Du Li-Jing, Zhang Xin-Ning, Li Sha-Sha, Sun Yuan-Fang, Jin Hui-Zi, Yan Shi-Kai, Han Chuan-Gang
Department of Anesthesiology, the First People's Hospital of Jiangxia District, Wuhan, China.
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Metab Brain Dis. 2022 Dec;37(8):2903-2914. doi: 10.1007/s11011-022-01067-5. Epub 2022 Sep 7.
Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).
开心散(KXS)是一种经典的中药方剂,广泛应用于抑郁症的治疗,但其作用机制尚不清楚。采用网络药理学方法构建“草药-成分-靶点”网络,阐明开心散治疗抑郁症的潜在作用机制。此外,应用分子对接验证成分与靶蛋白之间的重要相互作用。“草药-成分-靶点”网络表明,吴茱萸次碱、戈米辛B和细辛醚成分以及雌激素受体(ESR)、雄激素受体(AR)和核受体亚家族3成员C1(NR3C1)蛋白靶点对开心散的抗抑郁作用贡献最大。京都基因与基因组百科全书(KEGG)通路分析突出了与抑郁症治疗相关的最显著通路,包括神经活性配体-受体相互作用通路、血清素能突触通路、磷脂酰肌醇-3激酶(PI3K)-蛋白激酶B(Akt)信号通路和丝裂原活化蛋白激酶(MAPK)信号通路。基因本体(GO)富集分析表明,开心散治疗抑郁症的机制涉及G蛋白偶联受体(GPCR)信号转导、激素代谢和神经细胞凋亡的生物学过程。此外,分子对接结果显示,3-O-甲基-七叶皂苷元、吴茱萸次碱和茯苓酸与关键抗抑郁靶点5-羟色胺受体(5-HTR)具有更强的结合能力。总之,本研究初步揭示了开心散中的关键活性成分,包括戈米辛B、细辛醚、人参皂苷Rg1、3-O-甲基-七叶皂苷元和茯苓酸,可与多个靶点(5-HTR、多巴胺受体、肾上腺素能受体、AR、ESR、NR3C1)相互作用,并调节多个通路(神经活性配体-受体相互作用通路、血清素能突触通路、PI3K-Akt信号通路和MAPK信号通路)的激活。