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Publisher: John Wiley and Sons   (Total: 1594 journals)

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Pacing and Clinical Electrophysiology     Hybrid Journal   (4 followers)
Packaging Technology and Science     Hybrid Journal   (9 followers)
Paediatric and Perinatal Epidemiology     Hybrid Journal   (3 followers)
Pain Medicine     Hybrid Journal   (5 followers)
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Palaeontology     Hybrid Journal   (11 followers)
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Parasite Immunology     Hybrid Journal   (3 followers)
Parliamentary History     Hybrid Journal   (3 followers)
Particle & Particle Systems Characterization     Hybrid Journal  
Pathogens and Disease     Hybrid Journal  
Pathology International     Hybrid Journal  
Peace & Change     Hybrid Journal   (3 followers)
Pediatric Allergy and Immunology     Hybrid Journal   (3 followers)
Pediatric Anesthesia     Hybrid Journal   (1 follower)
Pediatric Blood & Cancer     Hybrid Journal   (2 followers)
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Pediatric Diabetes     Hybrid Journal   (13 followers)
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Pediatric Pulmonology     Hybrid Journal   (2 followers)
Pediatric Transplantation     Hybrid Journal   (1 follower)
Pediatrics International     Hybrid Journal   (3 followers)
Performance Improvement     Hybrid Journal   (2 followers)
Performance Improvement Quarterly     Hybrid Journal   (1 follower)
Periodontology 2000     Hybrid Journal   (1 follower)
Permafrost and Periglacial Processes     Hybrid Journal   (3 followers)
Personal Relationships     Hybrid Journal   (3 followers)
Personality and Mental Health     Hybrid Journal   (10 followers)
Personnel Psychology     Hybrid Journal   (14 followers)
Perspectives In Psychiatric Care     Hybrid Journal   (1 follower)
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (3 followers)
Perspektiven der Wirtschaftspolitik     Hybrid Journal   (1 follower)
Pest Management Science     Hybrid Journal   (4 followers)
Pharmaceutical Statistics     Hybrid Journal   (3 followers)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (20 followers)
Pharmacology Research & Perspectives     Open Access  
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy     Hybrid Journal   (12 followers)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (1 follower)
Philosophical Books     Hybrid Journal   (8 followers)
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Philosophy Compass     Hybrid Journal   (8 followers)
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Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (3 followers)
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physica status solidi (a)     Hybrid Journal   (1 follower)
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physica status solidi (c)     Hybrid Journal   (1 follower)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal  
Physik in unserer Zeit     Hybrid Journal  
Physik Journal     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (1 follower)
Physiological Entomology     Hybrid Journal   (2 followers)
Physiological Reports     Open Access  
Physiotherapy Research International     Hybrid Journal   (18 followers)
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Pigment Cell & Melanoma Research     Hybrid Journal   (2 followers)
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Plasma Processes and Polymers     Hybrid Journal  
Poe Studies     Partially Free   (5 followers)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (6 followers)
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Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (26 followers)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (2 followers)
Process Safety Progress     Hybrid Journal   (2 followers)
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Progress In Cardiovascular Nursing     Hybrid Journal   (1 follower)
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Phytotherapy Research    Follow    
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
     Published by John Wiley and Sons Homepage  [1594 journals]   [SJR: 0.718]   [H-I: 65]
  • Asiatic Acid Reduces Blood Pressure by Enhancing Nitric Oxide
           Bioavailability with Modulation of eNOS and p47phox Expression in
           l‐NAME‐induced Hypertensive Rats
    • Abstract: We investigated the effect of asiatic acid (AA) on hemodynamic status, vascular function, oxidative stress markers, endothelial nitric oxide synthase (eNOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression in Nω‐nitro‐l‐arginine methyl ester hydrochloride (l‐NAME)‐induced hypertensive rats. Male Sprague–Dawley rats treated with l‐NAME (40 mg/kg/day) in drinking water for 5 weeks showed significant increases in mean arterial pressure, heart rate, hindlimb vascular resistance, vascular dysfunction, superoxide anion (O2•−) production, and plasma malondialdehyde. Moreover, NO metabolite (NOx) levels were reduced, aortic eNOS expression was downregulated, and NADPH oxidase subunit p47phox was upregulated in hypertensive rats (p 
       
  • In Vitro and In Silico Evaluation of NF‐κB Targeted Costunolide
           Action on Estrogen Receptor‐Negative Breast Cancer Cells—A
           Comparison with Normal Breast Cells
    • Abstract: Costunolide, a sesquiterpene lactone is a plant‐derived secondary metabolite found to be present in most of the pharmacologically active herbs, being the cause for their medicinal values. The present study aims to evaluate the cytotoxic effect of costunolide isolated from Costus speciosus rhizome extract on MDA‐MB‐231 cells and explore its targeted action in comparison with its action on the normal breast cells (MCF 10A). The effect of costunolide on cell viability of the cells was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide viability assay. The targeted action of the compound was analyzed comparing the effectiveness of the compound to alter the protein expression levels of NF‐κB subunits in the normal and the cancer cells using western blotting analysis. In silico studies were performed to predict the targeted interaction of costunolide with the NF‐κB subunit proteins. Costunolide inhibited the cell viability of MDA‐MB‐231 cells in a dose‐dependent manner leaving no significant change in the viability of the normal breast cells. The over expressed NF‐κB subunits – p65, 52 and 100 in the cancer cells were found to be downregulated when treated with costunolide at an effective dose of 20 and 40 μM costunolide. In silico results provided stable interactions between costunolide and the target proteins, supporting the in vitro results in addition. Thus, costunolide derived from C. speciosus plant source elevates a fresh conviction for its use in breast cancer therapy for its cytotoxic efficacy and non‐toxic nature. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Triggering of p38 MAPK and JNK Signaling is Important for Oleanolic
           Acid‐Induced Apoptosis via the Mitochondrial Death Pathway in
           Hypertrophic Scar Fibroblasts
