Pretreatment with Commelina communis L. improves survival following influenza a virus infection and enhances innate interferon signaling

The objectives of this study were to evaluate the pre-exposure protective effects of Commelina communis L. (CCL) against influenza A virus (IAV) infection and to investigate its associated immunomodulatory mechanisms. Using RAW 264.7 cells and BALB/c mouse models, we demonstrated that CCL pretreatment reduced viral replication markers and suppressed viral protein expression in vitro . In vivo , prophylactic administration of CCL improved survival from 0% to 40% and attenuated body-weight loss following IAV challenge. Mechanistically, CCL enhanced the secretion of type I interferon IFN-β through activation of TANK-binding kinase 1 (TBK1) and interferon regulatory factors 3 and 7 (IRF3/7). Activation of this signaling pathway was associated with STAT1/2 phosphorylation and increased expression of antiviral interferon-stimulated genes, including Isg20 and Isg56 . Phytochemical profiling using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-UV-HRMS) identified four phytochemicals in CCL, among which rutin showed the greatest activity among the tested compounds in the in vitro screening assay. Collectively, these findings suggest that CCL and rutin may enhance host antiviral defense by modulating innate interferon signaling when administered before IAV exposure period.