Puerarin induces Nrf2 as a cytoprotective mechanism to prevent cadmium-induced autophagy inhibition and NLRP3 inflammasome activation in AML12 hepatic cells

Liver is the main target organ of cadmium (Cd) toxicity and puerarin (PU) has been shown to prevent Cd-induced hepatic cell damage via its antioxidant activity. Nrf2 acts as a critical regulator of cellular defense against various oxidative insults, but its role in the protection of PU against Cd-induced hepatic damage has not yet been clarified. Hereby, this study was designed to investigate the underlying mechanism using mouse hepatocyte line AML-12. Data firstly showed that Cd-inhibited Nrf2 pathway was markedly restored by PU treatment, assessed by Nrf2 nuclear translocation, protein levels of Keap1 and Nrf2 downstream target genes. Accordingly, Cd-reduced protein levels of antioxidant enzymes were significantly up-regulated by PU. Next, Nrf2 silencing cellular model was established to further elucidate the role of Nrf2 in the protection of PU against Cd-induced hepatic damage. Attenuation of Cd-induced autophagy inhibition and autophagosome accumulation by PU was remarkably countered by Nrf2 silencing. Moreover, alleviation of Cd-induced NLRP3 inflammasome activation by PU was distinctly prevented by Nrf2 knockdown, assessed by protein levels of NLRP3 inflammosome complex and downstream IL-18 and IL-1? production. Collectively, our data suggest that PU restores Cd-induced Nrf2 inhibition to prevent autophagy inhibition and NLRP3 inflammasome activation, providing novel insights into the protection of PU against Cd-induced hepatic cell damage.

Automated summary

The study found that puerarin can prevent autophagy inhibition and NLRP3 inflammasome activation induced by cadmium by restoring Nrf2 pathway, providing novel insights into the protection of puerarin against cadmium-induced hepatic cell damage.