Molecular Mechanism of Baicalin in Ameliorating Chronic Pancreatitis: Insights From Network Pharmacology and Metabolomics

Abstract

In this study, we explored the therapeutic effects and mechanisms of baicalin (BA) in a dibutyltin dichloride (DBTC)–induced chronic pancreatitis (CP) rat model using metabolomics and network pharmacology. The results showed that BA significantly reduced inflammatory cell infiltration and fibrosis in pancreatic tissues, lowered serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), amylase (AMS), and lipopolysaccharide (LPS) and thereby decreased expression of alpha-smooth muscle actin (α-SMA) and fibronectin (FN) in pancreatic tissues. Metabolomic analyses revealed that BA influences multiple metabolic pathways, including glycerophospholipid and arachidonic acid metabolism, in serum and urine. Network pharmacology identified key targets, such as phospholipase A2 group IVA (PLA2G4A) and transient receptor potential vanilloid 4 (TRPV4), which are primarily involved in IL-17 signaling, as well as other pathways beyond inflammation. Further integrated analysis demonstrated that BA inhibits pancreatic stellate cell activation and reduces pancreatic fibrosis by regulating metabolites, such as arachidonic acid, that act on the PLA2G4A/TRPV4 and transforming growth factor-beta 1 (TGF-β1)/SMAD family member 3 (SMAD3) pathways. Molecular docking studies confirmed that BA binds strongly to these targets. In summary, BA exerts anti-inflammatory and antifibrotic effects through multiple targets and pathways, thereby alleviating the pathological progression of CP.