金银花抗肺癌作用机制的网络药理学研究

Study of Lonicera japonica Thunb aganist lung cancer based on pharmacological network

目的采用网络药理学方法研究金银花抗肺癌的主要有效成分和潜在作用靶点,探讨其"多成分-多靶点-多通路"的抗肺癌作用机制。方法通过PubMed、TCMSP数据库筛选金银花的主要活性成分和相关成分的作用靶点,并把口服生物利用度(OB)≥20%和类药性(DL)≥0.1作为筛选金银花活性成分的条件。通过CTD在线数据库检索与肺癌有关的作用靶点,采用String数据库分别构建金银花成分靶点和肺癌相关作用靶点的PPI网络图,并利用cytoscape 3.7获得两个PPI网络图的交集网络,筛选出与肺癌有关的关键作用靶点。最后对关键靶点进行通路富集分析研究其作用的信号通路。结果金银花治疗肺癌的主要活性成分有槲皮素、芹黄素、山柰酚、毛地黄黄酮等。金银花与肺癌相关的潜在作用靶点有38个,如PON1、NQO1、AHR、MMP10、CYP1A2、CYP1B1、GJA1、NOS2、RXRA、IL10等。共富集出18条与以上38个关键靶点有关的信号通路,如膀胱癌、细胞色素p450氧化酶、甲状腺癌、小细胞肺癌、子宫内膜癌等。此外,金银花还参与调节炎症反应、脂质代谢、细胞凋亡等生物过程,显示了金银花"多成分-多靶点-多通路"共同发挥协同作用的特点。结论为研究金银花抗肺癌的药效物质基础和作用机制提供新思路,为金银花的进一步开发应用提供了科学依据。

Objective The main effective components and action pathway of Lonicera japonica against lung cancer were studied by network pharmacology,to explore the anti-lung cancer mechanism of"multi-component-multi-target-multi-pathway".Methods PubMed and TCMSP databases were used to screen the main active ingredients of Lonicera japonica,and oral bioavailability(OB)≥20%and chemotherapy-like(DL)≥0.1 were used as the conditions for screening the active components of Lonicera japonica,then Cytoscape 3.7 was used to construct the network diagram of"component-target".PPI network graph between honeysuckle component targets and lung cancer related targets was constructed through CTD and String database,then the intersection network of the two PPI network graphs was analyzed.Results The main active ingredients of Lonicera japonica in treatment of lung cancer include quercetin,coniferin,kaempferol and foxglove and so on.It may act on 38 lung cancer related targets,such as PON1,NQO1,AHR,MMP10,CYP1A2,CYP1B1,GJA1,NOS2,RXRA,IL10 and so on.It was regulated by 18 signaling pathways including bladder cancer,cytochrome P450,drug metabolism-cytochrome p450,thyroid cancer and endometrial cancer and so on.The results showed that Lonicera japonica anti-lung cancer"multi-component-multi-target-multi-pathway"action mechanism characteristics.Conclusions This study provides a scientific basis for the analysis of the mechanism of action of Lonicera japonica in the treatment of lung cancer,and points out the direction for the further experimental confirmation of the anti-lung cancer target and its signaling pathway of the active components of Lonicera japonica.