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Abstract Title:

Ferulic acid alleviates myocardialischemia reperfusioninjury via upregulating AMPKα2 expression-mediated ferroptosis depression.

Abstract Source:

J Cardiovasc Pharmacol. 2021 Dec 10. Epub 2021 Dec 10. PMID: 34935700

Abstract Author(s):

Xinliang Liu, Kai Qi, Yi Gong, Xiang Long, Shuqiang Zhu, Feng Lu, Kun Lin, Jianjun Xu

Article Affiliation:

Xinliang Liu

Abstract:

Ferroptosis, a recently discovered form of regulated cell death that is characterized by iron accumulation and excessive ROS generation, has been favoured by the majority of researchers. Increasing evidence suggest that ferulic acid could exert markedly effects to myocardial ischemia reperfusion injury, while the understanding of its molecular mechanism is still limited. In our study, the myocardial ischemia reperfusion injury model was established to explore the relationship between ischemia reperfusion injury and ferroptosis. First, we successfully constructed myocardial ischemia reperfusion injury model with changes in ST segment, increased CK,LDH activities and NT-proBNP content, and a significantly larger infarct size. Then, the increased levels of the Ptgs2 mRNA, Fe2+ accumulation, and a decreased GSH/GSSG ratio were detected in ischemia-reperfusion-injuryed heart which highly consistent with ferroptosis. However, these effects were significantly improved after ferulic acid treatment. Based on these results, ferulic acid increased the activities of the antioxidant enzymes SOD, CAT and GSH-Px, decreased the MDA level, ameliorated the production of ROS and promoted the generation of ATP. These effects of ferulic acid are similar to those of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Upregulation of AMPKα2 and GPx4 expression were also observed in the FA group. Compound C, a specific AMPK inhibitor, significantly blocked the protective effect of ferulic acid. These findings underlined that FA inhibits ferroptosis by upregulating the expression of AMPKα2 serves as a cardioprotective strategy.

Study Type : In Vitro Study

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