Zhu Haohao, Du Zhiqiang, Lu Rongrong, Zhou Qin, Shen Yuan, Jiang Ying
Mental Health Center of Jiangnan University, Wuxi, Jiangsu 214151, China.
ACS Omega. 2024 Mar 6;9(11):12698-12710. doi: 10.1021/acsomega.3c08350. eCollection 2024 Mar 19.
: To investigate the antidepressant effect and potential mechanism of the Chufan Yishen Formula (CFYS) through network pharmacology, molecular docking, and experimental verification. : The active ingredients and their target genes of CFYS were identified through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed genes in patients with depression from the GEO database and screened out the genes intersecting with the target genes of CFYS to construct the PPI network. The key pathways were selected through STRING and KEGG. Then, molecular docking and experimental verification were performed. : A total of 113 effective components and 195 target genes were obtained. After intersecting the target genes with the differentially expressed genes in patients with depression, we obtained 37 differential target genes, among which HMOX1, VEGFA, etc., were the key genes. After enriching the differential target genes by KEGG, we found that the "chemical carcinogenesis-reactive oxygen species" pathway was the key pathway for the CFYS antidepressant effect. Besides, VEGFA might be a key marker for depression. Experimental verification found that CFYS could significantly improve the behavioral indicators of rats with depression models, including improving the antioxidant enzyme activity and increasing VEGFA levels. The results are consistent with the network pharmacology analysis. : CFYS treatment for depression is a multicomponent, multitarget, and multipathway complex process, which may mainly exert an antidepressant effect by improving the neuron antioxidant stress response and regulating VEGFA levels.
通过网络药理学、分子对接和实验验证，研究除烦益肾方（CFYS）的抗抑郁作用及潜在机制。通过中药系统药理学数据库（TCMSP）和中医整合药理学平台（TCM-ID）鉴定CFYS的活性成分及其靶基因。从基因表达综合数据库（GEO）中获取抑郁症患者的差异表达基因，筛选出与CFYS靶基因相交的基因构建蛋白质-蛋白质相互作用（PPI）网络。通过搜索工具检索蛋白质相互作用数据库（STRING）和京都基因与基因组百科全书（KEGG）筛选关键通路。然后进行分子对接和实验验证。共获得113个有效成分和195个靶基因。将靶基因与抑郁症患者的差异表达基因相交后，得到37个差异靶基因，其中血红素加氧酶1（HMOX1）、血管内皮生长因子A（VEGFA）等为关键基因。通过KEGG对差异靶基因进行富集后发现，“化学致癌-活性氧”通路是CFYS抗抑郁作用的关键通路。此外，VEGFA可能是抑郁症的关键标志物。实验验证发现，CFYS可显著改善抑郁症模型大鼠的行为学指标，包括提高抗氧化酶活性和增加VEGFA水平。结果与网络药理学分析一致。CFYS治疗抑郁症是一个多成分、多靶点、多途径的复杂过程，可能主要通过改善神经元抗氧化应激反应和调节VEGFA水平发挥抗抑郁作用。
