Department of Food Science and Technology, Keimyung University, Daegu 42601, Korea.
Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea.
Molecules. 2022 Jul 25;27(15):4765. doi: 10.3390/molecules27154765.
Recent studies have shown that Nur77 and AMPKα play an important role in regulating adipogenesis and isoalantolactone (ISO) dual-targeting AMPKα and Nur77 inhibits adipogenesis. In this study, we hypothesized that (elecampane) root extract (IHE), which contains two sesquiterpene lactones, alantolactone (ALA) and ISO, as major compounds, might inhibit adipogenesis. Here, we found that ALA and IHE simultaneously target AMPKα and Nur77 and inhibited adipogenic differentiation of 3T3-L1 cells, accompanied by the decreased expression of adipocyte markers. Further mechanistic studies demonstrated that IHE shares similar mechanisms of action with ISO that reduce mitotic clonal expansion during the early phase of adipogenic differentiation and decrease expression of cell cycle regulators. These results suggest that IHE inhibits adipogenesis, in part, through co-regulation of AMPKα and Nur77, and has potential as a therapeutic option for obesity and related metabolic dysfunction.
最近的研究表明，Nur77 和 AMPKα 在调节脂肪生成中发挥重要作用，并且异土木香内酯（ISO）靶向 AMPKα 和 Nur77 抑制脂肪生成。在本研究中，我们假设含有两种倍半萜内酯土木香内酯（ALA）和 ISO 的土木香根提取物（IHE）可能作为主要化合物抑制脂肪生成。我们发现，ALA 和 IHE 同时靶向 AMPKα 和 Nur77，并抑制 3T3-L1 细胞的脂肪生成分化，伴随着脂肪细胞标志物表达降低。进一步的机制研究表明，IHE 与 ISO 具有相似的作用机制，可减少脂肪生成分化早期的有丝分裂克隆扩增，并降低细胞周期调节剂的表达。这些结果表明，IHE 通过共同调节 AMPKα 和 Nur77 抑制脂肪生成，并且可能成为肥胖和相关代谢功能障碍的治疗选择。
