QiShenYiQi Dripping Pill Alleviates Myocardial Ischemia-Induced Ferroptosis Via Improving Mitochondrial Dynamical Homeostasis and Biogenesis

Abstract PurposeQiShenYiQi dripping pill (QSYQ) is a traditional Chinese medicine for alleviating cardiovascular diseases. Whereas, the potential mechanism remains to be further elucidated. Thus, this paper is designed to explore the protective mechanism of QSYQ in myocardial ischemia (MI)-induced injury.MethodsMyocardial ischemia was induced in mice by left anterior descending coronary artery ligation (CAL). Then, mice were treated by QSYQ dripping pills (12, 35 and 105 mg/kg) for 14 days. The effect and mechanism of QSYQ against MI injury were investigated in vivo.ResultsTreatment with QSYQ significantly improved the contractile function, and extenuated myocardial fibrosis and inflammatory cell infiltration after MI injury. QSYQ administration also reduced the level of LDH and NT-pro BNP in serum. Additionally, myocardial iron content and serum MDA, 4-HNE were decreased and GSH was increased after QSYQ administration. The mRNA expression of GPX4 and SLC7A11 were increased, and PTGS2 mRNA expression level was reduced by QSYQ treatment. Moreover, QSYQ ameliorated myocardial mitochondrial ultrastructure damage and decreased mitochondrial ROS production. Furthermore, QSYQ heightened the expressions of PGC-1α, TFAM and Nrf1, which indicated that QSYQ could promote mitochondrial biogenesis. In addition, QSYQ treatment also increased MFN2 and OPA1 expressions, while the expression of p-DRP1 was decreased.ConclusionsAll these suggested that QSYQ could promote mitochondrial dynamic homeostasis to improve myocardial injury. QSYQ could alleviate MI-induced ferroptosis via improving mitochondrial dynamical homeostasis and biogenesis, which provided references for its clinical application.