| 528 | 0 | 110 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 采用网络药理学和细胞实验探讨青藤碱(SIN)对D-半乳糖(D-gal)诱导巨噬细胞衰老的作用。方法 利用PubChem、SwissTargetPrediction、PharmMapper和GeneCards数据库获取SIN-衰老共同基因；通过DAVID数据库和微生信平台进行GO和KEGG通路富集分析；采用Cytoscape 3.10.2构建化合物-靶点网络，绘制蛋白互作(PPI)网络并获取核心基因。体外培养RAW 264.7细胞，将细胞分为对照组、D-gal衰老模型组和D-gal+SIN组。通过衰老相关β-半乳糖苷酶染色评估SIN对RAW264.7细胞衰老的影响；通过Western blot检测p53蛋白、p-AKT1/AKT1蛋白表达变化。结果 富集分析共涉及914条信号通路及541种生物过程、144种分子功能、73种细胞组分，主要涉及癌症的发病途径与PI3K-AKT信号通路等SIN治疗衰老的关键通路。与正常对照组比较，衰老模型组的衰老相关β-半乳糖苷酶染色阳性细胞比例、p53蛋白表达升高、p-AKT1/AKT1蛋白表达降低(P均<0.05);与衰老模型组比较，D-gal+SIN组的衰老相关β-半乳糖苷酶染色阳性细胞比例降低、p53蛋白表达降低、p-AKT1/AKT1蛋白表达升高(P均<0.05)。结论 SIN通过调控p-AKT1/AKT1信号通路延缓D-gal诱导的RAW 264.7巨噬细胞衰老。
Abstract：Objective To explore the effect of sinomenine(SIN)on D-galactose-induced macrophage senescence by using network pharmacology and cell experiments.Methods Data sources such as PubChem, SwissTargetPrediction, PharmMapper, and GeneCards were used to obtain common genes related to sinomenine and senescence.GO and KEGG pathway enrichment analyses were performed using the DAVID database and the Microbial Information Platform.A compound-target network was constructed using Cytoscape 3.10.2,and a protein-protein interaction(PPI) network was plotted to identify core genes.RAW264.7 cells were cultured in vitro and divided into three groups: the control group, the D-galactose-induced senescence model group, and the D-galactose+sinomenine group.The effect of sinomenine on RAW264.7 cell senescence was evaluated by β-galactosidase staining associated with senescence, and Western blot was used to detect changes in p53 and p-AKT1/AKT1 protein expression.Results The enrichment analysis involved a total of 914 signaling pathways, 541 biological processes, 144 molecular functions, and 73 cellular components, mainly focusing on pathways related to cancer pathogenesis, and the PI3K-AKT signaling pathway in SIN therapy for aging.Compared with the normal control group, the proportion of β-galactosidase-positive cells and the expression of p53 protein were increased, while the expression of p-AKT1/AKT1 protein was decreased in the senescence model group(all P<0.05).Compared with the senescence model group, the proportion of β-galactosidase-positive cells and the expression of p53 protein were decreased, while the expression of p-AKT1/AKT1 protein was increased in the D-galactose+sinomenine group(all P<0.05).Conclusion Sinomenine can delay the senescence of RAW264.7 macrophages induced by D-galactose by regulating p-AKT1/AKT1 signaling pathway.
