Supplementary Material for: 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 (IL-6, IL-1β, TNF-α, and 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.

引言：鉴于全球范围内动脉粥样硬化相关心血管死亡的疾病负担，本研究针对从升麻属（Cimicifuga spp.）中分离得到的9,19-环丁烷三萜类化合物Actein的抗动脉粥样硬化活性展开探究。
方法：本研究采用体外与体内相结合的实验方案。体外实验中，考察了Actein对氧化低密度脂蛋白（oxLDL）诱导的巨噬源性泡沫细胞的作用。体内实验中，通过高脂饮食构建动脉粥样硬化模型的载脂蛋白E基因敲除（ApoE-deficient）小鼠，随后分别给予Actein（10 mg/kg）或阿托伐他汀（Atorvastatin）干预，持续8周。
结果：实验结果显示，Actein可显著降低oxLDL诱导的巨噬源性泡沫细胞内脂质堆积。在体内动脉粥样硬化模型中，Actein干预可显著降低小鼠血清总胆固醇、甘油三酯及低密度脂蛋白胆固醇水平，同时升高高密度脂蛋白胆固醇含量。此外，Actein可降低血清炎症标志物白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）及基质金属蛋白酶-9（MMP-9）的水平，并上调肝脏组织中ABCG1与LXR蛋白的表达。Actein的干预效果与阿托伐他汀相当，且在部分维度上更具优势。
结论：上述研究结果证实，Actein是一种极具开发潜力的抗动脉粥样硬化天然化合物，其临床治疗价值有待进一步深入探究。