Synthesis and Evaluation of Bakuchiol Derivatives as Potent Anti-inflammatory Agents and .

Bakuchiol, a prenylated phenolic monoterpene derived from the fruit of L. (Buguzhi), is widely used to treat tumors, viruses, inflammation, and bacterial infections. In this study, we designed and synthesized 30 bakuchiol derivatives to identify new anti-inflammatory drugs. The anti-inflammatory activities of the derivatives were screened using lipopolysaccharide-induced RAW264.7 cells. To evaluate the anti-inflammatory activity of the compounds, we measured nitric oxide (NO), interleukin-6, and tumor necrosis factor-α production. Based on the screening results, compound displayed more pronounced activity than bakuchiol and celecoxib. Furthermore, the mechanistic studies indicated that inhibited pro-inflammatory cytokine release, which was correlated with activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and blockade of the nuclear factor-κB/mitogen-activated protein kinase signaling pathway. The anti-inflammatory activity in zebrafish indicated that inhibited NO and reactive oxygen species production in a dose-dependent manner. These results indicate that is a potential candidate for development as an anti-inflammatory agent.