Kang Ye, Jing Shi, Ping Gong, Zhongsheng Zhu
These findings demonstrate that liquiritin protects against AS and hepatic lipid accumulation by modulating SIRT1-mediated lipid metabolism (P<0.001), emphasizing its potential as a treatment option for metabolic and cardiovascular disorders.
OBJECTIVES: Atherosclerosis (AS) and dyslipidemia are major contributors to cardiovascular disease; however, safe and effective therapeutic strategies remain limited. Liquiritin, a natural flavonoid, exhibits potential metabolic and cardiovascular benefits in human beings. This study investigated the effects of liquiritin on AS, lipid metabolism, and hepatic steatosis in high-fat diet (HFD)-induced ApoE-/- mice.
MATERIALS AND METHODS: Mice were intraperitoneally administered liquiritin (20 mg/kg/day) for 12 weeks. Histological and biochemical analyses revealed that chronic liquiritin treatment did not induce hepatotoxicity, nephrotoxicity, or growth impairment, as evidenced by preserved liver and kidney architecture, unchanged serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels, and stable body weight.
RESULTS: Liquiritin markedly attenuated aortic root plaque formation, lipid deposition, and fibrotic areas (P<0.001) in ApoE-/- mice. Furthermore, liquiritin significantly improved serum and hepatic lipid profiles by reducing triglyceride, total cholesterol, and LDL-C levels (P<0.001) and alleviating hepatic steatosis (P<0.001), as confirmed by histological analyses. Mechanistic studies demonstrated that liquiritin restored hepatic SIRT1 expression, down-regulated PPARγ and LXRα, and up-regulated ABCA1 (P<0.001), suggesting the modulation of key lipid metabolism pathways.
CONCLUSION: These findings demonstrate that liquiritin protects against AS and hepatic lipid accumulation by modulating SIRT1-mediated lipid metabolism (P<0.001), emphasizing its potential as a treatment option for metabolic and cardiovascular disorders.