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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  [1577 journals]
  • 4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses
           Inflammatory Responses Through TRPV1 Activation
    • Abstract: Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca2+ levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC50 = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd.
  • Plants of the Melaleuca Genus as Antimicrobial Agents: From Farm to
    • Abstract: Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad-spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80–90% several monoterpenes (terpinen-4-ol, α-terpinene, 1,8-cineol, p-cymene, α-terpineol, α-pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8-cineol, terpinen-4-ol and methyl eugenol play the key role in mediating this oil's antimicrobial activity. Copyright © 2017 John Wiley & Sons, Ltd.
  • Low Doses of Curcuma longa Modulates Cell Migration and Cell–Cell
    • Abstract: Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell–cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p 
  • The Preparation of Hyaluronic Acid Nanoparticles from Aspicilia lichens
           Using Bifido Bacteria for Help in the Treatment of Diabetes in Rats In
    • Abstract: Many common herbs and spices are claimed to have blood sugar lowering properties that make them useful for people with or at high risk of diabetes. The main of compounds of kiwifruit (Actinidia deliciosa), rhubarb (Rheum ribes), membrane inner of egg shell, wool of sheep, human fingernail (unguis), hyaluronic acid produced by the Bifidobacterium, and usnic acid of Aspicilia lichen were extracted by different methods. All compounds of the extract were divided into five groups. We used variables such as pH, different compounds, concentration, number of injections, and blood glucose monitoring in different situations. Our study, extracts changed to nanoform. The extract compounds and nanoparticles were analyzed by gas chromatography mass spectroscopy, Fourier transform infrared spectroscopy, hydrogen-1 nuclear magnetic resonance, and scanning electron microscope. The average size of the nanoparticles was found to be 55 nm. Five groups of nanoparticles were injected into rats, and they reduced their blood glucose levels significantly (statistical significance was declared at p 
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  • Bioactive Triterpenes from the Root of Salvia miltiorrhiza Bunge
    • Abstract: Danshen (Salvia miltiorrhiza) is a well-known medicinal herb in the oriental medicine. The current study on bioactive triterpenoid in the root of S. miltiorrhiza led to the isolation of a new highly hydroxylated ursane-type triterpene, urs-12-ene-2α,3β,7β,16α-tetraol (1) and five known ones including 2β-hydroxypomolic acid (2), maslinic acid (3), asiatic acid (4), ursolic acid (5), and oleanolic acid (6). Their structures were elucidated on the basis of extensive spectroscopic analyses and comparison with literature data. The antiproliferative testing against HL-60 cells revealed that the new compound 1 and ursolic acid (5) showed weak and moderate activities with IC50 values of 42.2 and 11.7 μM. In addition, compounds 1–3 showed inhibitory effect on ghrelin activity. Copyright © 2017 John Wiley & Sons, Ltd.
  • Enhanced Oral Bioavailability of Diltiazem by the Influence of Gallic Acid
           and Ellagic Acid in Male Wistar Rats: Involvement of CYP3A and P-gp
    • Abstract: The oral bioavailability of diltiazem is very low due to rapid first pass metabolism in liver and intestine. The purpose of the study was to investigate the effect of gallic acid and ellagic acid on intestinal transport and oral bioavailability of diltiazem in rats. The intestinal transport and permeability of diltiazem was evaluated by in vitro non-everted sac method and in situ single pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study. The intestinal transport and apparent permeability of diltiazem were significantly enhanced in duodenum, jejunum, and ileum of gallic and ellagic acid-treated groups. The effective permeability of diltiazem was significantly enhanced in ileum part of gallic and ellagic acid-treated groups. When compared with control group, the presence of these two phytochemicals significantly enhanced the area under plasma concentration-time curve and the peak plasma concentration of diltiazem (Cmax). Gallic acid and ellagic acid significantly increased the bioavailability of diltiazem due to the inhibition of both CYP3A-mediated metabolism and P-glycoprotein-mediated efflux in the intestine and/or liver. Based on these results, the clinical experiments are warranted for the confirmation to reduce the dose of diltiazem when concomitantly administered with these phytochemicals. Copyright © 2017 John Wiley & Sons, Ltd.
  • Therapeutic Effects of 6-Gingerol, 8-Gingerol, and 10-Gingerol on Dextran
           Sulfate Sodium-Induced Acute Ulcerative Colitis in Rats
    • Abstract: Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg−1 d−1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three gingerols obviously accelerated mucosal damage healing. It is concluded that 6-gingerol, 8-gingerol, and 10-gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd.
  • Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast
           Cancer Cells
    • Abstract: Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p 
  • Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium
           (Bitter Orange) Extract and p-Synephrine
    • Abstract: Citrus aurantium L. (bitter orange) extracts that contain p-synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p-synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p-synephrine. Numerous studies have been conducted with respect to p-synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p-synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p-synephrine exerts its effects through multiple actions, which are discussed. Because p-synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
  • Influence of Prostanoids in the Diuretic and Natriuretic Effects of
           Extracts and Kaempferitrin from Bauhinia forficata Link Leaves in Rats
    • Abstract: Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis, no scientific investigation has focused on demonstrating its efficacy in preclinical trials. For that, normotensive male Wistar and spontaneously hypertensive rats were used to test the effect of extracts and kaempferitrin obtained from Bauhinia forficata leaves in the experimental model of diuresis. Cumulative urine volume, Na+ and K+ excretion, calcium, creatinine, prostaglandin E2, pH, density, and conductivity were measured at the end of the experiment (after 8 or 24 h). The treatment with aqueous infusion, methanolic extract, trichloromethane, or ethyl acetate–butanolic fractions significantly increase urinary volume and electrolytes levels when orally given to rats, without altering the pH or density parameters. Kaempferitrin induced diuretic, natriuretic, but not kaliuretic effects in both normotensive and hypertensive rats. In addition, kaempferitrin enhanced urinary creatinine and prostaglandin E2 excretion, without modifying calcium levels. Kaempferitrin-induced diuresis was unaffected by previous treatment with a nonselective inhibitor of nitric oxide synthase and neither with a nonselective muscarinic receptor antagonist. On the other hand, a cyclooxygenase inhibitor was able to decrease its effect when compared with vehicle-treated rats, suggesting that the diuretic and natriuretic properties from kaempferitrin are associated with endogenous prostanoids generation. Copyright © 2017 John Wiley & Sons, Ltd.
  • Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and
           Astragaloside IV via Down-Regulating Connexin 43
    • Abstract: Paeoniflorin (PF) and astragaloside IV (AS-IV) have protective effects on cerebral ischemia. We aimed to test the effects of combined use of PF and AS-IV on ischemic brain edema and investigate whether the effects were dependent on connexin43 (Cx43). We detected the expression of Cx43 induced by PF and AS-IV after cerebral ischemia. We also examined the effects of combined use of PF and AS-IV on ischemic edema and further investigated the related pathways. We demonstrated PF and AS-IV decreased Cx43 and aquaporin4 (AQP4) associating with reduction of brain edema by dry-wet weight and brain-specific gravity methods after cerebral ischemia. Administration of PF and AS-IV displayed a further attenuation of brain edema with lower Cx43 levels. Meanwhile, Cx43 blockade inhibited AQP4 down-regulation by the two drugs. Moreover, phosphorylation of C-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) were increased by PF and AS-IV, respectively. The effects of PF and AS-IV to down-regulate Cx43 were suppressed by JNK and ERK inhibitors, respectively. Our data indicate that PF and AS-IV alleviate ischemic brain edema, which has close relation to Cx43 down-regulation causing decrease of AQP4 via JNK and ERK pathways activation, respectively. Combined administration elicits synergistic effects on brain edema reduction. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antiproliferative Activity of Phenylpropanoids Isolated from Lagotis
           brevituba Maxim
    • Abstract: The aim of the present study was to evaluate the antiproliferative effect of phenylpropanoids isolated from the n-BuOH-soluble fraction of an ethanolic extract of Lagotis brevituba Maxim. The phenylpropanoids were identified as echinacoside, lagotioside, glucopyranosyl(1–6)martynoside, plantamoside, and verbascoside. Three of the compounds, lagotioside, glucopyranosyl(1–6)martynoside, and plantamoside, were isolated from L. brevituba for the first time. The antiproliferative activity of the isolates was evaluated in human gastric carcinoma (MGC-803), human colorectal carcinoma (HCT116), human hepatocellar carcinoma (HepG2), and human lung cancer (HCT116) cells using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Plantamoside showed promising activity against MGC-803 cells, with a half maximal inhibitory concentration value of 37.09 μM. The mechanism of the pro-apoptosis effect of plantamoside was then evaluated in MGC-803 cells. Changes in cell morphology, including disorganization of the architecture of actin microfilaments and formation of apoptotic bodies, together with cell cycle arrest in G2/M phases, were observed after treatment of plantamoside. The antiproliferative and pro-apoptotic effects were associated with a decrease in the ratio of Bcl-2/Bax and reduced mitochondrial membrane potential, which was accompanied by the release of reactive oxygen species and Ca2+ into the cytoplasm. Taken together, the results indicated that plantamoside promotes apoptosis via a mitochondria-dependent mechanism. Copyright © 2017 John Wiley & Sons, Ltd.
  • Anti-myocardial Ischemia Effect and Components of Litchi Pericarp Extracts
    • Abstract: Litchi (Litchi chinensis Sonn.) is a famous fruit in south China, and it is also effective for chest tightness or chest pain, irritability, flatulence, epigastric pain and neuralgic pain, hernia pain and testicular swelling, cough, etc. It is valued because a great amount of polyphenol was found in litchi pericarp. In this paper, we got litchi pericarp pure extract by a simple purification method, then evaluated its activity to clear oxygen free radicals in vitro, and evaluated its myocardial protection effect in vivo through acute myocardial ischemia rat model. The results showed that the pure extract had protective effect on myocardial ischemia injury in a certain dose–effect relationship, which reflected in the electrocardiogram, myocardial pathological morphology and other indicators such as cardiac function enzymes, serum and myocardial antioxidant capacity, and eNOS, Bcl-2 and Bax gene expression. Furthermore, we analyzed the components of pure extract by UPLC-MS, ESI-MS and NMR. The main components of PLPE were procyanidin which were identified as procyanidin B2(1), (−)-epicatechin(2), epicatechin-(4β  8,2β  O  7)-epicatechin-(4β  8)-epicatechin(3), A-type procyanidin trimer(4), B-type procyanidin dimer(5) and procyanidin A2(6).This study proved that litchi pericarp extract may have antioxidant activity and cardioprotection effect. It suggested that litchi pericarp may be good for cardiovascular disease. Copyright © 2017 John Wiley & Sons, Ltd.Litchi is a famous fruit in south China. We got litchi pericarp extract by a simple purification method and evaluated its activity to clear oxygen free radicals in vitro and its myocardial protection effect in vivo. Furthermore, we analyzed the components of the extract. This study proved that litchi pericarp extract may have antioxidant activity and cardioprotection effect. It suggested that litchi pericarp may be good for cardiovascular disease.
  • Nephroprotective Effects of Anthocyanin from the Fruits of Panax ginseng
           (GFA) on Cisplatin-Induced Acute Kidney Injury in Mice
    • Abstract: Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase-1, cytochrome P450 E1 and 4-hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor-α and interleukin-1β induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase-2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2-associated X protein expression. In conclusion, the findings from the present investigation demonstrate that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity, which may be related to its antioxidant, anti-apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley & Sons, Ltd.
