Actein, a 9,19-Cyclobutane Triterpenoid from Cimicifuga spp., Ameliorates Atherosclerosis via ABCG1 and LXR Upregulation

INTRODUCTION: Considering the global burden of atherosclerosis-related cardiovascular mortality, this study investigates the anti-atherosclerotic potential of Actein, a 9,19-cyclobutane triterpenoid isolated from Cimicifuga spp. METHODS: The study employed both in vitro and in vivo experiments. In vitro, the effect of Actein on oxLDL-induced macrophage foam cells was examined. In vivo, ApoE-deficient mice were fed a high-fat diet to induce atherosclerosis and were then treated with actein (10 mg/kg) or atorvastatin for 8 weeks. RESULTS: Actein significantly reduced lipid accumulation in oxLDL-induced foam cells. In the in vivo model, actein treatment significantly lowered serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol. Furthermore, actein diminished the levels of inflammatory markers (interleukin [IL]-6, IL-1β, tumor necrosis factor-α, and matrix metalloproteinase-9 [MMP-9]) and upregulated the expression of ABCG1 and LXR proteins in liver tissue. The efficacy of actein was comparable to, and in some aspects superior to, that of atorvastatin. CONCLUSION: These findings establish actein as a promising natural compound for the treatment of atherosclerosis, warranting further investigation into its therapeutic potential.