"Mechanistic insights into the protective effect of Tongfu Huayu Formula in severe acute pancreatitis: a transcriptomic-proteomic study.".

Abstract

BACKGROUND: Acute pancreatitis involves the self-digestion of pancreatic tissue caused by the abnormal activation of pancreatic enzymes. The disease progresses rapidly, and severe acute pancreatitis (SAP) has a high mortality rate. Currently, there are no satisfactory treatments for SAP. The Tongfu Huayu Formula (TFHYF) is a modified version of the Dachengqi decoction, which has proven to be effective against SAP in clinical research. However, the mechanism of action is unclear. PURPOSE: The aim of this study was to investigate the mechanism and pathways that mediate the protective effect of the TFHYF against SAP in rats using transcriptomic and proteomic techniques. METHODS: We used ultra-high performance liquid chromatography to identify the main components of the TFHYF, applied Network pharmacology to investigate compound-disease target interaction and used L-arginine to induce SAP in rats. Serum inflammatory factors were detected via enzyme-linked immunosorbent assay, and pathological changes in the pancreatic tissues were evaluated using histochemical staining. Transcriptomic, proteomic analyses and western bolt(WB) were performed to identify potential mechanisms. RESULTS: The main components of the TFHYF were determined to be terpenoids, flavonoids, alkaloids, amino acids and their derivatives, coumarins, and phenolic acids. Based on network pharmacological analysis, TNF, STAT3, IL6, AKT1, IL1B, PPARG, etc., were identified as core therapeutic targets. Luteolin, quercetin, and baicalin may represent key bioactive components of TFHYF in treating acute pancreatitis (AP), potentially exerting anti-inflammatory effects on the pancreas by regulating the PI3K-Akt signaling pathway. The histochemical analysis showed that the TFHYF could reduce the degree of pancreatic tissue damage in rats with SAP. ELISA showed that TFHYF could reduce serum levels of AMY2A, IL-6, IL-1β, and TNF-α.Transcriptomic and proteomic analyses demonstrate that TFHYF inhibits pancreatic enzyme secretion and inflammatory responses. CONCLUSION: The findings show that the TFHYF can reduce the severity of SAP in rats by decreasing pancreatic secretion and the levels of inflammatory factors.