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Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.42, h-index: 28)
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Process Safety Progress     Hybrid Journal   (Followers: 2, SJR: 0.366, h-index: 20)
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Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)
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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  [1603 journals]   [SJR: 0.718]   [H-I: 65]
  • Effect of Kuwanon G Isolated from the Root Bark of Morus alba on
           Ovalbumin‐induced Allergic Response in a Mouse Model of Asthma
    • Authors: Hyo Won Jung; Seok Yong Kang, Jong Seong Kang, A Ryun Kim, Eun‐Rhan Woo, Yong‐Ki Park
      Pages: n/a - n/a
      Abstract: The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)‐induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA‐specific IgE and Th2 cytokines (IL‐4, IL‐5, and IL‐13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA‐specific IgE and IL‐4, IL‐5, and IL‐13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-13T06:05:25.635971-05:
      DOI: 10.1002/ptr.5191
  • Alkali‐Soluble Polysaccharide, Isolated from Lentinus edodes,
           Induces Apoptosis and G2/M Cell Cycle Arrest in H22 Cells Through
           Microtubule Depolymerization
    • Authors: Ru‐xu You; Jin‐yu Liu, Shi‐jun Li, Liu Wang, Kai‐ping Wang, Yu Zhang
      Pages: n/a - n/a
      Abstract: The aim of the study was to evaluate the pro‐apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN‐induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca2+. In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN‐induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti‐tumour effect of LTN. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-11T06:28:19.018762-05:
      DOI: 10.1002/ptr.5209
  • Antiinflammatory Properties of the Stem‐bark of Anopyxis klaineana
           and its Major Constituent, Methyl Angolensate
    • Authors: Evelyn A. Mireku; Abraham Y. Mensah, Merlin L. K. Mensah, Derek A. Tocher, Solomon Habtemariam
      Pages: n/a - n/a
      Abstract: Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West African folkloric medicines that has never been investigated for its pharmacological effects or phytochemical constituents. In the present study, the antiinflammatory properties of the stem‐bark extracts were evaluated using the carrageenan‐induced paw oedema model in chicks. The petroleum ether, ethyl acetate and methanol extracts all showed a time and dose‐dependent antiinflammatory effect over the 5‐h observation period. Phytochemical analysis of the most active extract (methanol extract) yielded the principal constituent that was identified as methyl angolensate through extensive spectroscopic and X‐ray analysis studies. Although slightly less potent (ED50, 4.05 ± 0.0034 mg/kg, orally) than the positive control, diclofenac (ED50, 2.49 ± 0.023, intraperitoneally n = 5), this first ever compound isolated from A. klaineana showed promising antiinflammatory activity that may account to some of the reported medicinal uses of the plant. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-11T05:59:44.307133-05:
      DOI: 10.1002/ptr.5212
  • Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and
           Hairless Mice
    • Authors: Eunson Hwang; Sang‐Yong Park, Hyun Ji Lee, Tae Youp Lee, Zheng‐wang Sun, Tae Hoo Yi
      Abstract: Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin‐6, and MMP‐1 were significantly suppressed, and type I procollagen expression was stimulated in UVB‐irradiated and GA‐treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP‐1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor‐β1. Our data indicate that GA is a potential candidate for the prevention of UVB‐induced premature skin aging. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-08T01:33:04.742814-05:
      DOI: 10.1002/ptr.5198
  • Eugenia punicifolia (Kunth) DC. as an Adjuvant Treatment for Type‐2
           Diabetes Mellitus: A non‐Controlled, Pilot Study
    • Authors: Débora Simone Sales; Fabio Carmona, Bruna Cestari Azevedo, Silvia Helena Taleb‐Contini, Ana Carolina Duó Bartolomeu, Fernando B. Honorato, Edson Z. Martinez, Ana Maria Soares Pereira
      Abstract: Type‐2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type‐2 DM. Fifteen patients were enrolled in a pilot, non‐controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid‐stimulating hormone, C‐reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin‐3‐O‐rhamnoside, quercetin‐3‐O‐galactoside, quercetin‐3‐O‐xyloside, quercetin‐3‐O‐rhamnoside, kaempferol‐3‐O‐rhamnoside, phytol, gallic acid, and trans‐caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type‐2 DM and deserve further investigation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-06T07:40:47.985891-05:
      DOI: 10.1002/ptr.5206
  • Lipid‐Lowering Effects of Curcumin in Patients with Metabolic
           Syndrome: A Randomized, Double‐Blind, Placebo‐Controlled Trial
    • Authors: Yi‐Sun Yang; Ying‐Fang Su, Hui‐Wen Yang, Yu‐Hsien Lee, Janet I. Chou, Kwo‐Chang Ueng
      Abstract: Human studies of curcumin extract on lipid‐lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty‐five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high‐density lipoprotein cholesterol (HDL‐C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p 
      PubDate: 2014-08-06T07:35:50.344871-05:
      DOI: 10.1002/ptr.5197
  • Effects of Smilaxchinoside A and Smilaxchinoside C, Two Steroidal
           Glycosides from Smilax riparia, on Hyperuricemia in a Mouse Model
    • Authors: Xiao‐Hui Wu; Chong‐Zhi Wang, Jun Zhang, Shu‐Qing Wang, Lide Han, Yan‐Wen Zhang, Chun‐Su Yuan
      Abstract: The roots and rhizomes of Smilax riparia, called ‘Niu‐Wei‐Cai’ in traditional Chinese medicine, are believed to be effective in treating the symptoms of gout. However, the active constituents and their uricosuric mechanisms are unknown. In this study, we isolated two steroidal glycosides, named smilaxchinoside A and smilaxchinoside C, from the total saponins obtained from the ethanol extract of the roots of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We observed that these two steroidal glycosides possess potent uricosuric activities, and the observed effects accompanied the reduction of renal mURAT1 and the inhibition of xanthine oxidase, which contribute to the enhancement of uric acid excretion and the reduction of hyperuricemia‐induced renal dysfunction. Smilaxchinoside A and smilaxchinoside C may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-06T00:13:47.100955-05:
      DOI: 10.1002/ptr.5207
  • Investigation of the Efficacy of Adjunctive Therapy with
           Bioavailability‐Boosted Curcuminoids in Major Depressive Disorder
    • Authors: Yunes Panahi; Roghayeh Badeli, Nima Karami, Amirhossein Sahebkar
      Abstract: Current medications have limited efficacy in controlling the symptoms of major depressive disorder (MDD), and are associated with several adverse events on long‐term use. Curcuminoids are extremely safe and multifunctional phytopharmaceuticals that have been shown to alleviate depressive symptoms in a variety of experimental models. The present study aimed to investigate the efficacy of curcuminoids as an add‐on to standard antidepressants in patients with MDD. One hundred and eleven subjects were assigned to standard antidepressive therapy plus curcuminoids–piperine combination (1000–10 mg/day; n = 61) or standard antidepressive therapy alone (n = 50) for a period of 6 weeks. Efficacy measures were changes in the psychological status on the basis of the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI‐II). The BDI‐II and HADS total and subscale scores were reduced by the end of trial in both study groups. There were significantly greater reductions in total HADS score and subscales of anxiety and depression in the curcuminoids versus control group (p 
      PubDate: 2014-08-04T06:26:29.744501-05:
      DOI: 10.1002/ptr.5211
  • Effects of Five Ayurvedic Herbs on Locomotor Behaviour in a Drosophila
           melanogaster Parkinson's Disease Model
    • Authors: R. L. M. Jansen; B. Brogan, A. J. Whitworth, E. J. Okello
      Abstract: Current conventional treatments for Parkinson's disease (PD) are aimed at symptom management, as there is currently no known cure or treatment that can slow down its progression. Ayurveda, the ancient medical system of India, uses a combination of herbs to combat the disease. Herbs commonly used for this purpose are Zandopa (containing Mucuna pruriens), Withania somnifera, Centella asiatica, Sida cordifolia and Bacopa monnieri. In this study, these herbs were tested for their potential ability to improve climbing ability of a fruit fly (Drosophila melanogaster) PD model based on loss of function of phosphatase and tensin‐induced putative kinase 1 (PINK1). Fruit flies were cultured on food containing individual herbs or herbal formulations, a combination of all five herbs, levodopa (positive control) or no treatment (negative control). Tests were performed in both PINK1 mutant flies and healthy wild‐type (WT) flies. A significant improvement in climbing ability was observed in flies treated with B. monnieri compared with untreated PINK1 mutant flies. However, a significant decrease in climbing ability was observed in WT flies for the same herb. Centella asiatica also significantly decreased climbing ability in WT flies. No significant effects were observed with any of the other herbs in either PINK1 or WT flies compared with untreated flies. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-04T06:01:37.095359-05:
      DOI: 10.1002/ptr.5199
  • The Protective Effects of a Polyphenol‐Enriched Protein Powder on
           Exercise‐Induced Susceptibility to Virus Infection
    • Authors: Maryam Ahmed; Dru A. Henson, Matthew C. Sanderson, David C. Nieman, Nicholas D. Gillitt, Mary Ann Lila
