摘要
利用药物协同效应延缓衰老是一种极具潜力的抗衰新策略,以D-gal诱导HUVEC细胞衰老构建衰老模型,探究两种小分子乙酰氨基酚和乙酰半胱氨酸的协同抗衰效应及其协同抗衰的相关机制。首先利用网络药理学筛选具有潜在抗衰活性的小分子群,以D-gal诱导HUVEC细胞衰老为模型检测小分子的抗衰活性,并通过Chou-Talalay模型筛选出两种具有协同抗衰效应的小分子组合,进一步利用生化与细胞生物学等手段研究获得小分子协同组合介导抗衰的相关机制。结果显示,乙酰氨基酚和乙酰半胱氨酸是具有极佳抗衰活性的小分子对,两者组合可产生协同效应并介导抗衰。该协同组合可显著降低细胞内活性氧水平,有效解除D-gal诱导的细胞周期阻滞,显著降低早期炎症因子(IL-1β、COX-2)的转录,该协同组合还显著降低细胞衰老标志物p53和p16的蛋白水平,并显著降低p-p38和细胞核内p65的蛋白水平。乙酰氨基酚和乙酰半胱氨酸协同组合可能通过MAPK/NF-κB通路抑制细胞衰老。以上结果为进一步开发利用乙酰氨基酚和乙酰半胱氨酸协同抗衰提供理论基础。
Drug synergy is a promising new anti-aging strategy.Construction of the aging model induced by D-galactose in HUVEC cells was aimed to explore the potential synergistic anti-aging effect of acetylsalicylic acid and acetylcysteine,and to investigate the un-derlying mechanisms of their synergy in anti-aging.Network pharmacology was used to screen a group of small molecules with poten-tial anti-aging activity.D-galactose-induced HUVEC cells was employed to detect the anti-aging activity of small molecules,and Chou-Talalay model was used to screen two small molecule combinations with synergistic anti-aging effects.Further investigation of the mechanisms underlying the anti-aging activity mediated by the selected small molecule combinations was conducted using biochemical and cell biological approaches.Results showed that acetaminophen acid and acetylcysteine were a highly effective pair of small mole-cules with anti-aging activity,which could produce synergistic effects in mediating anti-aging.The synergistic combination significantly reduced intracellular reactive oxygen species levels,effectively relieved cell cycle arrest induced by D-galactose,and significantly re-duced the transcription levels of early inflammatory factors(IL-1β,COX-2).In addition,the synergistic combination significantly re-duced the protein levels of cell senescence markers(p53,p16),as well as p-p38 and nuclear p65 protein levels,indicating that the ace-tylsalicylic acid and N-acetylcysteine synergistic combination may inhibit cell aging via the MAPK/NF-κB pathway.These results provide a theoretical basis for the further development and utilization of acetylsalicylic acid and N-acetylcysteine as a synergistic anti-aging com-bination.
作者
蒋立翔
韩琼
段嘉欣
李涵
曹前
黄新河
JIANG Lixiang;HAN Qiong;DUAN Jiaxin;LI Han;CAO Qian;HUANG Xinhe(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China)
出处
《生物学杂志》
CAS
CSCD
北大核心
2024年第3期77-84,共8页
Journal of Biology
基金
四川省自然科学基金面上项目(No.23NSFSC0920)。
