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

Biapigenin is a naturally occurring biflavonoid found in Selaginella 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)-alpha, interleukin (IL)-1 beta, and macrophage inflammatory protein (MIP)-2 cytokine release. Moreover, biapigenin completely inhibited IL-1 beta, inducible nitric oxide synthases (iNOS), and MIP-2 mRNA expression and partially suppressed MIP-1 and TNF-alpha 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 x 10(6) M-1. These results suggest that biapigenin demonstrates anti-inflammatory activities by the regulation of phosphorylation of p38 MAPK pathway. Our results strongly suggest that biapigenin may be a potent biflavonoid inhibitor of p38 MAPK and have therapeutic applications in the treatment of inflammatory diseases.