      Abstract: Prolonged and intensive exercise induces transient immunosuppression and is associated with an increased risk and severity of infections. The goal of this study was to characterize the antiviral and antibacterial properties of the bioactive metabolites of a blueberry–green tea‐polyphenol soy protein complex (PSPC) in the serum of supplemented subjects during a 3‐day intensified training period. Long‐distance runners, randomly divided into two groups, ingested 40 g/day PSPC or placebo (soy protein and colorings) for 17 days, with a 3‐day running period inserted at day 14. Blood serum samples were collected pre‐14 days and post‐14 days supplementation, and immediately and 14 h after the third day of running. The post‐exercise serum from both groups significantly promoted the growth of Escherichia coli and Staphylococcus aureus in culture by 20–70%, but returned to normal levels following recovery. Furthermore, the serum from subjects ingesting PSPC did not display antibacterial properties at any time point. In contrast, there was a significant difference in the ability of serum from PSPC‐supplemented versus placebo‐supplemented athletes to protect cells in culture from killing by vesicular stomatitis virus following strenuous exercise. In addition, the serum of subjects who ingested PSPC significantly delayed an exercise‐induced increase in virus replication. These results indicate that polyphenol complexes containing blueberry and green tea have the potential to protect athletes from virus infections following rigorous exercise. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T03:21:43.671858-05:
      DOI: 10.1002/ptr.5208
  • Involvement of Cerebral Nervous System Areas and Cytokines on
           Antihyperalgesic and Anti‐Inflammatory Activities of Kielmeyera
           rugosa Choisy (Calophyllaceae) in Rodents
    • Authors: M.S. Melo; R.G. Brito, P.L. Santos, P.C.L. Nogueira, V.R.S. Moraes, M.C.P. Matos, J.N.S. Ferro, E.O. Barreto, W. Lucca Junior, M.A. Botelho, L.J. Quintans Junior
      Abstract: Kielmeyera rugosa is a medicinal plant known in Northeastern Brazil as ‘pau‐santo’, and it is used in the treatment of several tropical diseases such as malaria, schistosomiasis, and leishmaniasis. We evaluated antihyperalgesic and anti‐inflammatory activities of methanol stem extract of K. rugosa (MEKR) in mice. The mechanical hyperalgesia induced by carrageenan and tumor necrosis factor‐alpha (TNF‐α), prostaglandin E2, and dopamine were assessed. We also investigated the anti‐inflammatory effect of MEKR on carrageenan‐induced pleurisy and paw edema. Ninety minutes after the treatment, the animals were submitted to an imunofluorescence for Fos protein. MEKR (100, 200, and 400 mg/kg; p.o.) inhibited the development of mechanical hypernociception and edema. MEKR significantly decreased TNF‐α and interleukin 1β levels in pleural lavage and suppressed the recruitment of leukocytes. MEKR (1, 10, and 100 mg/mL) did not produce cytotoxicity, determined using the methyl‐thiazolyl‐tetrazolium assay in vitro. The locomotor activity was not affected. MEKR activated significantly the bulb olfactory, piriform cortex, and periaqueductal gray of the central nervous system. Our results provide first time evidence to propose that MEKR attenuates mechanical hyperalgesia and inflammation, in part, through an activation of central nervous system areas, mainly the periaqueductal gray and piriform cortex areas. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T01:46:38.761566-05:
      DOI: 10.1002/ptr.5205
  • Effects of Eucommia ulmoides Extract on Longitudinal Bone Growth Rate in
           Adolescent Female Rats
    • Authors: Ji Young Kim; Jeong‐Il Lee, MiKyung Song, Donghun Lee, Jungbin Song, Soo Young Kim, Juyeon Park, Ho‐Young Choi, Hocheol Kim
      Abstract: Eucommia ulmoides is one of the popular tonic herbs for the treatment of low back pain and bone fracture and is used in Korean medicine to reinforce muscles and bones. This study was performed to investigate the effects of E. ulmoides extract on longitudinal bone growth rate, growth plate height, and the expressions of bone morphogenetic protein 2 (BMP‐2) and insulin‐like growth factor 1 (IGF‐1) in adolescent female rats. In two groups, we administered a twice‐daily dosage of E. ulmoides extract (at 30 and 100 mg/kg, respectively) per os over 4 days, and in a control group, we administered vehicle only under the same conditions. Longitudinal bone growth rate in newly synthesized bone was observed using tetracycline labeling. Chondrocyte proliferation in the growth plate was observed using cresyl violet dye. In addition, we analyzed the expressions of BMP‐2 and IGF‐1 using immunohistochemistry. Eucommia ulmoides extract significantly increased longitudinal bone growth rate and growth plate height in adolescent female rats. In the immunohistochemical study, E. ulmoides markedly increased BMP‐2 and IGF‐1 expressions in the proliferative and hypertrophic zones. In conclusion, E. ulmoides increased longitudinal bone growth rate by promoting chondrogenesis in the growth plate and the levels of BMP‐2 and IGF‐1. Eucommia ulmoides could be helpful for increasing bone growth in children who have growth retardation. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-02T00:34:35.834751-05:
      DOI: 10.1002/ptr.5195
  • Review of the Botanical Characteristics, Phytochemistry, and Pharmacology
           of Astragalus membranaceus (Huangqi)
    • Authors: Juan Fu; Zenghui Wang, Linfang Huang, Sihao Zheng, Dongmei Wang, Shilin Chen, Haitao Zhang, Shihai Yang
      Abstract: Astragalus membranaceus is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The current paper reviews the botanical characteristics, phytochemistry, and pharmacology of Astragali Radix. Information on Astragali Radix was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Medline Plus, CNKI, and Web of Science) as well as from libraries and local books. More than 100 compounds, including flavonoids, saponins, polysaccharides, and amino acids, have so far been identified, and the various biological activities of the compounds have been reported. As an important traditional Chinese medicine, further studies on Astragali Radix can lead to the development of new drugs and therapies for various diseases. The improvement of its utilization should be studied further. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-08-01T23:09:05.80425-05:0
      DOI: 10.1002/ptr.5188
  • Apple Polyphenol Extracts Protect Against Aspirin‐induced Gastric
           Mucosal Damage in Rats
    • Authors: Gunaranjan Paturi; Christine A. Butts, Kerry L. Bentley‐Hewitt, Tony K. McGhie, Zaid S. Saleh, Andrew McLeod
      Abstract: The protective role of two apple polyphenol extracts, Douglas‐FB (FB) and Douglas‐EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague–Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10‐day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10−2 m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10‐day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-28T06:20:14.25098-05:0
      DOI: 10.1002/ptr.5210
  • Phytochemistry and Antileishmanial Activity of the Leaf Latex of Aloe
           calidophila Reynolds
    • Authors: Fetene Abeje; Daniel Bisrat, Asrat Hailu, Kaleab Asres
      Abstract: Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC50 values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, 1H NMR, and 13C NMR spectral data. The isolated compounds showed strong antileishmanial activity with IC50 values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC50 = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost‐effective antileishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-28T05:29:48.454181-05:
      DOI: 10.1002/ptr.5204
  • A Chemically Standardized Extract of Ziziphus jujuba Fruit (Jujube)
           Stimulates Expressions of Neurotrophic Factors and Anti‐oxidant
           Enzymes in Cultured Astrocytes
    • Authors: Jianping Chen; Artemis L. Yan, Kelly Y. C. Lam, Candy T. W. Lam, Ning Li, Ping Yao, Aizhen Xiong, Tina T. X. Dong, Karl W. K. Tsim
      Abstract: The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as a health supplement worldwide. To study the role of jujube in brain benefits, the expression of neurotrophic factors and anti‐oxidant enzymes in the jujube‐treated cultured astrocytes was determined. Application of a chemical standardized water extract of jujube in cultured astrocytes for 24 h stimulated the expressions of nerve growth factor, brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor in a concentration‐dependent manner. The pre‐treatment with H89, a protein kinase A inhibitor, attenuated the jujube‐induced expression of neurotrophic factors. In parallel, the treatment of jujube water extract induced the transcriptional expressions of the enzymes responsible for anti‐oxidation, i.e. NAD(P)H: quinine oxidoreductase 1, glutamate‐cysteine ligase catalytic subunit, glutamate‐cysteine ligase modifier subunit and glutathione S‐transferase, in a concentration‐dependent manner. These results proposed the benefits of jujube in regulating expressions of neurotrophic factors and anti‐oxidant enzymes in cultured astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-28T05:21:06.635852-05:
      DOI: 10.1002/ptr.5202
  • Anti‐inflammatory Effects of Ginsenosides Rg5, Rz1, and Rk1:
           Inhibition of TNF‐α‐induced NF‐κB,
           COX‐2, and iNOS transcriptional expression
    • Authors: Sang Myung Lee
      Abstract: In the course of this experiment on the anti‐inflammatory effect of ginsenosides, protopanaxdiol ginsenosides have shown inhibition activities in inflammatory responses: NF‐κB, COX‐2, and iNOS were induced by TNF‐α. The responses of this experiment were evaluated by NF‐κB‐luciferase assay and RT‐PCR experiment of COX‐2 and iNOS genes. The NF‐κB expressions were inhibited by ginsenosides Rd, Rg5, Rz1, and Rk1 in a dose‐dependent manner. The IC50 values were 3.47, 0.61, 0.63, and 0.75 μM, respectively. Particularly, ginsenosides Rg5, Rz1, and Rk1 as converted ginsenosides from primary protopanaxdiol ginsenosidess significantly inhibited COX‐2 and iNOS gene expression. These inhibition levels were similar to sulfasalazine as reference material. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-20T23:19:11.100975-05:
      DOI: 10.1002/ptr.5203
  • Antiinflammatory, Antioxidant, and Immunological Effects of Carum copticum
           L. and Some of Its Constituents
    • Authors: Azam Alavinezhad; Mohammad Hossein Boskabady
      Abstract: Carum copticum L. has been used traditionally for its various therapeutic effects. The plant contains various components such as thymol and carvacrol. Different therapeutic effects such as antifungal, antioxidant, antibacterial, antiparasitic, and antilipidemic were described for the plant and its constituents. Therefore, antiinflammatory, antioxidant, and immunological effects of C. copticum and its constituents, thymol and carvacrol, were discussed in the present review. Previous studies have shown potent antiinflammatory, antioxidant, and immunological effects for C. copticum and its constituents, thymol and carvacrol. Therefore, the plant and its constituents have therapeutic values in several inflammatory and immunological disorders as well as in the oxidative stress conditions. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-20T22:11:24.051702-05:
