ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Tianhuang Formula Attenuates Cardiomyocyte Pyroptosis in Myocardial Infarction by Suppressing Oxidative Stress and the cGAS–STING–NLRP3 Axis
Mei ling Yan
Yifan Chen
Guida Cai
Xi Zhang
Kun-Ping Li
Duosheng Luo
Lexun Wang
Xianglu Rong
Jiao Guo
Guangdong Pharmaceutical University, Guangzhou, 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
Abstract
Background: Myocardial infarction (MI) remains a leading cause of morbidity and mortality, driven by ischemia/reperfusion injury, excessive inflammation, and maladaptive ventricular remodeling. Although acute reperfusion strategies have improved short-term outcomes, effective interventions targeting post-infarction inflammation and structural deterioration remain limited. Tianhuang Formula (THF), a patented two-herb prescription traditionally used to promote circulation and alleviate stasis, has shown potential cardioprotective properties, yet its mechanisms in MI remain insufficiently defined. Aim of the study: To evaluate the therapeutic effects of THF in a mouse MI model induced by left anterior descending (LAD) coronary artery ligation and elucidate its underlying molecular mechanisms. Materials and methods: Echocardiography was performed at 3 and 28 days post-MI to assess cardiac function. Network pharmacology integrated with transcriptomic profiling identified pathways potentially targeted by THF. Western blotting, immunohistochemistry, primary cardiomyocyte assays, and molecular docking were used for mechanistic validation. Results: THF significantly improved cardiac function during both the acute (day 3) and remodeling (day 28) phases of MI and reduced circulating inflammatory cytokines. Mechanistic analyses showed that THF mitigated myocardial hypertrophy by suppressing oxidative stress and inhibiting activation of the cGAS–STING pathway, thereby preventing downstream NLRP3 inflammasome-mediated pyroptosis and inflammatory cytokine production. Docking results further demonstrated strong binding affinities of key THF components—berberine, coptisine, and palmatine—to human Keap1 and cGAS. Conclusions: THF exerts cardioprotective effects by reducing oxidative stress, modulating the cGAS–STING–NLRP3 axis, and inhibiting cardiomyocyte pyroptosis, supporting its traditional use and highlighting its potential as a therapeutic candidate for MI.
Summary
Keywords
cardiomyocyte pyroptosis, cGAS–STING pathway, immune-inflammatory response, Myocardial infarction (MI), Tianhuang Formula (THF)
Received
05 December 2025
Accepted
03 February 2026
Copyright
© 2026 Yan, Chen, Cai, Zhang, Li, Luo, Wang, Rong and Guo. 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: Jiao Guo
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.