Tanyu Tongzhi decoction ameliorates atherosclerosis by inhibiting trimethylamine N-oxide-induced vascular inflammation via PI3K/Akt/NF-κB pathway regulation

Tanyu Tongzhi decoction (TYTZD) is an orally administered traditional Chinese medicine formula that is used to treat atherosclerosis (AS). Trimethylamine N-oxide (TMAO), a gut microbial metabolite, has been shown to accelerate AS development and progression. Despite its various health benefits, it is unclear whether TYTZD can ameliorate TMAO-mediated vascular inflammation. Therefore, we investigated the effect and molecular mechanisms of TYTZD in TMAO-induced vascular inflammation during AS progression. Key ingredients of TYTZD were detected using high-performance liquid chromatography (HPLC). Additionally, we established an AS model by feeding ApoE -/- mice high-fat and high-choline diet (HFCD). We examined the anti-AS effects of TYTZD using histological assay, immunohistochemical staining, and western blotting. Furthermore, we examined the effect of TYTZD on the viability of human umbilical vein endothelial cells (HUVECs) treated with TMAO using CCK-8 assay. In vivo experiment showed that TYTZD treatment ameliorated AS by preventing dyslipidemia, reducing lipid deposition area in the intimal plaque, inhibiting arterial inflammation, and suppressing serum levels of TMA and TMAO in ApoE -/- mice. Additionally, TYTZD significantly inhibited TMAO-induced endothelial activation, suppressed the expression of pro-inflammatory factors (IL-1β, IL-6, IL-8, TNF-α and MCP-1), and downregulated PI3K, Akt, and NF-κB protein expression in HUVECs. TYTZD ameliorates AS by inhibiting TMAO-induced vascular inflammation via the PI3K/Akt/NF-κB signaling pathway; these findings highlight its potential application for the treatment of AS and associated disorders.