Department of Intensive Care Unit, The First Affiliated Hospital of University of South China, Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
School of Pharmacy and Life Science College, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Jan 12;53(1):63-71. doi: 10.1093/abbs/gmaa146.
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.
肉豆蔻是一种传统的草药，已被证明可以缓解动脉粥样硬化的发展。然而，肉豆蔻的抗动脉粥样硬化机制仍有待解决。在这项研究中，我们探讨了肉豆蔻对 THP-1 衍生的巨噬细胞中脂质代谢和炎症的影响及其机制。定量聚合酶链反应和 Western blot 分析结果表明，肉豆蔻促进 THP-1 衍生的巨噬细胞中的胆固醇流出，并呈剂量和时间依赖性降低细胞内总胆固醇、胆固醇酯和游离胆固醇含量。进一步的研究发现，肝 X 受体α（LXRα）拮抗剂 GGPP 可显著阻断肉豆蔻处理时 ABCA1 表达的上调。此外，染色质免疫沉淀试验证实 GATA 结合蛋白 3（GATA3）可与 LXRα 启动子结合，抑制 GATA3 导致 LXRα 和 ATP 结合盒亚家族 A 成员 1 的表达下调。此外，肉豆蔻减少了 THP-1 衍生的巨噬细胞中的脂质积累，随后减少了肿瘤坏死因子-α、白细胞介素（IL）-6 和 IL-1β 的产生，增加了 IL-10 的产生。因此，肉豆蔻被鉴定为治疗动脉粥样硬化性心血管疾病的有价值的治疗药物。
