Tianhuang formula attenuates cardiomyocyte pyroptosis in myocardial infarction by suppressing oxidative stress and the cGAS-STING-NLRP3 axis.

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.