Anti‐Inflammatory Activities of Biapigenin Mediated by Actions on p38 MAPK Pathway

Biapigenin is a naturally occurring biflavonoid found inSelaginella tamariscina. This study aimed to investigate the anti‐inflammatory activity of biapigenin and its mechanisms of action, and to identify possible target proteins. Biapigenin suppressed nitric oxide (NO) production, as well as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and macrophage inflammatory protein (MIP)‐2 cytokine release. Moreover, biapigenin completely inhibitedIL‐1β, inducible nitric oxide synthases (iNOS), andMIP‐2mRNAexpression and partially suppressedMIP‐1 andTNF‐α expression. Lipopolysaccharide (LPS)‐induced upregulation of p38 mitogen‐activated protein kinase (MAPK) phosphorylation was significantly reduced by biapigenin. Fluorescence titration experiment revealed that biapigenin bound to p38 with a high binding affinity of 2.57 × 106 M−1. These results suggest that biapigenin demonstrates anti‐inflammatory activities by the regulation of phosphorylation of p38MAPKpathway. Our results strongly suggest that biapigenin may be a potent biflavonoid inhibitor of p38MAPKand have therapeutic applications in the treatment of inflammatory diseases.