  • The Potential Impact of Radix Paeoniae Alba in Embryonic Development of
    • Abstract: Although Radix Paeoniae Alba (RPA) has been ranked as one of the top 6 herbs used frequently to prevent and treat miscarriages clinically, there is no clear evidence regarding its safety in embryonic development. This study aims to evaluate the potential impacts of RPA on embryonic stem cells (ESCs) and pregnant mice. Cytotoxicity assays of the extract were performed in ESCs and 3T3 cells. Pregnant ICR mice were orally treated with RPA extracts at dosages of 0 (G1 group as negative controls), 2, 8 and 32 g/kg/day (G2, G3 and G4 groups) respectively from the gestation day (Gd) 6–15. On Gd 18, there was no significant difference in the IC50 values between ESCs and 3T3 cells (p > 0.05). There was no significant difference in the maternal and fetal evaluations among four groups (p > 0.05). Fetal IL-2, IL-2r, TNF-α, TNF-αr, IL-4, IL-4r, IL-10r, IL-17 and IL-17r of G4 group were significantly lower than G1 group (p 
  • Anticandidal Activity of Extracts and a Novel Compound, Amnomopin,
           Isolated From Petriella setifera
    • Abstract: A novel triterpenoidal compound named ‘amnomopin’ (3β-diglucoside-5,12-28-oic acid), which is named IUPAC as 3-O-(2′ ➔ 1″diglucoside)1,2,3,4,4a,5,6,6a,6b,7,9,10,11,12,12a,12b,13,14b-octadecahydro-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethylpicene-4a-carboxylic acid, was isolated from the extract Petriella setifera. The total alcoholic extract of P. setifera showed a great activity against clinically isolated Candida species, including Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida inconspicua, Candida kefyr, Candida krusei, Candida norvegensis, Candida parapsilosis and Candida tropicalis. Also, the new compound amnomopin was active against all the investigated Candida species. The highest anticandidal activity of P. setifera extract was obtained against C. kefyr (22.6 ± 1.5 mm), C. albicans and C. norvegensis (21.3 ± 0.63 mm) and C. krusei (20.6 ± 1.5 mm). Moreover, the minimum inhibitory concentrations of both the total extract and the isolated compound were low. The minimum inhibitory concentration of the compound isolated from P. setifera was 0.49 μg/mL against C. kefyr, 0.98 μg/mL against C. albicans and C. norvegensis and 1.95 μg/mL against C. krusei. The oral dosing of the extract and the isolated compound did not show any significant effect on the activity of alanine aminotransferase, aspirate aminotransferase and the levels of blood urea and serum creatinine. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antiangiogenic Effects of Ziyuglycoside II, a Major Active Compound of
           Sanguisorba officinalis L.
    • Abstract: Ziyuglycoside II, a major bioactive compound of Sanguisorba officinalis L., displays anticancer potential against several human cancer cells. However, little information concerning its antiangiogenic properties and possible mechanisms is available. The aim of this study was to investigate the inhibitory effects of ziyuglycoside II on angiogenesis. Ziyuglycoside II inhibited the proliferation, migration, and tubule formation of human umbilical vein endothelial cells, as well as the number of microvessels growing from the aortic rings. The underlying antiangiogenic mechanism of ziyuglycoside II correlated with blocking vascular endothelial growth factor receptor-2 and the fibroblast growth factor receptor-1 mediated signaling pathway. Moreover, an in vivo Matrigel plug assay in mice showed a significant decrease in vascularization and hemoglobin content in the plugs from ziyuglycoside II-treated mice compared with control mice. Overall, these results suggest that ziyuglycoside II inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects. Copyright © 2017 John Wiley & Sons, Ltd.
  • Efficacy of a Proprietary Trigonella foenum-graecum L. De-Husked Seed
           Extract in Reducing Menopausal Symptoms in Otherwise Healthy Women: A
           Double-Blind, Randomized, Placebo-Controlled Study
    • Abstract: Trigonella foenum-graecum seed extract has demonstrated hormone modulatory activity, providing biological plausibility for relieving menopausal symptoms. The study aimed to assess efficacy of a standardized T. foenum-graecum de-husked seed extract in reducing menopausal symptoms in healthy aging women. The study was a double-blind, randomized, placebo-controlled trial that recruited 115 women aged 40 to 65 years of which 59 were allocated to active (n = 54 completed) and 56 to placebo (n = 50 completed). Active treatment was T. foenum-graecum de-husked seed extract, 600 mg per day for 12 weeks. Outcome measures included Menopause-Specific Quality of Life (MENQOL) questionnaire, frequency of hot flushes and night sweats and serum estradiol levels. There was a significant reduction in menopausal symptoms in the active group compared with placebo as assessed by total MENQOL score (p 
  • Stephanine from Stephania venosa (Blume) Spreng Showed Effective
           Antiplasmodial and Anticancer Activities, the Latter by Inducing Apoptosis
           through the Reverse of Mitotic Exit
    • Abstract: Extracts from the tubers of Stephania venosa (Blum) Spreng growing in Vietnam significantly inhibited cell proliferation against a number of cancer cells including HeLa, MDA-MB231 and MCF-7 cells. A bioassay-guided fractionation led to the isolation of four aporphine and one tetrahydroprotoberberine alkaloids: dehydrocrebanine 1, tetrahydropalmatine 2, stephanine 3, crebanine 4 and O-methylbulbocapnine 5. The characterization of these compounds was based on MS, NMR and published data. A study by structure–bioactivity relationship on these isolates showed that stephanine is the most active compound. Cell biological studies showed that stephanine induces the reverse of mitotic exit, eventually leading to cell death by apoptosis. This data suggests that stephanine has a unique mode of cell-killing activity against cancer cells, which is seldom observed with known synthetic compounds. In addition to its anticancer property, our data from an in vitro study showed that S. venosa also possesses effective antiplasmodial activity and stephanine was also the most interesting compound but is the most cytotoxic with the lowest selectivity index. Copyright © 2017 Her Majesty the Queen in Right of Canada Phytotherapy Research and StartCopTextCopyright © 2017 John Wiley & Sons, Ltd.Stephanine isolated from bio-activity-guided fractionation of the methanolic extract of the tuber of Stephania venosa displayed effective antiproliferative against a number of cancer cell lines. It causes G2-M arrest by 24 h and induces the reverse of mitotic exit, which eventually leads to apoptosis. In addition to anticancer activity, stephanine also possess antiplasmodial activity.
  • Chemical Characterization, Antileishmanial Activity, and Cytotoxicity
           Effects of the Essential Oil from Leaves of Pluchea carolinensis (Jacq.)