      DOI: 10.1002/ptr.5200
  • Evaluation of the Effect of Curcumin Capsules on Glyburide Therapy in
           Patients with Type‐2 Diabetes Mellitus
    • Authors: Prasad Neerati; Raju Devde, Anil Kumar Gangi
      Abstract: This study aimed to assess the possible beneficial effects of curcumin capsules as lipid‐lowering effects and as a permeability glycoprotein (P‐gp) inhibitor on the pharmacokinetics and pharmacodynamics of glyburide and as a P‐gp substrate with glyburide in patients with type‐2 diabetes mellitus. Open‐label, randomized control trial was carried out for 11 days on eight type‐2 diabetic patients on glyburide therapy. On the first day of the study, following the administration of 5 mg of glyburide, blood samples were collected from the patients at various time intervals ranging from 0.5 to 24 h. Blood sampling was repeated on the 11th day of the study, after treating the patients with curcumin for ten consecutive days. Glyburide concentrations changed at the second hour, Cmax was unchanged, the glucose levels were decreased, Area Under first Movement Curre (AUMC) was increased, and no patient has experienced the hypoglycaemia. The low‐density lipoprotein, very‐low‐density lipoprotein and triglycerides were decreased significantly, and the high‐density lipoprotein content increased. The co‐administration of curcumin capsules with glyburide may be beneficial to the patients in better glycaemic control. The lipid lowering and antidiabetic properties of the curcumin show as a potential future drug molecule. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-17T02:42:15.002799-05:
      DOI: 10.1002/ptr.5201
  • A Pilot Study on the Effectiveness of a Rose Hip Shell Powder in Patients
           Suffering from Chronic Musculoskeletal Pain
    • Authors: S. Chrubasik‐Hausmann; C. Chrubasik, E. Neumann, U. Müller‐Ladner
      Abstract: We carried out a 3‐month preliminary investigation on the effectiveness of a rose hip shell powder and its mechanism of action. Of 52 patients suffering from acute exacerbations of low back pain (n = 39) or knee pain (n = 13), 29 had participated earlier in the pilot study with the pseudofruit powder Litozin®. After assessing the baseline values, patients were offered up to 20 g of a rose hip shell powder per day. Patients were encouraged to adjust the daily dose upwards or downwards according to their symptoms for the period of 3 months. The examination for possible effectiveness was by intention‐to‐treat analysis with last observation carried forward. There was no difference in any generic or disease‐specific outcome variables between the patients consuming the rose hip shell powder and those consuming the pseudofruit powder Litozin® in the previous surveillance study. A human protein array system and fractions from the rose powders were used to study their effect on cytokine expression in vitro. The data indicate that lipophilic rose hip fractions from the shell and the pseudofruit inhibit cytokine expression and that the shell powder may be the better starting material for a future rose hip extract prepared with a lipophilic solvent. Copyright © 2014 John Wiley & Sons, Ltd.
      PubDate: 2014-07-17T02:39:23.665587-05:
      DOI: 10.1002/ptr.5192
  • Alhagi: A Plant Genus Rich in Bioactives for Pharmaceuticals
    • Abstract: Alhagi, a plant genus from family Fabaceae, is widely distributed in many countries of Asia, Australia and Europe. Commonly known as camel thorn, Alhagi has many species famous for feed and folk medicinal uses. Different species of Alhagi such as Alhagi pseudalhagi, A. graecorum, A. sparsifolia, A. kirgisorum, A. maurorum, A. camelorum and A. persarum have been explored for their antioxidant potential and nutritive value along with various medicinal properties. A wide array of pharmacologically active secondary metabolites such as flavonoids, alkaloids (alhacidin and alhacin), steroids, pseudalhagin A, phospholipids and polysaccharides have been reported from different parts of Alhagi species. A broad range of biological activities such as antioxidant, cardiovascular, anti‐ulcer, hepatoprotective, antispasmodic, antidiarrheal, antinociceptive, antipyretic, anti‐inflammatory, anti‐rheumatic, antibacterial and antifungal have been ascribed to different parts of Alhagi. In addition, Alhagi plants are also valued as a rich source of digestible protein and important minerals. This review focuses on the medicinal applications and detailed profile of high‐value bioactive phytochemicals along with pharmacological attributes and therapeutic potential of these multi‐purpose plants. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anti‐Inflammatory and Antinociceptive Activity of Urera aurantiaca
    • Abstract: Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti‐inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti‐inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan‐induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose‐dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azinobis 3‐ethylbenzothiazoline 6‐sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anticancer Activities of Selected Species of North American Lichen
    • Abstract: Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0/G1 stage, and caused apoptosis in a dose‐dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs. Copyright © 2014 John Wiley & Sons, Ltd.
  • A Novel Diterpene Skeleton: Identification of a Highly Aromatic, Cytotoxic
           and Antioxidant
           5‐Methyl‐10‐demethyl‐abietane‐type Diterpene
           from Premna serratifolia
    • Abstract: Premna serratifolia Linn. (syn: . P. corymbosa (Burm. f.) Merr., P. integrifolia L. and P. obtusifolia R. Br.) is a member of the Verbenaceae family that is extensively used in the Ayurvedic system of medicine in India. As part of our continuous pharmacological and phytochemical studies on medicinal plants, we have screened the methanolic extracts of leaves, root bark (RB) and root wood of P. serratifolia for cytotoxic activity against two cancer cell lines: SHSY‐5Y neuroblastoma and B16 melanoma cells. The RB extract that showed promising activity was fractionated using solvents of increasing polarity followed by a combination of Sephadex LH‐20 column and Combiflash chromatography as well as HPLC to afford the active principle. Comprehensive spectroscopic analysis including 1D and 2D NMR (COSY, HMQC, HMBC, NOESY) and MS analysis revealed the identity of the isolated compound as 11,12,16‐trihydroxy‐2‐oxo‐5‐methyl‐10‐demethyl‐abieta‐1[10],6,8,11,13‐pentene that appears to be a novel compound based on a new diterpene skeleton. The cytotoxic activity of the isolated compound was 21 and 23 times higher than the crude extract against the SHSY‐5Y and B16 cells, respectively. The novel compound also possesses in vitro antioxidant effects as evidenced by the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging effect where an IC50 value of 20.4 ± 1.3 μM was obtained. In comparison, the positive control, caffeic acid, showed an IC50 value of 14.4 ± 1.6 μM. Copyright © 2014 John Wiley & Sons, Ltd.
  • Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter
           pylori Based on Inhibition of Urease
    • Abstract: The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H. pylori and jack bean in concentration‐dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver‐Burk plots indicated that the type of inhibition was non‐competitive against H. pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA‐inactivated urease assay showed DL‐dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H. pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H. pylori infection. Copyright © 2014 John Wiley & Sons, Ltd.
  • Phloroglucinols from Anti‐Microbial Deposit‐Resins of
           Australian Stingless Bees (Tetragonula carbonaria)
    • Abstract: Stingless bees accumulate deposits of plant resins that are mixed with beeswax to produce propolis. Previous studies have reported anti‐microbial constituents of stingless bee (Tetragonula carbonaria) propolis from East Australia, but several components remained to be characterized. In the search of natural products yet unreported for Australian propolis, four bee deposit‐resins of T. carbonaria bees were analysed by gas and liquid chromatography mass spectrometry with accurate mass measurements. Ethanolic extracts of the deposit‐resins were tested in vitro against Staphylococcus aureus ATCC 25983 and Pseudomonas aeruginosa ATCC 27853 by the agar diffusion method. Phloroglucinols, flavonoids and isoprenoids were identified in samples. The crude extracts showed strong anti‐staphylococcal effects but were less active against the Gram‐negative bacterium. The diagnostic data enabled the identification of markers that can be used for profiling other Australian propolis sources and to target the isolation of bioactive phloroglucinols in future studies against antibiotic resistant S. aureus strains. Copyright © 2014 John Wiley & Sons, Ltd.
  • Modulating Potential of L‐Sulforaphane in the Expression of
           Cytochrome P450 to Identify Potential Targets for Breast Cancer
           Chemoprevention and Therapy Using Breast Cell Lines
    • Abstract: The L‐sulforaphane (SFN) component of broccoli sprout showed anticancer activity in several preclinical studies including breast cancer. Estrogens are considered major risk factors in breast carcinogenesis. The aim of this study was to evaluate the effect of SFN on the expression of cytochrome P450 involved in the estrogen metabolism in breast cancer cell lines MCF7 and MDA‐MB‐231 and in non‐tumorigenic MCF10A cell line. The expression of CYP19, CYP1A1, 1A2, 1B1 was determined at the transcript and protein levels. There were found some remarkable differences in the effect of SFN at a dose of 5 µmol/L on CYP19 expression: in ER(+) MCF7 significant reduction, in ER(−) MDA‐MB‐231 an increased expression and unchanged expression in MCF10A cell line. The effect of SFN on CYPs (1A1, 1A2, 1B1) involved in estrogen catabolism was to a lesser extent dependent on breast cell line. The slightly reduced CYP1A1 protein level was observed in all cell lines tested. An increased level of CYP1A2 and decreased level of CYP1B1 expression were found in MCF10A. These results indicate that the naturally occurring L isomer of SFN may affect the expression of P450s involved in estrogen metabolism. This effect may contribute to the anticancer activity of SFN in breast tissue. Copyright © 2014 John Wiley & Sons, Ltd.
