Naringin Alleviates Atherosclerosis in ApoE<sup>–/–</sup> Mice by Regulating Cholesterol Metabolism Involved in Gut Microbiota Remodeling
Feng Wang, Chengying Zhao, Guifang Tian, Xue Wei, Zihan Ma, Jiefen Cui, Rujun Wei, Yuming Bao, Wei Kong, Jinkai Zheng
Abstract
mice fed with a high-fat diet. Nontarget metabolomics showed that naringin modulated the hepatic levels of cholesterol derivatives and bile acids. Naringin increased the excretion of bile acids and neutral sterols by 1.6- and 4.3-fold, respectively. The main potential pathway by which naringin alleviated atherosclerosis was the gut microbiota-liver-cholesterol axis. Naringin modulated the abundances of bile salt hydrolase- and 7α-dehydroxylase-producing bacteria, promoting bile acid synthesis from cholesterol by upregulating CYP7A1 via suppression of the FXR/FGF15 pathway. In addition, naringin facilitated reverse cholesterol transport by downregulating PCSK9/IDOL. The results provide insight into the atherosclerosis-alleviation mechanisms of citrus flavonoids and a scientific basis for the development of functional foods containing citrus flavonoids.