           G. Don. (Asteraceae)
    • Abstract: Current strategies to control leishmaniasis are mainly based on chemotherapy. However, none of the available drugs can be considered to be ideal to treat this disease. Because of the hydrophobic nature and bioactivities of their components, essential oils (EOs) can be considered as important sources for developing agents against intracellular pathogens, such as Leishmania parasites. In this study, we report the chemical characterization, antileishmanial activities, and cytotoxicity effect of the EO from Pluchea carolinensis (Jacq.) G. Don. (Asteraceae). Chemical analysis revealed that EO from aerial part from P. carolinensis is composed of 44 compounds. The main component was selin-11-en-4α-ol, which made up 51.0%. In vitro antileishmanial studies showed that P. carolinensis EO inhibited the growth of promastigotes (IC50 = 24.7 ± 7.1 μg/mL) and amastigotes (IC50 = 6.2 ± 0.1 μg/mL) of Leishmania amazonensis, while cytotoxicity evaluation revealed fivefold higher values than those for the parasites. In a model of experimental cutaneous leishmaniasis in BALB/c mice, five doses of EO at 30 mg/kg by intralesional route demonstrated smaller lesion size and parasite burden (p 
  • Synergistic Effect of TPD7 and Berberine against Leukemia Jurkat Cell
           Growth through Regulating Ephrin-B2 Signaling
    • Abstract: TPD7, a novel biphenyl urea taspine derivative, and berberine have presented inhibition on VEGFR2 that can be regulated by ephrin-B2 reverse signaling through interactions with the PDZ domain. The purpose of this study is to investigate the inhibitory effect of the combination of TPD7 and berberine (TAB) on T-cell acute lymphoblastic leukemia cell growth. TPD7 and berberine together synergistically inhibited the proliferation of Jurkat cells. Also, the combination of TAB induced G1-phase cell-cycle arrest by downregulating the level of cyclin D1, cyclin E, and CDC2. Furthermore, the combination of TAB significantly enhanced apoptosis in Jurkat cells, and the apoptosis most likely resulted from the modulation of the level of Bcl-2 family members. Most importantly, the concomitant treatment simultaneously regulated the ephrin-B2 and VEGFR2 signaling, as well as modulated the MEK/ERK and PTEN/PI3K/AKT/mTOR signaling. Therefore, the combination treatment of TAB may be a promising therapeutic method in treating T-cell acute lymphoblastic leukemia. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Davallia formosana Hayata Water and Alcohol Extracts on
           Osteoblastic MC3T3-E1 Cells
    • Abstract: The Taiwanese native fern Davallia formosana Hayata (DFH) is used to treat bone diseases in classical Chinese medicine. We analyzed MC3T3E1 osteoblasts treated with different concentrations of water and ethanol extracts (10, 25, and 50 [both], and 100 μg/mL [DFE only]) using cell viability, expression of osteoblast differentiation markers [bone morphogenetic protein 2 (BMP-2), collagen 1 (CoL-1), alkaline phosphatase (ALP), and Runt-related transcription factor 2 (Runx 2)], and mineralization. These were significantly increased by DFW or DFE after 24-h incubation compared with the untreated controls. Compared with other treatments, DFW 50 and DFE 100 μg/mL significantly increased MC3T3E1 cell survival. DFW 25 and 50 μg/mL increased bone BMP-2, CoL-1, ALP, and Runx2 protein expression, ALP activity, and mineralization more than DFE did. Repeated chromatographic separation of DFW yielded compound (−)-epicatechin-3-O-d-allipyranoside (ECAP), which was characterized using 1H and 13C nuclear magnetic resonance spectroscopy. (−)-Epicatechin-3-O-d-allipyranoside (0.01 μg/mL) significantly increased cell survival (118.9%) and mineralization (218.7%) compared with that of the control treatment. We inferred that ECAP could mediate the main activity of DFW in bone formation, likely through BMP-2-induced Runx2 transcription, which increased bone cell differentiation factors ALP and CoL-1 and promoted mineralization. (−)-Epicatechin-3-O-d-allipyranoside could be an anti-osteoporotic agent. Copyright © 2017 John Wiley & Sons, Ltd.
  • Combined Lifestyle and Herbal Medicine in Overweight Women with Polycystic
           Ovary Syndrome (PCOS): A Randomized Controlled Trial
    • Abstract: Polycystic ovary syndrome (PCOS) is a common, complex reproductive endocrinopathy characterized by menstrual irregularities, hyperandrogenism and polycystic ovaries. Lifestyle modification is a first-line intervention; however, there are barriers to success for this form of self-care, and women often seek adjunct therapies including herbal medicines. This pragmatic, randomized controlled trial, delivered in communities of Australia in overweight women with PCOS, compared the effectiveness and safety of a lifestyle intervention plus herbal medicine against lifestyle alone. All participants were helped to construct a personalized lifestyle plan. The herbal intervention consisted of two tablets. Tablet 1 contained Cinnamomum verum, Glycyrrhiza glabra, Hypericum perforatum and Paeonia lactiflora. Tablet 2 contained Tribulus terrestris. The primary outcome was oligomenorrhoea/amenorrhoea. Secondary outcomes were hormones; anthropometry; quality of life; depression, anxiety and stress; pregnancy; birth outcomes; and safety. One hundred and twenty-two women gave their consent. At 3 months, women in the combination group recorded a reduction in oligomenorrhoea of 32.9% (95% confidence interval 23.3–42.6, p 
  • Synergy between Auraptene, Ionizing Radiation, and Anticancer Drugs in
           Colon Adenocarcinoma Cells
    • Abstract: Colorectal cancer is a growing health concern with increasing mortality rates, and resistance to anticancer drugs and radiotherapy is a serious drawback in its treatment. Auraptene is a natural prenyloxycoumarin with valuable anticancer effects. The aim of current study was to determine the synergy between auraptene, ionizing radiation, and chemotherapeutic drugs in colon adenocarcinoma cells for the first time. To do so, HT29 cells were treated with combination of auraptene + cisplatin, + doxorubicin, or + vincristine. Furthermore, cells were pretreated with nontoxic auraptene and then exposed to various doses of X-radiation. Assessment of cell viability not only indicated significant (p 
  • Review of Garcinia mangostana and its Xanthones in Metabolic Syndrome and
           Related Complications
    • Abstract: Metabolic syndrome is coexistence of abdominal obesity, hyperglycemia, hyperlipidemia and hypertension that causes cardiovascular diseases, diabetes and their complications, low quality and short lifespan. Garcinia mangostana and its xanthones such as α-mangostin have been shown desirable effects such as anti-obesity, anti-hyperglycemic, anti-dyslipidemia, anti-diabetic and antiinflammatory effects in experimental studies. Various databases such as PubMed, Scopus and Web of Science with keywords of ‘Garcinia mangostana’, ‘mangosteen’, ‘α-mangostin’, ‘metabolic syndrome’, ‘hypoglycemic’, ‘antihyperglicemic’, ‘antidiabetic’, ‘hypotensive’, ‘antihypertensive’, ‘atherosclerosis’, ‘arteriosclerosis’ and ‘hyperlipidemia’ have been investigated in this search without publication time limitation. This study reviewed all pharmacological effects and molecular pathways of G. mangostana and its xanthones in the management of metabolic syndrome and its complications in in-vitro and in-vivo studies. Based on these studies, mangosteen and its xanthones have good potential to design human studies for controlling and modification of metabolic syndrome and its related disorders such as obesity, disrupted lipid profile, diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd.
