基于网络药理学和分子对接技术探讨壶瓶碎米荠治疗糖尿病脑病的分子靶点和机制

Molecular Targets and Mechanisms of Cardamine Hupingshanensis K in the Treatment of Diabetic Encephalopathy Based on Network Pharmacology and Molecular Docking Techniques

目的利用网络药理学、分子对接技术探讨壶瓶碎米荠对应靶基因治疗糖尿病脑病(DE)的分子靶点和机制。方法基于文献研究筛选后得到壶瓶碎米荠主要活性成分,利用相关数据库寻找壶瓶碎米荠及DE的相关靶标,取壶瓶碎米荠与DE的交集靶标,在string数据库中输入交集靶标作出蛋白与蛋白相互作用(PPI)网络图,根据作用关系强度挑选出核心靶标。构建“中药—成分—靶点—疾病”相互作用网络图。对交集靶点进行GO功能分析和KEGG富集分析。最后将筛选核心靶标与对应有效成分进行分子对接。结果通过文献收集到壶瓶碎米荠活性成分33个,筛选出有效成分24个。得到壶瓶碎米荠潜在靶点771个,获取DE靶点2046个。取交集得到壶瓶碎米荠的治疗靶点51个,主要作用于YARS、INSR、PIK3CG、KIF11、MAPK10、PDE5A等多个靶标。GO功能分析显示壶瓶碎米荠治疗DE的生物进程主要涉及生殖结构发育、蛋白质磷酸化、激素的反应、氮化合物的细胞反应、脂质的细胞反应等;KEGG富集分析提示壶瓶碎米荠治疗DE可能与癌症信号通路、PI3K-AKT信号通路、钙离子信号通路等多个通路相关;分子对接结果显示挑选出的核心靶标EGFR与对接成分异硫代氰酸烯丙酯亲和力最好。结论壶瓶碎米荠通过多成分—多靶点—多通路治疗DE。

Objective To study the molecular target and mechanism of Cardamine hupingshanensis K in the treatment of diabetes encephalopathy(DE) by network pharmacology and molecular docking technology.Methods Based on the literature research, the main active components of Cardamine hupingshanensis K were screened.The relevant targets of Cardamine hupingshanensis K and DE were searched by using the relevant database, and their intersections were taken.A protein-protein interaction(PPI) network was created by entering intersecting targets into the string database, and core targets were selected based on the intensity of the interaction relationship.The “Traditional Chinese Medicine-component-target-disease” interaction network was constructed.The intersection targets were analyzed by GO function and KEGG enrichment.Finally, the core targets screened were molecularly docked to the corresponding active ingredients.Results 33 active constituents were collected from the literature, and 24 active ingredients were kept.771 potential targets of Cardamine hupingshanensis K and 2 046 DE targets were obtained.The intersection was taken to obtain 51 therapeutic targets of Cardamine hupingshanensis K,mainly acting on several targets such as YARS,INSR,PIK3CG,KIF11,MAPK10 and PDE5A.GO functional analysis showed that the biological processes of Cardamine hupingshanensis K in the treatment of DE mainly involved in the development of reproductive structures, protein phosphorylation, hormones responses, nitrogen compounds cell responses, and lipids cell responses.KEGG enrichment analysis suggested that Cardamine hupingshanensis K treatment for DE may be associated with several pathways, including cancer signal pathway, PI3K-AKT signal pathway and calcium ion signal pathway.Molecular docking results showed that the selected core target EGFR had the best affinity with the docking component allyl isothiocyanate.Conclusion The potential pharmacodynamic basis, relevant targets and mechanism of Cardamine hupingshanensis K in the treatment of DE were explored.