Baicalin Inhibits Influenza A Virus InfectionviaPromotion of M1 Macrophage Polarization

Background and Aims The natural compound baicalin (BA) possesses potent antiviral properties against the influenza virus. However, the underlying molecular mechanisms of this antiviral activity and whether macrophages are involved remain unclear. In this study, we, therefore, investigated the effect of BA on macrophages. Methods We studied macrophage recruitment, functional phenotypes (M1/M2), and the cellular metabolismviaflow cytometry, qRT-PCR, immunofluorescence, a cell culture transwell system, and GC-MS-based metabolomics bothin vivoin H1N1 A virus-infected mice andin vitro. Results BA treatment drastically reduced macrophage recruitment (CD11b(+), F4/80(+)) by approximately 90% while maintaining the proportion of M1-polarized macrophages in the bronchoalveolar lavage fluid of infected mice. This BA-stimulated macrophage M1 phenotype shift was further verifiedin vitroin ANA-1 and primary peritoneal macrophages by measuring macrophage M1 polarization signals (CD86, iNOS, TNF-alpha,iNOS/Arg-1ratio, and IL-1 beta cleavage). Meanwhile, we observed an activation of the IFN pathway (upregulation ofIFN-beta andIRF-3), an inhibition of influenza virus replication (as measured by theMgene), and distinct cellular metabolic responses in BA-treated cells. Conclusion BA triggered macrophage M1 polarization, IFN activation, and other cellular reactions, which are beneficial for inhibition of H1N1 A virus infection.