  • Preventive Effects of Ginseng Total Saponins on Chronic
           Corticosterone-Induced Impairment in Astrocyte Structural Plasticity and
           Hippocampal Atrophy
    • Abstract: To further explore the underlying antidepressant mechanism of ginseng total saponins (GTS), this study observed the effects on hippocampal astrocyte structural plasticity and hippocampal volume in the corticosterone-induced mouse depression model. Corticosterone (20 mg/kg/day) was administered subcutaneously for 5 weeks, and GTS (12.5, 25, and 50 mg/kg/day; namely GTSL, GTSM, and GTSH) or fluoxetine (10 mg/kg/day) were given intragastrically during the last 3 weeks. On day 33 and day 34, depression-like behavior was observed via a forced swimming test and a tail suspension test, respectively. At 6 h after the last dose of corticosterone (day 35), all mice were sacrificed followed by serum corticosterone assays, stereological analysis of hippocampal glial fibrillary acidic protein-positive (GFAP+) astroctyes and hippocampal volume, and hippocampal glycogen tests. Results showed that all doses of GTS ameliorated depression-like behavior and the decrease in hippocampal glycogen without normalizing hypercortisolism. Moreover, GTSH and GTSM reversed the corticosterone-induced reduction in the total number of hippocampal GFAP+ astrocytes and hippocampal volume. Additionally, GTSH alleviated the diminished protrusion length and somal volume of GFAP+ astrocytes induced by corticosterone. These findings imply that the effects of GTS on corticosterone-induced depression-like behavior may be mediated partly through the protection to hippocampal astrocyte structural plasticity. Copyright © 2017 John Wiley & Sons, Ltd.
  • The In Vitro and In Vivo Biological Activities of the Leaf of Cape Myrtle,
           Myrsine africana L.
    • Abstract: The cape myrtle, Myrsine africana L., is a widely used medicinal plant, which has not been well investigated. We assessed the in vivo hepatoprotective and in vitro antiproliferative and antioxidant effects of leaf extracts of M. africana chemically profiled using high-performance liquid chromatography. Three flavonoids were quantified, and gas chromatography–mass spectrometry analysis revealed the presence of common fatty acids. The animal study was conducted on mice treated with CCl4, using three doses each of the methanol and chloroform extract (100, 200 and 300 mg/kg b.w.),with silymarin as a positive control. Hepatoprotective effects were determined by analyzing blood for liver marker and antioxidant enzymes, direct bilirubins and total proteins. The methanol extract (300 mg/kg b.w.) showed the strongest hepatoprotective effects against abnormalities produced by CCl4. The in vivo hepatoprotective effects correlated well with the in vitro antioxidant and antiproliferative activities and with high levels of flavonoids in the extracts. Finally, molecular docking studies of the constituent quercetin were undertaken in silico and several sites of binding to human estrogen receptor (ER) protein, linked with alkaline phosphatase, identified. Copyright © 2017 John Wiley & Sons, Ltd.
  • Bakuchiol Contributes to the Hepatotoxicity of Psoralea corylifolia in
    • Abstract: Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured. Many abnormalities were observed in the bakuchiol-treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, and increased weight of liver. The mRNA expression of CYP7A1, HMG-CoA reductase, PPARα, and SREBP-2 decreased in bakuchiol-treated group, the expression of BSEP increased in bakuchiol-treated low dosage, and the expression of BSEP decreased in bakuchiol-treated high dosage. In conclusion, we provide evidence for the first time that bakuchiol can induce cholestatic hepatotoxicity, suggesting potential hepatotoxicity. The mechanism may be related to effects on liver lipid metabolism, but further investigation is necessary. Copyright © 2017 John Wiley & Sons, Ltd.
  • Topical Silymarin Administration for Prevention of Capecitabine-Induced
           Hand–Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled
           Clinical Trial
    • Abstract: Hand–foot syndrome (HFS) is a frequent dose-limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine-induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9th week (p 
  • Neuro-Protective Effects of Resveratrol on Carbon Monoxide-Induced
           Toxicity in Male Rats
    • Abstract: Acute carbon monoxide (CO) poisoning causes neurotoxicity through induction of necrosis, apoptosis, lipid peroxidation and oxidative stress. Resveratrol (RES) is a natural polyphenolic phytoalexin that exhibits neuroprotective effects in ischemia/reperfusion due to its anti-apoptotic, anti-necrotic and strong anti-oxidant properties as well as its ability to activate pro-survival pathways. In this study, rats were exposed to CO 3000 ppm for 1 h. Immediately after poisoning and on the next four consecutive days, RES (1, 5 and 10 mg/kg) was administered intraperitoneally. On the fifth day, animals' brains were excised, and necrosis, lipid peroxidation level and the level of Akt, BAX and BCL2 expression were evaluated. The results showed that RES 10 mg/kg significantly reduced lipid peroxidation, but RES 1 and 5 mg/kg had no significant effect on this parameter. Furthermore, RES 5 and 10 mg/kg significantly increased Akt expression level, while BAX/BCL2 ratio was reduced by RES 1, 5 and 10 mg/kg. Moreover, RES reduced necrotic foci in the brain, but the best results were seen following treatment with RES 10 mg/kg. In summary, RES showed neuroprotective effect in CO-poisoned rats as it decreased necrosis and BAX/BCL2 ratio and increased Akt expression levels. Copyright © 2017 John Wiley & Sons, Ltd.
