Zhang Tingting, Wei Wei, Chang Surui, Liu Nanyang, Li Hao
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Pharmacol. 2022 Apr 25;13:853375. doi: 10.3389/fphar.2022.853375. eCollection 2022.
The Yizhiqinxin formula (YZQX) has been used to treat Alzheimer's disease (AD) or major depression disorder (MDD). However, its specific underlying mechanisms and therapeutic targets remain unclear. The ingredients and putative targets of YZQX were screened using the TCMSP and Drugbank databases. Next, the GEO database was used to retrieve relevant differentially expressed genes (DEGs) in AD or MDD and normal tissues. The PPI network was established, merged, and further screened to identify the main ingredients and core targets of YZQX against AD and MDD comorbidities. We performed enrichment analysis of core targets to identify biological processes and pathways. Finally, AutoDock software was used to validate the binding affinity between the crucial targets of direct action and their corresponding ingredients. A total of 43 ingredients were identified from YZQX, of which 43 were screened to yield 504 targets. By establishing the PPI network, 92 targets were regarded as targets of YZQX against AD and MDD comorbidities in the core network. Promising targets (, , , , , , , , , , and ) and signaling pathways (PI3K-Akt signaling pathway, ubiquitin-mediated proteolysis, MAPK signaling pathway, etc.) were filtered and refined to elucidate the underlying mechanism of YZQX against AD and MDD comorbidities. Molecular docking confirmed the ingredients of YZQX (quercetin and kaempferol) could bind well to multiple crucial targets. The ingredients of YZQX, such as quercetin and kaempferol, might treat AD and MDD comorbidities by acting on multiple targets and pathways.
益智清心方（YZQX）已被用于治疗阿尔茨海默病（AD）或重度抑郁症（MDD）。然而，其具体的潜在机制和治疗靶点仍不清楚。使用中药系统药理学数据库与分析平台（TCMSP）和药物银行（Drugbank）数据库筛选YZQX的成分和潜在靶点。接下来，利用基因表达综合数据库（GEO）检索AD或MDD以及正常组织中相关的差异表达基因（DEG）。建立、合并并进一步筛选蛋白质-蛋白质相互作用（PPI）网络，以确定YZQX针对AD和MDD共病的主要成分和核心靶点。我们对核心靶点进行富集分析，以确定生物学过程和信号通路。最后，使用自动对接（AutoDock）软件验证直接作用的关键靶点与其相应成分之间的结合亲和力。从YZQX中总共鉴定出43种成分，其中筛选出43种成分得到504个靶点。通过建立PPI网络，在核心网络中有92个靶点被视为YZQX针对AD和MDD共病的靶点。筛选并优化了有前景的靶点（……）和信号通路（PI3K-Akt信号通路、泛素介导的蛋白水解、MAPK信号通路等），以阐明YZQX针对AD和MDD共病的潜在机制。分子对接证实YZQX的成分（槲皮素和山奈酚）能与多个关键靶点良好结合。YZQX的成分，如槲皮素和山奈酚，可能通过作用于多个靶点和信号通路来治疗AD和MDD共病。
