Baicalin protects AML-12 cells from lipotoxicity via the suppression of ER stress and TXNIP/NLRP3 inflammasome activation.

Abstract

Baicalin (BA) is an active flavonoid compound originating from the root of Scutellaria baicalensis Georgi that has been reported to exert anti-inflammation and anti-oxidant effects in liver diseases with a long history. However, its protective and regulatory mechanisms on palmitic acid (PA) induced hepatocyte lipotoxicity remain elusive. In the present work, we investigated the cytoprotective effects of BA in AML-12 hepatocytes against lipotoxicity by inhibiting ER stress, oxidative stress and apoptosis. Our results demonstrated that ER stress was induced by 400 μM PA in AML-12 cells with elevated expression of ER stress marker IRE1α hyperphosphorylation. BA at 12.5 μM and 25 μM effectively inhibited the expression of p-IRE1α as TUDCA. Flow cytometry analysis and immunofluorescence staining revealed that PA-induced ROS and cell apoptosis were reversed by BA. Furthermore, western blotting revealed that PA-challenged expressions of TXNIP and NLRP3 were dramatically suppressed by BA and TUDCA, suggesting that BA inhibited ER stress through a TXNIP/NLRP3 pathway. Overall, our results indicate that BA alleviates PA-induced cytotoxicity in AML-12 cells via suppression of ER stress and TXNIP/NLRP3 inflammasome activation. These results provide a possible basis of the underlying mechanism and a new insight into the application for BA in the treatment of NAFLD.