94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1557681
Tetramethylpyrazine alleviates acute pancreatitis inflammation by inhibiting pyroptosis via the NRF2 pathway
Provisionally accepted- 1Quanzhou First Hospital, Fujian Medical University, Quanzhou, China
- 2Xiamen Changgeng Hospital Affiliated to Huaqiao University, Xiamen, China
- 3Huaqiao University, Quanzhou, Fujian, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
ObjectiveTetramethylpyrazine (TMPZ), an active alkaloid derived from traditional Chinese medicine, has shown anti-inflammatory and anti-pyroptotic properties. However, its role in acute pancreatitis (AP)-induced pyroptosis remains unclear. This study aims to investigate the effects of TMPZ on AP-induced pyroptosis and its potential mechanisms.Materials and methodsA cerulein-induced AP rat model was used to evaluate TMPZ’s protective effects in vivo, and its mechanisms were explored using AR42J cells in vitro. Pancreatic injury was assessed by hematoxylin-eosin staining, TUNEL assay, and serum biochemistry. Transmission electron microscopy, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to examine pyroptosis and related signaling pathways. Cytotoxicity and apoptosis were measured by CCK-8, LDH assays, and Hoechst 33342/PI staining. The role of NRF2 in TMPZ’s effects was further evaluated using NRF2 siRNA.ResultsTMPZ alleviated pancreatic histopathological damage, reduced apoptosis, and decreased serum amylase levels and pro-inflammatory cytokines (IL-1β, IL-18). TMPZ also suppressed pyroptosis by inhibiting NLRP3 inflammasome activation and downregulating pyroptosis-related proteins (NLRP3, caspase-1, ASC, GSDMD) while upregulating NRF2 and HO-1 expression. NRF2 siRNA attenuated TMPZ’s anti-inflammatory and pyroptosis-inhibitory effects, confirming the involvement of the NRF2 pathway.ConclusionTMPZ mitigates AP-induced inflammation and injury by modulating pyroptosis via the NRF2 signaling pathway. These findings suggest TMPZ’s therapeutic potential for AP.
Keywords: Active alkaloid, anti-inflammatory, Anti-pyroptotic, NLRP3 inflammasome, nuclear factor erythroid 2-related factor 2
Received: 09 Jan 2025; Accepted: 08 Apr 2025.
Copyright: © 2025 Li, Gao, Huang, Zhang, Wu, Huang, Ye and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaotong Ye, Huaqiao University, Quanzhou, 362021, Fujian, China
Weiwen Chen, Quanzhou First Hospital, Fujian Medical University, Quanzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.