Cinnamomum migao Active Extracts Ameliorate Acute Myocardial Ischemia via Modulation of the HIF-1α/Nrf2/NF-κB/MAPK Pathway Downstream of Oxidative Stress

Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce. Cinnamomum migao is a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and mechanisms remain largely unclear. This study investigated the efficacy and underlying mechanism of C. migao ethyl acetate extract (MGE) against AMI. MGE significantly improved the viability of H9c2 cardiomyocytes subjected to OGD/R injured. UPLC-MS/MS and molecular networking identified 30 constituents in MGE, among which sesquiterpenoids predominated. In ISO-induced AMI rats, MGE dose-dependently mitigated myocardial injury, as reflected by reduced ST-segment elevation, serum CK-MB and LDH levels, and alleviated histopathological damage. MGE enhanced SOD and CAT activities, decreased MDA content, and inhibited the secretion of TNF-α, IL-6 and IL-1β. Mechanistically, MGE downregulated the expression of NOX4, HIF-1α, p38 MAPK and NF-κB p65, while activating the Nrf2/HO-1 pathway. Oxyphyllenone A and magnodelavin C were identified as key active sesquiterpenoids that stably bound to IL-17 and TNF. Collectively, MGE alleviates AMI injury via anti-oxidative, anti-hypoxic, and anti-inflammatory effects through modulation of the HIF-1α/Nrf2/NF-κB/MAPK axis downstream of oxidative stress, with sesquiterpenoids serving as its key bioactive components. This work provides robust experimental evidence supporting C. migao as a promising natural antioxidant candidate for the prevention and treatment of AMI.