Zhengtu Li1, Junling Zhao2, Hongxia Zhou1, Li Li3, Yuyang Ding4, Jing Li1, Beixian Zhou1, Haiming Jiang1, Nanshan Zhong5, Wenhui Hu6, Zifeng Yang7. 1. State 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. 2. Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China. 3. The First Hospital of Yulin, Yulin 719000, China. 4. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China. 5. State 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. 6. Guangzhou Medical University, Guangzhou 511436, China. 7. State 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.
Abstract
AIMS: This study aimed to evaluate the efficacy and mechanisms of Cappariloside A, a chemically synthesized compound, against virus and inflammation induced by influenza virus. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: This study aimed to evaluate the efficacy and mechanisms of Cappariloside A, a chemically synthesized compound, against virus and inflammation induced by influenza virus. MAIN METHODS: 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. KEY FINDINGS: 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 virusH9N2 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. SIGNIFICANCE: 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.