Saringosterol from <i>Sargassum fusiforme</i> Modulates Cholesterol Metabolism and Alleviates Atherosclerosis in ApoE-Deficient Mice

• Main Authors: Ying Yan, Zhoumin Niu, Boyang Wang, Shangge Zhao, Chao Sun, Yuting Wu, Yuying Li, Hao Ying, Hongbing Liu
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Marine Drugs
• Subjects: saringosterol; liver X receptor; cholesterol metabolism; atherosclerosis; <i>Sargassum fusiforme</i>
• Online Access: https://www.mdpi.com/1660-3397/19/9/485

Dysregulation of cholesterol homeostasis is a major risk factor of atherosclerosis, which can lead to serious health problems, including heart attack and stroke. Liver X receptor (LXR) α and β are transcription factors belonging to the nuclear receptor superfamily, which play important roles in cholesterol homeostasis. Selectively activating LXRβ provides a promising strategy for the treatment of atherosclerosis. Here, we employed atherosclerotic apoE-knockout mice to evaluate the effects of saringosterol, a phytosterol with potent and selective action for LXRβ, which we identified previously in edible marine seaweed <i>Sargassum fusiforme</i>. We found that saringosterol treatment reduced the atherosclerotic plaque burden without having undesirable adverse hepatic effects in apoE-deficient mice fed an atherogenic diet. Meanwhile, reduced serum levels of cholesterol, accompanied by altered expression of LXR-regulated genes involved in cholesterol absorption, transport, efflux, excretion, and elimination, were observed in apoE-knockout mice after saringosterol treatment. Together, our study not only establishes saringosterol as an effective cholesterol-lowering and anti-atherogenic phytosterol but also provides insights into the underlying mechanism.