    • Abstract: Hypertrophic scarring is characterized by collagen overproduction and excessive deposition of extracellular matrix. No consensus arises currently about the best therapeutics to produce complete and permanent improvement of scars with few side effects. In the present study, the mechanism of oleanolic acid (OA)‐induced apoptosis in hypertrophic scar fibroblasts (HSFs) was investigated for the first time. OA activated the protein phosphorylation of p38 MAPK and JNK but not ERK. OA did not antagonize the inhibitory effects of SB203580 on p38 MAPK pathway activity but sharply enhanced JNK phosphorylation when HSFs were pretreated with SB203580. Similarly, the inhibition of JNK signal pathway activation by pretreatment with SP600125 facilitated the protein phosphorylation of p38 MAPK caused by OA. Inhibition of p38 MAPK and/or JNK by inhibitors significantly enhanced cell viability and OA only partially depressed the increased cell viability. Moreover, OA increased Bax translocation, MMP loss, mitochondrial cytochrome c and AIF release, Bax and caspase‐3 protein expression and the ratio of Bax to Bcl‐2, decreased Bcl‐2 protein expression, and elevated the mRNA expression of Apaf‐1, caspase‐9, and capase‐3. These results suggest that OA elicits apoptosis through triggering of p38 MAPK and JNK signaling and activation of the mitochondrial death pathway. OA might be a good and useful natural drug against hypertrophic scars. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Inhibition of LPS‐Induced TNF‐α and NO Production in
           Mouse Macrophage and Inflammatory Response in Rat Animal Models by a Novel
           Ayurvedic Formulation, BV‐9238
    • Abstract: Rheumatoid arthritis is a chronic crippling disease, where protein‐based tumor necrosis factor‐alpha (TNF‐α) inhibitors show significant relief, but with potentially fatal side effects. A need for a safe, oral, cost‐effective small molecule or phyto‐pharmaceutical is warranted. BV‐9238 is an Ayurvedic poly‐herbal formulation containing specialized standardized extracts of Withania somnifera, Boswellia serrata, Zingiber officinale and Curcuma longa. The anti‐inflammatory and anti‐arthritic effects of BV‐9238 were evaluated for inhibition of TNF‐α and nitric oxide (NO) production, in lipopolysaccharide‐stimulated, RAW 264.7, mouse macrophage cell line. BV‐9238 reduced TNF‐α and NO production, without any cytotoxic effects. Subsequently, the formulation was tested in adjuvant‐induced arthritis (AIA) and carrageenan‐induced paw edema (CPE) rat animal models. AIA was induced in rats by injecting Freund's complete adjuvant intra‐dermally in the paw, and BV‐9238 and controls were administered orally for 21 days. Arthritic scores in AIA study and inflamed paw volume in CPE study were significantly reduced upon treatment with BV‐9238. These results suggest that the anti‐inflammatory and anti‐arthritic effects of BV‐9238 are due to its inhibition of TNF‐α, and NO, and this formulation shows promise as an alternate therapy for inflammatory disorders where TNF‐α and NO play important roles. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • The Puzzling Issue of ‘Vehicle‐Treated Control’ when
           Using Ethanol as Drug Carrier for MCF‐7 Cells
    • Abstract: Ethanol has been commonly used as a vehicle for drug discovery purpose in vitro. The human breast cancer MCF‐7 estrogen dependent cell line is a common in vitro model used for hormonal therapy study. However, special precaution is suggested when ethanol is used in pharmacological tests as solvent in order to evaluate the biological activity of potential drugs especially concerning about the MCF‐7. Ethanol was shown to stimulate the proliferation of this estrogen receptor positive cell line. Here, we have further demonstrated that the dose responsive stimulatory effect of ethanol on the MCF‐7 cells after pre‐incubating the breast carcinoma cells with phenol red‐free medium and stripped fetal bovine serum. Our findings open a discussion for the evaluation of ethanol as solvent for drug discovery and screening when using MCF‐7 cells as a testing model. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Effects of Black Raspberry on Lipid Profiles and Vascular Endothelial
           Function in Patients with Metabolic Syndrome
    • Abstract: Black raspberry (Rubus occidentalis) has been known for its anti‐inflammatory and anti‐oxidant effects. However, short‐term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12‐week follow‐up. Lipid profiles, brachial artery flow‐mediated dilatation (baFMD), and inflammatory cytokines such as IL‐6, TNF‐α, C‐reactive protein, adiponectin, sICAM‐1, and sVCAM‐1 were measured at the baseline and at the 12‐week follow‐up. Decreases from the baseline in the total cholesterol level (−22.8 ± 30.4 mg/dL vs. −1.9 ± 31.8 mg/dL, p 
       
  • Topical Anti‐inflammatory Potential of Standardized Pomegranate Rind
           Extract and Ellagic Acid in Contact Dermatitis
    • Abstract: The present study evaluated the topical anti‐inflammatory potential of a standardized pomegranate rind extracts (SPRE) in parallel with its marker compound ellagic acid (EA, 13% w/w) against a mouse model of contact dermatitis. In the phenol‐induced mouse ear edema, topical application of SPRE (5, 2.5, and 1 mg/ear) and EA (0.65, 0.325, and 0.13 mg/ear, equivalent to its content in SPRE) dose‐dependently reduced the ear edema with the maximal inhibition of 79.12% and 73.63%, respectively. Triamcinolone (0.1 mg/ear) and diclofenac (1 mg/ear) as reference drugs inhibited the edema by 73.63% and 37.91%. Myeloperoxidase (MPO) activity in the mouse ear was also decreased by SPRE and EA up to 69.68% and 68.79%, respectively. Triamcinolone and diclofenac decreased the MPO activity by 76.66% and 80.14% similarly. The results indicated that topical application of SPRE and EA is promising for use in the treatment of inflammatory skin disorders. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • A Rhodiola Rosea Root Extract Protects Skeletal Muscle Cells Against
           Chemically Induced Oxidative Stress by Modulating Heat Shock Protein 70
           (HSP70) Expression
    • Abstract: Rhodiola rosea is a perennial plant in the Crassulaceae family, recently postulated to exert its adaptogenic functions partially by modulating the expression of molecular factors such as heat shock proteins (HSP). The aim of this study was to analyze the efficacy of a Rhodiola rosea extract (Rhodiolife) in protecting murine skeletal muscle cells (C2C12 myotubes) from chemically induced oxidative stress and to establish whether modulation of HSP70 expression is observed. C2C12 cells treated with Rhodiolife did not experience any loss of viability (p > 0.05) at concentrations of 1–100 µg/mL for up to 24 h. In control cultures, viability decreased 25% following exposure to 2 mM H2O2 (1 h). However, no significant decrease in viability in cells pre‐treated with extract at concentrations as low as 1 µg/mL was observed. HSP70 mRNA levels were up‐regulated two‐fold in cell cultures treated with Rhodiolife (10 µg/mL), and expression was further enhanced by exposure to H2O2 (six‐fold, p 
       
  • The Anti‐Obesity Effects of the Dietary Combination of Fermented Red
           Ginseng with Levan in High Fat Diet Mouse Model
