Capsiate attenuates atherosclerosis by activating Nrf2/GPX4 pathway and reshaping the intestinal microbiota in ApoE −/− mice

作者：Yongbin Shen, Chuanqi Zhang, Xue Jiang, Xianwei Li, Bo Chen, Weiliang Jiang · 发表于：Microbiology Spectrum · 年份：2025 · DOI：10.1128/spectrum.03155-24 · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、Cancer, Lipids, and Metabolism、Cancer-related molecular mechanisms research

ABSTRACT Atherosclerosis (AS) is the basis of cardiovascular diseases (CVDs) and remains the major contributor to death worldwide. Capsiate is derived from sweet pepper fruit and exhibits numerous pharmacological activities. The objective of this study was to elucidate the protective role of capsiate in atherosclerosis by examining its effect and the underlying regulatory pathways. Here, we showed that capsiate treatment alleviates atherosclerosis in atherosclerosis-prone apolipoprotein E-deficient (ApoE −/− ) mice. We found that capsiate effectively reduced the plaque area and body weight compared to the Model group. Capsiate inhibited inflammatory response by downregulating phosphoinositide 3-kinase/protein kinase B/nuclear factor-κB pathway. Additionally, further investigation indicated that capsiate could regulate lipid levels in mice via reducing the expressions of 3-hydroxy-3-methylglutaryl coenzyme A reductase and low-density lipoprotein receptor, and increasing the expression of recombinant cytochrome P450 7A1. Furthermore, capsiate effectively activated transient receptor potential vanilloid subfamily member 1 in ApoE −/− mice fed a high-fat diet. The microbial sequencing demonstrated capsiate administration significantly regulated the gut microbiota disturbance and increased some beneficial bacterial ( Lachnospiraceae NK4A136 group) levels in ApoE −/− mice. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low-density lipoprotein (ox-LDL) to s...