基于网络药理学预测积雪草提取物改善皮肤屏障受损的机制

Prediction of the Mechanism of Improving Skin Barrier Damage by Centella Asiatica Extract Based on Network Pharmacology

目的:利用过氧化氢(H_(2)O_(2))诱导人永生化角质形成细胞(HaCaT)损伤模型,评价积雪草提取物(Centella Asiatica Extract,CAE)对皮肤屏障受损的改善作用,并结合网络药理学探讨其作用机制。方法:构建H_(2)O_(2)诱导HaCaT细胞损伤模型,检测CAE对人封闭蛋白1(Claudin-1,CLDN1)和人紧密连接蛋白1(Zonula Occludens-1,ZO-1)含量的影响。收集CAE改善皮肤屏障受损的潜在作用靶点,并对其进行蛋白质相互作用(Protein-protein interaction,PPI)网络分析、基因本体论(Gene Ontology,GO)功能注释和Kyoto Encyclopedia of Genes and Genomes(KEGG)信号通路富集分析。结果:CAE可以显著提升H_(2)O_(2)诱导的HaCaT细胞CLDN1和ZO-1含量降低。SRC、MAPK1、EGFR、STAT3、PIK3R1等可能是CAE改善皮肤屏障受损的重要靶点。CAE改善皮肤屏障受损可能与PI3K信号的正向调节、ATP结合等功能和PI3K-Akt信号通路、VEGF信号通路、MAPK信号通路等通路密切相关。结论:CAE能够改善皮肤屏障受损,作用机制可能与调控PI3K-Akt信号通路、VEGF信号通路、MAPK信号通路等有关。

Objective:To evaluate the improvement effect of Centella Asiatica Extract(CAE)on impaired skin barrier using human immortalized epidermal cells(HaCaT)damage model induced by hydrogen peroxide(H_(2)O_(2)),and explore its mechanism by network pharmacology.Methods:Using a model of damaged HaCaT cells caused by H_(2)O_(2),detected the effect of CAE on the content of Claudin-1(CLDN1)and Zonula Occludens-1(ZO-1).Collected potential targets of CAE for improving impaired skin barrier,and conducted Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)functional enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.Results:CAE can significantly reverse the decrease of CLDN1 and ZO-1 content in HaCaT cells caused by H_(2)O_(2).SRC,MAPK1,EGFR,STAT3,PIK3R1,etc.may be important targets for CAE to improve impaired skin barrier.The improvement of impaired skin barrier by CAE may be closely related to the positive regulation of PI3K signaling,ATP binding,as well as the PI3K Akt signaling pathway,VEGF signaling pathway,MAPK signaling pathway,and other pathways.Conclusions:CAE can improve impaired skin barrier,and its mechanism may be related to regulating the PI3K Akt signaling pathway,VEGF signaling pathway,MAPK signaling pathway,etc.