    • Abstract: In this study, to evaluate the anti‐obesity effects of fermented red ginseng (FG), levan (L), and their combination (FGL), we investigated their effects on the weights of body, liver and white adipose tissue, lipid profiles, and biomarkers for insulin resistance in high fat diet (HFD)‐induced obese C57BL/6J male mice. Furthermore, the levels of leptin in the serum were measured. FG (150 mg/kg/d), L (100 mg/kg/d), and FGL (150 mg/kg/d of FG plus 100 mg/kg/d of L) were administered orally to mice daily for 11 weeks. After 11 weeks feeding, FGL showed significantly lower body weight and fat mass with decreasing food efficiency ratio than the HFD control mice. In addition, the FGL group was significantly lower in the levels of total cholesterol and fasting blood glucose and score of the homeostatic model assessment of insulin resistance. Furthermore, FGL decreased serum leptin levels compared to the HFD control group. Taken together, FGL showed a significant anti‐obesity effect in HFD‐induced obese mice and prevent insulin and leptin resistance. FGL may be potentially useful for the prevention of obesity. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • In vitro Inhibition of Human CYP1A2, CYP2D6, and CYP3A4 by Six Herbs
           Commonly Used in Pregnancy
    • Abstract: Black elderberry, cranberry, fennel, ginger, horsetail, and raspberry leaf, herbs frequently used in pregnancy, were investigated for their in vitro CYP1A2, 2D6, and 3A4 inhibitory potential. Aqueous or ethanolic extracts were made from commercially available herbal products, and incubations were performed with recombinant cDNA‐expressed human CYP enzymes in the presence of positive inhibitory controls. Metabolite formation was determined by validated LCMS/MS or HPLC methodologies. IC50 inhibition constants were estimated from CYP activity inhibition plots using non‐linear regression. The most potent inhibition was shown for fennel towards CYP2D6 and 3A4 with respective IC50 constants of 23 ± 2 and 40 ± 4 µg/ml, horsetail towards CYP1A2 with an IC50 constant of 27 ± 1 µg/ml, and raspberry leaf towards CYP1A2, 2D6, and 3A4 with IC50 constants of 44 ± 2, 47 ± 8, and 81 ± 11 µg/ml, respectively. Based on the recommended dosing of the different commercial herbal products, clinically relevant systemic CYP inhibitions could be possible for fennel, horsetail, and raspberry leaf. In addition, fennel and raspberry leaf might cause a clinically relevant inhibition of intestinal CYP3A4. The in vivo inhibitory potential of these herbs towards specific CYP enzymes should be further investigated. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Curcumin I Mediates Neuroprotective Effect Through Attenuation of
           Quinoprotein Formation, p‐p38 MAPK Expression, and Caspase‐3
           Activation in 6‐Hydroxydopamine Treated SH‐SY5Y Cells
    • Abstract: 6‐Hydroxydopamine (6‐OHDA) selectively enters dopaminergic neurons and undergoes auto‐oxidation resulting in the generation of reactive oxygen species and dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the pathogenesis of Parkinson's disease and has been used to induce experimental Parkinsonism in both in vitro and in vivo systems. In this study, we investigated the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on quinoprotein production, phosphorylation of p38 MAPK (p‐p38), and caspase‐3 activation in 6‐OHDA‐treated SH‐SY5Y dopaminergic cells. Pretreatment of SH‐SY5Y with curcumin I at concentrations of 1, 5, 10, and 20 μM, significantly decreased the formation of quinoprotein and reduced the levels of p‐p38 and cleaved caspase‐3 in a dose‐dependent manner. Moreover, the levels of the dopaminergic neuron marker, phospho‐tyrosine hydroxylase (p‐TH), were also dose‐dependently increased upon treatment with curcumin I. Our results clearly demonstrated that curcumin I protects neurons against oxidative damage, as shown by attenuation of p‐p38 expression, caspase‐3‐activation, and toxic quinoprotein formation, together with the restoration of p‐TH levels. This study provides evidence for the therapeutic potential of curcumin I in the chemoprevention of oxidative stress‐related neurodegeneration. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Hawthorn (Crataegus oxyacantha L.) Bark Extract Regulates Antioxidant
           Response Element (ARE)‐Mediated Enzyme Expression Via Nrf2 Pathway
           Activation in Normal Hepatocyte Cell Line
    • Abstract: Hawthorn (Crataegus oxyacantha L.), a plant used in traditional medicine, is a rich source of procyanidins which have been reported to exhibit antioxidant and anti‐carcinogenic activity. In this study, we assessed the effect of hawthorn bark extract (HBE) on Nrf2 pathway activation in THLE‐2 and HepG2 cells. Treatment with 1.1 µg/mL, 5.5 µg/mL and 11 µg/mL of HBE resulted in the translocation of Nrf2 from the cytosol to the nucleus in both cell lines; however, the accumulation of phosphorylated Nrf2 was observed only in THLE‐2. Accordingly, treatment of cells with HBE was associated with an increase in the mRNA and protein level of such Nrf2‐dependent genes as glutathione S‐transferases (GSTA, GSTP, GSTM, GSTT), NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase‐1 (HO‐1) (0.2–1.1‐fold change, p 
       
  • Efficacy and Safety of Curcumin in Major Depressive Disorder: A Randomized
           Controlled Trial
    • Abstract: Curcumin, an active ingredient of Curcuma longa Linn (Zingiberaceae), has shown potential antidepressant‐like activity in animal studies. The objectives of this trial were to compare the efficacy and safety of curcumin with fluoxetine in patients with major depressive disorder (MDD). Herein, 60 patients diagnosed with MDD were randomized in a 1:1:1 ratio for six weeks observer‐masked treatment with fluoxetine (20 mg) and curcumin (1000 mg) individually or their combination. The primary efficacy variable was response rates according to Hamilton Depression Rating Scale, 17‐item version (HAM‐D17). The secondary efficacy variable was the mean change in HAM‐D17 score after six weeks. We observed that curcumin was well tolerated by all the patients. The proportion of responders as measured by the HAM‐D17 scale was higher in the combination group (77.8%) than in the fluoxetine (64.7%) and the curcumin (62.5%) groups; however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM‐D17 score at the end of six weeks was comparable in all three groups (P = 0.77). This study provides first clinical evidence that curcumin may be used as an effective and safe modality for treatment in patients with MDD without concurrent suicidal ideation or other psychotic disorders. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Costunolide Inhibits Osteoclast Differentiation by Suppressing c‐Fos
           Transcriptional Activity
    • Abstract: Costunolide, a sesquiterpene lactone, exhibits anti‐inflammatory and anti‐oxidant properties and mediates apoptosis. However, its effects and mechanism of action in osteoclasts remain unknown. Herein, we found that costunolide significantly inhibited RANKL‐induced BMM differentiation into osteoclasts in a dose‐dependent manner without affecting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen‐activated protein kinase and NF‐κB pathways. However, costunolide suppressed nuclear factor of activated T‐cells, cytoplasmic 1 (NFATc1) expression via inhibition of c‐Fos transcriptional activity without affecting RANKL‐induced c‐Fos expression. The inhibitory effects of costunolide were rescued by overexpression of constitutively active (CA)‐NFATc1. Taken together, our results suggest that costunolide inhibited RANKL‐induced osteoclast differentiation by suppressing RANKL‐mediated c‐Fos transcriptional activity. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Pharmacokinetics and Metabolism of 4‐O‐Methylhonokiol in Rats