  • Expression of BDNF and TH mRNA in the Brain Following Inhaled
           Administration of α‐Pinene
    • Abstract: Essential oils are mainly administered by inhalation. Administration by inhalation is considered to occur through two pathways, neurological transfer and pharmacological transfer. However, the relationship between the two routes is not clear. To clarify this relationship, we administered α‐pinene, which has an anxiolytic‐like effect, to mice. Emotional behavior and accumulation and expression of relevant mRNAs in the brain (brain‐derived neurotrophic factor (BDNF); tyrosine hydroxylase (TH)) were examined following inhaled administration of α‐pinene (10 μL/L air for 60 or 90 min). To evaluate the anxiolytic‐like effect, the elevated plus maze (EPM) test was used. Inhalation of α‐pinene for 60 min produced a significant increase in the total distance traveled in the EPM test compared with control (water). The concentration of α‐pinene in the brain after 60 min of inhalation was significantly increased compared with that after 90 min of inhalation. The expression of BDNF mRNA in the olfactory bulb and in the hippocampus was almost the same after 60 min of inhalation compared to that after 90 min of inhalation. The expression of TH mRNA in the midbrain after 60 min of inhalation was significantly increased compared with that of the control. Thus, an increase in α‐pinene in the brain induces an increase in TH mRNA expression and increases locomotor activity. The anxiolytic‐like effect may be related to both neurological transfer and pharmacological transfer. Copyright © 2014 John Wiley & Sons, Ltd.
  • Chemical Composition and Antimicrobial Activity of the Essential Oil of
           Apricot Seed
    • Abstract: In traditional oriental medicine, apricot (Prunus armeniaca L.) seed has been used to treat skin diseases such as furuncle, acne vulgaris and dandruff, as well as coughing, asthma and constipation. This study describes the phytochemical profile and antimicrobial potential of the essential oil obtained from apricot seeds (Armeniacae Semen). The essential oil isolated by hydrodistillation was analysed by gas chromatography–mass spectroscopy. Benzaldehyde (90.6%), mandelonitrile (5.2%) and benzoic acid (4.1%) were identified. Disc diffusion, agar dilution and gaseous contact methods were performed to determine the antimicrobial activity against 16 bacteria and two yeast species. The minimum inhibitory concentrations ranged from 250 to 4000, 500 to 2000 and 250 to 1000 µg/mL for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The minimum inhibitory doses by gaseous contact ranged from 12.5 to 50, 12.5 to 50 and 3.13 to 12.5 mg/L air for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The essential oil exhibited a variable degree of antimicrobial activity against a range of bacteria and yeasts tested. Copyright © 2014 John Wiley & Sons, Ltd.
  • Modulation of Radiation‐Induced Alterations in Oxidative Stress and
           Cytokine Expression in Lung Tissue by Panax Ginseng Extract
    • Abstract: We investigated the modulating effect of Panax ginseng extract (PGE) on radiation‐induced lung injury (RILI) by measuring early changes in oxidative stress levels, cytokine expression, and the histopathology of mouse lung tissue treated with high dose of X‐ray radiation. The mice were pretreated with 25, 50, and 100‐mg/kg doses of PGE orally for four consecutive days, and their thoraces were then exposed to 15‐Gy X‐ray radiation 1 h after the last administration of PGE on day 4. The pretreatments with 50 and 100 mg/kg PGE led to significant reductions in the elevation of lipid peroxidation levels at 2 and 10 days, respectively, after irradiation. The mice pretreated with PGE exhibited dose‐dependent reductions in the irradiation‐induced production of tumor necrosis factor α and transforming growth factor β1 cytokines 10 days after irradiation, with these reductions nearly reaching the control levels after the 100‐mg/kg dose. Furthermore, together with providing significant protection against reductions in catalase activity and glutathione content, pretreatment with 100 mg/kg PGE resulted in a marked attenuation of the severity of inflammatory changes in lung tissue 10 days after irradiation. A high pretreatment dose of PGE may be a useful pharmacological approach for protection against RILI. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Standardized BHH10 Extract, a Combination of Astragalus membranaceus,
           Cinnamomum cassia, and Phellodendron amurense, Reverses Bone Mass and
           Metabolism in a Rat Model of Postmenopausal Osteoporosis
    • Abstract: Jasin‐hwan‐gagambang (BHH10), a modified prescription of Jasin‐hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)‐induced rats. Sprague–Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17β‐estradiol (E2). BHH10 treatment significantly inhibited OVX‐induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low‐density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C‐telopeptide type 1 collagen, and bone morphogenetic protein‐2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10‐treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN‐treated or E2‐treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity. © 2014 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
  • Tolerance of Phellodendron amurense Bark Extract (Nexrutine®) in
           Patients with Human Prostate Cancer
    • Abstract: Phellodendron amurense bark extract (Nexrutine®) has shown a favorable effect on prostate cancer in vivo and in vitro. We evaluated its tolerance in patients undergoing surgery or radiation for prostate cancer. Patients received Nexrutine® orally (500 mg tid) either 1 to 2 months preoperatively or 1 to 2 months prior to and with radiation therapy. Common Terminology Criteria for Adverse Events were used to measure tolerance. In total, 21 patients (9 surgery and 12 radiation) underwent treatment. During the Nexrutine® alone component, there were two transient grade 3 toxicities (hypokalemia and urinary incontinence). There was no grade 4 toxicity. For the combined Nexrutine® and radiation component, no additional patients suffered a grade 3 toxicity. All the toxicities were transient. By the end of the neoadjuvant treatment, 81% of the patients had a decline in prostate‐specific antigen. This is the first report of patients with prostate cancer being treated with P. amurense bark extract, and it was very well tolerated. Toxicities were minimal and self‐limited. This compound can be safely used in further evaluation of a treatment effect on cancer. Copyright © 2014 John Wiley & Sons, Ltd.
  • In Vitro Evaluation of Bacopa monniera Extract and Individual Constituents
           on Human Recombinant Monoamine Oxidase Enzymes
    • Abstract: Bacopa monniera is a traditional Ayurvedic medicinal plant that has been used worldwide for its nootropic action. Chemically standardized extract of B. monniera is now available as over the counter herbal remedy to enhance memory in children and adults. Considering the nootropic action of B. monniera, we evaluated the effect of clinically available B. monniera extract and six of B. monniera constituents (bacoside A3, bacopaside I, bacopaside II, bacosaponin C, bacosine, and bacoside A mixture) on recombinant human monoamine oxidase (MAO) enzymes. The effect of B. monniera extract and individual constituents on human recombinant MAO‐A and MAO‐B enzymes was evaluated using MAO‐GloTM assay kit (Promega Corporation, USA), following the instruction manual. IC50 and mode of inhibition were measured for MAO enzymes. Bacopaside I and bacoside A mixture inhibited the MAO‐A and MAO‐B enzymes. Bacopaside I exhibited mixed mode of inhibition with IC50 and Ki values of 17.08 ± 1.64 and 42.5 ± 3.53 µg/mL, respectively, for MAO‐A enzyme. Bacopaside I is the major constituent of B. monniera, which inhibited the MAO‐A enzyme selectively. 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.
  • 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.
  • 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.
  • 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 
  • 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.
  • 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.
  • Anti‐Proliferative Properties of Kahweol in Oral Squamous Cancer
           Through the Regulation Specificity Protein 1
    • Abstract: Kahweol, the coffee‐specific deterpene, has been shown to have potential anti‐cancer effects against several cancers. However, the molecular mechanisms underlying the anti‐cancer activity of kahweol have not yet established. In this study, we investigated whether kahweol could show anti‐cancer effects on oral squamous cell lines (OSCCs), HN22 and HSC4. We conducted an 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxy‐phenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay, 4′‐6‐diamidino2‐phenylindole (DAPI) staining, propidium iodide staining, immunocytochemistry, and Western blot analysis for the characterization of kahweol and the underlying signaling pathway. We determined that kahweol‐treated cells showed significantly decreased cell viability and increased nuclear condensation and an increased sub‐G1 population in OSCCs. Interestingly, suppression of the transcription factor specificity protein 1 (Sp1) was followed by induced apoptosis by kahweol in a dose‐dependent manner. In addition, kahweol modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and anti‐apoptotic proteins, resulting in apoptosis. Taken together, results from these findings suggest that kahweol may be a potential anti‐cancer drug candidate to induce apoptotic cell death through downregulation of Sp1 in OSCCs. Copyright © 2014 John Wiley & Sons, Ltd.
  • Daily Inhalation of α‐Pinene in Mice: Effects on Behavior and
           Organ Accumulation
    • Abstract: In phytotherapy, essential oils tend to be used daily for a period of days or weeks, rather than in a single application. However, the literature contains very little information on repeated use of essential oils. In this study, we investigated the effects on behavior and the accumulation in the brain and liver of α‐pinene, an essential oil component, when inhaled by mice. Animals were individually housed in cages for 1 week. Mice inhaled α‐pinene or water vapor (negative control) for 90 min/day for 1 day, 3 days, or 5 days, and they were then submitted to the elevated plus maze test for 10 min. We used gas chromatography with flame ionization detection to quantify concentrations of α‐pinene in the brain and liver. There was significant anxiolytic‐like activity, which remained constant for the 5 days' inhalation of α‐pinene. On the other hand, the accumulation of α‐pinene in the brain and liver peaked on the third day of inhalation. The existence of stress related to the new environment appears to have affected the change in the accumulation of α‐pinene in the internal organs, keeping the anxiolytic‐like action constant. Copyright © 2013 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 
  • 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.
