Dihydroquercetin derived from Huanglong Decoction improves acute pancreatitis and related intestinal damage through...

Acute pancreatitis (AP) is an inflammatory disorder frequently associated with systemic complications, yet the therapeutic potential of Huanglong Decoction (HLT) in severe AP remains unclear. This study investigated the protective effects of HLT and its candidate bioactive constituent dihydroquercetin (DHQ) against AP. Through integrated network pharmacology and molecular docking analyses, DHQ was identified as a candidate active compound of HLT, and STAT3/ERK signaling was predicted to be involved in its therapeutic mechanism. These predictions were further validated using in vitro and in vivo models. HLT dose-dependently protected pancreatic acinar cells through modulation of this pathway. DHQ reduced ROS accumulation, restored mitochondrial function, and suppressed necrotic cell death in vitro. In vivo, DHQ alleviated pancreatic and multi-organ injury and improved survival, accompanied by inhibition of STAT3/ERK signaling and ZBP1-mediated necroptosis. These results suggest that DHQ, the primary active constituent of HLT, markedly ameliorates SAP and multi-organ injury, likely by downregulating STAT3/ERK and ZBP1-mediated necroptosis pathways, positioning it as a compelling therapeutic candidate for SAP and HTG-AP.