Modulation of inflammation of lipid metabolism by sesamin, forskolin, α-linolenic acid, and their combination in a zebrafish model of cryo-injury and high cholesterol diet-induced myocardial infarction, followed by atherosclerosis.

Abstract

Cryo-injury has been a standard model used to simulate myocardial infarction (MI), which may induce reproducible myocardial necrosis under controlled conditions. In a Zebrafish (ZF) model of cryoinjury and a high-cholesterol diet (HCD), the study evaluates the preventive effects of sesamin, forskolin, and α-linolenic acid, either alone or in combination, against myocardial infarction with atherosclerosis. Various physiological, biochemical, and histological endpoints were used to evaluate the effectiveness of the treatment. A notable recovery of cardiac activity (as measured by ECG) and body weight regulation was observed when comparing the treated groups with the cryo-injured control. Decreased TNF-α and iNOS levels demonstrated effective molecular control of cryoinjury-induced inflammation. An improved lipid balance was also observed through lipid profiling of cardiac tissue and serum, which revealed significant increases in HDL levels and decreases in triglycerides, total cholesterol, LDL, and VLDL. The treatment with a combination of test compounds especially shows good efficacy towards myocardial infarction and the myocardial structure of ZF, followed by atherosclerosis. In our study, the combination effect of sesamin, forskolin, and α-linolenic acid has significant potential for regulating lipid levels, inflammatory markers, and myocardial structure integrity. It can be concluded that the combination treatment of the sesamin, forskolin, and α-linolenic acid may protect the cardiovascular system, and this combination can be used for further preclinical study with a rodent model for cardiovascular disease.