Work

Bufalin alleviates myocardial ischemia-reperfusion injury by targeting PTGR2 to regulate NF-κB mediated inflammation

Year: 2025

Type: article

Abstract: INTRODUCTION: Myocardial ischemia-reperfusion injury (MIRI) significantly affects patient prognosis, with inflammation being a key pathogenic mechanism. OBJECTIVE: This study aimed to investigate the effect and mechanism of Bufalin in alleviating MIRI. METHODS: Using a murine MIRI model, we evaluated cardiac function, myocardial injury, and inflammation after Bufalin intervention. Through Huprot™ human protein microarray,SPR, and molecular dynamics simulation. RESULTS: we identified PTGR2 as a direct target of Bufalin. Bulk RNA-seq, flow cytometry, WB, and immunofluorescence showed that Bufalin reduced macrophage infiltration in ischemic myocardium, downregulated proinflammatory factors like IL-1β, and inhibited NF-κB pathway activation. Mechanistically, Bufalin competes with C1QTNF3 to bind PTGR2 to relieve the inhibition of C1QTNF3, thereby inhibiting NF-κB-mediated inflammation and alleviating oxidative stress by regulating Nrf2/HO-1. Notably, moderate-dose Bufalin improved cardiac function and reduced myocardial infarction area, though it showed potential hepatotoxicity. CONCLUSION: These findings suggest Bufalin alleviates MIRI by targeting PTGR2 to regulate C1QTNF3/NF-κB signaling, providing a candidate for MIRI treatment.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118895