College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
Sci Rep. 2023 Jul 11;13(1):11225. doi: 10.1038/s41598-023-38444-8.
Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.
抑郁症是一种常见的精神疾病，有些患者表现出自残和自杀等想法和行为。目前用于治疗抑郁症的药物并未取得良好效果。据报道，肠道微生物群产生的代谢物会影响抑郁症的发展。在这项研究中，通过数据库中的特定算法筛选出核心靶点和核心化合物，并使用分子对接和分子动力学软件模拟这些化合物和蛋白质的三维结构，以进一步研究肠道微生物群代谢物对抑郁症发病机制的影响。通过分析 RMSD 旋转半径和 RMSF，最终确定 NR1H4 与染料木黄酮的结合效果最好。最后，根据 Lipinski 的五规则，鉴定出雌马酚、染料木黄酮、槲皮素和甘氨胆酸是治疗抑郁症的有效药物。总之，肠道微生物群可以通过代谢物雌马酚、染料木黄酮和槲皮素影响抑郁症的发展，这些代谢物作用于 DPP4、CYP3A4、EP300、MGAM 和 NR1H4 等关键靶点。
