Investigation of ED4 supplementation on cardiovascular parameters in rats with elevated systemic TMAO

Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, is strongly linked to metabolic disorders, cardiovascular diseases, and liver injury. This study aimed to evaluate the therapeutic effects of 3-O-butanoylresveratrol (ED4), a resveratrol derivative, in a rat model with elevated systemic TMAO induced via osmotic pump infusion. ED4 supplementation significantly reduced serum triglycerides, cholesterol, low-density lipoprotein cholesterol, and the total cholesterol/high-density lipoprotein cholesterol ratio while improving liver function and reducing hepatic fat accumulation associated with high systemic TMAO levels. Additionally, ED4 restored short-chain fatty acid levels and modulated gut microbiota composition, increasing the abundance of beneficial species such as Romboutsia ilealis and Parabacteroides merdae . Serum metabolomics revealed ED4's role in enhancing energy and amino acid metabolism, contributing to improved metabolic health. These findings demonstrate that ED4 alleviates TMAO-associated risks by improving lipid metabolism, protecting liver function, and reshaping gut microbiota, highlighting its potential as a functional food component for managing cardiovascular disorders.