Baicalein alleviates pyroptosis and inflammation in hyperlipidemic pancreatitis by inhibiting NLRP3/Caspase-1 pathway through the miR-192-5p/TXNIP axis.

OBJECTIVE

Hyperlipidemia is a main reason of pancreatitis. Baicalein can ameliorate the pathological manifestations of pancreatitis. This study evaluated underlying molecular mechanism of baicalein in hyperlipidemic pancreatitis (HP).

METHODS

HP rat model was successfully established and treated with baicalein. Amylase (AMY) activity and concentrations of triglyceride (TG) and total cholesterol (TC) were detected. Levels of pyroptosis-related proteins (GSDMD, IL-1β, IL-18) were detected by Western blot. Expressions of inflammatory factors (IL-6, TNF-α, IL-4) were detected by ELISA. Toxicity of baicalein on pancreatic acinar cells (PACs) was detected by MTT assay. HP cell model was established by 0.1 mM palmitic acid and CCK-8 stimulation. Target relation of miR-192-5p and TXNIP was predicted and verified by RNA22 v2 database and dual-luciferase reporter assay. Expressions of miR-192-5p and TXNIP were detected by RT-qPCR. Pyroptosis and inflammation in PACs were detected after baicalein treatment combined with silencing miR-192-5p or TXNIP overexpression. Protein levels of NLRP3/Caspase-1 pathway in vivo and vitro were detected.

RESULTS

Baicalein reduced concentrations of TG and TC, AMY activity, and pathological scores in HP rat model, reduced LDH activity, pyroptosis and alleviated inflammation in vivo and in vitro. Mechanically, miR-192-5p targeted TXNIP, and baicalein inhibited pyroptosis and inflammation by up-regulating miR-192-5p and down-regulating TXNIP. Silencing miR-192-5p or TXNIP overexpression partially abolished the anti-pyroptosis and anti-inflammatory effect of baicalein on PACs. Baicalein attenuated HP by inhibiting the NLRP3/Caspase-1 pathway.

CONCLUSION

Baicalein alleviated pyroptosis and inflammation in HP by inhibiting the NLRP3/Caspase-1 pathway through miR-192-5p upregulation and TXNIP inhibition.