  • Adjuvant Treatment with Qilin Pill for Men with Oligoasthenospermia: A
           Meta-Analysis of Randomized Controlled Trials
    • Abstract: Qilin pill has been used in the management of oligoasthenospermia. This meta-analysis aimed to evaluate the effects of Qilin pill as an adjunctive therapy on semen parameters in oligoasthenospermic men. A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Wanfang, CNKI, and VIP databases until June 2016. Randomized controlled trials (RCTs) that evaluated Qilin pill as an adjunctive therapy in oligoasthenospermic were included. Dichotomous data and continuous data were calculated as the risk ratio (RR) and mean difference (MD) with their 95% confidence interval (CI), respectively. Eight RCTs involving 778 patients were identified. Adjunctive treatment with Qilin pill significantly improved the semen volume (MD 0.50 mL; 95% CI 0.42–0.59), sperm concentration (MD 5.01 × 106/mL; 95% CI 3.28–6.75), sperm motility (MD 7.54%; 95% CI 5.64–9.45), grade A sperm (MD 9.75%; 95% CI 4.05–15.45), serum testosterone level (MD 1.66 nM; 95% CI 0.40–2.92), and pregnancy rate (RR 1.46; 95% CI 1.08–1.99) during follow-up. However, differences in the serum follicle-stimulating and luteinizing hormone levels were not significant. Adjunctive treatment with Qilin pill significantly improves the sperm quality in patients with oligoasthenospermia. However, further trials are necessary to investigate the efficacy of Qilin pill on oligoasthenospermia-induced male infertility. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Copaiba Oil Topical Administration on Oral Wound Healing
    • Abstract: The effects of topical copaiba oil extract and topical corticosteroid were assessed on oral wound healing in an in vivo model using 96 male Wistar rats. Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The animals were divided into: Control; Corticosteroid; Placebo and Copaiba oil Group. The animals received two daily applications of the products. The control group received only daily handling. Six rats in each group were euthanized at days 3, 5, 10 and 14. The animals were monitored daily to determine wound status. The weigh was assessed at day 0 and euthanasia day. The percentage of repair was calculated, and histopathological aspects were analyzed. The Kruskal–Wallis test was used to compare the results between groups and times of evaluation. Closing time was assessed through the log-rank test. The corticosteroid group lost more weight at days 10 and 14 than the control group (p 
  • Protective Effects Induced by Microwave-Assisted Aqueous Harpagophytum
           Extract on Rat Cortex Synaptosomes Challenged with Amyloid β-Peptide
    • Abstract: Harpagophytum procumbens is a plant species that displays anti-inflammatory properties in multiple tissues. The iridoid glycosides arpagoside, harpagide, and procumbide appear to be the most therapeutically important constituents. In addition, harpagoside treatment exerted neuroprotective effects both in vitro and in vivo. Considering these findings, the aim of the present work is to explore the possible protective role of the previously described microwave-assisted aqueous extract of H. procumbens on rat hypothalamic (Hypo-E22) cells, and in rat cortex challenged with amyloid β-peptide (1–40). In this context, we assayed the protective effects induced by H. procumbens by measuring the levels of malondialdehyde, 3-hydroxykynurenine (3-HK), brain-derived neurotrophic factor, and tumor necrosis factor-α, 3-HK. Finally, we evaluated the effects of H. procumbens treatment on cortex levels of dopamine, norepinephrine, and serotonin. H. procumbens extract was well tolerated by Hypo-E22 cells and upregulated brain-derived neurotrophic factor gene expression but down-regulated tumor necrosis factor-α gene expression. In addition, the extract reduced amyloid β-peptide stimulation of malondialdehyde and 3-HK and blunted the decrease of dopamine, norepinephrine, and serotonin, in the cortex. In this context, our work supports further studies for the evaluation and confirmation of Harpagophytum in the management of the clinical symptoms related to Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.
  • Panax notoginseng Preparations for Unstable Angina Pectoris: A Systematic
           Review and Meta-Analysis
    • Abstract: This paper assessed the evidence of Panax notoginseng preparations in patients suffering from UAP using meta-analysis and systematic review methods. Methods were according to the Cochrane Handbook and analysed using Revman 5.3. A search of PubMed, Cochrane Library, Embase, MEDLINE, Chinese national knowledge infrastructure (CNKI), Vip information database, Wanfang data and Chinese Biomedical Literature Database (SinoMed) was conducted to identify randomized controlled trials (RCTs) of P. notoginseng preparations on UAP regardless of blinding, sex and language. The outcomes include all-cause mortality, cardiac mortality, cardiovascular events, UAP symptoms, improvement of electrocardiogram and adverse events. Eighteen RCTs including 1828 patients were identified. The level of reporting is generally poor. Among 18 studies, 16 studies were prescribed P. notoginseng injections, and two studies were oral P. notoginseng preparations. Reduction of cardiovascular events (RR:0.35;95% CI:0.13 to 0.94), alleviation of angina pectoris symptoms (RR:1.23;95% CI 1.18 to 1.29), improvement of ECG (RR:1.22;95% CI 1.15 to 1.28) and reduced frequency of angina pectoris (MD:−1.48; 95% CI −2.49 to −0.48) were observed. Cardiac mortality and duration of angina pectoris were not statistically significant. Panax notoginseng is beneficial to UAP patients; the results of these reviews may have important implications to clinical work. Copyright © 2017 John Wiley & Sons, Ltd.
  • Protective Effects of Lepidium meyenii (Maca) Aqueous Extract and Lycopene
           on Testosterone Propionate-Induced Prostatic Hyperplasia in Mice
    • Abstract: The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate-induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]. Benzyl glucosinolate was used in order to evaluate its pharmacological activity on BPH to find out whether it is the major active component of maca aqueous extract. Finasteride was used as positive control. The compounds were administered once for 30 successive days. Compared with solvent BPH model group, BPH mice fed with maca (30 mg/kg) and lycopene (7.5 mg/kg) combination exhibited significant reductions in the prostatic index, prostatic acid phospatase, estradiol, testosterone, and dihydrotestosterone levels in serum. They also had similar histological compared with those aspects observed in the mice in the solvent control group. The results indicated that combination of maca and lycopene synergistically inhibits BPH in mice. Copyright © 2017 John Wiley & Sons, Ltd.
