藏药沙棘防治高原红细胞增多症作用机制的网络药理学研究

Study on Network Pharmacology of Tibetan Medicine Hippophae Rhamnoides in Preventing and Treating High Altitude Polycthemia

目的采用网络药理学思路、方法研究藏药沙棘防治高原红细胞增多症(HAPC)的作用机制。方法应用TCMSP数据库搜索关键词"沙棘"[设置条件:DL(药物相似度)≥30%,OB(口服生物利用度)≥0.18],获取有关"沙棘的活性成分"的文献资料。通过PharmMapper服务器预测沙棘活性成分靶点,利用UniProt数据库校正不规范的靶点名称,并获取靶点的基因名称。利用STRING数据库构建靶点蛋白相互作用(PPI)网络,并将靶点输入David6.8数据库进行GO富集和KEGG通路分析。最后通过Cytoscape3.7.2软件构建藏药沙棘防治HAPC的"成分-靶点-通路"网络图。结果本研究检索获得沙棘有效成分共33个,作用靶点包括MAPK14、MAPK10、DAPK1、MAPK8、CYP2C8、RHOA、RORA、PDK2、AKT1等24个。GO富集分析结果显示沙棘主要参与细胞凋亡、MAPK级联、蛋白自身磷酸化、核受体功能等生物过程。KEGG通路分析表明沙棘防治HAPC涉及MAPK、Leukocyte transendothelial migration、PPAR signaling pathway等21条信号通路。结论沙棘的活性成分通过作用于体内多个靶点及多条信号通路,参与调节细胞增殖、分化、凋亡;通过改善机体炎症反应,减少活性氧的生成,增强机体免疫力及抗应激能力达到防治HAPC的作用。

Objective To study the mechanism of Tibetan medicine Hippophae rhamnoides in preventing and treating high altitude polycythemia(HAPC)by network pharmacology.Methods TCMSP database was uesd to obtain the literatures on the active ingredients ofHippophae rhamnoides[Setting conditions:DL(Drug-Like)≥30%,OB(Oral Bioavailability)≥0.18].The targets were predicted by PharmMapper server,the UniProt database was used to correct non-standard target names and obtain gene names of targets.PPI network was constructed by using STRING database,and potential targets were imported into David6.8 database for GO enrichment and KEGG pathway analysis.Finally,Cytoscape3.7.2 software was used to construct the"compound-target-pathway"network of Tibetan medicine Hippophae rhamnoides in the prevention and treatment of high altitude polycythemia(HAPC).Results In this study,33 active components of Hippophae rhamnoides are retrieved,including 24 targets of MAPK14、MAPK10、DAPK1、MAPK8、CYP2 C8、RHOA、RORA、PDK2、AKT1 etc.GO enrichment analysis shows that Hippophae rhamnoides is mainly involved in biological processes including apoptosis,MAP kinase activity,protein phosphorylation and nuclear receptor function etc.KEGG pathway analysis shows that Hippophae rhamnoides prevent and treat HAPC involving 21 signaling pathways including MAPK signaling pathways,Leukocyte transendothelial migration pathway,PPAR signaling pathway etc.Conclusion The active components of Hippophae rhamnoides areinvolved in the regulation of cell proliferation,differentiation and apoptosis by acting on multiple targets and multiple signaling pathways.HAPC can be prevented and treated by improving the body′s inflammatory reaction,reducing the generation of reactive oxygen species,enhancingimmunity and anti-stress ability of the organism.