Baicalin clears inflammation by enhancing macrophage efferocytosis via inhibition of RhoA/ROCK signaling pathway and regulating macrophage polarization.

Effective efferocytosis of apoptotic polymorphonuclear leukocytes (PMNs) in the initiation and resolution of inflammation iscrucial for preventing progression to chronicinflammatorydisease. Baicalin, a bioactive flavonoid drug, exerts multiple anti-inflammatory effects; however, its underlying mechanism remains to be elucidated. Here, we investigated the role of baicalin in efferocytosis in vitro and in a Porphyromonas gingivalis lipopolysaccharide (LPS)-inducedmurinemodelofpleurisy. We found that the macrophage engulfment of apoptotic PMNs was significantly promoted by baicalin in an inflammatory environment with an effectiveness similar to that of N-acetylcysteine. Meanwhile, the production of reactive oxygen species was significantly blocked in P. gingivalis LPS-stimulated J774A.1 macrophages by baicalin, and the RhoA/ROCK signaling pathway was inhibited in the same way as the ROCK inhibitor, Y-27632. In addition, the M1/M2macrophage ratio and the proinflammatory cytokine TNF-α were downregulated, whereas the anti-inflammatory cytokine IL-10 was upregulated both in vitro and in vivo. Therefore, we propose that baicalin may increase efferocytosis by acting as an antioxidant via a RhoA-dependent pathway and regulate macrophage polarization, thus promoting inflammatory resolution.