Danthron attenuates experimental atherosclerosis by targeting foam cell formation.

Area of Science:

• Pharmacology
• Cardiovascular Research
• Natural Products

Background:

• Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation in artery walls.
• Foam cell formation is a critical step in atherosclerotic plaque development.
• Danthron, a natural compound, has shown potential in reducing lipid accumulation.

Purpose of the Study:

• To investigate the effects of danthron on experimental atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice.
• To elucidate the underlying mechanisms by which danthron alleviates atherosclerosis, particularly its role in foam cell formation and related signaling pathways.

Main Methods:

• In vivo studies involved administering danthron to high-fat diet-fed ApoE-/- mice.
• In vitro studies used oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 macrophages treated with danthron.
• Key molecular markers of lipid metabolism and the AMP-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) pathway were analyzed.

Main Results:

• Danthron significantly improved serum lipid profiles and reduced atherosclerotic plaque area and lipid accumulation in mice.
• Danthron inhibited foam cell formation in vitro and upregulated ATP-binding cassette transporter A1 (ABCA1), ABCG1, and liver X receptor α (LXRα) expression.
• The compound activated the AMPK-SIRT1 signaling pathway, which was crucial for its effects on lipid metabolism and foam cell formation.

Conclusions:

• Danthron demonstrates significant potential in alleviating experimental atherosclerosis.
• Its therapeutic effects are mediated, at least in part, by inhibiting foam cell formation via the AMPK-SIRT1 pathway.
• Danthron represents a promising natural compound for further investigation in atherosclerosis treatment.