Grape Seed Proanthocyanidin Extract Alleviates Atherosclerosis by Modulating the Production of Trimetlylamine N-Oxide

Abstract

Background: Trimetlylamine N-oxide (TMAO) is an important factor in the development of atherosclerosis. Research suggests that grape seed proanthocyanidin extract (GSPE) modulates gut microbiota and alleviates obesity. Therefore, we speculate that GSPE may alleviate atherosclerosis by regulating TMAO production. This study aims to explore the effect of GSPE on the TMAO content and atherosclerosis. Methods: A high fat diet mice model was established for performing this study. Low-dose/high-dose GSPE (GSPE-L/GSPE-H) and Atorvastatin (Ato) were used to treat the mice for 6 weeks. The body weight, fat, blood glucose, and blood lipid of the mice were recorded and compared. The plaques and pathological changes of mouse aorta were observed by Oil Red O, Hematoxylin-Eosin and Masson staining. Serum and caecal contents of mice were collected, where TMAO level was assessed by enzyme-linked immunosorbent assay (ELISA) and gut microbial content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: GSPE-H down-regulated blood glucose and blood lipid levels, and reduced aortic plaque generation and atherosclerotic damage in model mice (p < 0.05). More importantly, it reduced the TMAO content in the serum of model mice and regulated the gut microbial content (p < 0.05). The therapeutic effect of GSPE-H was similar to that of Ato. Conclusions: GSPE-H alleviates atherosclerosis by reducing production of TMAO.