  • Insulin‐Sensitizing and Beneficial Lipid‐Metabolic Effects of
           the Water‐Soluble Melanin Complex Extracted from Inonotus obliquus
    • Abstract: Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water‐soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)‐fed obese mice. When the melanin complex was treated to 3T3‐L1 adipocytes, insulin‐stimulated glucose uptake was increased significantly, and its phosphoinositide 3‐kinase‐dependent action was proven with wortmannin treatment. Additionally, dose‐dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex‐treated cells. Adiponectin gene expression in 3T3‐L1 cells incubated with melanin complex increased which was corroborated by increased AMP‐activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3‐L1 culture. Melanin complex‐treated 3T3‐L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex‐treated HF‐fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water‐soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid‐metabolic effects, making it a candidate for promising antidiabetic agent. Copyright © 2014 John Wiley & Sons, Ltd.
  • Crocetin, a Carotenoid from Gardenia jasminoides Ellis, Protects against
           Hypertension and Cerebral Thrombogenesis in Stroke‐prone
           Spontaneously Hypertensive Rats
    • Abstract: Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke‐prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He‐Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8‐hydroxy‐2′‐deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine‐induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species. Copyright © 2014 John Wiley & Sons, Ltd.
  • Evaluation of Inhibitory Effects of Caffeic acid and Quercetin on Human
           Liver Cytochrome P450 Activities
    • Abstract: When herbal drugs and conventional allopathic drugs are used together, they can interact in our body which can lead to the potential for herb–drug interactions. This work was conducted to evaluate the herb–drug interaction potential of caffeic acid and quercetin mediated by cytochrome P450 (CYP) inhibition. Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of caffeic acid and quercetin. IC50, Ki values, and the types of inhibition were determined. Both caffeic acid and quercetin were potent competitive inhibitors of CYP1A2 (Ki = 1.16 and 0.93 μM, respectively) and CYP2C9 (Ki = 0.95 and 1.67 μM, respectively). Caffeic acid was a potent competitive inhibitor of CYP2D6 (Ki = 1.10 μM) and a weak inhibitor of CYP2C19 and CYP3A4 (IC50 > 100 μM). Quercetin was a potent competitive inhibitor of CYP 2C19 and CYP3A4 (Ki = 1.74 and 4.12 μM, respectively) and a moderate competitive inhibitor of CYP2D6 (Ki = 18.72 μM). These findings might be helpful for safe and effective use of polyphenols in clinical practice. Our data indicated that it is necessary to study the in vivo interactions between drugs and pharmaceuticals with dietary polyphenols. Copyright © 2014 John Wiley & Sons, Ltd.
  • Extracts of Devil's Club (Oplopanax horridus) Exert Therapeutic Efficacy
           in Experimental Models of Acute Myeloid Leukemia
    • Abstract: Acute myeloid leukemia (AML) is a group of hematological malignancies defined by expanded clonal populations of immature progenitors (blasts) of myeloid phenotype in blood and bone marrow. Given a typical poor prognostic outlook, there is great need for novel agents with anti‐AML activity. Devil's club (Oplopanax horridus) is one of the most significant medicinal plants used among the indigenous people of Southeast Alaska and the coastal Pacific Northwest, with different linguistic groups utilizing various parts of the plant to treat many different conditions including cancer. Studies identifying medically relevant components in Devil's club are limited. For this research study, samples were extracted in 70% ethanol before in vitro analysis, to assess effects on AML cell line viability as well as to study regulation of tyrosine phosphorylation and cysteine oxidation. The root extract displayed better in vitro anti‐AML efficacy in addition to a noted anti‐tyrosine kinase activity independent of an antioxidant effect. In vivo therapeutic studies using an immunocompetent murine model of AML further demonstrated that Devil's club root extract improved the murine survival while decreasing immunosuppressive regulatory T cells and improving CD8+ T‐cell functionality. This study defines for the first time an anti‐AML efficacy for extracts of Devil's club. Copyright © 2014 John Wiley & Sons, Ltd.
  • Influence of the Gastrointestinal Microflora and Efflux Transporters on
           the Absorption of Scutellarin and Scutellarein
    • Abstract: Scutellarin (SG) and its aglycone, Scutellarein (S), are flavonoids of therapeutic cardiocerebrovascular disease. SG was hydrolyzed by bacterial enzyme into S which was absorbed in the intestine. The aim of this study was to determine the effects of the microflora in the intestinal lumen and the efflux transporter of intestinal epithelial cells on the absorption process of SG and S. After oral administration of antibiotics in Sprague–Dawley rats, the reduced bacterial enzyme formation significantly hinders the absorption of SG, whereas scarcely that of S. The absorption study in situ single‐pass intestinal perfusion revealed that S could be absorbed throughout the intestine of rats. The effective intestinal permeability of S in the jejunum was much lower than in the other sections of the GI tract. The efflux transporter promoted SG secretion into lumen from enterocytes, which hindered the absorption of both SG and S into the bloodstream. The efflux transporter protein inhibitor (verapamil, probenecid and reserpine) remarkably enhanced the absorption of S and the bioconversion of S into SG in both the rat intestine and Caco‐2‐monolayer models. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Effects of Low and High Concentrations of Luteolin on Cultured Human
           Endothelial Cells Under Normal and Glucotoxic Conditions: Involvement of
           Integrin‐Linked Kinase and Cyclooxygenase‐2
    • Abstract: Luteolin protects against high glucose (HG)‐induced endothelial dysfunction whereas its cytotoxicity has been reported against normal endothelial cells. This study was undertaken to determine luteolin cytoprotective and cytotoxic dose ranges and to elucidate their respective mechanisms. Luteolin prevented HG‐induced human umbilical vein endothelial cell (HUVEC) death with an EC50 value of 2.0 ± 0.07 μM. The protective effect of luteolin was associated with decreased intracellular reactive oxygen species (ROS) and Ca2+ (Cai2+) levels and enhanced nitric oxide (NO) production. At high concentrations, luteolin caused HUVEC death in normal glucose (NG) and HG states (LC50 40 ± 2.23 and 38 ± 1.12 μM, respectively), as represented by increased ROS and Cai2+ and decreased NO. Western blots illustrated that exposure to HG increased cyclooxygenase‐2 (COX‐2) and integrin‐linked kinase (ILK) expression. Luteolin at low concentrations suppressed HG‐mediated up‐regulation of COX‐2 but maintained HG‐induced over‐expression of ILK while at high concentrations significantly increased COX‐2 and decreased ILK expression in both HG and NG states. Our data indicated that cytoprotective action of luteolin was manifested with much lower concentrations, by a factor of approximately 20, compared with cytotoxic activity under both normal or glucotoxic conditions. It appears that luteolin exerts its action, in part, by modulating ILK expression which is associated with regulation of COX‐2 expression and NO production in endothelial cells. Copyright © 2014 John Wiley & Sons, Ltd.
  • Transport Properties of Puerarin and Effect of Extract of Radix Angelicae
           dahuricae on Puerarin Intestinal Absorption Using In Situ and In Vitro
    • Abstract: The root of Angelica dahurica (Radix Angelicae Dahuricae, RAD), which contains coumarins and volatile oil as its main classes of active components, is often given in conjunction with Pueraria root (Radix Puerariae, RP), which contains the phytoestrogen puerarin. The two herbs are considered to be compatible ‘herb‐pairs’ in traditional Chinese medicine. The present investigation investigates the absorption of puerarin from RP and the effect of the total coumarins and volatile oil from RAD on its absorption. The everted gut sac and single‐pass intestinal perfusion methods were used, respectively. The results showed that the absorption of puerarin in the jejunum was significantly increased in the presence of the coumarins and/or volatile oil. The absorption rate constant (Ka) of puerarin increased gradually until the concentration reached 160 µg · mL−1, after which its absorption became saturated and the apparent permeability (Papp) values significantly decreased. The results showed that the intestinal absorption mechanisms of puerarin involved active transportation processes and that puerarin is likely to be a substrate of P‐gp because verapamil significantly affected its Papp and Ka. The absorption of puerarin significantly increased (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.
  • Protective Effect of Hydroalcoholic Olive Leaf Extract on Experimental
    • Abstract: The aim of the present study is to investigate the possible protective effect of dry olive leaf extract (OLE) against acetic acid‐induced ulcerative colitis in rats, as well as the probable modulatory effect of nitrergic and opioidergic systems on this protective impact. Olive leaf extract was administered (250, 500 and 750 mg/kg) orally for two successive days, starting from the colitis induction. To assess the involvement of nitrergic and opioidergic systems in the possible protective effect of OLE, L‐NG‐Nitroarginine Methyl Ester (10 mg/kg) and naltrexone (5 mg/kg) intraperitoneal (i.p.) were applied 30 min before administration of the extract for two successive days, respectively. Colonic status was investigated 48 h following induction through macroscopic, histological and biochemical analyses. Olive leaf extract dose‐dependently attenuated acetic acid‐provoked chronic intestinal inflammation. The extract significantly reduces the severity of the ulcerative lesions and ameliorated macroscopic and microscopic scores. These observations were accompanied by a significant reduction in the elevated amounts of TNF‐α and interlukin‐2 markers. Moreover, both systems blockage reversed protective effects of OLE in the rat inflammatory bowel disease model. These finding demonstrated, for the first time, a possible role for nitrergic and opioidergic systems in the aforementioned protective effect, and the extract probably exerted its impact increasing nitric oxide and opioid tones. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anticancer Effects of Baicalein on Hepatocellular Carcinoma Cells
    • Abstract: The therapeutic potential of baicalein against hepatoma cells was evaluated in vitro and in vivo. In cell viability assays, baicalein showed significant cytotoxicity against the hepatocellular carcinoma cell lines H22, Bel‐7404, and Hep G2 and moderate cytotoxicity against immortalized human hepatocytes. Baicalein induced G0/G1‐phase arrest in hepatocellular carcinoma cells, inhibited AKT, and promoted the degradation of β‐catenin and cyclin D1 without activation of GSK‐3β. Furthermore, baicalein significantly inhibited H22 xenograft tumor growth without causing obvious adverse effects on weight or liver and spleen weight indexes in ICR mice. Immunohistochemical analysis showed that the inhibition of tumor growth in baicalein‐treated mice was associated with decreased AKT, β‐catenin, and cyclin D1 expression ex vivo. Our data indicate that baicalein might regulate cyclin D1 transcription via a β‐catenin‐dependent mechanism, leading to cell cycle arrest at G0/G1 phase and impaired cancer cell proliferation. These results suggest that baicalein is a potential candidate for the treatment of hepatocellular carcinoma. 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.