    • Abstract: The purpose of this study was to characterize the pharmacokinetics and metabolism of 4‐O‐methylhonokiol in rats. The absorption and disposition of 4‐O‐methylhonokiol were investigated in male Sprague–Dawley rats following a single intravenous (2 mg/kg) or oral (10 mg/kg) dose. Its metabolism was studied in vitro using rat liver microsomes and cytosol. 4‐O‐Methylhonokiol exhibited a high systemic plasma clearance and a large volume of distribution. The oral dose gave a peak plasma concentration of 24.1±3.3 ng/mL at 2.9±1.9 h and a low estimated bioavailability. 4‐O‐Methylhonokiol was rapidly metabolized and converted at least in part to honokiol in a concentration‐dependent manner by cytochrome P450 in rat liver microsomes, predicting a high systemic clearance consistent with the pharmacokinetic results. It was also shown to be metabolized by glucuronidation and sulfation in rat liver microsomes and cytosol, respectively. 4‐O‐Methylhonokiol showed a moderate permeability with no apparent vectorial transport across Caco‐2 cells, suggesting that intestinal permeation process is not likely to limit its oral absorption. Taken together, these results suggest that the rapid hepatic metabolism of 4‐O‐methylhonokiol could be the major reason for its high systemic clearance and low oral bioavailability. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Inhibitory Effects of Nobiletin on Hepatocellular Carcinoma In Vitro and
           In Vivo
    • Abstract: Nobiletin (5, 6, 7, 8, 3′ 4′‐hexamethoxyflavone) is a major anticancer component in juice from zhishi (Rutaceae). This study aimed to investigate the inhibitory effect of Nobiletin on hepatic cancer cells both in vitro and in vivo. The 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT), growth curve, and clonogenic assay showed that nobiletin inhibited the proliferation of SMMC‐7721 cells in vitro. Hoechst staining observed the characteristics of cell apoptosis in nobiletin‐treated cells, and the apoptotic rates of treated groups were increased in a dose‐dependent manner. Flow cytometric analysis demonstrated that nobiletin could block the cell cycle arrested at G2 phase. Cell cycle analysis was performed using flow cytometry. Results showed that cell cycle phase distribution analysis showed G2 arrest. It was found that nobiletin downregulated the expressions of Bcl‐2 and COX‐2 and up‐regulated the expressions of Bax and caspase‐3 in SMMC‐7721 cells by western blotting. The experiment in vivo demonstrated that nobiletin significantly inhibited the growth of H22 transplantable tumor, downregulated the expressions of COX‐2, up‐regulated the expressions of Bax and caspase‐3 detected by immunohistochemistry and western blotting, and the ratios of Bcl‐2/Bax were decreased. Our results suggest that nobiletin has significant inhibitory effects on hepatocellular carcinoma both in vitro and in vivo. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • An Acute, Double‐Blind, Placebo‐Controlled Cross‐over
           Study of 320 mg and 640 mg Doses of Bacopa monnieri (CDRI 08)
           on Multitasking Stress Reactivity and Mood
    • Abstract: Little research exists in humans concerning the anxiolytic, antidepressant, sedative, and adaptogenic actions the traditional Ayurvedic medicine Bacopa monnieri (BM) possesses in addition to its documented cognitive‐enhancing effects. Preclinical work has identified a number of acute anxiolytic, nootropic, and adaptogenic effects of BM that may also co‐occur in humans. The current double‐blind, placebo‐controlled cross‐over study assessed the acute effects of a specific extract of BM (KeenMind® ‐ CDRI 08) in normal healthy participants during completion of a multitasking framework (MTF). Seventeen healthy volunteers completed the MTF, at baseline, then 1 h and 2 h after consuming a placebo, 320 mg BM and 640 mg of BM. Treatments were separated by a 7‐day washout with order determined by Latin Square. Outcome measures included cognitive outcomes from the MTF, with mood and salivary cortisol measured before and after each completion of the MTF. Change from baseline scores indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612000834853). Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Safety and Efficacy of Shilajit (Mumie, Moomiyo)
    • Abstract: Shilajit (mumie; moomiyo, mummiyo) has been used for a wide variety of illnesses and conditions for many years. However, relatively few well‐controlled human studies have been conducted on the effects of shiliajit, although a growing number of studies have been published in recent years involving animal and in vitro systems. The safety of shilajit is well documented based on animal and human studies. Various research studies indicate that shilajit exhibits antioxidant, anti‐inflammatory, adaptogenic, immunomodulatory, and anti‐dyslipidemic properties. Animal and human studies indicate that shilajit enhances spermatogenesis. Furthermore, animal and human data support its use as a ‘revitalizer’, enhancing physical performance and relieving fatigue with enhanced production of ATP. Key constituents in shilajit responsible for these effects appear to be dibenzo‐α‐pyrones and fulvic acid and their derivatives. Various mechanistic studies provide support for the above observed effects. Additional well‐controlled human and animal studies involving the use of standardized products are needed. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Steroidal Glycosides with Antiproliferative Activities from Digitalis
           trojana
    • Abstract: The phytochemical investigation of Digitalis trojana led to the isolation of two cardiac glycosides (1, 2), one pregnane glycoside (3), three furostanol type saponins (4–6), along with three cleroindicins (7–9), four phenylethanoid glycosides (10–13), two flavonoids (14, 15) and two phenolic acid derivatives (16, 17). The structure elucidation of the isolates was carried out by NMR experiments as well as ESI‐MS. The cytotoxic activity of compounds 1–13 against a small panel of cancer cell lines, namely MCF‐7, T98G, HT‐29, PC‐3, A375 and SH‐SY5Y, was investigated. Compounds 1–6 showed antiproliferative activity against human breast MCF‐7 and colon HT‐29 cancer cell lines with IC50 values ranging from 8.3 to 50 μM. In order to understand the mechanism involved in the cell death, the active compounds were tested as pro‐apoptotic agents using propidium iodide staining by flow cytometry method. No significant increase was observed in the apoptosis of the MCF‐7 and HT‐29 cancer cells. Moreover, the effects of the active compounds on cell proliferation were assessed on the same cancer cell lines by cell cycle analysis of DNA content using flow cytometry. No significative changes were observed in the cell cycle of MCF‐7, while significant changes in G2/M cell cycle phase of HT‐29 cells were observed after treatment with digitalin (1), cariensoside (3) and 22‐O‐methylparvispinoside B (6) at 10 μM. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Potentiating Therapeutic Effects by Enhancing Synergism Based on Active
           Constituents from Traditional Medicine
