Discovery of bakuchiol as an AIM2 inflammasome activator and cause of hepatotoxicity

Psoralea corylifolia (P. corylifolia Linn.) is a traditional Chinese medicinal plant that exhibits significant aphrodisiac, diuretic, and anti-rheumatic effects. However, it has been reported to cause hepatic injury, but the precise mechanisms remain unclear. To evaluate the safety and risk of P. corylifolia and to elucidate the underlying mechanisms of drug-induced liver injury. Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, quantitative polymerase chain reaction (Q-PCR), and flow cytometry were used to explore the effect of bakuchiol (Bak), one of the most abundant and biologically active components of P. corylifolia, on the AIM2 inflammasome activation and the underlying mechanism. Furthermore, we used the lipopolysaccharides (LPS)-induced drug-induced liver injury (DILI) susceptible mice model to study the Bak-mediated hepatotoxicity. Bak induced the maturation of caspase-1 P20, and significantly increased the expression of IL-1β and TNF-α (P