基于网络药理学探讨“高良姜-广藿香”药防治糖尿病胃轻瘫胃排空的作用机制

Study on mechanism of two related Chinese herbs A.officinarum-Pogostemon in treatment of delayed emptying in diabetic gastroparesis based on network pharmacology

目的:采用网络药理学预测“高良姜-广藿香”药在糖尿病胃轻瘫(Diabetic Gastroparesis),DGP治疗中的潜在药效化合物、关键靶点及相关机制途径。方法:利用TCMSP等数据库整理“高良姜-广藿香”的主要药效成分及对应的靶点;通过GeneCards疾病靶点平台筛选DGP相应靶点后,将“高良姜-广藿香”药与DGP的各自对应靶基因导入Venny 2.1.0分析平台筛选共同靶点;利用STRING数据库查找共同靶基因间蛋白相互作用信息,并绘制相互作用(PPI)网络图。采用R语言ClusterProfiler软件对“高良姜-广藿香”与DGP的共同靶基因进行基因富集分析及相关机制通路预测。结果:经筛选获得药物活性成分23个,相关的靶点97个,与DGP相关的靶点映射后得到共同靶点46个,包括ESR1,EGFR和IL6等。共同靶点主要富集在氧化应激、凋亡信号调控等生物过程,酶结合、蛋白磷酸酶结合等分子功能有关以及核染色质、线粒体外膜等细胞组分,并主要作用于PI3K-Akt、HIF-1和MAPK等信号通路。槲皮素、山柰酚、高良姜素等化合物可能是“高良姜-广藿香”作用于DGP的潜在药效成分,主要通过介导MAPK/PI3K/AKT和P53等信号通路,参与氧化应激和细胞凋亡等过程发挥治疗作用。结论:基于网络药理学方法,本研究初步揭示“高良姜-广藿香”药治疗DGP具有多成分、多靶点、多途径的作用特点,能够为进一步使用“高良姜-广藿香”药治疗DGP的研究提供新的思路。

Objective:To explore the potential active components,therapeutic targets and critical path of Alpinia officinarum and Pogostemonis Herba in the treatment of diabetic gastroparesis(DGP)by using network pharmacology.Methods:The main chemical components and corresponding targets genes of A.officinarum-Pogostemonis Herba were screened through TCMSP database retrieval[oral bioavailability(OB)≥30%and drug like(DL)≥0.18].Tgenes of diabetic gastroparesis were screened by the Human Gene Database(GeneCards),and Venny 2.1 software was used to obtained common targets for the active ingredients of A.officinarum-Pogostemonis Herba and DGP.Then,the protein-protein interaction(PPI)network of the common targets was constructed by STRING database and analyzed to performed the core targets.GO function and KEGG pathway enrichment analysis of the common target genes were obtained by using ClusterProfiler R package.Finally,the network diagram of"active ingredient-pathway-target"was used to establish by Cytoscape3.8 software.Results:Totally 23 ingredients of A.officinarum-Pogostemonis Herba,97 active ingredients targets and 533 DGP related targets,including 46 common targets were selected.The common targets were mainly enriched in the cell constituents such as the nuclear chromatin and mitochondria outer membrane,involved in the biological processes as oxidative stress,apoptosis signal regulation,and molecular functions as enzyme binding,protein phosphatase binding,and cytokine activity.They were also concentrated in the signal pathways such as PI3K/Akt,HIF-1 and MAPK.The network of“active ingredients-targets-pathways”indicated the active components such as quercetin,kaempferol and galangin in A.officinarum-Pogostemonis Herba played an anti-delayed gastric emptying in diabetic gastroparesis by acting on PTGS2,NOS2,BCL2,IL6,VEGFA and other targets to jointly regulate PI3K-Akt,HIF-1 and MAPK pathways.Conclusion:This study initially reveals that the combined treatment of A.officinarum-Pogostemonis Herbafor delayed gastric emptying in diabetic gastroparesis is a complex process with multi-components,multi-targets and multi-pathways,and provides a new idea for follow-up researches.