  • Immune Tolerance Effect in Mesenteric Lymph Node Lymphocytes of Geniposide
           on Adjuvant Arthritis Rats
    • Abstract: Rheumatoid arthritis (RA) is a systemic, Th1 cytokine-predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague–Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Levels of interleukin-2 (IL-2), IL-4, and transforming growth factor-β1 were tested by ELISA. The expression of β2-AR, GRK2, and β-arrestin-1 and β-arrestin-2 was detected by western blot. Geniposide was found to relieve the secondary hind paw swelling and arthritis scores, along with attenuating histopathologic changes and decreasing IL-2 and increasing IL-4, transforming growth factor-β1 in mesenteric lymph node (MLN) lymphocytes of AA rats. In addition, GE in vivo increased the expression of β2-AR and decreased the expression of GRK2, β-arrestin-1 and β-arrestin-2, and level of cyclic adenosine monophosphate of MLN lymphocytes in AA rats. From these results, we can infer that GE on immune tolerance effects, β2-AR desensitization, and β2-AR-AC-cyclic adenosine monophosphate transmembrane signal transduction of MLN lymphocytes plays crucial roles in antiinflammatory and immunoregulatory pathogeneses of RA. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pterostilbene Inhibits Lipogenic Activity similar to Resveratrol or
           Caffeine but Differently Modulates Lipolysis in Adipocytes
    • Abstract: The anti-obesity effects of resveratrol shown in rodents are not transposed into an efficient therapy of human obesity. Consequently, the search for molecules mimicking or surpassing resveratrol actions is ongoing. The natural phenolic compound pterostilbene exhibits beneficial health effects and has the capacity to limit fat mass in animal models. In this study, we tested whether pterostilbene modulates triacylglycerol accumulation/breakdown. Prolonged exposure to pterostilbene or resveratrol inhibited adipocyte differentiation in 3T3-F442A preadipocytes. Acute effects on lipolysis, antilipolysis and lipogenesis were determined for pterostilbene in mouse adipocytes, and compared with resveratrol. Pterostilbene was also tested on glycerol release and glucose uptake in subcutaneous human adipocytes. Dose–response analyses did not reveal a clear lipolytic effect in both species. The antilipolytic effect of insulin was improved by pterostilbene at 1–10 μM in mouse fat cells only, while at 1 mM, the phenolic compound was antilipolytic in human fat cells in a manner not additive to insulin. Pterostilbene dose-dependently inhibited glucose incorporation into lipids similarly to resveratrol and caffeine. However, only the former did not inhibit insulin-stimulated glucose uptake. Indeed, pterostilbene abolished the insulin lipogenic effect without inhibiting its antilipolytic action and rapid activation of glucose uptake. Pterostilbene therefore exhibits a unique panel of direct interactions with adipocytes that relies on its reported anti-obesity and antidiabetic properties. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Tilianin on Proliferation, Migration and TGF-β/Smad Signaling
           in Rat Vascular Smooth Muscle Cells Induced with Angiotensin II
    • Abstract: Flavonoid Tilianin was isolated from Dracocephalum moldavica, and its pharmacological mechanism on proliferation, migration and the TGF-β/Smad signaling pathway in rat vascular smooth muscle cells (VSMCs) induced with Angiotensin II (Ang II) was systematically evaluated. Primary rat VSMCs were stimulated with Ang II to induce proliferation. The cells were then treated with Tilianin for 24 or 48 h. MTT assay and Transwell assays were used to evaluate the effects of Tilianin on proliferation and migration. The expression of intracellular proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by immunohistochemistry as verification of effects on proliferation and migration. The expression of TGF-β1, Smad2 and Smad3 mRNA was measured by qRT-PCR, and the expression of TGF-β1 and P-Smad2/3 protein was measured by Western blotting. The results show that Tilianin can inhibit proliferation and expression of intracellular PCNA in VSMCs induced with Ang II, in a dose-dependent manner. Tilianin also mediates a dose-dependent inhibition of migration and the expression of intracellular ICAM-1, VCAM-1, MMP-2 and MMP-9. Furthermore, TGF-β1, Smad2, Smad3, Smad2/3 and P-Smad2/3 in Ang II-induced VSMCs are suppressed by Tilianin. The inhibitory effects of Tilianin support its use in the suppression and treatment of atherosclerosis. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacognosy, Phytochemistry and Pharmacological Properties of Achillea
           millefolium L.: A Review
    • Abstract: Achillea millefoilum L. (Yarrow) is an important species of Asteraceae family with common utilization in traditional medicine of several cultures from Europe to Asia for the treatment of spasmodic gastrointestinal disorders, hepatobiliary, gynecological disorders, against inflammation and for wound healing. An extensive review of literature was made on A. millefoilum L. using ethno botanical text books, published articles in peer-reviewed journals, unpublished materials and scientific databases. The Plant List, International Plant Name Index and Kew Botanical Garden databases were used to authenticate the scientific names. Monoterpenes are the most representative metabolites constituting 90% of the essential oils in relation to the sesquiterpenes, and a wide range of chemical compounds have also been reported. Different pharmacological experiments in many in-vitro and in-vivo models have proved the potential of A. millefoilum with antiinflammatory, antiulcer, anticancer activities etc. lending support to the rationale behind numerous of its traditional uses. Due to the noteworthy pharmacological activities, A. millefoilum will be a better option for new drug discovery. The present review will comprehensively summarize the pharmacognosy, phytochemistry and ethnopharmacology of A. millefoilum reported to date, with emphasis on more in vitro, clinical and pathological studies needed to investigate the unexploited potential of this plant. Copyright © 2017 John Wiley & Sons, Ltd.
  • Morin Suppresses Astrocyte Activation and Regulates Cytokine Release in
           Bone Cancer Pain Rat Models
    • Abstract: As inflammatory and immune responses are involved in pathophysiology of debilitating neuropathic pain, reagents that can modulate these two responses may have therapeutic potential. Morin, derived from the moraceae family of plants, benefits inflammation-related diseases, but its antinociceptive effects on cancer pain remain elusive. In the present study, we investigated antinociceptive effects of morin on bone cancer pain using a rat model, where rats were subject to implantation of Walker 256 mammary gland carcinoma cells into the tibia. Morin (5–20 mg/kg) dose-dependently attenuated behavioral hypersensitivities, including mechanical allodynia and free movement pain, which was accompanied by downregulation of astrocyte marker glial fibrillary acidic protein in the spinal cord in cancer-bearing rats. Treatment with morin also induced reduction of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 and upregulation of an antiinflammatory cytokine IL-10. Furthermore, intrathecal injection of AM630 (an antagonist of cannabinoid receptor 2, CB2), but not naloxone (an antagonist of opioid receptors), significantly blocked morin attenuation of behavioral hypersensitivities. Taken together, these results suggest that morin suppresses astrocyte activation and neuro-inflammation induced by bone cancer pain and its antinociceptive effects on bone cancer pain may be associated with activation of CB2 receptors in the spinal cord. Copyright © 2017 John Wiley & Sons, Ltd.
