Abstract

Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the development of atherosclerosis. However, the anti-atherogenic mechanisms of M. fragrans are still to be addressed. In this study, we explored the effect of M. fragrans on lipid metabolism and inflammation and its mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction and western blot analysis results showed that M. fragrans promotes cholesterol efflux from THP-1-derived macrophages and reduces intracellular total cholesterol, cholesterol ester, and free cholesterol contents in a dose- and a time-dependent manner. Further study found that liver X receptor alpha (LXRα) antagonist GGPP significantly blocked the upregulation of ABCA1 expression with M. fragrans treatment. In addition, chromatin immunoprecipitation assay confirmed that GATA binding protein 3 (GATA3) can bind to the LXRα promoter, and inhibition of GATA3 led to the downregulation of LXRα and ATP-binding cassette subfamily A member 1 expression. Furthermore, M. fragrans reduced lipid accumulation, followed by decreasing tumor necrosis factor-α, interleukin (IL)-6, and IL-1β and increasing IL-10 produced by THP-1-derived macrophages. Therefore, M. fragrans is identified as a valuable therapeutic medicine for atherosclerotic cardiovascular disease.

中文翻译：

---

肉豆蔻促进THP-1来源的巨噬细胞中ABCA1表达和胆固醇外流

抽象的

肉豆蔻是一种传统草药，已被证明可以缓解动脉粥样硬化的发展。但是，尚需解决苦草莓分枝杆菌的抗动脉粥样硬化机制。在这项研究中，我们探讨了苦果分支杆菌对脂质代谢和炎症及其在THP-1衍生的巨噬细胞中的作用。定量聚合酶链反应和蛋白质印迹分析结果表明，M。fragrans促进源自THP-1的巨噬细胞的胆固醇外流，并以剂量​​和时间依赖性方式降低细胞内总胆固醇，胆固醇酯和游离胆固醇的含量。进一步的研究发现，肝脏X受体α（LXRα）拮抗剂GGPP显着阻断了fragrans处理对ABCA1表达的上调。此外，染色质免疫沉淀测定法证实GATA结合蛋白3（GATA3）可以与LXRα启动子结合，并且对GATA3的抑制导致LXRα和ATP结合盒亚家族A成员1表达的下调。此外，M。fragrans降低脂质积聚，然后降低肿瘤坏死因子-α，白介素（IL）-6和IL-1β并增加由THP-1衍生的巨噬细胞产生的IL-10。因此，苦果分支杆菌被鉴定为用于动脉粥样硬化性心血管疾病的有价值的治疗药物。