Anti-inflammatory and antiviral activities of cynanversicoside A and cynanversicoside C isolated from Cynanchun paniculatum in influenza A virus-infected mice pulmonary microvascular endothelial cells

BackgroundOutbreaks of the influenza A virus (IAV) often occur in various avian and mammalian species, including humans, causing serious respiratory injury worldwide. Therapeutic actions are limited to vaccines and a few antiviral drugs. Combination antiviral compounds and anti-inflammatory modulators to control the propagation of viruses would be more efficient therapeutic strategies for infectious diseases.PurposeThis study was designed to isolate anti-inflammatory and antiviral compounds from Cynanchun paniculatum and elucidate their potential molecular mechanisms.Methods/Study designsBioactivity-guided isolation (via in vitro anti-inflammatory assay) was performed on the ethanolic extract of C. paniculatum, the structures of active compounds were elucidated by comparing spectral data (ESI-MS, 1H NMR and 13C NMR) with literature values. The antiviral activity of active compounds against Influenza A virus (IAV) was determined using the cytopathic effect (CPE) inhibition assay. Inhibitory effects of active compounds on influenza A/FM1/1/47 (H1N1) virus infection were also determined by RT-PCR. Effect of active compounds on NF-kB and MAPK signaling pathways after virus infection was determined by ELISA.ResultsTwo compounds that showed great anti-inflammatory activity were isolated from C. paniculatum and elucidated as cynanversicoside A and cynanversicoside C. Cytokine assay demonstrated that cynanversicoside A and cynanversicoside C can suppress the production of TNF-α, IL-6 and IL-1β in Mice Pulmonary Microvascular Endothelial Cells (MPMEC) after Influenza virus A/FM/1/47 infection (p < .05) and also decreased the expressions of p-p65 and p-IκBα in infected cells. Furthermore, the phosphorylation of p38, ERK and JNK was also significantly attenuated. Subsequently, cynanversicoside A and cynanversicoside C treatment resulted in decreased viral replication and viral mRNA synthesis.ConclusionsThese results indicate that cynanversicoside A isolated from C. paniculatum has potent anti-inflammatory and antiviral effects on IAV-infected MPMEC by the regulation of NF-κB and MAPK signaling pathways.