Morin attenuates ferroptosis via activation of the SIRT1/p53/SLC7A11 signaling pathway to alleviate diabetic cardiomyopathy in vivo.

Abstract

Diabetic cardiomyopathy (DCM) is a serious complication in patients with diabetes, which still lacks adequate therapy. Ferroptosis has recently been emphasized as a main contributor to the development of DCM. Hence, the current study aimed to assess the effects of morin, a well-known phytochemical, on the DCM. In this regard, DCM in Wistar rats was induced by streptozotocin (STZ). After treatment of animals with a dose of 25, 50, and 100 mg/kg of morin orally for 60 days, Sirtuin 1 (SIRT1), p53, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in gene and protein levels in cardiac tissue were measured. Moreover, determination of redox status (GSH, SOD, CAT, and MDA) and inflammatory markers (IL-6, IL-1, and TNF-) in the cardiac tissue was performed and the levels of glucolipid profile, iron profile, and cardiac markers (troponin T and CK-MB) were assessed. The findings demonstrated that the administration of morin restored glucolipid and iron profiles, improved hypertension and cardiac hypertrophy, and suppressed inflammatory responses (p-value<0.001). Moreover, morin at a dose of 100 mg/kg/day was able to increase the levels of SLC7A11, SIRT1, GSH, SOD, CAT, and GPX4 while decreasing the cardiac levels of p53 and MDA (p-value<0.05). In conclusion, the findings suggest morin could alleviate DCM probably through modulation of ferroptosis via the SIRT1/p53/SLC7A11 signaling pathway activation and suppression of oxidative stress and inflammation.