Evaluation of the anti-neuraminidase activity of the traditional Chinese medicines and determination of the anti-influenza A virus effects of the neuraminidase inhibitory TCMs in vitro and in vivo |
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Authors: | Tian Li Wang Zhiyong Wu Hao Wang Song Wang Ye Wang Yanyan Xu Jingwei Wang Liying Qi Fengchun Fang Minli Yu Dahai Fang Xuexun |
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Institution: | a Key Laboratory of Molecular Enzymology and Enzyme Engineering of Ministry Education, Jilin University, Changchun 130012, PR China b Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China c Department of Molecular Biology or Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China d Changchun Institute of Biological Products, Changchun 130062, PR China |
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Abstract: | Etnopharmacological relevanceNeuraminidase (NA) inhibitors are currently the most effective drugs to treat influenza A viruses infection. Many traditional Chinese medicines (TCMs) have been used in the clinics to treat influenza. The anti-viral mechanisms of these TCMs and their inhibitory effects towards NA need to be systematically tested.Aim of the studyTo evaluate the anti-NA activity of the TCMs and the anti-influenza A virus effects of the NA inhibitory TCMs in vitro and in vivo.Material and methodsWe tested the inhibitory activity of water extracts from 439 TCMs towards NA. The in vitro anti-influenza virus activities of the 5 TCMs were evaluated using the strain A/California/7/2009 (H1N1) NYMC X-179A of influenza A virus. A randomly selected TCM with NA inhibitory activity, Melia toosendan extract, was further evaluated using a mouse model infected with influenza A virus.ResultsFive TCMs, Duchesnea indica (Andr.) Focke Fragaria indica Andr.], Liquidambar formosana Hance., Lithospermum erythrorhizon Sieb. et Zucc., Melia toosendan Sieb. et Zucc., and Prunella vulgaris L., exerted potent inhibitory activity towards NA. These TCMs in the range of 25-250 μg/mL had the ability to reduce virus-induced cytopathic effect (CPE) and the virus yield in MDCK cells. Melia toosendan significantly reduced death rate and prolonged mean day to death (MDD) of the viral infected mice.ConclusionsThis study describes five TCMs exerted strong inhibitory activities towards NA, and exhibited antiviral effect against influenza A virus by reducing viral reproduction and reduced CPE of the viral infected cells. Melia toosendan, significantly reduced death rate and prolonged survival of the H1N1 viral infected mice. |
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Keywords: | NA neuraminidase HA hemagglutinin TCID50 50% tissue culture infective dose IC50 50% inhibitory concentration CC50 half-maximum cytotoxic concentration DMEM Dulbecco's modified Eagle's medium MTT 3-[4 5-dimethyl-thiazol-2-yl]-2 5-diphenyl tetrazolium bromide TCMs traditional Chinese medicines CPE cytopathic effect MES 2-N-morpholino-ethanesulfonic acid MU-NANA 2&prime d-N-acetylneuraminic acid" target="_blank">-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid FBS fetal bovine serum MDD mean day to death LD50 50% median lethal dose KLP Melia toosendan Sieb et Zucc |
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