Perillaldehyde improves diabetic cardiomyopathy by upregulating miR-133a-3p to regulate GSK-3ß.

Diabetic cardiomyopathy (DCM) is part of the most important causes of death from cardiovascular disease. Perillaldehyde (PAE), a major component of the herb perilla, has been shown to ameliorate doxorubicin-induced cardiotoxicity, but it is unclear whether PAE exerts beneficial effects on DCM. Exploring the potential molecular mechanisms of PAE for the treatment of DCM through network pharmacology and molecular docking. The SD rat type 1 diabetes model was established by a single intraperitoneal injection of streptozotocin (60 mg/kg), the cardiac function indexes of each group were detected by echocardiography; the morphological changes, apoptosis, protein expression of P-GSK-3ß (S9), collagen I (Col-Ⅰ), collagen III (Col-Ⅲ) and alpha-smooth muscle actin (α-SMA), and miR-133a-3p expression levels were detected. An DCM model of H9c2 cells was established in vitro and transfected with Mimic and Inhibitor of miR-133a-3p. The results showed that PAE ameliorated cardiac dysfunction, reduced fasting glucose and cardiac weight index, and improved myocardial injury and apoptosis in DCM rats. It reduced high glucose-induced apoptosis, promoted migration and improved mitochondrial division injury in H9c2 cells. PAE decreased P-GSK-3ß (S9), Col-Ⅰ, Col-Ⅲ and α-SMA protein expression and upregulated miR-133a-3p expression levels. After miR-133a-3p Inhibitor treatment, the expression of P-GSK-3ß (S9) and α-SMA expression were significantly increased; after miR-133a-3p Mimic treatment, the expression of P-GSK-3ß (S9) and α-SMA decreased significantly in H9c2 cells. It suggests that the mechanism of action of PAE to improve DCM may be related to the upregulation of miR-133a-3p and inhibition of P-GSK-3ß expression.

Cardioprotective role of A-cycloglycosylated derivative of Rubiadin in diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DCM) is a kind of idiopathic heart disease, which is one of the main complications of diabetes and seriously threatens the life of diabetic patients. Rubiadin, an anthraquinone compound extracted from the stems and roots of rubiaceae, has been widely discussed for its anti-diabetes, anti-oxidation and other pharmacological effects. However, Rubiadin can cause drug-induced liver injury. Therefore, A-cycloglycosylated derivative of Rubiadin (ACDR) was obtained by modifying its structure. The purpose of this study was to investigate the effect of ACDR on DCM cardiac injury and its mechanism. The DCM animal model was established by streptozotocin, and the success of DCM was verified by blood glucose level, echocardiographic evidence of impaired myocardial functions along with enhanced myocardial fibrosis. We performed liver function tests, morphological staining of the heart and tests for oxidative stress to evaluate cardiac functional and structural changes. Finally, the expression of Na+/H+ exchanger (NHE1) protein was analyzed by immunohistochemistry and western bolt, and the expression of hairy/enhancer-of-split related with YRPW motif 1 (Hey1) and P-p38 protein was detected by immunofluorescence chemistry and western blotting. The results showed that ACDR can improve cardiac dysfunction, reduce myocardial injury, reduce oxidative stress, and protect the liver in DCM rats. Interestingly, all variations were countered by LiCl. Our study suggests that, along with controlling hyperglycemia, ACDR may improve DCM by reducing NHE1 expression, further inhibiting P-p38 activity and increasing Hey1 expression to reduce oxidative stress.