Revealing the temporal metabolic trajectory and potential pharmacodynamic substances of Da-Cheng-Qi Decoction in treating patients with acute pancreatitis: A serum metabolomics-based study.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Acute Pancreatitis (AP) is a pancreatic inflammatory disease lacking specific therapeutics. Da-Cheng-Qi Decoction (DCQD) has been proven to alleviate the severity and mortality of AP. However, its underlying mechanisms remain to be fully elucidated. AIM OF THE STUDY: This study aimed to explore DCQD's dynamic metabolic regulatory effects on AP patients and potential pharmacodynamic substances via serum metabolomics and serum pharmacochemistry analysis, with validation in animal models. MATERIALS AND METHODS: AP patients were randomized into conventional therapy (Con) and Con + DCQD groups. Fasting venous blood samples were collected at four time points (admission, 24 h/96 h post-admission, pre-discharge) for biochemical assays and UHPLC-Q-Exactive-Orbitrap-MS analysis. Metabolomics was used to screen AP-related biomarkers, evaluate the two regimens' reversal effects, and compare inter-group differences in metabolic recovery trajectories. Prototypes and metabolites of DCQD were identified, with potential pharmacodynamic substances screened via correlation analysis with AP biomarkers. L-arginine-induced SAP mouse model was used for validation. RESULTS: Serum amylase normalization and C-reactive protein decline were accelerated in Con + DCQD group. Both regimens reversed AP-related energy, amino acid, and lipid metabolic disorders. Adjuvant DCQD therapy accelerated inflammation alleviation and energy homeostasis restoration in early stage, and improved lipid metabolism more comprehensively in middle-to-late stage, with efficacy validated in SAP mice. Forty-eight and 35 blood-migrated components were identified in patients and mice, respectively, with 8 key pharmacodynamic substances screened. CONCLUSIONS: Integrating serum metabolomics and multi-time-point monitoring, this study delineated AP's metabolic recovery trajectory and clarified DCQD's efficacy and dynamic metabolic regulation, providing guidance for its clinical application.