Oral Presentation The Pancreas Summit 2025

Bupleurum and Scutellaria Purgative Decoction Mitigates Obesity-Related Acute Pancreatitis by Regulating Fatty Acid Metabolism (126982)

Yuying Li 1 , Wenhao Cai 1 , Shaoqi Zhong 2 , Lijia Huang 2 , Rajarshi Mukherjee 3 4 , Robert Sutton 4 , Tingting Liu 1 , Qing Xia 1 , wei huang 1 2
  1. West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China- Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  2. West China Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  3. Liverpool EmerGenT Academy, Department of Emergency General and Major Trauma Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  4. Liverpool Pancreatitis Research Group, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK

Background: Obesity contributes to acute pancreatitis (AP) pathogenesis and progression, with rising global prevalence. Fatty acid metabolism in obesity-related acute pancreatitis (ORAP) remains poorly characterized. Bupleurum and Scutellaria Purgative Decoction (BSPD) shows protective effects in AP, but whether it modulates fatty acid metabolism in ORAP require further elucidation.

Methods: Mice were fed high-fat diet (HFD) or chow diet to establish obesity models and corresponding controls, respectively. AP was induced by seven intraperitoneal injections of caerulein (50 μg/kg) at hourly intervals. BSPD (5.5 g/kg) was administered by gavage at 1, 5, and 9 hours after disease induction. Pancreatic injury was evaluated using histopathology and serum biomarkers. Transcriptomic profiling, targeted acyl-coenzyme A metabolomics, and network pharmacology were applied to investigate alterations in metabolic pathways and related metabolites. Functional enrichment analysis was performed using DAVID, and protein-protein interaction network was constructed using the STRING database and visualized with Cytoscape (v3.10.1). Long chain acyl-coenzyme A (LC-CoA) induced cytotoxicity in acinar cells was assessed using propidium iodide staining, and RT-qPCR was conducted to validate the expression of key metabolic enzymes.

Results: Compared with CD-AP, HFD-AP exhibited more severe pancreatic injury accompanied by hepatic damage, both of which were ameliorated by BSPD treatment. Transcriptomic analysis revealed dysregulated fatty acid metabolism in HFD-AP, characterized by upregulation of LC-CoA synthases (Acsl4/5) and elongation (Elovl7, Hacd1, and Hsd17b12) enzymes, alongside downregulation of key β-oxidation enzymes (Cpt1a and Acox1). Targeted metabolomics confirmed pathological accumulation of LC-CoAs (16:3, 20:0, 22:0–22:3) in pancreatic tissue, which was normalized by BSPD, particularly for 16:3, 20:0, and 22:0–22:1. LC-CoAs induced acinar cell death in a dose-dependent manner. Network pharmacology suggested that BSPD primarily targets lipid metabolic processes. RT-qPCR further showed that Cpt1a expression was significantly reduced in HFD-AP and did not recover following BSPD treatment. In contrast, expression of Elovl7, Hacd1, and Hsd17b12 was elevated in HFD-AP, with all three genes partially regulated by BSPD; notably, Elovl7 expression was significantly reduced following treatment.

Conclusion: Fatty acid metabolism is disrupted in the pancreas of ORAP mice, characterized by elevated LC-CoA levels. BSPD mitigates ORAP severity, partially via modulating key enzymes involved in the LC-CoA elongation pathway.