Chalcone derivative 1m mitigates hepatic fibrosis and inflammation, enhances cholesterol efflux and reduces atherosclerosis

The synthesized chalcone derivative 1m ameliorated liver injury and atherosclerosis in high-cholesterol diet-fed mice.

• 1m effectively reduced hepatic lipid accumulation and improved lipid profiles in atherosclerosis-prone mouse models.
• The treatment promoted the expression of cholesterol regulatory genes in the liver, resulting in decreased triglyceride and cholesterol content.
• Increased hepatic bile acid and fecal cholesterol and bile acid contents were observed in HCD-fed mice treated with 1m.
• RNA sequencing identified NR5A2 as a potential mediator of gene expression changes induced by 1m.
• In vitro studies indicated that 1m activates a liver receptor, promoting its nuclear translocation and upregulating related gene expressions.
• 1m reduced palmitic acid-induced cell death and suppressed liver fibrosis and inflammation.

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