M2C Polarization by Baicalin Enhances Efferocytosis via Upregulation of MERTK Receptor

Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2(C) phenotype by baicalin. The signatures of M2(C) macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF-alpha), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2(A) rather than M2(C) subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2(C) macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2(C) macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity.