title: Magnesium lithospermate B and rosmarinic acid, two compounds present in Salvia miltiorrhiza, have potent antiviral activity against enterovirus 71 infections.
abstract: The aim of this study was to identify the active ingredients responsible for the anti-EV71 activity produced by Salvia miltiorrhiza extracts. A pGS-EV71 IRES-based bicistronic reporter assay platform was used for rapid analysis of compounds that could specifically inhibit EV71 viral IRES-mediated translation. The analysis identified 2 caffeic acid derivatives, magnesium lithospermate B (MLB) and rosmarinic acid (RA), which suppressed EV71 IRES-mediated translation at concentrations of 30μg/ml. We also found that MLB and RA inhibited EV71 infection when they were added to RD cells during the viral absorption stage. MLB had a low IC50 value of 0.09mM and a high TI value of 10.52. In contrast, RA had an IC50 value of 0.50mM with a TI value of 2.97. MLB and RA (100µg/ml) also reduced EV71 viral particle production and significantly decreased VP1 protein production. We propose that these two derivatives inhibit EV71 viral entry into cells and viral IRES activity, thereby reducing viral particle production and viral RNA expression and blocking viral VP1 protein translation. This study provides useful information for the development of anti-EV71 assays and reagents by demonstrating a convenient EV71 IRES-based bicistronic assay platform to screen for anti-EV71 IRES activity, and also reports 2 compounds, MLB and RA, which are responsible for the anti-EV71 activity of S. miltiorrhiza.
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chung
authors.affiliation: Biopesticide Department, Agricultural Chemicals and Toxic Substances Research Institute, Taichung 41300, Taiwan, ROC.
authors.forename: Feng-Chia
authors.initials: FC
authors.lastname: Hsieh
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Science Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan, ROC.
authors.forename: Tzong-Yuan
authors.initials: TY
authors.lastname: Wu
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Nou-Ying
authors.initials: NY
authors.lastname: Tang
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, ROC. Electronic address: jinn@mail.cmu.edu.tw.
authors.forename: Tzyy-Rong
authors.initials: TR
authors.lastname: Jinn
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D019556:COS Cells; D036022:Capsid Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004769:Enterovirus Infections / Q000188:drug therapy; D006801:Humans; D018517:Plant Roots; D027561:Salvia miltiorrhiza; D014779:Virus Replication / Q000187:drug effects; D000097123:Rosmarinic Acid
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D002934:Cinnamates; D053630:Depsides; D004365:Drugs, Chinese Herbal; D000097123:Rosmarinic Acid; C061091:lithospermate B
keywords: Amantadine (PubChem CID: 64150); Enterovirus 71; Internal ribosome entry site; Magnesium lithospermate B; Magnesium lithospermate B (PubChem CID: 6918234); Rosmarinic acid; Rosmarinic acid (PubChem CID: 528179); Salvia miltiorrhiza; Salvianolic acid A (PubChem CID: 5281793); Salvianolic acid B (PubChem CID: 119177); Sodium danshensu (PubChem CID: 23711819); VP-1 proteins