Dysregulated B7H4/JAK2/STAT3 Pathway Involves in Hypertriglyceridemia Acute Pancreatitis and Is Attenuated by Baicalin

Dig Dis Sci. 2023 Feb;68(2):478-486. doi: 10.1007/s10620-022-07606-5. Epub 2022 Jul 4.

Abstract

Background: Patients with hypertriglyceridemia (HTG) are prone to develop more severe acute pancreatitis (AP). However, the specific molecular mechanism still has not been elaborated clearly, and effective drugs for treating HTG-AP are not yet readily available. Baicalin is an ingredient isolated from a natural product that with potential to attenuate inflammation and pain in AP.

Aims: The aim of the present study was to explore the effect of baicalin on HTG-AP and the possible mechanism involved.

Methods: A mouse model of HTG-AP was successfully established by administering Poloxamer 407 and L-arginine intraperitoneally. We analyzed pathological changes, and performed TUNEL staining, DHE staining, and western blot to detect apoptosis, inflammation, oxidative stress, and B7H4/JAK2/STAT3 signaling in the pancreas.

Results: Treatment with baicalin decreased serum triglyceride, cholesterol, lipase, amylase levels, and attenuated pancreatic edema. After intervention with baicalin, apoptosis and inflammation in HTG-AP mice were alleviated, as indicated by the decrease of Bax, cleaved-caspase-3, IL-6, TNF-α, and IL-1β. Baicalin also alleviated oxidative stress by decreasing NOX2, increasing SOD2 protein expression, and regulating Nrf2/Keap1 signaling in HTG-AP mice. Furthermore, baicalin decreased the upregulated B7H4/JAK2/STAT3 pathway in HTG-AP.

Conclusions: In conclusion, our data suggested that baicalin could attenuate HTG-AP, possibly through regulating B7H4/JAK2/STAT3 signaling.

Keywords: Acute pancreatitis; B7H4; Baicalin; Hypertriglyceridemia; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Hypertriglyceridemia*
  • Inflammation / drug therapy
  • Kelch-Like ECH-Associated Protein 1
  • Mice
  • NF-E2-Related Factor 2
  • Pancreatitis* / pathology

Substances

  • baicalin
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2