Aloe-Emodin Relieves Myocardial Intracellular Calcium Homeostasis Imbalance Induced by High-Fat Diet via Protein Arginine Methyltransferase/ Ca2+/Calmodulin- Dependent Protein Kinase II Signaling Pathway in Rats.

Background Chronic high-fat diets (HFDs) lead to an imbalance of calcium homeostasis in cardiomyocytes, which contributes to the development of myocardial ischemia-reperfusion injury, dilated cardiomyopathy, and other cardiovascular diseases. Aloe-emodin (AE) is an anthraquinone component isolated from aloe, rhubarb, and cassia seed, having cardiovascular protective, hepatoprotective, anti-inflammatory, and other pharmacological effects. Objective This study aimed to explore the specific role of AE in obesity/hyperlipidemia-induced myocardial intracellular calcium homeostasis imbalance. Methods Wistar rats (male, 220 ± 20 g) were fed HFD for four weeks and AE (100 mg/kg) was administrated for six weeks after confirmation of the HFD model. Serum lipids, reactive oxygen species levels, malondialdehyde levels, and superoxide dismutase levels were measured by commercial biochemical kits. Electrocardiograms of rats were recorded with the BL-420F biological function experimental system. Calcium transients and resting intracellular Ca²⁺ concentrations were determined by the Langendorff-perfused heart model. Protein levels of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), protein arginine methyltransferase 1 (PRMT1), and cardiac Ca²⁺ handling proteins were evaluated by western blot analysis. Results HFD-induced hearts exhibited a reduced amplitude of Ca2+ transients and increased resting levels of [Ca2+] in the heart; AE treatment significantly improved these parameters. Furthermore, the HFD-induced heart showed downregulation of PRMT1, upregulation of CaMKII, and abnormalities in the levels of Ca²⁺ handling proteins. All these deleterious changes were significantly suppressed by the AE treatment. Moreover, AE treatment prevented palmitic acid (PA)-induced calcium overload in H9C2 cells; this effect was reduced by the application of an inhibitor of PRMT1. Conclusion Taken together, this study demonstrates that AE could alleviate HFD/PA-induced myocardial intracellular calcium homeostasis imbalance via the PRMT1/CaMKII signaling pathway.