Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors

Abstract

Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes.

Thymoquinone Produces Cardioprotective Effect in β-Receptor Stimulated Myocardial Infarcted Rats via Subsiding Oxidative Stress and Inflammation

“…Our study also showed that TQ stabilizes the ST-segment. Previous studies postulated that ISO injection leads to morphological and functional changes in the myocardial tissue [35], which is well retained by treatment with TQ. ISO-induced MI is distinguished by myocardial dysfunction, lipid peroxidation, the reformed activity of cardiac biomarkers, and diminution of the heart's natural oxidant/antioxidant equilibrium and antioxidant enzymes (notably SOD, CAT, and GSH).…”

“…When ISO was delivered, the magnitude of the T-wave reduced significantly. The T-wave represents ventricular repolarization; deviations may suggest electrolyte imbalance, left ventricular hypertrophy, or left bundle branch block [35,36]. Earlier data suggest that the electrical activity of the myocardium was significantly impaired by the necrosis induced by ISO [35].…”

The Dose‐Dependent Effect of Curcumin Supplementation on Inflammatory Response and Gut Microbiota Profile in High‐Fat Fed C57BL/6 Mice

“…[37] The improvement in lipid profile in the present study corroborates the results of previous studies where curcumin prevented HFD-induced dyslipidemia. [38] The mechanism is attributed to modulation of hepatic gene expression related to lipid metabolism, such as sterol regulatory element binding proteins (SREBP)-mediated lipid biosynthesis. [39] Curcumin exerted effects on anti-inflammatory markers by increasing the protein expression of IL-10 at doses of 250 and 500 mg kg −1 of body weight.…”

CB2 Cannabinoid Receptor as a Potential Target in Myocardial Infarction: Exploration of Molecular Pathogenesis and Therapeutic Strategies

“…It has been suggested that the CB2 receptor modulates the development of a variety of immunological and inflammatory illnesses, including atherosclerosis and ischemic heart disease [30][31][32][33][34]. Further, the activation of CB2 receptors in cardiomyocytes alleviates several pathological changes associated with myocardial injury, by modulating several downstream molecular pathways [35][36][37][38][39].…”