  • Evaluation of Hemostatic and Anti‐inflammatory Activities of
           Extracts from Different Lagochilus Species in Experimental Animals:
           Comparison of Different Extractives and Sources
    • Abstract: Different members of Lagochilus genus have been used in folkloric medicine to treat hemorrhages and inflammation. However, only a few species of them have received scientific attention supporting their efficacy. Here, the hemostatic and antiinflammatory activities of five Lagochilus species were determined and compared by using in vivo assays. The results showed that the extracts of Lagochilus lanatonodus and Lagochilus diacanthophyllus showed better hemostatic activities among five species. The high doses of L. lanatonodus extracts were able to shorten the values of thrombin time, activated partial thromboplastin time and prothrombin time in a rat model. Moreover, the extracts of L. lanatonodus and L. diacanthophyllus showed strong inhibitory effects on the acute phase of inflammation in both xylene‐induced ear edema mouse model and carrageenan‐induced paw edema rat model. In parallel, the treatment of these extracts modulated the expressions of those inflammatory parameters, that is, nitric oxide, prostaglandin E2, inducible nitric oxide synthase, malondialdehyde and superoxide dismutase. L. lanatonodus and L. diacanthophyllus showed better hemostatic and antiinflammatory activities in several test models: these results therefore supported the folkloric utilization. L. lanatonodus was found to be the most active Lagochilus species. Copyright © 2014 John Wiley & Sons, Ltd.
  • Cancer Patients at Risk of Herb/Food Supplement–Drug Interactions: A
           Systematic Review
    • Abstract: Herbal medicines and dietary supplements are commonly taken by patients with cancer, leading to concern over interactions with conventional medicines. A literature search was carried out to identify published studies exploring supplement use by patients with a cancer diagnosis. A total of 818 articles were retrieved using the key words, but only 41 are judged to be relevant based on title. Following the review of the abstracts, ten papers were considered to be potentially relevant, but of these, only two met the selection criteria, and three additional papers were identified from published reviews. Of 806 patients surveyed, 433 (53.7%) were reported to be taking combinations of supplements and drugs, and 167 incidents of risk were identified, affecting 60 patients (13.9%). The interactions identified were mainly theoretical and not supported by clinical data. No studies reported any adverse events associated with these combinations; most did not record the actual drug combinations taken, and the risk potential of some supplements appears to have been over‐estimated. More effort should be made to investigate supplement use in this vulnerable patient group, based on sound evidence of plausible interaction, not only to avoid harm but also to provide reassurance where appropriate if the patient wishes to take a particular supplement. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Protective Effects of Rhodiola crenulata Extracts on Drosophila
           melanogaster Gut Immunity Induced by Bacteria and SDS Toxicity
    • Abstract: The aim of this study was to observe the effect of the Rhodiola crenulata extracts on gut immunity of Drosophila melanogaster. Wild‐type flies fed standard cornmeal–yeast medium were used as controls. Experimental groups were supplemented with 2.5% R. crenulata aqueous extracts in standard medium. Survival rate was determined by feeding pathogenic microorganisms and toxic compounds. The levels of reactive oxygen species and dead cells were detected by dihydroethidium and 7‐amino‐actinomycin D staining, respectively. The expression of antimicrobial peptides was evaluated by quantitative polymerase chain reaction, and morphological change of the intestine was imaged by an Axioskop 2 plus microscope. The results demonstrate that R. crenulata increased the survival rates of adult flies and expression of antimicrobial peptide genes after pathogen or toxic compound ingestion. Moreover, decreased levels of reactive oxygen species and epithelial cell death were associated with results in improved intestinal morphology. The pharmacological action of R. crenulata from Tibet was greater than that from Sichuan. These results indicate that the R. crenulata extracts from Tibet had better pharmacological effect on D. melanogaster gut immunity after ingestion of pathogens and toxic compounds. These results may provide the pharmacological basis for prevention of inflammatory diseases of the intestine. Copyright © 2014 John Wiley & Sons, Ltd.
  • Effects of Supplementation with Heracleum persicum Fruit Extract on Serum
           Lipids in Patients Undergoing Coronary Angiography: A Pilot Trial
    • Abstract: Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the Iranian traditional medicine and also a safe and common dietary spice. The present pilot study aimed to investigate the impact of supplementation with H. persicum fruits on serum lipid concentrations in a group of patients with minimal coronary artery disease. Subjects who were diagnosed with  0.05). However, serum triglycerides levels were reduced after H. persicum extract supplementation in a borderline significant manner (p = 0.063). Short‐term supplementation with H. persicum fruit extract might be used as an adjunctive treatment for patients with hypertriglyceridemia. Copyright © 2014 John Wiley & Sons, Ltd.
  • Turmeric Toxicity in A431 Epidermoid Cancer Cells Associates with
           Autophagy Degradation of Anti‐apoptotic and Anti‐autophagic
           p53 Mutant
    • Abstract: The keratinocyte‐derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin‐mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small‐interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric‐treated or Curcumin‐treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53. Copyright © 2014 John Wiley & Sons, Ltd.
  • Review on Liver Inflammation and Antiinflammatory Activity of Andrographis
           paniculata for Hepatoprotection
    • Abstract: Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation. Copyright © 2014 John Wiley & Sons, Ltd.
  • The Isolation of Antiprotozoal Compounds from Libyan Propolis
    • Abstract: Propolis is increasingly being explored as a source of biologically active compounds. Until now, there has been no study of Libyan propolis. Two samples were collected in North East Libya and tested for their activity against Trypanosoma brucei. Extracts from both samples had quite high activity. One of the samples was fractionated and yielded a number of active fractions. Three of the active fractions contained single compounds, which were found to be 13‐epitorulosal, acetyl‐13‐epi‐cupressic acid and 13‐epi‐cupressic acid, which have been described before in Mediterranean propolis. Two of the compounds had a minimum inhibitory concentration value of 1.56 µg/mL against T. brucei. The active fractions were also tested against macrophages infected with Leishmania donovani, and again moderate to strong activity was observed with the compounds having IC50 values in the range 5.1–21.9 µg/mL. Copyright © 2014 John Wiley & Sons, Ltd.
  • Gelidium elegans, an Edible Red Seaweed, and Hesperidin Inhibit Lipid
           Accumulation and Production of Reactive Oxygen Species and Reactive
           Nitrogen Species in 3T3‐L1 and RAW264.7 Cells
    • Abstract: Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3‐L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose‐dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator‐activated receptor gamma and CCAAT/enhancer‐binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide‐induced nitric oxide production was significantly reduced in G. elegans extract‐treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator‐activated receptor gamma, CCAAT/enhancer‐binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents. Copyright © 2014 John Wiley & Sons, Ltd.
  • Autophagy Activation and Antiviral Activity by a Licorice Triterpene
    • Abstract: The triterpene glycyrrhizic acid (GRA), the main product from the Glycyrrhiza glabra medicinal plant, is known for its antiinflammatory and antimicrobial activity. In this work, GRA was studied for its ability to induce the autophagic process activator Beclin 1 in epithelial cells and to observe how this property could influence its antiviral activity. After 24 h of treatment, GRA induced a Beclin 1 production that was more than twofold higher than that produced by rapamycin, used as a reference compound. When the compounds were added to HeLa cells together with the viruses, GRA demonstrated a strong antiherpes simplex virus type 1 (HSV1) activity, whereas rapamycin had no activity. However, if the compounds were added to the cells 24 h before the viruses, GRA induced the production of an even higher amount of Beclin 1 and showed an improved antiviral effect; under these conditions, rapamycin was also able to exert a significant anti‐HSV1 activity. In conclusion, GRA is a strong inducer of the autophagy activator Beclin 1, which establishes a resistance state to HSV1 replication. Copyright © 2014 John Wiley & Sons, Ltd.
  • A Review of the Pharmacological Effects of Piceatannol on Cardiovascular
    • Abstract: The incidence of cardiovascular diseases (CVDs) is high in both developed and developing countries. It has a high global rate of mortality and causes heavy social burden. Drugs are available for managing or treating CVDs and its complications. Consumption of dietary supplements or functional foods for reducing the risk of CVDs has also gained wide recognition by the general public. Piceatannol, an analog and metabolite of resveratrol, is a natural stilbene commonly found in the skin of grapes and wine. Piceatannol is believed to be a potent compound with certain cardiovascular therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, and angiogenesis. It also has vasorelaxation and antioxidant activities. A comprehensive review of piceatannol concludes that piceatannol has the potential to be developed into health products for the cardiovascular system to help modern society reduce the high CVD incidence. However, further investigations are warranted in order to increase the bioavailability and understand the biological mechanisms and safety of using piceatannol. Copyright © 2014 John Wiley & Sons, Ltd.
