Rhein alleviates myocardial ischemic injury by inhibiting mitochondrial division, activating mitochondrial autophagy and suppressing myocardial cell apoptosis through the Drp1/Pink1/Parkin pathway
- PMID: 38302764
- DOI: 10.1007/s11033-023-09154-1
Rhein alleviates myocardial ischemic injury by inhibiting mitochondrial division, activating mitochondrial autophagy and suppressing myocardial cell apoptosis through the Drp1/Pink1/Parkin pathway
Abstract
Background: Rhein, which has antioxidant and anti-inflammatory response properties, is a beneficial treatment for different pathologies. However, the mechanism by which rhein protects against myocardial ischemic injury is poorly understood.
Methods and results: To establish an acute myocardial infarction (AMI) rat model, we performed left anterior descending (LAD) ligation. Sprague‒Dawley rats were randomly divided into four groups: sham, AMI, AMI + rhein (AMI + R), and AMI + mitochondrial fission inhibitor (AMI + M). The extent of myocardial injury was evaluated by TTC staining, serum myocardial injury markers, and HE and Masson staining. Cardiac mitochondria ultrastructure was visualized by transmission electron microscopy. TUNEL assay and flow cytometry analysis were used to estimate cell apoptosis. Protein expression levels were measured by Western blotting. In vitro, the efficacy of rhein was assessed in H9c2 cells under hypoxic condition. Our results revealed that rats with AMI exhibited increased infarct size and indicators of myocardial damage, along with activation of Drp1-dependent mitochondrial fission, decreased mitophagy and increased apoptosis rates. However, pretreatment with rhein significantly reversed these effects and demonstrated similar efficacy to Mdivi-1. Furthermore, rhein pretreatment protected against myocardial ischemic injury by inhibiting mitochondrial fission, as evidenced by decreased Drp1 expression. It also enhanced mitophagy, as indicated by increased expression of Beclin1, Pink1 and Parkin, an increased LC3-II/LC3-I ratio and increased formation of autolysosomes. Additionally, rhein pretreatment mitigated apoptosis in AMI. These results were also confirmed in vitro in H9c2 cells.
Conclusion: Our results demonstrate that rhein pretreatment exerts cardioprotective effects against myocardial ischemic injury via the Drp1/Pink1/Parkin pathway.
Keywords: Acute myocardial infarction; Apoptosis; Mitochondrial fission; Mitophagy; Rhein; Traditional Chinese medicine.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Similar articles
-
[Apelin-13 promotes mitochondrial autophagy and improves rat myocardial ischemia-reperfusion injury by blocking PINK1/parkin signaling pathway].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2023 Number;39(11):981-987. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2023. PMID: 37980549 Chinese.
-
Active fraction of Polyrhachis vicina (Roger) alleviated cerebral ischemia/reperfusion injury by targeting SIRT3-mediated mitophagy and angiogenesis.Phytomedicine. 2023 Dec;121:155104. doi: 10.1016/j.phymed.2023.155104. Epub 2023 Sep 18. Phytomedicine. 2023. PMID: 37797433
-
[Effect of ligustrazine on hypoxic-ischemic encephalopathy in neonatal rats by regulating autophagy through the PINK1/Parkin pathway].Zhongguo Dang Dai Er Ke Za Zhi. 2023 Jul 15;25(7):751-758. doi: 10.7499/j.issn.1008-8830.2302026. Zhongguo Dang Dai Er Ke Za Zhi. 2023. PMID: 37529959 Free PMC article. Chinese.
-
Decreased dynamin-related protein 1-related mitophagy induces myocardial apoptosis in the aging heart.Acta Biochim Biophys Sin (Shanghai). 2021 Oct 12;53(10):1354-1366. doi: 10.1093/abbs/gmab112. Acta Biochim Biophys Sin (Shanghai). 2021. PMID: 34532739
-
AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy.Life Sci. 2021 May 1;272:119228. doi: 10.1016/j.lfs.2021.119228. Epub 2021 Feb 16. Life Sci. 2021. PMID: 33607150
References
-
- Tsao CW, Aday AW, Almarzooq ZI et al (2022) Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation 145(8):e153–e639. https://doi.org/10.1161/cir.0000000000001052 - DOI - PubMed
-
- Andersson C, Vasan RS (2018) Epidemiology of cardiovascular disease in young individuals. Nat Rev Cardiol 15(4):230–240. https://doi.org/10.1038/nrcardio.2017.154 - DOI - PubMed
-
- Sawalha K, Norgard N, López-Candales A (2023) Epigenetic regulation and its effects on aging and cardiovascular disease. Cureus 15(5):e39395. https://doi.org/10.7759/cureus.39395 - DOI - PubMed - PMC
-
- Zhu H, Toan S, Mui D, Zhou H (2021) Mitochondrial quality surveillance as a therapeutic target in myocardial infarction. Acta Physiol (Oxf, Engl) 231(3):e13590. https://doi.org/10.1111/apha.13590 - DOI
-
- Ramachandra CJA, Hernandez-Resendiz S, Crespo-Avilan GE, Lin YH, Hausenloy DJ (2020) Mitochondria in acute myocardial infarction and cardioprotection. EBioMedicine 57:102884. https://doi.org/10.1016/j.ebiom.2020.102884 - DOI - PubMed - PMC
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous