Micheliolide alleviates myocardial ischemia/reperfusion injury in rats via KEAP1/NRF2-mediated suppression of oxidative stress and inflammation.

BACKGROUND

After acute myocardial infarction (AMI), reperfusion therapy can help restore blood flow and nutritional support to the ischemic myocardium, thereby limiting ongoing myocardial injury. However, its effectiveness is increasingly challenged by myocardial ischemia-reperfusion (I/R) injury. In this regard, micheliolide (MCL) has been reported to exert beneficial effects in cardiovascular disease. Herein, we aimed to determine the mechanism underlying the cardioprotective effects of MCL in a rat I/R model.

METHOD: Rats were randomly divided into a control group, an I/R group, and an I/R + MCL group. After a two-week intervention, their serum and heart tissues were collected. Myocardial histopathology was assessed using Hematoxylin-Eosin (HE) staining, and cardiomyocyte apoptosis was evaluated by TUNEL staining. Levels of CK-MB, cTnI, BNP, TNF-α, IL-1β, and IL-6 in serum and cardiac tissue were measured using the enzyme-linked immunosorbent assay (ELISA). Commercial kits were used to measure cardiac MDA, SOD, GSH-Px, and ROS. Western blotting was performed to detect KEAP1, NRF2, and apoptosis-related proteins in the rats' cardiac tissues.

RESULT: MCL treatment reduced KEAP1 expression and increased NRF2 expression in myocardial tissue, decreased cardiomyocyte apoptosis, improved cardiac function, alleviated myocardial tissue damage, and lowered inflammatory and oxidative stress levels in I/R rats.

CONCLUSION

MCL regulates the KEAP1/NRF2 signaling pathway to reduce oxidative stress and inflammation, producing a cardioprotective effect in rats with acute myocardial infarction undergoing ischemia-reperfusion injury.