    • Abstract: Shifting current drug discovery tide from ‘finding new drugs’ to ‘screening natural products’ may be helpful for overcoming the ‘more investment, fewer drugs’ challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the ‘synergism’, that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Tongkat Ali as a Potential Herbal Supplement for Physically Active Male
           and Female Seniors—A Pilot Study
    • Abstract: Tongkat Ali (Eurycoma longifolia; TA) is known to increase testosterone levels and alleviate aging males' symptoms. This study aimed at investigating TA as an ergogenic supplement for elderly people. Thirteen physically active male and 12 physically active female seniors (57–72 years) were supplemented with 400‐mg TA extract daily for 5 weeks. Standard hematological parameters were taken. In addition, the concentrations of total and free testosterone, dihydroepiandrosterone, cortisol, insulin‐like growth factor‐1, and sex hormone‐binding globulin were analyzed. As additional biochemical parameters, blood urea nitrogen and creatine kinase as parameters of kidney function and muscle damage, respectively, as well as the muscle strength by a simple handgrip test were determined. After treatment, hemoglobin, testosterone, and dihydroepiandrosterone concentrations, and the ratio of total testosterone/cortisol and muscle force remained significantly lower in female seniors than in male seniors. Hematocrit and erythrocyte count in male seniors increased slightly but were significantly higher than in female seniors. Treatment resulted in significant increases in total and free testosterone concentrations and muscular force in men and women. The increase in free testosterone in women is thought to be due to the significant decline in sex hormone‐binding globulin concentrations. The study affirms the ergogenic benefit of TA through enhanced muscle strength. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Effect of Crocus sativus L. (Saffron) on Coagulation and Anticoagulation
           Systems in Healthy Volunteers
    • Abstract: Saffron showed some effects on blood coagulation and platelet aggregation in in vitro and in vivo studies. In a clinical trial with a limited number volunteers, saffron tablets influenced on bleeding time. In this study, the effect of saffron on plasma level of fibrinogen, factor VII (as coagulant agent), C and S protein (as anti‐coagulant agent), PT and PTT in a larger sample size was evaluated. The study was a double‐blind, placebo‐controlled study consisting of 1 week treatment with 200 mg and 400 mg saffron tablets. Sixty healthy volunteers (age range 20–50 years) were selected for the study. The volunteers were divided into three groups of 20 each. Group 1 received placebo; Groups 2 and 3 received 200 mg and 400 mg saffron tablets, respectively, for 7 days (1 tablet per day). Before and after 7 days treatment and also 1 month after that, blood samples were taken. The plasma levels of fibrinogen, factor VII, C and S protein, PT and PTT were evaluated. Statistical analysis showed no difference between groups for any of evaluated factors. This study rejected any effect of saffron with dose of 200 and 400 mg for 1 week on coagulant and anticoagulant system. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Anti‐Diabetic Potential of Panax Notoginseng Saponins (PNS): A
           Review
    • Abstract: Herbal medicines have traditionally played a major role in the management of diabetes in Asian countries for centuries. Panax notoginseng (Burk) F. H. Chen (Araliaceae) known as Tiánqī or san qi is a well‐known medicinal herb in Asia for its long history of use in Chinese medicine. Qualified as ‘the miracle root for the preservation of life’, it has been used in China for 600 years, for treatment of various diseases. Panax notoginseng saponins (PNS) are the key active components. PNS have been widely used in China for treatment of cardiovascular diseases. However, scientific studies have shown a wide range of other pharmacological applications including anti‐cancer, neuroprotective and anti‐inflammatory agents, immunologic adjuvant and prevention of diabetes complications. Recently, hypoglycemic and anti‐obesity properties of PNS have also been demonstrated. The present review highlights the effects of PNS on glucose production and absorption, and on inflammatory processes that seem to play an important role in the development of diabetes. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Therapeutic Potential of Turmeric in Alzheimer's Disease: Curcumin or
           Curcuminoids'
    • Abstract: Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple‐site‐targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Icariin: Does It Have An Osteoinductive Potential for Bone Tissue
           Engineering'
    • Abstract: Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi‐component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Most interestingly, it has been reported that icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. This review focuses on the performance of icariin in bone tissue engineering and on blending the information from icariin with the current knowledge relevant to molecular mechanisms and signal pathways. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti‐osteoporosis, osteogenesis, anti‐osteoclastogenesis, chondrogenesis, angiogenesis, and anti‐inflammation. The osteoinductive potential and the low price of icariin make it a very attractive candidate as a substitute of osteoinductive protein–bone morphogenetic proteins (BMPs), or as a promoter for enhancing the therapeutic effects of BMPs. However, the effectiveness of the local delivery of icariin needs to be investigated further. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • Topical Herbal Formulae in the Management of Psoriasis: Systematic Review
           with Meta‐Analysis of Clinical Studies and Investigation of the
           Pharmacological Actions of the Main Herbs
    • Abstract: This systematic review and meta‐analysis of randomized controlled trials (RCTs) examined the topical use of multi‐herbal formulations for the management of psoriasis vulgaris. Studies were identified from PubMed, Cochrane library, EMBASE, and the Chinese databases CNKI and CQVIP. Methods were according to the Cochrane Handbook and meta‐analyses used RevMan 5.1. Nine studies met the inclusion/exclusion criteria. The comparisons were with placebo and/or anti‐psoriatic pharmacotherapy (APP) with two studies having three arms. The pooled meta‐analysis data indicated the topical herbal formulae improved overall clinical efficacy (defined as 50% improvement or greater) when compared with: topical placebo (plus oral herbal co‐intervention); topical APP alone; and topical APP (plus pharmaceutical co‐intervention). Improvement was evident in Modified Psoriasis Area and Severity Index (PASI) score when topical herbal formula was compared to placebo (plus oral herbal co‐intervention). No serious adverse events were reported. The most commonly used herbs were Sophora flavescens root and Lithospermum erythrorhizon root. Experimental studies reported that these herbs and/or their constituents have anti‐inflammatory, anti‐proliferative, anti‐angiogenic, and tissue repair actions. These actions may at least partially explain the apparent benefits of the topical multi‐herbal formulations in psoriasis. Copyright © 2013 John Wiley & Sons, Ltd.
       
  • (−)‐Epigallocatechin‐3‐Gallate Ameliorates
           Photodynamic Therapy Responses in an In Vitro T Lymphocyte Model
    • Abstract: (−)‐Epigallocatechin‐3‐gallate (EGCG), the most abundant polyphenolic constituent in green tea, is known as a powerful antioxidant but concomitantly possesses a prooxidant property. We investigated the effect of EGCG on phloxine B (PhB)‐induced photocytotoxicity in human T lymphocytic leukemia Jurkat cells. EGCG significantly potentiated PhB‐induced photocytotoxic effects, including the inhibition of cell proliferation, DNA fragmentation, and caspase‐3 activity induction in Jurkat cells. Catalase attenuated the enhanced cytotoxicity by EGCG, suggesting the involvement of extracellularly produced hydrogen peroxide. Indeed, EGCG significantly enhanced extracellular hydrogen peroxide formation induced by photo‐irradiated PhB. The EGCG also enhanced intracellular reactive oxygen species accumulation, c‐Jun N‐terminal kinase (JNK) phosphorylation, and interferon‐γ (IFN‐γ) gene expression, all of which are involved in PhB‐induced apoptosis. Taken together, our data suggest that EGCG is capable of potentiating photodynamic therapy responses, presumably through the intracellular oxidative stress‐sensitive JNK/IFN‐γ pathway by exogenous hydrogen peroxide formation. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Anti‐Metastatic Effect of Supercritical Extracts from the Citrus
           hassaku Pericarp via Inhibition of C‐X‐C Chemokine Receptor
           Type 4 (CXCR4) and Matrix Metalloproteinase‐9 (MMP‐9)
    • Abstract: The fruit of hassaku (Citrus hassaku Hort. ex Tanaka) is locally known as phalsak in Korea. Recently, the fruit extract has been known to exhibit in vivo preventive effects against UVB‐induced pigmentation, antiallergic activity, and enhancement of blood fluidity. However, the exact mechanisms of how supercritical extracts of phalsak peel (SEPS) inhibits tumor metastasis and invasion are still not fully understood. We found that SEPS could downregulate the constitutive expression of both CXCR4 and HER2 in human breast cancer MDA‐MB‐231 cells as compared with other cells. SEPS also suppressed matrix metalloproteinase‐9 (MMP‐9) expression and its enzymatic activity under non‐cytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the SEPS‐induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, suppression of NF‐κB activity, and inhibition of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by SEPS correlated with the inhibition of CXCL12‐stimulated invasion of MDA‐MB‐231 cells. Overall, our results indicate, for the first time, that SEPS can suppress CXCR4 and MMP‐9 expressions through blockade of NF‐κB activation and thus has the potential to suppress metastasis of breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • The Influence of Selected Flavonoids from the Leaves of Cirsium palustre
           (L.) Scop. on Collagen Expression in Human Skin Fibroblasts
    • Abstract: Ten flavonoids belonging to the subclasses of flavones, flavanones and aurones were isolated from methanolic extract of Cirsium palustre leaves after multistep chromatographic separation. Their structures were elucidated with spectroscopic methods. All compounds, except for luteolin 7‐O‐glucoside, were isolated for the first time. Four compounds—eriodictyol 7‐O‐glucoside (6), 6‐hydroxyluteolin 7‐O‐glucoside (11), scutellarein 7‐O‐glucoside (12) and pedalitin (14)—were tested for their effect on collagen expression in normal human dermal fibroblasts. Among them, compound 11 at 40 μM and compound 14, at all concentrations used (1, 20, 40 μM), significantly enhanced the level of total collagen secreted into the medium. Furthermore, compound 11 significantly stimulated type I collagen expression, whereas compound 14 activated type I and III collagen expression at the mRNA level, depending on concentration. MMP‐2 activity was inhibited by all study compounds, with the greatest effect recorded with compound 14 at 20 μM. The lack of effect on collagen content in the medium of compound 6‐ and compound 12‐treated cells, besides an increase in COL1A1 and COL1A2 expression, might be caused by diminished expression of HSP47 gene, resulting in decreased procollagen secretion. Future study of compounds 11 and 14 for their potential therapeutic use in conditions connected with collagen biosynthesis deficiency is required. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Stimulative Effect of Ginsenosides Rg5:Rk1 on Murine Osteoblastic
           MC3T3‐E1 Cells
    • Abstract: Panax ginseng C.A. Meyer (P. ginseng), hereafter referred to as P. ginseng, is known to exert a wide range of pharmacological effects both in vitro and in vivo; however, few studies have investigated the effects of ginseng on bone metabolism. We therefore investigated the potential antiosteoporotic properties of ginseng on the growth and differentiation of murine MC3T3‐E1 cells. Rg5:Rk1 is a mixture of protopanaxadiol‐type ginsenosides, isolated from fresh P. ginseng root, via a repetitive steaming and drying process. In this study, we examined the stimulatory effects of Rg5:Rk1 on the differentiation and mineralization of MC3T3‐E1 cells. Undifferentiated cells were treated with a range of concentrations of Rg5:Rk1 (1–50 µg/mL), and cell viability was measured with the 3‐(4,5‐dimethyl‐thiazol‐2yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Treatment with Rg5:Rk1 significantly increased cell viability in a dose‐dependent manner. To investigate the possible mechanisms by which Rg5:Rk1 affects the early differentiation phase of MC3T3‐E1 cells, the cells were treated with Rg5:Rk1 for 14–24 days before assessing the levels of multiple osteoblastic markers. The markers examined included alkaline phosphatase (ALP) activity type I collagen content (Coll‐I), calcium deposition (by Alizarin Red S staining), extracellular mRNA expression of bone morphogenetic protein‐2 (BMP‐2), and the level of Runt‐related transcription factor 2 (Runx2). Rg5:Rk1 treatment also increased the activities of proteins associated with osteoblast growth and differentiation in a dose‐dependent manner. Overall, we found that the Rg5:Rk1 mixture of ginsenosides improved the osteoblastic function of MC3T3‐E1 cells by increasing their proliferative capacity. This improvement is due to the action of Rg5:Rk1 on BMP‐2, which is mediated by Runx2‐dependent pathways. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Preliminary Safety Evaluation and Biochemical Efficacy of a Carum carvi
