolysaccharide (LPS) to produce inflammatory cytokines, and then assessed the effects of PELJ on these cytokines. PELJ significantly inhibited LPS‐induced interleukin‐1β and tumor necrosis factor‐α expressions and LPS‐induced nitric oxide (NO) and prostaglandin E2 expressions by down‐regulating inducible enzyme NO synthase and cyclooxygenase‐2 at the protein and mRNA levels. All the suppression of these mediators did not cause any significant cytotoxicity. PELJ also inhibited the nuclear translocation of nuclear factor‐kappa B and phosphorylated Akt. These findings suggest that PELJ may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases by inhibiting pro‐inflammatory cytokines through inhibiting phosphoinositol 3‐kinase /Akt/nuclear factor‐kappa B signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.
  • Magnolol Enhances Hippocampal Neurogenesis and Exerts
           Antidepressant‐Like Effects in Olfactory Bulbectomized Mice
    • Abstract: Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain‐derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin‐related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5‐bromo‐2′‐deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX‐induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein after 3 h. The present data indicate that magnolol exerts antidepressant‐like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin‐related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.
  • Aqueous and Ethanolic Extracts of Boswellia serrata Protect Against Focal
           Cerebral Ischemia and Reperfusion Injury in Rats
    • Abstract: Oxidative stress and cell apoptosis play major roles in neuronal injury after ischemia–reperfusion (I‐R) injury. Boswellia serrata is a medicinal plant with antioxidant properties. Acetyl‐11‐keto‐β‐boswellic acid (AKBA) is an active triterpenoid compound from B. serrate. In the current study, the neuroprotective effects of aqueous and ethanolic extracts of B. serrata (named ABS and EBS, respectively) and AKBA were investigated against middle cerebral artery occlusion‐induced cerebral I‐R injury in rats. ABS and EBS with doses of 125, 250 and 500 and AKBA with a dose of 50 mg/kg were administered (intraperitoneally) just after middle cerebral artery occlusion induction for 30 min and reperfusion for 24 h. HPLC analysis suggested that ABS and EBS had AKBA of 8.8% and 9.5% (w/w), respectively. B. serrata and AKBA significantly improved neurological deficit and reduced brain infarction, neuronal cell loss and apoptosis and also attenuated lipid peroxidation while increasing glutathione content and superoxide dismutase activity in the cerebral cortex following a stroke. Apoptosis suppression was found to be mediated through regulating caspase‐3 and bax/bcl‐2 expressions. In conclusion, our results demonstrated that B. serrata and AKBA attenuate oxidative damage and inhibit cell apoptosis, subsequently protecting cerebral I‐R injury in rats. Copyright © 2016 John Wiley & Sons, Ltd.
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  • Effect of Ginkgo Biloba Extract on the Pharmacokinetics and Metabolism of
           Clopidogrel in Rats
    • Abstract: Ginkgo biloba extract (GBE), a traditional herbal product used worldwide as both medicine and supplement, is often supplied with clopidogrel for the treatment of cerebrovascular diseases. The aim of the current study was to explore the effect of GBE on the metabolism and pharmacokinetics of clopidogrel. The in vitro study using rat liver microsomes revealed that GBE significantly induced the conversion of clopidogrel into its active metabolite. The effect of GBE on the pharmacokinetics of clopidogrel was also investigated in vivo. Compared to rats without GBE pretreatment, administration of 4 mg/kg, 20 mg/kg, and 100 mg/kg of GBE significantly decreased the Cmax and the AUC0–∞ of clopidogrel in a dose‐dependent manner. As expected, pretreatment of high dose GBE significantly increased the Cmax and AUC0–∞ of the clopidogrel active metabolite. However, no marked change was observed following medium and low dose of GBE, suggesting that the biotransformation of clopidogrel was altered differently by high dose of GBE. Our study suggested that the awareness of the potential herb–drug interactions between GBE and clopidogrel should be increased in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.
  • Obovatol Induces Apoptosis in Non‐small Cell Lung Cancer Cells via C/EBP
           Homologous Protein Activation
    • Abstract: Although obovatol, a phenolic compound from the bark of Magnolia obovata, was known to have antioxidant, neuroprotective, antiinflammatory, antithrombotic and antitumour effects, its underlying antitumour mechanism is poorly understood so far. Thus, in the present study, the antitumour molecular mechanism of obovatol was investigated in non‐small cell lung cancer cells (NSCLCs). Obovatol exerted cytotoxicity in A549 and H460 NSCLCs, but not in BEAS‐2B cells. Also, obovatol increased sub‐G1 accumulation and early and late apoptotic portion in A549 and H460 NSCLCs. Consistently, obovatol cleaved PARP, activated caspase 9/3 and Bax and attenuated the expression of cyclin D1 in A549 and H460 NSCLCs. Interestingly, obovatol upregulated the expression of endoplasmic reticulum stress proteins such as C/EBP homologous protein (CHOP), IRE1α, ATF4 and p‐elF2 in A549 and H460 NSCLCs. Conversely, depletion of CHOP blocked the apoptotic activity of obovatol to increase sub‐G1 accumulation in A549 and H460 NSCLCs. Overall, our findings support scientific evidences that obovatol induces apoptosis via CHOP activation in A549 and H460 NSCLCs. Copyright © 2016 John Wiley & Sons, Ltd.
