基于网络药理学的当归补血汤辅助治疗肺癌的作用机制研究

Action mechanism of Danggui Buxue Decoction in adjuvant treatment of lung cancer based on network pharmacology

关键词:  当归补血汤  网络药理学  肺癌  作用机制  成分  靶点

Key words:  Danggui Buxue Decoction  network pharmacology  lung cancer  mechanism  component  target

摘要:

[目的]运用网络药理学的方法，探究当归补血汤作为化疗后辅助用药治疗肺癌的可能作用机制。[方法]通过中药系统药理学分析平台（TCMSP）数据库查询当归补血汤中的成分，并通过口服生物利用度（OB）≥30%，类药性（DL）≥0.18，筛选出活性成分，通过中药成分靶点数据库（HIT）及Swiss Target Prediction Database进行成分靶点的垂钓，通过Therapeutic Target Database（TTD）、Drugbank、DisGeNET数据库查询肺癌相关靶点，利用Cytoscape 3.2.1构建成分-靶点等多层次网络图。使用DAVID数据库对当归补血汤辅助治疗肺癌的潜在作用靶点进行GO富集分析和KEGG通路富集分析。[结果]当归补血汤中共筛选得到27个活性成分，其中23个属于黄芪，4个属于当归，黄芪中的山奈酚、槲皮素、芒柄花素可能是辅助治疗肺癌比较重要的成分，微管相关蛋白Tau（MAPT）、细胞色素P450 19A1（CYP19A1）、雌激素受体α（ESR1）可能是当归补血汤辅助治疗肺癌比较重要的潜在作用靶点。GO富集分析显示，靶点涉及到170个生物过程相关条目、30个细胞组成相关条目、54个分子功能相关条目。KEGG通路富集分析显示，癌症通路（pathwanys in cancer）、癌症蛋白聚糖（proteoglycans in cancer）、磷脂酰肌醇3激酶-蛋白激酶B信号通路（PI3K-Akt signaling pathway）等是比较重要的通路。[结论]当归补血汤中的活性成分山奈酚、槲皮素、芒柄花素可能通过作用于MAPT、CYP19A1、ESR1发挥辅助治疗肺癌的作用，为进一步研究其辅助治疗肺癌的作用机制奠定基础。

Abstract:

[Objective] Using the method of network pharmacology to explore the possible mechanism of Danggui Buxue Decoction as an adjuvant drug in the treatment of lung cancer after chemotherapy.[Methods] Firstly,the components of Danggui Buxue Decoction were searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened with "Oral Bioavailability (OB) ≥ 30%" as well as "Drug Likeness (DL) ≥ 0.18". Secondly,the targets of compounds were fished by Herb Ingredients' Targets Database (HIT) and Swiss Target Prediction Database while the targets of lung cancer were searched by TTD,Drugbank and DisGeNET database. Thirdly,Cytoscape 3.2.1 was used to construct multilayer network for compounds and targets. Finally,DAVID database was employed to conduct Gene Ontology and KEGG pathway enrichment analysis.[Results] Twenty-seven ingredients were screened and twenty-three comes from Astragali Radix while four comes Angelicae Sinensis Raix. Kaempferol,quercetin and formononetin in Astragali Radix and microtubule-associated protein tau (MAPT),cytochrome P450 19A1 (CYP19A1) as well as estrogen receptor α (ESR1) may be important components and targets for Danggui Buxue Decoction in adjuvant treatment of lung cancer. GO enrichment analysis showed that the targets involved 170 items related to biological processes,30 items related to cell composition and 54 items related to molecular function. And KEGG analysis demonstrated that pathways in cancer,proteoglycans in cancer and PI3K-Akt signaling pathway were important pathways.[Conclusion] The active components of Danggui Buxue Decoction,kaempferol,quercetin and formononetin,may play an important role in assistant treatment of lung cancer by acting on MAPT,CYP19A1 and ESR1,which can lay a foundation for further study on the mechanism of Danggui Buxue Decoction as an adjuvant drug in the treatment of lung cancer after chemotherapy.