Natural Saponins on Cholesterol‐Related Diseases: Treatment and Mechanism

ABSTRACT Saponins are compounds composed of lipophilic aglycones linked to hydrophilic sugars. Natural saponins are isolated from plants and some Marine organisms. As important cholesterol‐lowering drugs, natural saponins have attracted wide attention for their therapeutic potential in a variety of cholesterol‐related metabolic diseases. To review the effects of natural saponins on cholesterol‐related metabolic diseases, and to deepen the understanding of the cholesterol‐lowering mechanism of saponins. The literature related to saponins and cholesterol‐lowering diseases was collected using keywords “saponins” and “cholesterol” from PubMed, Web of Science, and Google Scholar from January 2000 to May 2024. The total number of articles related to saponins and cholesterol‐lowering diseases was 240 after excluding irrelevant articles. Natural saponins can regulate cholesterol to prevent and treat a variety of diseases, such as atherosclerosis, diabetes, liver disease, hyperlipidemia, cancer, and obesity. Mechanistically, natural saponins regulate cholesterol synthesis and uptake through the AMPK/SREBP2/3‐hydroxy‐3‐methyl‐glutaryl coenzyme A reductase pathway and PCSK9/LDLR pathway, and regulate cholesterol efflux and esterification targeting Liver X receptor/ABC pathway and ACAT family. Natural saponins have broad application prospects in regulating cholesterol metabolism, for the development of more cholesterol‐lowering drugs provides a new train of thought. However, it is still necessary to further explore the molecular mechanism and expand clinical trials to provide more evidence.