  • Silibinin Inhibits Neutrophilic Inflammation and Mucus Secretion Induced
           by Cigarette Smoke via Suppression of ERK‐SP1 Pathway
    • Abstract: Silibinin, the main ingredient of silymarin, has been used as a traditional drug for over 2000 years to treat a range of liver diseases. Recent studies have also demonstrated that silibinin possesses antiinflammatory and anticancer properties. In the study, we researched the efficacy of silibinin on the development of COPD using a cigarette smoke (CS)‐induced and lipopolysaccharide (LPS)‐induced COPD model mice and stimulation of NCI‐H292 cells with CS condensate. Silibinin was administered to mice by oral gavage 1 h before CS exposure for 10 days. In in vitro experiment, we evaluated the effect of silibinin on the expression of MUC5AC in H292 cells stimulated with CS condensate. Furthermore, silibinin suppressed the CS and LPS treatment‐induced extracellular signal‐regulated kinase (ERK) phosphorylation and SP‐1 expression. Silibinin also decreased airway inflammation and reduced the expression of MUC5AC and myeloperoxidase. Furthermore, co‐treatment with silibinin and ERK inhibitors considerably decreased the levels of pro‐inflammatory mediators, ERK phosphorylation, and SP‐1 expression. Taken together, the results indicate that silibinin effectively suppressed the neutrophilic airway inflammation provoked by treatment with LPS and CS, which was closely associated with downregulation of ERK phosphorylation. Therefore, our searching offers that silibinin has a remedical probable for COPD disease. Copyright © 2016 John Wiley & Sons, Ltd.
  • Apigenin Inhibits Cancer Stem Cell‐Like Phenotypes in Human Glioblastoma
           Cells via Suppression of c‐Met Signaling
    • Abstract: Glioblastoma (GBM) is a highly malignant human brain tumor with limited treatment choices. The extremely aggressive characteristics of GBM result from GBM stem cells (GSCs), a subpopulation in tumor having self‐renewal potential and resistance to chemotherapy and radiotherapy. Therefore, eliminating GSCs is an effective strategy to treat this fatal disease. In this study, we investigated the therapeutic effects of dietary flavonoids, including apigenin, quercetin, and naringenin, against cancer stem cell‐like phenotypes of human GBM cell lines U87MG and U373MG. Among flavonoids studied, apigenin and quercetin significantly suppressed not only the self‐renewal capacity such as cell growth and clonogenicity, but also the invasiveness of GBM stem‐like cells. Notably, apigenin blocked the phosphorylation of c‐Met and its downstream effectors, transducer and activator of transcription 3, AKT (Protein kinase B), and mitogen‐activated protein kinase in the GSCs, thereby reducing the expression levels of GSC markers such as CD133, Nanog, and Sox2. These results suggest that the GSC inhibition effect of apigenin may be caused by downregulation of c‐Met signaling pathway.
  • In Vitro Assessment of Plants Growing in Cuba Belonging to Solanaceae
           Family Against Leishmania amazonensis
    • Abstract: In this study, an in vitro antileishmanial assessment of plant extracts from 12 genera and 46 species growing in Cuba belonging to Solanaceae family was performed. A total of 226 extracts were screened against promastigotes of Leishmania amazonensis, and cytotoxicity of active extracts [median inhibitory concentration (IC50) promastigotes 5 were then assayed against intracellular amastigote. Metabolomics analysis of promissory extracts was performed using chemical profile obtained by ultra performance liquid chromatography. Only 11 extracts (4.9%) from nine plants were selected as potentially actives: Brunfelsia cestroides A. Rich, Capsicum annuum L., Capsicum chinense Jacq., Cestrum nocturnum L., Nicotiana plumbaginifolia Viv., Solanum havanense Jacq., Solanum myriacanthum Dunal, Solanum nudum Dunal and Solanum seaforthianum And., with IC50 5. Metabolomics analysis demonstrated significant differences in the chemical profiles with an average of 42.8 (range 31–88) compounds from m/z 104 to 1477, which demonstrated the complex mixture of compounds. In addition, no common markers among active extracts were identified. The results demonstrate the importance of the Solanaceae family to search new antileishmanial agents, particularly in unexplored species of this family. Copyright © 2016 John Wiley & Sons, Ltd.
  • Synergistic Effect of SH003 and Doxorubicin in Triple‐negative
           Breast Cancer
    • Abstract: Triple‐negative breast cancer (TNBC) is highly aggressive, resulting in poor prognosis. Chemotherapy of TNBC relies on anti‐cancer agents with strong cytotoxicity, but it causes several side effects with recurrence. While combinational approaches of chemotherapeutics have been highlighted as a new treatment strategy for TNBC to reduce side effects, combinations of anti‐cancer agents with herbal medicines have not been reported. We recently reported that newly modified traditional Chinese medicine named SH003 inhibited TNBC growth. Considering a combinational strategy for TNBC treatment, we further studied synergistic effects of SH003 with various anti‐cancer drugs in TNBC treatment. Here, we demonstrate that SH003 shows a synergistic effect with doxorubicin on TNBC treatment. Our in vitro cell viability assays revealed that SH003 and doxorubicin showed a synergistic effect in the well‐defined TNBC cell line, MDA‐MB‐231. Moreover, we found that the combinational treatment caused Caspase‐dependent apoptotic cell death. Our in vivo mouse xenograft tumor growth assays confirmed that combinational treatment of SH003 with doxorubicin repressed MDA‐MB‐231 tumor growth with no weight loss. Therefore, we conclude that the combinational treatment of SH003 with doxorubicin shows the synergism in TNBC treatment, and suggest that SH003 can be used together with conventional anti‐cancer drugs in chemotherapeutic approaches. Copyright © 2016 John Wiley & Sons, Ltd.
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