基于网络药理学与分子对接技术探讨乌梅-木瓜药对治疗小儿厌食症的作用机制

Mechanism of couplet medicinals Mume Fructus&Chaenomelis Fructus in treating pediatric anorexia based on network pharmacology and molecular docking technology

目的 基于网络药理学与分子对接技术探讨乌梅-木瓜药对治疗小儿厌食症的作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)获取乌梅-木瓜药对的潜在活性成分及其作用靶点,通过人类基因组注释数据库(GeneCards)、疗效药靶数据库(TTD)、人类孟德尔遗传数据库(OMIM)筛选出小儿厌食症的疾病靶点。利用蛋白-蛋白相互作用网络数据库(STRING 11.5)构建蛋白互作(PPI)网络模型;运用Metascape平台进行GO功能富集与KEGG通路分析,运用Cytoscape3.7.2软件构建网络图,最后通过AutodockTools软件对筛选的核心靶点及成分进行分子对接。结果 筛选得到乌梅-木瓜药对11个潜在活性成分及116个潜在作用靶点及9个核心作用靶点。GO功能分析获得生物过程1411条、细胞组成42条、分子功能83条,主要集中在细胞凋亡信号通路、细胞因子受体结合等条目;KEGG富集分析共获得156条通路,与晚期糖基化终产物及其受体通路(AGE-RAGE)、核转录因子-κB信号通路(NF-κB)等信号通路密切相关。分子对接结果显示,丝/苏氨酸蛋白激酶1(AKT1)等核心靶点与槲皮素有良好的结合活性。结论 基于网络药理学方法与分子对接技术分析乌梅-木瓜药对中药活性成分,构建成分、厌食靶点相关网络,并对主要靶点进行富集分析,发现乌梅-木瓜药对可能通过槲皮素、β-谷甾醇等多种潜在活性成分,多靶点调控AKT1、肿瘤坏死因子(TNF)、白细胞介素-1B(IL-1B)、白细胞介素-6(IL-6)等核心基因,进而作用于NF-κB信号通路,从抗炎、改善胃肠平滑肌蠕动等多个方面共同发挥治疗小儿厌食症的作用。

Objective To explore the action mechanism of couplet medicinals Mume Fructus Chaenomelis Fructus in the treatment of pediatric anorexia based on network pharmacology and molecular pair technology.Methods The potential active ingredients and their targets of action of the couplet medicinals Mume Fructus Chaenomelis Fructus were obtained through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP).Disease targets for pediatric anorexia were screened through the Human Genome Annotation Database(GeneCards),Therapeutic Drug Target Database(TTD),and Human Mendelian Genetic Database(OMIM).Construct a protein protein interaction(PPI)network model using the protein protein interaction network database(STRING 11.5);Using the Metascape platform for GO functional enrichment and KEGG pathway analysis,constructing a network diagram using Cytoscape 3.7.2 software,and finally conducting molecular docking on the selected core targets and components using AutodockTools software.Results 11 potential active ingredients,116 potential action targets,and 9 core action targets in the couplet medicinals Mume Fructus Chaenomelis Fructus were obtained.GO functional analysis obtained 1411 biological processes,42 cell compositions,and 83 molecular functions,mainly focusing on items such as apoptosis signaling pathways and cytokine receptor binding;KEGG enrichment analysis obtained a total of 156 pathways,which were associated with AGE-RAGE and NF-κB signaling pathways are closely related.The molecular docking results show that core targets such as AKT1 have good binding activity with quercetin.Conclusion Based on network pharmacology methods and molecular docking technology,the active ingredients of traditional Chinese medicine in Mume Fructus Chaenomelis Fructus medicine were analyzed,and a network related to ingredients and anorexia targets was constructed.The main targets were enriched and analyzed,and it was found that the the couplet medicinals Mume Fructus Chaenomelis Fructus may be affected by quercetinβ-Multiple potential active ingredients such as sitosterol regulate core genes such as AKT1,TNF,IL-1B,and IL-6 at multiple targets,thereby acting on NF-κB signaling pathway plays a combined role in treating pediatric anorexia from multiple aspects such as anti-inflammatory and improving gastrointestinal smooth muscle peristalsis.