Saringosterol from Sargassum fusiforme Modulates Cholesterol Metabolism and Alleviates Atherosclerosis in ApoE-Deficient Mice

Abstract

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 Sargassum fusiforme. 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.

Marine Compounds and Age-Related Diseases: The Path from Pre-Clinical Research to Approved Drugs for the Treatment of Cardiovascular Diseases and Diabetes

“…Note that manzamine A also presents anti-viral effects [36], which is particularly interesting considering that age-related cardiovascular diseases are frequently reported to be associated with certain bacterial and viral infections [41]. Conversely, saringosterol, a phytosterol derived from the marine algae Sargassum fusiforme, acts as a potent activator of the liver X receptor β, involved in cholesterol absorption, transport, and elimination [42]. Thus, it may impact the metabolism of lipids with a distinctive cellular target and specific metabolic transformation, inducing further pharmacological effects.…”

Marine-Derived Compounds Applied in Cardiovascular Diseases: Submerged Medicinal Industry

“…reported that saringosterol treatment reduced the burden of atherosclerotic plaques while having no negative effects on the liver of apoE-deficient rats. Saringosterol reduces cholesterol homeostasis disruption, influencing atherosclerosis’s progression [ 79 ]. However, asperlin is derived from the marine fungus Aspergillus versicolor LZD4403 and possesses antifungal and anti-inflammatory properties.…”

Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases

“…24(S)-Saringosterol 24(S)-Saringosterol or (3β)-stigmasta-5,28-diene-3,24-diol is a marine phytosterol commonly isolated from the edible seaweed Sargassum fusiforme. 24(S)-saringosterol was shown to be a potential anti-atherosclerotic natural agent by lowering cholesterol and a selective LXR-β agonist [75,76]. An in vivo study of APPswePS1DE9 mice treated with 24(S)-saringosterol for 10 weeks revealed a slowing of cognitive decline based on enhanced spatial and object memory assessments.…”