AUTHOR=Geng Ping , Zhu Haiyan , Zhou Wei , Su Chang , Chen Mingcang , Huang Chenggang , Xia Chengjie , Huang Hai , Cao Yiou , Shi Xunlong TITLE=Baicalin Inhibits Influenza A Virus Infection via Promotion of M1 Macrophage Polarization JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.01298 DOI=10.3389/fphar.2020.01298 ISSN=1663-9812 ABSTRACT=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 metabolism via flow cytometry, qRT-PCR, immunofluorescence, a cell culture transwell system, and GC-MS–based metabolomics both in vivo in H1N1 A virus-infected mice and in 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 verified in vitro in ANA-1 and primary peritoneal macrophages by measuring macrophage M1 polarization signals (CD86, iNOS, TNF-α, iNOS/Arg-1 ratio, and IL-1β cleavage). Meanwhile, we observed an activation of the IFN pathway (upregulation of IFN-β and IRF-3), an inhibition of influenza virus replication (as measured by the M gene), 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.