人参抗疲劳的作用机制和潜在靶点研究

Analysis of anti-fatigue mechanism and potential targets of ginseng

人参大补元气,能够增强机体功能,缓解疲劳症状,而人参总皂苷(GS)是其发挥抗疲劳作用的主要成分。该研究通过数据库获得17个人参化合物成分,92个药物靶标,基于R语言技术获得78个疾病与药物靶点的交互基因,STRING 11.0软件构建了人参抗疲劳蛋白互作网络,马修斯相关系数算法筛选核心基因,并对关键基因进行基因本体富集分析和京都基因与基因组百科全书通路富集分析。结果显示,人参通过调节AKT丝氨酸/苏氨酸激酶(AKT1)、白细胞介素1β(IL-1β)、Toll样受体衔接分子1(ICAM1)、丝裂原活化蛋白激酶8(MAPK8)、AP-1转录因子亚单位(JUN)、转导子和转录激活子1(STAT1)和前列腺素内过氧化物合酶2(PTGS2)等10个核心基因,参与细胞因子受体结合、细胞黏附分子结合和肿瘤坏死因子受体超家族结合等功能发挥,并调节肿瘤坏死因子、白介素17及c型凝集素受体等信号通路,从而发挥抗疲劳作用。基于网络分析结果,将32只SPF级4周龄ACR雄性小鼠随机分为空白组、GS低剂量组、GS中剂量组和GS高剂量组,并给予相应药物治疗3周。结果显示,GS能显著上调小鼠肌肉组织中STAT1和AKT1 mRNA表达水平(P<0.01,P<0.05),下调PTGS2和JUN mRNA表达水平(P<0.01),而对MAPK8,IL-1β,ICAM1没有显著影响。该研究通过构建人参抗疲劳调控网络,并通过实验验证,揭示了人参抗疲劳的作用机制,为其临床应用提供了一定的参考依据。

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside(GS)is the main component of its anti-fatigue effect.Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology;and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology.The protein-protein interaction(PPI)network was constructed by STRING 11.0 software,and Matthews Correlation Coefficient(MCC)algorithm was used to screen core target genes.Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks.The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase(AKT1),interleukin-1β,Toll-like receptor binding molecule 1(ICAM1),mitogen-activated protein kinase 8(MAPK8),AP-1 transcription factor subunit(JUN),transducer and activator of transcription 1(STAT1)and prostaglandin peroxidase synthase 2(PTGS2).It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect.Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group.The corresponding drugs were administrated for 3 weeks.The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1(P<0.01,P<0.05),and downregulate the expressions of PTGS2 and JUN(P<0.01).However,there was no significant effect on MAPK8,IL-1βand ICAM1.Ginseng’s anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.