  • Review of Plants and Their Constituents in the Therapy of Cerebral
    • Abstract: Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to cerebral hypoxia and thus to the death of neuronal cells or stroke. The limited number of medicines currently available for patients following ischemic stroke and insufficient data on efficiency of these chemicals in the treatment of stroke led us to the search for novel therapeutic approaches. Recent studies have focused on the possible capacity of natural compounds extracted from vegetables and fruits, to prevent human disabilities caused by cerebral ischemia. In this review, we will discuss some plants and their constituents that may protect brain ischemia or delay the neurological disorders following a stroke. We have reviewed different studies in scientific databases that investigate herbal compounds and their effects on cerebral ischemia. Copyright © 2014 John Wiley & Sons, Ltd.
  • Anxiolytic‐Like Effect of Illicium verum Fruit Oil,
           trans‐Anethole and Related Compounds in Mice
    • Abstract: The fruit of Illicium verum Hook. f. (star anise) is used by many as a spice. The fragrance of I. verum fruit is characteristically anise‐like. In this study, hexane‐extracted I. verum fruit oil (IVO), trans‐anethole as the main component, and related compounds (propiophenone, 4′‐methoxy‐propiophenone, trans‐β‐methylstyrene) were analyzed in order to clarify the emotional effect of inhaling the fragrance of I. verum fruit. As a result, although 4 μL/L air IVO did not exhibit an anxiolytic‐like effect, 1 μL/L air trans‐anethole exhibited a significant effect (p 
  • Modulating Effects of Pycnogenol® on Oxidative Stress and DNA Damage
           Induced by Sepsis in Rats
    • Abstract: The aim of this study was to evaluate the protective effects of Pycnogenol® (Pyc), a complex plant extract from the bark of French maritime pine, on oxidative stress parameters (superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and total glutathione (GSH) and malondialdehyde (MDA) levels), an inflammatory cytokine (tumor necrosis factor alpha (TNF‐α) level) and also DNA damage in Wistar albino rats. Rats were treated with 100 mg/kg intraperitonally Pyc following the induction of sepsis by cecal ligation and puncture. The decreases in MDA levels and increases in GSH levels, and SOD and GPx activities were observed in the livers and kidneys of Pyc‐treated septic rats. Plasma TNF‐α level was found to be decreased in the Pyc‐treated septic rats. In the lymphocytes, kidney, and liver tissue cells of the sepsis‐induced rats, Pyc treatment significantly decreased the DNA damage and oxidative base damage using standard alkaline assay and formamidopyrimidine DNA glycosylase‐modified comet assay, respectively. In conclusion, Pyc treatment might have a role in the prevention of sepsis‐induced oxidative damage not only by decreasing DNA damage but also increasing the antioxidant status and DNA repair capacity in rats. Copyright © 2014 John Wiley & Sons, Ltd.
  • Black Tea Extract and its Thearubigins Relieve the
           Sildenafil‐Induced Delayed Gut Motility in Mice: A Possible Role of
           Nitric Oxide
    • Abstract: In this study we hypothesize that a standardized black tea aqueous extract (BTE) and thearubigins, its main polyphenolic pigments, will improve sildenafil‐induced delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty groups of mice (n = 8) were given a phenol red meal, and three sets of experiments were performed. In the first and second sets, effects of different concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in combinations, on GE and SIT were measured. In the third set, influence of nω‐Nitro‐l‐arginine methyl ester hydrochloride (l‐NAME) pretreatment on effects of these treatments was tested.Black tea extract (3% and 4.5%) and thearubigins (50 and 60 mg/kg) dose‐dependently increased GE and SIT, whereas BTE 6% and thearubigins 70 mg/kg did not affect them. Sildenafil dose‐dependently reduced both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l‐NAME with sildenafil (5 mg/kg) reversed its motility‐delaying effects. Pretreatment with l‐NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% + sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a standardized BTE and its thearubigins improve the sildenafil‐induced delayed gut motility in mice. This improvement was partially blocked by l‐NAME suggesting a possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be considered a reliever therapy for the sildenafil‐induced dyspepsia. Copyright © 2014 John Wiley & Sons, Ltd.
  • Sulforaphane Suppresses LPS‐Induced or TPA‐Induced
           Downregulation of PDCD4 in RAW 264.7 Cells
    • Abstract: Sulforaphane is a natural chemopreventive isothiocyanate and abundantly found in various cruciferous vegetables. Although chemopreventive activity of sulforaphane is well documented, the detailed biochemical mechanism(s), underlying how it regulates the protein translation process to antagonize pro‐inflammatory responses are largely unclear. In the present study, we show that lipopolysaccharide (LPS) or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) treatment reduces cellular levels of PDCD4, and this event is mediated by affecting both transcription and proteolysis in RAW 264.7 cells. We show that LPS‐mediated or TPA‐mediated PDCD4 downregulation is catalyzed by the activation of intracellular Akt1 or S6K1 kinases and that sulforaphane suppresses LPS‐induced or TPA‐induced Akt1 or S6K1 activation, thereby resulting in the attenuation of PDCD4 downregulation in RAW 264.7 cells. We propose that sulforaphane suppression of PDCD4 downregulation serves as a novel molecular mechanism to control proliferation in response to pro‐inflammatory signals. Copyright © 2014 John Wiley & Sons, Ltd.
  • Antiangiogenic Activity of Xanthomicrol and Calycopterin, Two
           Polymethoxylated Hydroxyflavones in Both In Vitro and Ex Vivo Models
    • Abstract: Our previous studies had shown xanthomicrol and calycopterin, two plant‐derived flavonoids, to have selective antiproliferative activity against some malignant cell lines. The present study is focused on the investigation of antiangiogenic potential of these two flavonoids, using in vitro and ex vivo models. Xanthomicrol and calycopterin were found to have potent inhibitory effects on microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to completely block microvessel sprouting at 10 µg/mL, and calycopterin suppressed microvessel outgrowth by 89% at 5 µg/mL. Suramin and thalidomide, used at 20 µg/mL as positive controls, inhibited microvessel formation by 23% and 64%, respectively. The flavones also inhibited endothelial cell tube formation and human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 µg/mL. In order to delineate the underlying mechanisms of antiangiogenic activity of these flavones, we investigated the influences of xanthomicrol and calycopterin on expression of vascular endothelial growth factor (VEGF) and basic‐fibroblast growth factor (b‐FGF) in endothelial cells. These flavones were able to inhibit VEGF expression at 0.5, 5, and 10 µg/mL, but they had little or no effect on b‐FGF expression. These findings suggest that xanthomicrol and calycopterin possess potent antiangiogenic activities, which may be due to their inhibitory influences on VEGF expression. Copyright © 2014 John Wiley & Sons, Ltd.
  • Pomegranate Juice and Prostate Cancer: Importance of the Characterisation
           of the Active Principle
    • Abstract: Two exploratory clinical studies investigating proprietary pomegranate products showed a trend of effectiveness in increasing prostate‐specific antigen doubling time in patients with prostate cancer. A recent clinical study did not support these results. We therefore analysed a lot of the marketed pomegranate blend for co‐active pomegranate compounds. The high‐performance liquid chromatography method was used to detect punicalagin, ellagic acid and anthocyanins. Total polyphenoles were determined by the Folin–Ciocalteu method using gallic acid as reference. The results show that the co‐active compounds in the daily dose of the pomegranate blend were far below those previously tested and that the photometric assessment is not reliable for the standardisation of study medications. Not pomegranate but the low amount of co‐active compounds in the proprietary pomegranate blend was responsible for its clinical ineffectiveness. Copyright © 2014 John Wiley & Sons, Ltd.
  • Zerumbone Suppresses IL‐1β‐induced Cell Migration and
           Invasion by Inhibiting IL‐8 and MMP‐3 Expression in Human
           Triple‐negative Breast Cancer Cells
    • Abstract: Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial‐mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)‐1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL‐1β‐induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL‐1β‐induced cell migration and invasion in breast cancer cells. The levels of IL‐8 and matrix metalloproteinase (MMP)‐3 mRNA were analyzed by real‐time polymerase chain reaction. The levels of secreted IL‐8 and MMP‐3 protein were analyzed by enzyme‐linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL‐8 and MMP‐3 expression were significantly increased by IL‐1β treatment in Hs578T and MDA‐MB231 cells. On the other hand, IL‐1β‐induced IL‐8 and MMP‐3 expression was decreased by ZER. Finally, IL‐1β‐induced cell migration and invasion were decreased by ZER in Hs578T and MDA‐MB231 cells. ZER suppresses IL‐1β‐induced cell migration and invasion by inhibiting IL‐8 expression and MMP‐3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple‐negative breast cancer patients. Copyright © 2014 John Wiley & Sons, Ltd.
  • Growth Inhibition Effects of Isoalantolactone on K562/A02 Cells:
           Caspase‐dependent Apoptotic Pathways, S Phase Arrest, and
           Downregulation of Bcr/Abl
    • Abstract: Isoalantolactone, a sesquiterpene lactone, is the active component of Inula helenium (Compositae). It has been reported that isoalantolactone has the capacity to inhibit tumor cell growth through induction of apoptosis. The purposes of this study were to evaluate the effects of isoalantolactone on the human erythroleukemia drug‐resistant cell line K562/A02 and to provide evidence of its function as a potent therapeutic agent in patients with chronic myelogenous leukemia with the Bcr/Abl phenotype. Our results showed that isoalantolactone significantly inhibited K562/A02 cell growth by downregulating Bcr/Abl expression. Isoalantolactone also induced apoptosis via increase generation of reactive oxygen species, modulation of the protein levels of Bcl‐2 family members, caspase activation, poly ADP‐ribose polymerase (PARP) cleavage, and release of cytochrome c. We also observed that isoalantolactone inhibited proliferation by inducing cell cycle arrest in the S phase. Taken together, all these findings support that growth inhibition effects of isoalantolactone on K562/A02 cells may be mediated through caspase‐dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl. Copyright © 2014 John Wiley & Sons, Ltd.
