基于网络药理学策略解析益髓清黄散作用于骨髓增生异常综合征的关键药理途径及靶点
Deciphering the Key Pharmacological Pathways and Targets of Yisui Qinghuang Powder That Acts on Myelodysplastic Syndromes Using a Network Pharmacology-Based Strategy.
作者信息
Han Zijian, Song Luping, Qi Kele, Ding Yang, Wei Mingjun, Jia Yongcun
机构信息
People's Hospital of Ningxia Hui Autonomous Region, Department of Medical Engineering, Yinchuan 750002, China.
The First Affiliated Hospital of Northwest University for Nationalities, Yinchuan 750002, China.
出版信息
Evid Based Complement Alternat Med. 2020 Dec 8;2020:8877295. doi: 10.1155/2020/8877295. eCollection 2020.
BACKGROUND
Yisui Qinghuang powder (YSQHP) is an effective traditional Chinese medicinal formulation used for the treatment of myelodysplastic syndromes (MDS). However, its pharmacological mechanism of action is unclear.
MATERIALS AND METHODS
In this study, the active compounds of YSQHP were screened using the traditional Chinese medicine systems pharmacology (TCMSP) and HerDing databases, and the putative target genes of YSQHP were predicted using the STITCH and DrugBank databases. Then, we further screened the correlative biotargets of YSQHP and MDS. Finally, the compound-target-disease (C-T-D) network was conducted using Cytoscape, while GO and KEGG analyses were conducted using R software. Furthermore, DDI-CPI, a web molecular docking analysis tool, was used to verify potential targets and pathways. Finally, binding site analysis was performed to identify core targets using MOE software.
RESULTS
Our results identified 19 active compounds and 273 putative target genes of YSQHP. The findings of the C-T-D network revealed that Rb1, CASP3, BCL2, and MAPK3 showed the most number of interactions, whereas indirubin, tryptanthrin, G-Rg1, G-Rb1, and G-Rh2 showed the most number of potential targets. The GO analysis showed that 17 proteins were related with STPK activity, PUP ligase binding, and kinase regulator activity. The KEGG analysis showed that PI3K/AKT, apoptosis, and the p53 pathways were the main pathways involved. DDI-CPI identified the top 25 proteins related with PI3K/AKT, apoptosis, and the p53 pathways. CASP8, GSK3B, PRKCA, and VEGFR2 were identified as the correlative biotargets of DDI-CPI and PPI, and their binding sites were found to be indirubin, G-Rh2, and G-Rf.
CONCLUSION
Taken together, our results revealed that YSQHP likely exerts its antitumor effects by binding to CASP8, GSK3B, PRKCA, and VEGFR2 and by regulating the apoptosis, p53, and PI3K/AKT pathways.
背景
益髓清黄散（YSQHP）是一种用于治疗骨髓增生异常综合征（MDS）的有效中药制剂。然而，其药理作用机制尚不清楚。
材料与方法
在本研究中，使用中药系统药理学（TCMSP）和HerDing数据库筛选YSQHP的活性成分，并使用STITCH和DrugBank数据库预测YSQHP的潜在靶基因。然后，我们进一步筛选YSQHP和MDS的相关生物靶点。最后，使用Cytoscape构建化合物-靶点-疾病（C-T-D）网络，同时使用R软件进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。此外，使用网络分子对接分析工具DDI-CPI验证潜在靶点和通路。最后，使用MOE软件进行结合位点分析以鉴定核心靶点。
结果
我们的结果鉴定出YSQHP的19种活性成分和273个潜在靶基因。C-T-D网络的结果显示，Rb1、半胱天冬酶3（CASP3）、B细胞淋巴瘤2（BCL2）和丝裂原活化蛋白激酶3（MAPK3）的相互作用最多，而靛玉红、色胺酮、人参皂苷Rg1、人参皂苷Rb1和人参皂苷Rh2的潜在靶点最多。GO分析表明，17种蛋白质与丝氨酸/苏氨酸蛋白激酶（STPK）活性、PUP连接酶结合和激酶调节活性相关。KEGG分析表明，磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）、凋亡和p53通路是主要涉及的通路。DDI-CPI鉴定出与PI3K/AKT、凋亡和p53通路相关的前25种蛋白质。半胱天冬酶8（CASP8）、糖原合成酶激酶3β（GSK3B）、蛋白激酶Cα（PRKCA）和血管内皮生长因子受体2（VEGFR2）被鉴定为DDI-CPI和蛋白质-蛋白质相互作用（PPI）的相关生物靶点，并且发现它们的结合位点是靛玉红、人参皂苷Rh2和人参皂苷Rf。
结论
综上所述，我们的结果表明，YSQHP可能通过与CASP8、GSK3B、PRKCA和VEGFR2结合并调节凋亡、p53和PI3K/AKT通路发挥其抗肿瘤作用。
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