Life sciences

1879-06312002018May01Life sciencesLife SciCappariloside A shows antiviral and better anti-inflammatory effects against influenza virus via regulating host IFN signaling, in vitro and vivo.115125115-12510.1016/j.lfs.2018.03.033S0024-3205(18)30139-5This study aimed to evaluate the efficacy and mechanisms of Cappariloside A, a chemically synthesized compound, against virus and inflammation induced by influenza virus.The inhibitory activity of Cappariloside A against influenza virus was determined by plaque assay and cytopathic effect inhibition assay. Quantitative real-time PCR, enzyme-linked immunosorbent assay and Bio-Plex methods were used to quantify cytokine and chemokine expression profiles. Effects of Cappariloside A were also evaluated in a mouse model of influenza virus infection.We successfully synthesized Cappariloside A, which could inhibit replication of a variety of viruses, including influenza viruses H1N1 and H3N2, PIV3 and ADV in vitro. Cappariloside A could also inhibit progeny virus replication at concentrations of 2 and 1 mg/mL. Simultaneously, it significantly reduced the expressions of IL-6, IP-10, MIG and RANTES/CCL-5 stimulated by A/PR/8/34 (H1N1) at a range of doses, even 0.5 mg/mL. Similar anti-inflammatory activity was detected in cells induced by avian influenza virus H9N2 or lipopolysaccharide. In addition, Cappariloside A clearly inhibited inflammatory response induced by mouse lung-adapted influenza strain PR8/H1N1. Furthermore, Cappariloside A strongly inhibited phosphorylated STAT1 levels and IFN-β and IL-29 expressions induced by PR8/H1N1. Cappariloside A also inhibited IP-10 and CCL-5/RANTES expressions induced by exogenous human recombinant IFN-β.Cappariloside A not only shows broad-spectrum antiviral efficacy, but more effectively impairs the upregulations of pro-inflammatory factors in host cells induced by influenza virus. The potential antiviral mechanism of Cappariloside A is through inhibiting the activation of the host IFN signaling pathway.Copyright © 2018 Elsevier Inc. All rights reserved.LiZhengtuZState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China.ZhaoJunlingJInstitute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.ZhouHongxiaHState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China.LiLiLThe First Hospital of Yulin, Yulin 719000, China.DingYuyangYGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.LiJingJState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China.ZhouBeixianBState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China.JiangHaimingHState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China.ZhongNanshanNState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China; Macau University of Science and Technology, Macau 519020, China.HuWenhuiWGuangzhou Medical University, Guangzhou 511436, China.YangZifengZState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China; Macau University of Science and Technology, Macau 519020, China. Electronic address: jeffyah@163.com.engJournal Article20180317