  • Catechin‐based Procyanidins from Peumus boldus Mol. Aqueous Extract
           Inhibit Helicobacter pylori Urease and Adherence to Adenocarcinoma Gastric
    • Abstract: In this work, the anti‐Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay‐guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP‐HPLC; HILIC‐HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50 = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin‐derived proanthocyanidins (LC‐MS and phloroglucinolysis). The anti‐adherent effect of boldo was assessed by co‐culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti‐adherent effect in a concentration‐dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti‐urease activity and anti‐adherent effect against H. pylori, properties directly linked with the presence of catechin‐derived proanthocyanidins. Copyright © 2014 John Wiley & Sons, Ltd.
  • Umbelliferone Increases the Expression of Adipocyte‐Specific Genes
           in 3 T3‐L1 Adipocyte
    • Abstract: Umbelliferone (UMB), a natural product of coumarin family, has been shown to reduce blood glucose and to improve lipid profiles in streptozotocin (STZ)‐induced diabetic rats. Our objective was to examine the effect of UMB on adipogenesis by investigating its stimulatory effect on lipid accumulation and mRNA expression of adipogenic transcription factors and adipocyte‐specific genes in 3 T3‐L1 preadipocyte culture. An Oil Red O staining was used to monitor lipid accumulation, and we found that UMB treatment at concentration range of 10–100 μM significantly increased lipid accumulation of differentiating 3 T3‐L1 cells. At the molecular level of adipogenesis, we examined the mRNA expression of adipogenic transcription factors, peroxisome proliferator‐activated receptor γ, CCAAT/enhancer‐binding protein α, and sterol regulatory element‐binding protein 1c. Those transcription factors were increased by UMB at 10–100 μM. Interestingly, UMB also stimulated the mRNA expression of adipocyte‐specific genes, adipocyte fatty acid‐binding protein, lipoprotein lipase, fatty acid synthase, fatty acid translocase, and adiponectin. Our findings indicate that the stimulatory effect of UMB on adipocyte differentiation likely occurs through up‐regulation of adipogenic transcription factors and downstream adipocyte‐specific gene expression. Copyright © 2014 John Wiley & Sons, Ltd.
  • Curcuminoid Treatment for Knee Osteoarthritis: A Randomized
           Double‐Blind Placebo‐Controlled Trial
    • Abstract: Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long‐term adverse events of currently available medications including non‐steroidal anti‐inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti‐inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double‐blind placebo‐control parallel‐group clinical trial was conducted among patients with mild‐to‐moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p 
  • Biliary Excretion of Glycyrrhetinic Acid: Glucuronide‐Conjugate
           Determination Following a Pharmacokinetic Study of Rat Bile
    • Abstract: Liquorice is a commonly prescribed herb in traditional Chinese medicine with the primary constituent, glycyrrhetinic acid (GA) responsible for the toxic effects arising from its chronic consumption. Hepatic transformation and biliary excretion of GA are significant and well‐documented pharmacokinetic pathways in humans, while glucuronide conjugates are the major identified metabolites. Here we report the role of bile in GA bioconversion in rats; this being achieved following intravenous administration of GA to Sprague–Dawley rats at a dose of 2 mg/kg with bile fluid analyzed for 3 h post‐injection using HPLC. The maximum concentration of glucuronides was detected about 30 min post‐administration, while the cumulative biliary excretion of glucuronides after 3 h was found to be 63.6 ± 6.4%. Our findings indicate a relatively high rate of biliary excretion for GA via the formation of glucuronide conjugates, and as a result of these findings, glucuronidation can be firmly regarded as a primary detoxification pathway for GA in rats. Copyright © 2014 John Wiley & Sons, Ltd.
  • Proanthocyanin Content in Cranberry CE Medicinal Products
    • Abstract: The CE marking is a statutory marking for certain products sold within the European Economic Area. Medicinal products with a CE label are not regulated by the European Medicines Agency but are licensed according to the directives of the European Community. We have analysed the proanthocyanin (PAC) content of four cranberry CE products by both a photometric (DMAC method using 4‐dimethylamino‐cinnamic‐aldehyde as colouring reagent) and a high‐performance liquid chromatography assay and have compared the daily dosages recommended for the products by their manufacturers with benchmark doses obtained from the literature. For all CE products, the identified DMAC values for the PAC content per unit were below those declared. For two of the CE medicinal products, not even the manufacturers' maximum daily dosages have type A PAC contents that would have any chance of providing the health benefits promised on the product information sheets; the other two might have some chance, but only at maximum dosage (nine capsules per day for one of them). CE medicinal products should be better controlled by regulatory authorities to prevent consumers from buying and taking doses that are inadequate to provide the benefits claimed. Copyright © 2014 John Wiley & Sons, Ltd.
  • α‐Glucosidase Inhibitors from the Stems of Embelia ribes
    • Abstract: From the ethyl acetate extract of the stems of Embelia ribes (Myrsinaceae), a new alkenylresorcinol, embeliphenol A (1), together with 11 known compounds have been isolated. Their structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α‐glucosidase inhibitory activity in a concentration‐dependent manner, except for 2 and 9. Compounds 1, 3–6, 8, and 12 showed more potent inhibitory activity, with IC50 values ranging from 10.4 to 116.7 μM, than that of a positive control acarbose (IC50, 214.5 μM). Copyright © 2014 John Wiley & Sons, Ltd.
  • Antihyperalgesic Effects of an Aqueous Stem Bark Extract of Mangifera
           indica L.: Role of Mangiferin Isolated from the Extract
    • Abstract: This study aimed to assess the effects of a Mangifera indica stem bark extract (MSBE) and mangiferin (MG) on pain‐related acute behaviors in the formalin 5% test. Rats received repeated oral MSBE (125–500 mg/kg) once daily for 7 days before formalin injection. Other four groups with the same treatments were performed in order to study the effect of MSBE on the formalin‐induced long‐term secondary mechano‐hyperalgesia at 7 days after the injury by means of the pin‐prick method. Additional groups received a single oral MSBE dose (250 mg/kg) plus ascorbic acid (1 mg/kg, i.p.). Also, repeated oral MG doses (12.5–50 mg/kg) during 7 days were administered. MSBE decreased licking/biting and flinching behaviors only in phase II and reduced the long‐term formalin injury‐induced secondary chronic mechano‐hyperalgesia. The combination of MSBE plus ascorbic acid produced a reinforcement of this effect for flinching behavior, advising that antioxidant mechanisms are involved, at least in part, in these actions. Chronic administration of MG reproduced the effects of MSBE. For the first time, the antihyperalgesic effects of MSBE and MG in formalin 5% test, a recommended concentration for studying the antinociceptive activity of nitric oxide‐related and N‐methyl‐d‐aspartate‐related compounds, were reported. These results could represent an important contribution to explain the analgesic ethnobotanical effects recognized to M. indica and other species containing MG. Copyright © 2014 John Wiley & Sons, Ltd.
  • Guarana (Paullinia cupana Mart.) Prevents β‐Amyloid
           Aggregation, Generation of Advanced Glycation‐end Products (AGEs),
           and Acrolein‐Induced Cytotoxicity on Human Neuronal‐Like Cells
    • Abstract: Advanced glycation end‐products (AGEs) are considered potent molecules capable of promoting neuronal cell death and participating in the development of neurodegenerative disorders such as Alzheimer's disease (AD). Previous studies have shown that AGEs exacerbate β‐amyloid (Aβ) aggregation and AGE‐related cross‐links are also detected in senile plaques. Acrolein (ACR) is an α, β‐unsaturated aldehyde found in the environment and thermally processed foods, which can additionally be generated through endogenous metabolism. The role of ACR in AD is widely accepted in the literature. Guarana (Paullinia cupana Mart.) is popularly consumed by the population in Brazil, mainly for its stimulant activity. In the present study, we showed that guarana (10, 100, and 1000 µg/mL) is able to prevent protein glycation, β‐amyloid aggregation, in vitro methylglyoxal, glyoxal, and ACR (20 μM)‐induced toxicity on neuronal‐like cells (SH‐SY5Y). Since these are considered typical AD pathological hallmarks, we propose that guarana may deserve further research as a potential therapeutic agent in such a neurodegenerative disease. Copyright © 2014 John Wiley & Sons, Ltd.
  • Biotransformation of Glucoaurantio‐Obtusin Towards
           Aurantio‐Obtusin Increases the Toxicity of Irinotecan Through
           Increased Inhibition Towards SN‐38 Glucuronidation
    • Abstract: The present study aims to investigate the influence of irinotecan's toxicity by the biotransformation of glucoaurantio‐obtusin to aurantio‐obtusin. Intraperitoneal administration (i.p.) of 100 mg/kg aurantio‐obtusin significantly increased the toxicity of irinotecan, but the i.p. administration of 100 mg/kg glucoaurantio‐obtusin showed negligible influence towards irinotecan's toxicity. Furthermore, the mechanism was explained through determining the inhibition potential of glucoaurantio‐obtusin and aurantio‐obtusin towards the glucuronidation metabolism of SN‐38 that has been regarded to be the major active product responsible for the toxicity of irinotecan. The results showed that aurantio‐obtusin exhibited strong competitive inhibition towards the glucuronidation of SN‐38, but negligible inhibition potential of glucoaurantio‐obtusin towards SN‐38 glucuronidation was observed. These results showed that biotransformation of glucoaurantio‐obtusin towards aurantio‐obtusin increased the toxicity of irinotecan through increased inhibition of SN‐38 glucuronidation. Copyright © 2014 John Wiley & Sons, Ltd.
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