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  • Title: Baicalein alleviates pyroptosis and inflammation in hyperlipidemic pancreatitis by inhibiting NLRP3/Caspase-1 pathway through the miR-192-5p/TXNIP axis.
    Author: Wang X, Cai H, Chen Z, Zhang Y, Wu M, Xu X, Yang L.
    Journal: Int Immunopharmacol; 2021 Dec; 101(Pt B):108315. PubMed ID: 34785144.
    Abstract:
    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.
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