  • Phytoestrogen-Rich Natural Preparation for Treatment of Climacteric
           Syndrome and Atherosclerosis Prevention in Perimenopausal Women
    • Abstract: The present study evaluated the risks and benefits of phytoestrogen treatment in healthy perimenopausal women in relation to the dynamics of climacteric syndrome and progression of atherosclerosis. Study participants were treated with placebo or phytoestrogen-rich natural preparation Karinat based on grape (Vitis vinifera) seeds, green tea (Camellia sinensis) leaves, hop (Hunulus lupulus) cone powder and garlic (Allium sativum) powder. The dynamics of climacteric syndrome was evaluated by Kupperman Index and Utian Quality of Life Scale. Atherosclerosis progression was evaluated by measuring carotid intima-media thickness. Significant changes of climacteric syndrome's severity in both Karinat and placebo groups (p = 0.005 and p = 0.001) were obtained after 24 months of follow-up. Detailed analysis of Kupperman Index suggested that Karinat possessed a significant effect on nervousness (p = 0.010), weakness (p = 0.020) and formication (p = 0.010). A significant improvement of medical (p = 0.070) and emotional (p = 0.060) components of Kupperman Index and Utian Quality of Life Scale was also observed in Karinat group. However, difference in carotid intima-media thickness between the two groups was not statistically significant at follow-up. A slight positive effect of phytoestrogens on climacteric syndrome manifestations was demonstrated in this study. Karinat can be used for alleviation of climacteric syndrome and cardiovascular disease prevention in perimenopausal women. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway
           Activation and Epithelial–Mesenchymal Transition In Vivo
    • Abstract: Tobacco smoke is a major risk factor for hepatic cancer. Epithelial–mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein-1 (AP-1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke-induced activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke-triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke-associated hepatic cancer. Copyright © 2017 John Wiley & Sons, Ltd.
  • Cytotoxic Properties of the Stem Bark of Citrus reticulata Blanco
    • Abstract: The bioassay-guided fractionation of the n-hexane extract of Citrus reticulata Blanco (Rutaceae) stem bark yielded scoparone (1), xanthyletin (2), lupeol (3), β-amyrin (4), stigmasterol (5), β-sitosterol (6) and palmitic acid. The structures of these compounds were determined by comprehensive spectroscopic analyses, i.e., 1D and 2D NMR and EI-MS, and by comparison with the reported data. Extracts, fractions and isolated compounds 1–6 were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) assay against three human cancer cell lines, i.e., human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7 and human Caucasian prostate adenocarcinoma cell line PC3. Significant activity of the n-hexane and the dichloromethane extracts was observed against the breast cancer cell line MCF7 with IC50s of 45.6 and 54.7 μg/mL, respectively. Moreover, the 70% ethyl acetate in n-hexane chromatographic fraction showed significant activity displaying IC50 values of 53.0, 52.4 and 49.1 μg/mL against the cancer cell lines A549, MCF7 and PC3, respectively. Encouragingly, an IC50 of 510.0 μg/mL against the human normal prostate cell line PNT2 indicated very low toxicity and hence favourable selectivity indices for the 70% ethyl acetate in n-hexane fraction in the range of 9.6–10.4 towards cell lines A549, MCF7 and PC3. Because compounds isolated from the above fraction only delivered IC50 values in the range of 18.2–96.3, 9.2–34.1 and 7.5–97.2 μg/mL against A549, MCF7 and PC3 cell lines, respectively, synergistic action between compounds is suggested. Bioassay results valorize the anticancer effectivity of the stem bark of this plant in Cameroonian pharmacopoeia. Copyright © 2017 John Wiley & Sons, Ltd.
  • Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced
           by Alcohol Withdrawal in Rats
    • Abstract: Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd.
  • Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their
           Derivatives: A Systematic Review
    • Abstract: Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd.
  • Elucidation of Compatibility Interactions of Traditional Chinese
           Medicines: In Vitro Absorptions Across Caco-2 Monolayer of Coptidis
           Rhizoma and Euodiae Fructus in Zuojin and Fanzuojin Formulas as A Case
    • Abstract: Traditional Chinese medicines are often combined as formulae and interact with each other. As for Coptidis Rhizoma (CR) and Euodiae Fructus (EF), the most classical compatibilities were Zuojin (ZJF) and Fanzuojin formulas (FZJF) with reverse mixture ratios and opposite effects. To compare in vitro absorption interactions between CR and EF, bidirectional transports across Caco-2 cell monolayer of extracts of two formulas and equivalent single herbs were studied. Eighteen alkaloids from CR and EF were determined by liquid chromatography coupled to tandem mass spectrometry. Parameter apparent permeability coefficient (Papp) and efflux rate (ER) values showed that most alkaloids were well or moderately absorbed and six quaternary protoberberine alkaloids from CR had obvious efflux. ZJF compatibilities reduced both Papp BLAP and ER values of three indole alkaloids, and increased ER values of two quinolone alkaloids from EF. FZJF compatibilities obviously affected the bidirectional Papp values of CR alkaloids, weakened ERs of five protoberberines from CR and enlarged ERs of two quinolones from EF. Conclusions were drawn that different compatibility ratios of CR and EF led to different interactions on the in vitro absorption of alkaloids. The results may provide a good reference for interaction studies on the compatibilities of traditional Chinese medicines. Copyright © 2017 John Wiley & Sons, Ltd.
  • Chemical Composition and Immuno-Modulatory Effects of Urtica dioica L.
           (Stinging Nettle) Extracts
    • Abstract: The purpose of this work was to determine the chemical profile of stinging nettle and to provide an insight into the mechanisms by which it ameliorates the immune response. Qualitative and quantitative liquid chromatography tandem mass spectrometry analyses indicated that phenolic acids (5-O-caffeoylquinic acid as dominant) and flavonol glycosides (rutin, isoquercitrin, and kaempferol 3-O-glucoside) are present in the aerial parts, while lignans (secoisolariciresinol, 9,9′-bisacetyl-neo-olivil and their glucosides) were detected in the root. Herb and root extracts expressed selective inhibition toward cyclooxygenase and lipoxygenase branches in human platelets: root extracts were better at inhibiting thromboxane production, while herb extracts were more specific toward inhibition of 12-lipoxygenase pathway. Stinging nettle extracts mildly increased monocyte chemoattractant protein-1 and growth-related oncogene release from nonstimulated intestinal epithelial cells, stimulating MyD88/NF-κB/p38 signaling, hence preserving the epithelial integrity and enhancing intestinal steady-state defense. Additionally, root extract reduced lipopolysaccharide-induced monocyte chemoattractant protein-1/growth-related oncogene secretion and cyclooxygenase-2 expression in intestinal epithelial cells, thus showing the potential protective effect against tissue damage caused by inflammation processes. These observations suggest that stinging nettle is an interesting candidate for the development of phytopharmaceuticals or dietary supplements for cotreatment of various inflammatory diseases, particularly inflammatory bowel diseases. Copyright © 2017 John Wiley & Sons, Ltd.
  • Neuroprotective Natural Products for the Treatment of Parkinson's Disease
           by Targeting the Autophagy–Lysosome Pathway: A Systematic Review
    • Abstract: The autophagy–lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.
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