[1]RUSSO G L,SPAGNUOLO C,RUSSO M,et al.Mechanisms of aging and potential role of selected polyphenols in extending healthspan[J].Biochemical Pharmacology,2020,173:113719
[2]FERRUCCI L,GONZALEZ-FREIRE M,FABBRI E,et al.Measuring biological aging in humans:a quest[J].Aging Cell,2020,19(2):e13080
[3]DING X,MA X,MENG P,et al.Potential effects of traditional chinese medicine in anti-aging and aging-related diseases:current evidence and perspectives[J].Clinical Interventions in Aging,2024,19:681
[4]PASCUAL-TORNER M,CARRERO D,PéREZ-SILVA J G,et al.Comparative genomics of mortal and immortal cnidarians unveils novel keys behind rejuvenation[J].Proc Natl Acad Sci U S A,2022,119(36):e2118763119
[5]LóPEZ-OTíN C,BLASCO M A,PARTRIDGE L,et al.Hallmarks of aging:an expanding universe[J].Cell,2023,186(2):243
[6]SALLAM N,LAHER I.Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases[J].Oxid Med Cell Longev,2016,2016:7239639
[7]KIM S J,MILLER B,KUMAGAI H,et al.Mitochondrial-derived peptides in aging and age-related diseases[J].GeroScience,2021,43(3):1113
[8]VATIC M,VON HAEHLING S,EBNER N.Inflammatory biomarkers of frailty[J].Exp Gerontol,2020,133:110858
[9]ZHANG S Q,NIU Z,ANISIMOV A,et al.NR1D1 inhibition enhances autophagy and mitophagy in alzheimer's disease models[J].Aging Dis,2025,14
[10]DING H,ZHANG Q,YANG R,et al.Aberrant STING activation promotes macrophage senescence by suppressing autophagy in vascular aging from diabetes[J].iScience,2024,28(1):111594
[11]BONDY S C,WU M.The critical role of autophagy and phagocytosis in the aging brain[J].Int J Mol Sci,2024,26(1):57
[12]LI D,ZHONG Z,KO C N,et al.From mundane to classic:sinomenine as a multi-therapeutic agent[J].Br J Pharmacol,2025,182(10):2159
[13]伍杰秀，白莎莎，谢冰冰，等.青藤碱对肺癌细胞A549中COX2、α7nAChR和A2A表达的影响[J].广州中医药大学学报，2017,34(3):381
[14]GAO Z,LIN Y,ZHANG P,et al.Sinomenine ameliorates intervertebral disc degeneration via inhibition of apoptosis and autophagy in vitro and in vivo[J].Am J Transl Res,2019,11(9):5956
[15]XIA B,LI Q,WU J,et al.Sinomenine confers protection against myocardial ischemia reperfusion injury by preventing oxidative stress,cellular apoptosis,and inflammation[J].Front Pharmacol,2022,13:922484
[16]FAN H,SHU Q,GUAN X,et al.Sinomenine protects PC12 neuronal cells against H(2)O(2)-induced cytotoxicity and oxidative stress via a ROS-dependent up-regulation of endogenous antioxidant system[J].Cell Mol Neurobiol,2017,37(8):1387
[17]陈圆，赵怡惠，黄燕，等.盐酸青藤碱的抑菌与抗氧化的研究[J].惠州学院学报，2018,38(3):52
[18]SHEN L,FAN L,LUO H,et al.Cow placenta extract ameliorates d-galactose-induced liver damage by regulating BAX/CASP3 and p53/p21/p16 pathways[J].J Ethnopharmacol,2024,323:117685
[19]HA? E,DIEUDONNé F X,SAIDAK Z,et al.N-cadherin/wnt interaction controls bone marrow mesenchymal cell fate and bone mass during aging[J].J Cell Physiol,2014,229(11):1765
[20]WANG W,YANG X,CHEN Q,et al.Sinomenine attenuates septic-associated lung injury through the Nrf2-Keap1 and autophagy[J].J Pharm Pharmacol,2020,72(2) :259
[21]RAHMAN S U,QADEER A,WU Z.Role and potential mechanisms of nicotinamide mononucleotide in aging[J].Aging Dis,2024,15(2):565
[22]CAMACHO-RUíZ J,V A,RENDóN-MACíAS M E,et al.Cognitive function groups in older people and risk factors[J].Rev Med Inst Mex Seguro Soc,2024,62(3):1
[23]NEVES J,SOUSA-VICTOR P,JASPER H.Rejuvenating strategies for stem cell-based therapies in aging[J].Cell Stem Cell,2017,20(2):161
[24]LIU S,LIU S,WANG X,et al.The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro[J].Aging Cell,2011,10(4):661
[25]BAO J,LIU B,WU C.Progress of anti-aging drugs targeting autophagy[J].Adv Exp Med Biol,2020,1207:681
[26]XU Z,ZHANG Z,ZHOU H,et al.Bazi bushen attenuates osteoporosis in SAMP6 mice by regulating PI3K-AKT and apoptosis pathways[J].J Cell Mol Med,2024,28(20):e70161
基本信息:
DOI：10.16751/j.cnki.2095-4646.2025050701
中图分类号:R965
引用信息:
[1]付晓俐,肖嘉琪,潘欣仪,等.基于网络药理学和细胞实验探究青藤碱抗衰老的作用机制[J].湖北科技学院学报(医学版),2026,40(01):17-22.DOI:10.16751/j.cnki.2095-4646.2025050701.
基金信息:
湖北科技学院糖尿病心脑血管病变湖北省重点实验室开放基金项目(2020TNB07)
2025-05-07
2025
2026-01-16
2026
2
2025-12-05
2025-12-05
2025-12-05