目的 基于网络药理学和体内实验探讨抗衰老片抗衰老的作用机制。方法 利用中药系统药理学数据库与分析平台（TCMSP）筛选抗衰老片中组方药材的主要化学成分及其靶点，并通过文献检索、Pubchem对抗衰老片中药材的主要成分进行补充，经SwissTargetPrediction数据库预测靶点；通过GeneCards、OMIM数据库获取衰老相关靶点；通过Venny2.1.0平台获得抗衰老片成分与衰老的共同靶点；基于STRING数据库和Cytoscape 3.8.0软件构建药物与疾病共同靶点的蛋白质相互作用网络（PPI）；基于R语言进行基因本体（GO）生物功能分析和京都基因与基因组百科全书（KEGG）通路富集分析。以秀丽隐杆线虫为实验对象，观察抗衰老片对N2野生型秀丽隐杆线虫寿命及百草枯诱导的N2野生型线虫及突变体CB1370、CF1038、MQ1333、MQ887、TJ1052寿命的影响，探究抗衰老片抗衰老的作用及潜在的作用机制。结果 筛选出抗衰老片221个活性成分和1 232个预测靶点，衰老相关靶点12 081个，抗衰老片成分和疾病的共同靶点1 020个。KEGG富集分析结果主要涉及磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信号通路、晚期糖基化终末产物/晚期糖基化终末产物受体（AGE/RAGE）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路等。线虫实验结果表明，抗衰老片可延长正常情况下及百草枯诱导下的N2野生型秀丽隐杆线虫的寿命，提高秀丽隐杆线虫对百草枯的耐性；与相应各对照组相比，抗衰老片无法延长突变体TJ1052和CF1038在氧化应激下的寿命，但突变体CB1370、MQ1333和MQ887在氧化应激下的寿命可被延长。结论 抗衰老片对秀丽隐杆线虫具有延长寿命的作用，其潜在的机制可能依赖于PI3K信号通路和叉头转录因子（FOXO）信号通路，而不依赖于胰岛素受体信号通路和线粒体相关信号通路。

Objective To explore the anti-aging mechanism of Kangshuailao Tablet (KSLT) based on network pharmacology and in vivo experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to screen the main chemical components and their targets of Chinese materia medica in KSLT and the major components of Chinese materia medica in KSLT were supplemented by literature and Pubchem, and the targets of supplemented components were predicted by the SwissTargetPrediction. Aging-related targets were obtained from the database of GeneCards and OMIM. Common targets of KSLT and aging were got by Venny2.1.0. The protein-protein interaction (PPI) network of the common targets of drugs and diseases was constructed based on the STRING and Cytoscape 3.8.0 software. Gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were carried out based on R language. To explore the anti-aging effect and potential mechanism of KSLP, N2 wild-type Caenorhabditis elegans (C. elegans) were performed to observe the anti-aging effect of KSLT on the life span, and the potential anti-aging mechanism of KSLT was investigated by paraquat-induced N2 wild-type C. elegans and mutants CB1370, CF1038, MQ1333, MQ887 and TJ1052. Results There were 221 active ingredients, 1 232 predicted targets in KSLT, 12 081 targets in aging-related targets, and 1 020 common targets of KSLT and aging. The selected signaling pathways of KEGG pathway analysis mainly included phosphatidylinositol 3- kinase and protein kinase B (PI3K/Akt) signaling pathway, advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. The experimental results showed that KSLT prolonged the lifespan of C. elegans and improved the tolerance of C. elegans to paraquat. Compared with the corresponding control groups, KSLT was unable to extend the lifespan of mutants TJ1052 and CF1038 under oxidative stress, but the lifespan of mutants CB1370, MQ1333, and MQ887 was prolonged by KSLT under oxidative stress. Conclusion KSLTP had anti-aging effects on C. elegans, and the underlying might depend on PI3K and forkhead box protein O (FOXO) signaling pathways, but not on insulin receptors signaling pathway and mitochondria-related signaling pathways.

R285.5

上海市科委专项“上海医药战略大品种二次开发”（15DZ1900100）