           Extract: Results from a Randomized, Triple‐Blind, and
           Placebo‐Controlled Clinical Trial
    • Abstract: Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple‐blind, placebo‐controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25‐item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p 
       
  • The Different Effects of Resveratrol and Naringenin on Isolated Human
           Umbilical Vein: The Role of ATP‐Sensitive K+ Channels
    • Abstract: The blood flow from the placenta to the fetus depends on human umbilical vein (HUV) vascular tone. ATP‐sensitive K+ (KATP) channels link the metabolic state of the cell to membrane potential, and their activation in the HUV represents protection against hypoxia. The aims of our study were to assess the effects of resveratrol and naringenin on the HUV and to define the roles of KATP channels in their effects. Serotonin or 100 mM K+ were used for precontraction of the HUV without endothelium. The cumulative concentration–response curves were obtained by adding increasing concentrations of resveratrol or naringenin. Glibenclamide was used, in order to test the role of KATP channels in its effect. Resveratrol induced more potent vasodilatation of serotonin‐ and 100 mM K+‐precontracted HUV than naringenin. Glibenclamide induced significant shift to the right of the concentration–response curves of resveratrol and P1075 (a specific opener of KATP channels). Western blotting showed that HUV expressed protein Kir6.1. Thus, resveratrol and naringenin produce dilatation of HUV. It seems that KATP channels are involved in the relaxation of HUV induced by resveratrol, while naringenin seems to interact with other ion channels. The K+ channel‐independent mechanism(s) of these polyphenols could not be excluded. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Adjuvant Therapy with Bioavailability‐Boosted Curcuminoids
           Suppresses Systemic Inflammation and Improves Quality of Life in Patients
           with Solid Tumors: A Randomized Double‐Blind
           Placebo‐Controlled Trial
    • Abstract: Curcuminoids are bioactive polyphenolics with potent antiinflammatory properties. Although several lines of in vitro and preclinical evidence suggest potent anticancer effects of curcuminoids, clinical findings have not been conclusive. The present randomized double‐blind placebo‐controlled trial aimed to evaluate the efficacy of curcuminoids as adjuvant therapy in cancer patients. Eighty subjects with solid tumors who were under standard chemotherapy regimens were randomly assigned to a bioavailability‐boosted curcuminoids preparation (180 mg/day; n = 40) or matched placebo (n = 40) for a period of 8 weeks. Efficacy measures were changes in the health‐related quality of life (QoL) score (evaluated using the University of Washington index) and serum levels of a panel of mediators implicated in systemic inflammation including interleukins 6 (IL‐6) and 8 (IL‐8), TNF‐α, transforming growth factor‐β (TGFβ), high‐sensitivity C‐reactive protein (hs‐CRP), calcitonin gene‐related peptide (CGRP), substance P and monocyte chemotactic protein‐1 (MCP‐1). Curcuminoid supplementation was associated with a significantly greater improvement in QoL compared with placebo (p 
       
  • Boswellia serrata has Beneficial Anti‐Inflammatory and Antioxidant
           Properties in a Model of Experimental Colitis
    • Abstract: Ulcerative colitis is an inflammatory disease that involves only the colon and rectum, being characterized by leukocyte infiltrate and superficial ulcers in the intestinal mucosa. To evaluate the anti‐inflammatory and antioxidant effects of extract from the Boswellia serrata plant in an experimental rat model of acute ulcerative colitis induced by the administration of acetic acid (AA). An extract of B. serrata (34.2 mg/kg/day) was administered by oral gavage for 2 days before and after the induction of colitis with 4 mL of 4% AA. The anal sphincter pressure in the colitis group showed a significant decrease compared to that of the control groups (p 
       
  • Hypolipidemic and antiinflammation activities of fermented soybean fibers
           from meju in C57BL/6 J mice
    • Abstract: Meju, a naturally fermented soy block used to produce soy paste and soy sauce in Korea, is suggested to exhibit hypolipidemic and antiinflammatory activities; however, its mechanisms of action are elusive. Here, we report that the water‐soluble fibers but not the amino acids and peptides from meju exhibited hypolipidemic activity in vivo. Feeding of fermented soybean fibers (FSF) from meju reduced plasma cholesterol, triglyceride, adipocyte size, and hepatic lipid accumulation in C57BL/6 J mice. FSF treatment reduced HMG‐CoA reductase expression, whereas the expression of genes in the fatty acid uptake and subsequent beta‐oxidation were significantly induced in the livers. Hepatic lipogenic genes, including Srebp1c and Lxrα, were unaltered. Feeding with the fermented soybean peptides and amino acids (FSPA) induced the expression of lipogenic genes, which may have canceled the induction of low‐density lipoprotein receptor and Cyp7a1 gene expressions in FSPA livers. The plasma concentrations of C‐reactive protein, TNF‐α, and interlukin‐6 were significantly reduced in the FSF, FSPA, and meju groups compared with the control groups, suggesting that both of the fibers and peptides/amino acids from meju may be beneficial. These findings suggest that soluble fibers from meju are critical hypolipidemic components that regulate hepatic gene expressions and reduce proinflammatory cytokines in vivo. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Beyond Organoleptic Characteristics: The Pharmacological Potential of
           Flavonoids and their Role in Leukocyte Migration and in L‐Selectin
           and β2‐Integrin Expression During Inflammation
