The Protective Effect of Cyanidin‐3‐Glucoside on Myocardial Ischemia‐Reperfusion Injury through Ferroptosis

Abstract

This study was conducted to estimate the protective effect of Cyanidin-3-glucoside (C3G) on myocardial ischemia-reperfusion (IR) injury and to explore its mechanism. The rats were subjected to left anterior descending ligation and perfusion surgery. In vitro experiments were performed on H9c2 cells using the oxygen-glucose deprivation/reoxygenation (OGD/R) model. The results showed the administration of C3G reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. C3G could inhibit the protein levels of USP19 and LC3II. C3G promoted K11-linked ubiquitination of Beclin1. Further evidence that C3G reduced ferroptosis and ameliorated myocardial I/R injury was demonstrated with the ferroptosis promoter RSL3. Taken together, C3G could be a potential agent to protect myocardium from myocardial I/R injury.

Targeting Ferroptosis: Pathological Mechanism and Treatment of Ischemia‐Reperfusion Injury

“…In experimental models, inhibition of glutaminolysis, an important part of ferroptosis, was shown to reduce I/R-induced heart injury [ 70 ]. Studies have confirmed that ROS accumulation and iron content increase during I/R injury [ 71 , 72 ], and iron overload is an important cause of myocardial cell injury [ 73 ]. A study by Li et al showed that iron deposition and ROS overproduction occurred during diabetic myocardial injury, and ferroptosis was involved in the I/R injury of diabetic myocardium through the endoplasmic reticulum stress pathway [ 31 ].…”

Ferroptosis: Opportunities and Challenges in Myocardial Ischemia‐Reperfusion Injury

“…Cyanidin-3-glucoside (C3G) treatment can effectively alleviate the expression of proteins related to apoptosis, reduce Fe 2+ content, and improve MIRI. Therefore, C3G is a potential medicine to prevent myocardial cells from being affected by MIRI [ 85 ].…”

Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored

“…Lv et al (2021) proved that Etomidate suppressed ferroptosis in IRI model via upregulation of Nrf2 and heme oxygenase-1 (HO-1) protein expression. Cyanidin-3-glucoside, a kind of anthocyanin, is verified to attenuate myocardial IRI via ferroptosis inhibition by reducing oxidative stress and Fe 2+ accumulation in vivo and in vitro ( Shan et al, 2021 ). Ma et al (2020) demonstrated that USP22 (ubiquitin-specific protease 22), a member of the deubiquitinase family, could inhibit ferroptosis in myocardial IRI via the SIRT1/p53/SLC7A11 association.…”