Poster Presentation The Pancreas Summit 2025

Dihydroquercetin derived from Huanglong decoction ameliorates sever acute pancreatitis by modulating STAT3/ERK signaling pathway (#23)

Yan Shen 1 2 , Sha Ran 1 , Cai Sun 1 , Liang Pan 1
  1. School of pharmacy and bioengineering, Chongqing University of Technology, Chongqing, China
  2. School of Medicine, University of Auckland, Auckland, New Zealand

BACKGROUD

Severe acute pancreatitis (SAP), a life-threatening condition with high mortality, imposes substantial clinical burdens due to ineffective therapies1. Although Huanglong decoctio, a traditional Chinese medicine, shows therapeutic potential in gastrointestinal dysfunction2, its bioactive components and mechanisms remain uncharacterized, hindering clinical translation. This study aims to investigate Huanglong decoction and its key compound dihydroquercetin (DHQ) against SAP.

METHODS

Computational biology identified key bioactive components and targets of Huanglong Decoction. In vitro, we characterized the protective effect and modulation of Huanglong Decoction and its key bioactive component in injured primary pancreatic acinar cell by propidium iodide staining, western blot, and qPCR. In vivo, two acute pancreatitis models were established: C57BL/6 mice received 11 hourly intraperitoneal injections of cerulein (100 μg/kg) followed by a single LPS dose (10 μg/kg) (CER-SAP), mice were pretreated with poloxamer 407 (0.5 g/kg, intraperitoneal injection every 48 hours for 1 month), followed by 7 hourly cerulein injections (100 μg/kg) (hypertriglyceridemic-acute pancreatitis, HTG-AP)3. The therapeutic effects of DHQ were evaluated through hematoxylin and eosin, immunohistochemistry and immunofluorescence, enzyme-linkedimmunosorbent assay, and qPCR.

RESULTS

Computational screening identified dihydroquercetin, didymin, gancaonin G, 1-methoxyglabridin, vestitol, and naringenin as core compounds interacting with STAT3/ERK nodes in acute pancreatitis. In vitro, Huanglong Decoction and DHQ significantly diminished acinar cell necrosis while suppressed phospho-STAT3/ERK expression. In HTG-AP model, DHQ decreased mortality from 30% to 10%, alongside with significantly lowered serum levels of triglycerides, total cholesterol, free fatty acids, and glucose. DHQ attenuated pancreatic injury in both models, evidenced by reduced pancreatic edema, inflammatory cell infiltration, and pancreatic necrosis. Systemic effects included markedly lowered serum amylase and lipase levels, alongside suppressed serum levels of IL-6, IL-1β, IFN-γ, and TNF-α. Notably, DHQ mitigated SAP-associated lung injury and restored intestinal barrier function by upregulating occludin and downregulating E-cadherin. Mechanistically, DHQ inhibited STAT3/ERK activation in both pancreatic and intestinal tissues.

CONCLUSION

Huanglong decoction mitigates SAP severity mechanistically linked to STAT3/ERK pathway inhibition. Its active ingredient DHQ emerges as a potential candidate for managing SAP. These findings provide a mechanistic bridge between traditional medicine formulations and modern targeted drug development for critical pancreatic disorders.

  1. de-Madaria E, Buxbaum JL. Advances in the management of acute pancreatitis. Nature Reviews Gastroenterology & Hepatology 2023;20:91–692.
  2. FU Y, Jiang S, Huang Y. Effects of Huanglong decoction on mRNA and protein expression levels of intestinal mucosal epithelial Claudin-1 and Occludin in sepsis rat. Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;2:138-141.
  3. Duan H, Zhang R, Asikaer A, et al. Nicotinamide mononucleotide ameliorates hypertriglyceridemia pancreatitis via NAD+/SIRT1-mediated TXNIP suppression and NOTCH pathway for accelerated repair-associated processes. International Immunopharmacology 2025;155:114620.