    • Abstract: Flavonoids are compounds responsible for several organoleptic characteristics of plant‐derived foods. They are also bioactive compounds with antiinflammatory role. Different mechanisms for this activity have been reported, but their effects on cell migration are not fully understood. In the present study, the role of flavonoids on leukocyte migration in vivo was investigated, using the carrageenan‐induced pleurisy model and intravital microscopy in rats. It was found that quercetin (1), rutin (2), flavone (5), apigenin (6) and flavonol (7) reduced cell migration to the pleural cavity and inhibited rolling, adhesion and transmigration. Additionally, flow cytometry assays showed that the in vitro treatment with all compounds (15–60 µm) did not cause cell death and 1 inhibited the cleavage of L‐selectin and the β2‐integrin expression, whereas 2 and 7 only inhibited the β2‐integrin expression. Together, data herein presented clearly show the ability of flavonoids to inhibit in vivo neutrophil influx into inflamed tissue, by acting in different mechanisms of neutrophil migration. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Luteolin Inhibits Hyperglycemia‐Induced Proinflammatory Cytokine
           Production and Its Epigenetic Mechanism in Human Monocytes
    • Abstract: Hyperglycemia is a key feature in diabetes. Hyperglycemia has been implicated as a major contributor to several complications of diabetes. High glucose levels induce the release of proinflammatory cytokines. Luteolin is a flavone isolated from celery, green pepper, perilla leaf, and chamomile tea. Luteolin has been reported to possess antimutagenic, antitumorigenic, antioxidant, and anti‐inflammatory properties. In this study, we investigated the effects of luteolin on proinflammatory cytokine secretion and its underlying epigenetic regulation in high‐glucose‐induced human monocytes. Human monocytic (THP‐1) cells were cultured under controlled (14.5 mM mannitol), normoglycemic (NG, 5.5 mM glucose), or hyperglycemic (HG, 20 mM glucose) conditions, in the absence or presence of luteolin. Luteolin (3–10 μM) was added for 48 h. While hyperglycemic conditions significantly induced histone acetylation, NF‐κB activation, and proinflammatory cytokine (IL‐6 and TNF‐α) release from THP‐1 cells, luteolin suppressed NF‐κB activity and cytokine release. Luteolin also significantly reduced CREB‐binding protein/p300 (CBP/p300) gene expression, as well as the levels of acetylation and histone acetyltransferase (HAT) activity of the CBP/p300 protein, which is a known NF‐κB coactivator. These results suggest that luteolin inhibits HG‐induced cytokine production in monocytes, through epigenetic changes involving NF‐κB. We therefore suggest that luteolin may be a potential candidate for the treatment and prevention of diabetes and its complications. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • In vitro Antitumoral Activity of Compounds Isolated from Artemisia
           gorgonum Webb
    • Abstract: Artemisia gorgonum (Asteraceae) is an endemic plant to the Cape Verde islands and plays an important role in traditional medicine. The chloroform extract of the plant aerial parts afforded six sesquiterpene lactones, two methoxylated flavonoids, two lignans, and one tetracyclic triterpene, which were isolated by chromatographic methods and their structure established by physical and spectroscopic techniques. The cytotoxic activity of the three major constituents, namely, arborescin, artemetin, and sesamin, was evaluated on neuroblastoma (SH‐SY5Y), hepatocarcinoma (HepG2), and nontumoral bone marrow stromal (S17) cell lines. The application of different concentrations of the compounds significantly decreased tumor cells viability at different extents, especially at the highest concentrations tested. Arborescin is the most promising compound as it was able to reduce tumoral cell viability with an IC50 significantly lower (229–233 μM; p 
       
  • Eruca sativa and its Flavonoid Components, Quercetin and Isorhamnetin,
           Improve Skin Barrier Function by Activation of Peroxisome
           Proliferator‐Activated Receptor (PPAR)‐α and Suppression
           of Inflammatory Cytokines
    • Abstract: Atopic dermatitis, which is related to dermatologic disorders and is associated with skin barrier dysfunction, represents an epidemic problem demanding effective therapeutic strategies. In the present study, we showed that the treatment with Eruca sativa extract resulted in a significant increase in the transactivation activity of peroxisome proliferator‐activated receptor (PPAR) response element such as PPAR‐α and suppression in the expression of inflammatory cytokine and antimicrobial peptides. In addition, E. sativa extract promotes the expression of filaggrin related to skin barrier protection. Quercetin and isorhamnetin, flavonoids' constituents of E. sativa, also promoted PPAR‐α activity. These results indicate that E. sativa extract may be an appropriate material for improving skin barrier function as a skin therapeutic agent for atopic dermatitis. Copyright © 2014 John Wiley & Sons, Ltd.
       
  • Pharmacological Basis for Medicinal Use of Lens culinaris in
           Gastrointestinal and Respiratory Disorders
    • Abstract: Crude extract of Lens culinaris (Lc.Cr), which tested positive for presence of anthraquinones, flavonoids, saponins, sterol, tannins, and terpenes exhibited protective effect against castor oil‐induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Lc.Cr caused relaxation of spontaneous contractions at 0.03–5.0 mg/mL. Lc.Cr inhibited carbachol (CCh, 1 μM) and K+ (80 mM)‐induced contractions in a pattern similar to dicyclomine, but different from verapamil and atropine. Lc.Cr shifted the Ca++ concentration‐response curves to the right, like dicyclomine and verapamil. Pretreatment of tissues with Lc.Cr (0.03–0.1 mg/mL) caused leftward shift of isoprenaline‐induced inhibitory CRCs, similar to papaverine. In guinea‐pig ileum, Lc.Cr produced rightward parallel shift of CCh curves, followed by non‐parallel shift at higher concentration with suppression of maximum response, similar to dicyclomine, but different from verapamil and atropine. Lc.Cr (3.0–30 mg/kg) caused suppression of carbachol (CCh, 100 µg/kg)‐induced increase in inspiratory pressure of anesthetized rats. In guinea‐pig trachea, Lc.Cr relaxed CCh and high K+‐induced contractions, shifted CCh curves to right and potentiated isoprenaline response. These results suggest that L. culinaris possesses antidiarrheal, antispasmodic, and bronchodilator activities mediated possibly through a combination of Ca++ antagonist, anticholinergic, and phosphodiesterase inhibitory effects, and this study provides sound mechanistic background to its medicinal use in disorders of gut and airways hyperactivity, like diarrhea and asthma. Copyright © 2014 John Wiley & Sons, Ltd.
       
 
 
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