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.