ceruletide and rhein

Acute pancreatitis (AP) is an acute inflammatory condition of pancreas with high morbidity and mortality, which has no effective medical treatment. Chaiqin chengqi decoction (CQCQD) has been clinically used for AP for many years in China. However, the underlying mechanisms are still unknown.. To investigate the mechanism of CQCQD on gasdermin D (GSDMD) -mediated pyroptosis in AP.. In this study, network pharmacology was used to screen the potential mechanism of CQCQD protecting against AP and then we focused to investigate the mechanism of CQCQD on GSDMD mediated pyroptosis. Mouse models of AP were conducted by caerulein and L-arginine. In order to clarify the mechanism of CQCQD, two kinds of GSDMD gene knockout mice (Gsdmd. In the caerulein-induced AP model, CQCQD ameliorated pancreatic pathological injury, attenuated systemic inflammation and serum enzymatic levers. Moreover, network pharmacology analysis showed GSDMD mediated pyroptosis was one of the core targets of CQCQD protecting against AP. Additionally, CQCQD appreciably decreased the levels of pyroptosis-related proteins N-terminal GSDMD, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3, and cleaved Caspase-1. Furthermore, the protective effect of CQCQD was neutralized in Gsdmd. CQCQD could reduce pancreatic necrosis and inflammatory response via inhibiting GSDMD-mediated pyroptosis in acinar cells of AP. Rhein may be the key active ingredient of CQCQD in suppressing pyroptosis.

Topics: Acute Disease; Animals; Ceruletide; Gasdermins; Humans; Mice; Molecular Docking Simulation; NLR Family, Pyrin Domain-Containing 3 Protein; Pancreatitis; Pyroptosis