基于网络药理学探讨黄芪改善原发性肌肉减少症的作用机制

The mechanism of Astragali Radix improving primary sarcopenia based on network pharmacology

目的原发性肌肉减少症,是一种与年龄相关的骨骼肌疾病。本文旨在探讨黄芪对原发性肌肉减少症的有效活性成分和治疗靶点。方法本研究采用网络药理学方法探究黄芪治疗肌肉减少症的作用机制。首先,在中药系统药理学数据库(TCMSP)和蛋白质数据库(Uniprot)中,筛选黄芪的有效活性成分及其对应基因靶点。接着,通过GeneCard、OMIM、PharmGkb、TTD这4个数据库,收集原发性肌肉减少症相关的基因靶点。然后,将药物基因靶点和疾病相关基因取交集,以构建黄芪-有效成分-肌少症-靶基因调控网络。在String平台绘制交集基因靶点的蛋白互作(Protein-protein interaction,PPI)关系图,通过基因本体(Gene ontology,GO)富集分析黄芪-原发性肌肉减少症交集靶点的特征生物学性质,并进行京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路分析。结果从数据库中获得黄芪的20个有效活性成分,181个黄芪作用靶点,498个原发性肌肉减少症相关基因靶点,取交集后共获得16个关键靶点,对这16个靶点进行GO和KEGG通路富集分析发现,黄芪可能通过抗氧化、抗炎和调节免疫功能,以介导细胞对氧化应激的反应、细胞对化学应激的反应等信号通路发挥治疗作用。结论黄芪可能通过其多种有效成分作用于多个基因靶点,从而改善老年性肌肉减少症的症状。这为黄芪在临床治疗老年性肌肉减少症中的应用提供了理论支持。

Objective Primary sarcopenia is an age-related skeletal muscle disease.This article aimed to explore the effective active ingredients and therapeutic targets of Astragali Radix for primary sarcopenia.Methods In this study,network pharmacology was used to explore the mechanism of Astragali Radix in the treatment of sarcopenia.Firstly,in the Traditional Chinese Medicine System Pharmacology Database(TCMSP)and Protein Database(Uniprot),the effective active ingredients and corresponding gene targets of Astragali Radix were screened.Next,gene targets related to primary sarcopenia were collected through four databases:GeneCard,OMIM,PharmGkb,and TTD.Then,the intersection of the drug gene targets and disease-related genes was taken to construct the Astragali Radix-active ingredient-sarcopenia-target gene regulatory network.A protein-protein interaction(PPI)network of intersecting target genes associated with Astragalus Radix-primary sarcopenia was visualized using the String platform.Gene ontology(GO)enrichment analysis revealed the characteristic biological properties of these targets.Additionally,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was conducted..Results 20 effective active ingredients of Astragali Radix were obtained from the databases,with 181 Astragali Radix action targets and 498 gene targets related to primary sarcopenia.After taking the intersection,16 key targets were acquired.Astragali Radix may exert therapeutic effects by mediating cellular responses to oxidative stress,chemical stress and other signaling pathways through antioxidant,anti-inflammatory,and immune regulation.Conclusion Astragali Radix may improve the symptoms of elderly sarcopenia by acting on multiple gene targets through its multiple active ingredients.This provides theoretical support for the application of Astragali Radix in the clinical treatment of elderly sarcopenia.