基于网络药理学的荔枝核抗肝纤维化作用机制研究

Mechanism of Litchi semen for anti-hepatic fibrosis based on network pharmacology

目的 运用网络药理学探讨荔枝核抗肝纤维化的作用机制。方法 通过中药系统药理学数据库与分析平台检索荔枝核的有效活性成分,采用Perl软件对荔枝核有效成分的作用靶点进行预测。通过GeneCards?和OMIM?数据库获取肝纤维化相关靶点,将其与荔枝核有效成分的作用靶点取交集,得到荔枝核-肝纤维化靶点。利用CytoScape软件构建“中药-活性成分-基因靶点-疾病”网络。针对荔枝核-肝纤维化靶点,构建蛋白-蛋白相互作用(PPI)网络并筛选核心基因,同时进行功能富集分析和通路富集分析。结果 (1)筛选得到8个荔枝核有效活性成分、87个有效活性成分的作用靶点、6 899个肝纤维化相关靶点,通过取交集得到79个荔枝核-肝纤维化靶点。(2)“中药-活性成分-基因靶点-疾病”网络提示荔枝核主要通过6种有效活性成分(甘露醇、β-谷甾醇、谷甾醇、豆甾醇、表儿茶素、槲皮素)作用于荔枝核-肝纤维化靶点发挥作用。(3)PPI网络共筛选出的30个核心基因。(4)荔枝核-肝纤维化靶点共参与101个生物学过程,涉及74条信号通路。结论 荔枝核可能通过甘露醇、β-谷甾醇、谷甾醇、豆甾醇、表儿茶素、槲皮素等有效活性成分,干预多靶点并调节多条信号通路,从而达到抗肝纤维化的效果。

Objective To explore the mechanism of Litchi semen for anti-hepatic fibrosis by employing network pharmacology.Methods The effectively active components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the Perl software was performed to predict the effect targets of effective components of Litchi semen.The targets related to hepatic fibrosis were obtained from GeneCards? and OMIM? database,and the intersection of hepatic fibrosis related targets with the effect targets of effective components of Litchi semen was conducted for acquiring the targets of Litchi semen-hepatic fibrosis.The CytoScape software was employed to establish "Traditional Chinese Medicine-active components-gene targets-disease" network.The protein to protein interaction(PPI) network was established and the core genes were screened with respect to Litchi semen-hepatic fibrosis targets;simultaneously,the function enrichment analysis and pathway enrichment analysis were conducted.Results(1) A total of 8 effectively active components of Litchi semen,87 effect targets of effectively active components,and 6899 targets related to hepatic fibrosis were screened,and 79 Litchi semen-hepatic fibrosis targets were obtained by the intersection.(2) "Traditional Chinese Medicine-active components-gene targets-disease" network implied that Litchi semen mainly acted on Litchi semen-hepatic fibrosis targets through six effectively active components(mannitol,beta-sitosterol,sitosterol,stigmasterol,epicatechin,and quercetin).(3) A total of 30 core genes were screened by the PPI network.(4) Litchi semen-hepatic fibrosis targets were involved in 101 biological processes and 74 signaling pathways.Conclusion Litchi semen may intervene multiple targets and regulate multiple signaling pathways to achieve the anti-hepatic fibrosis effect through effectively active components of mannitol,beta-sitosterol,sitosterol,stigmasterol,epicatechin,quercetin,etc.