Extract of radish (R. Sativus Linn) promotes anti-atherosclerotic effect using urine metabolomics in ApoE(-/-) mice

Abstract

Natural products such as Raphanus sativus Linn would be the potential candidate to benefit to atherosclerosis without side effects. Thus, this study aimed to investigate anti-atherosclerotic effect of radish extracts and to determine their mechanism. For that purpose, ApoE-/mice were fed with a high-cholesterol diet for 12 weeks and treated with radish extracts. Then, histological observation, plasma lipid profile, mRNA expression, and urine metabolomics were performed. As a result, the formation of aortic plaque was attenuated by atorvastatin, white radish extract, and purple radish extract. Treatment of white radish extract provided the most beneficial effects on reducing triglycerides (9.236 mM), while treatment of purple radish extract significantly reduced low density lipoprotein-cholesterol (202.5 mg/dL). In detail, purple radish extract improved the level of total cholesterol (219.3 mg/dL) and high-density lipoprotein-cholesterol (64.3 mg/dL) and thereby significantly lowered atherogenic index (3.47) and cardiac risk factor (4.47). Both radish extracts significantly reduced expression of inflammatory cytokines including TNF-alpha, IL-1 beta, and IL-6 as well as urinary arachidonate. In addition, radish extracts regulated NO synthesis by increasing urinary arginine and balancing iNOS and eNOS expressions. High expression of VCAM-1 and ICAM-1 were lowered by radish extracts. In conclusion, we demonstrated the anti-atherosclerotic effect of white and purple radish extracts comparable to atorvastatin and further revealed their mechanisms in which include regulation of mRNA expression of inflammatory mediators and endothelial factors along with regulation of urinary arachidonate and arginine. These findings may provide a potential clinical implication in not only prevention but also treatment of atherosclerosis.