摘要
目的基于网络药理学原理全面分析黄芪和厚朴治疗前列腺癌的作用机制。方法通过TCMSP和Swiss数据库预测黄芪与厚朴中的活性分子靶点,并通过Genecards、DisGeNET和OMIM数据库筛选出前列腺癌相关靶点。利用Venny软件构建“疾病-活性成分-靶点”网络,得到69个候选关键靶点基因。进一步通过STRING数据库构建蛋白质互作网络,并使用R语言进行GO和KEGG富集通路分析。再用AutoDockvina对靶点对应的蛋白分子晶体结构与活性成分三维结构进行分子对接。体内实验构建裸鼠皮下瘤模型,使用黄芪-厚朴活性成分进行干预。结果分子对接分析表明,黄芪甲苷(MOL000438)和厚朴酚(MOL000398)等活性成分与前列腺癌关键靶点蛋白(包括ATK1、ESR1、PPARG、PTGS2及SRC)表现出显著结合活性,其中厚朴酚与雌激素受体α(ESR1,PDB:1a52)的结合能达-8.7 kcal/mol,通过LEU-391残基形成稳定氢键作用。体内实验进一步证实,黄芪-厚朴活性成分组裸鼠皮下移植瘤体积较模型组小(P<0.05),且显示肿瘤组织PPARG和PTGS2蛋白表达显著下调(P<0.05)。RT-qPCR检测表明,该复方可双向调控基因表达:促凋亡因子AKT1水平上调(P<0.05),而癌相关基因PTGS2、PPARG、SRC及ESR1表达下调(P<0.05)。结论黄芪与厚朴可能通过多靶点、多通路协同,具有良好结合活性和抗前列腺癌作用。
Objective To comprehensively analyze the mechanism of Astragalus and Magnolia officinalis in treating prostate cancer based on the principles of network pharmacology.Methods Active molecular targets of Astragalus and Magnolia officinalis were predicted using the TCMSP and SwissTargetPrediction databases.Prostate cancer-related targets were screened via Genecards,DisGeNET,and OMIM databases.A"disease-active ingredient-target"network was constructed using Venny software,identifying 69 candidate key target genes.A protein-protein interaction(PPI)network was built using the STRING database,followed by GO and KEGG enrichment pathway analyses performed with R language.Constructing a subcutaneous tumor model in nude mice through in vivo experiments and intervening with active ingredients from Astragalus membranaceus and Magnolia officinalis.Results Molecular docking analysis revealed that active components such as astragaloside IV(MOL000438)and honokiol(MOL000398)exhibited significant binding activity with the key target proteins of prostate cancer,including AKT1,ESR1,PPARG,PTGS2,and SRC.Notably,Honokiol demonstrated a binding energy of-8.7 kcal/mol with estrogen receptorα(ESR1,PDB:1a52),forming stable hydrogen bond interaction with the LEU-391 residue.The in vivo experiments further confirmed that the Astragalus-Magnolia active component group showed smaller subcutaneous xenograft tumor volumes in nude mice as compared to the model group(P<0.05).Immunohistochemical analysis revealed significant downregulation of PPARG and PTGS2 protein expression in tumor tissues(P<0.05).QPCR results indicated that the formula bidirectionally regulated gene expression:pro-apoptotic factor AKT1 was upregulated(P<0.05),while cancer-associated genes PTGS2,PPARG,SRC,and ESR1 were downregulated(P<0.05).Conclusion The combination of Astragalus and Magnolia may exert anti-prostate cancer effects through multi-target and multi-pathway synergistic mechanisms,demonstrating favorable binding activity and therapeutic potential.
作者
任李玥
赵明智
王思捷
刘勤
刘家佳
REN Liyue;ZHAO Mingzhi;WANG Sijie;LIU Qin;LIU Jiajia(Center for Food and Drug Inspection of Yunnan Province,Kunming Yunnan 650032;Haiyuan College,Kunming Medical University,Kunming Yunnan 650101;Yunnan Institute of Food and Drug Supervision and Inspection,Kunming Yunnan 650101;Yunnan University of Chinese Medicine,Kunming Yunnan 650500,China)
出处
《昆明医科大学学报》
2025年第9期63-71,共9页
Journal of Kunming Medical University
基金
云南省教育厅科学研究基金(2022J1174)。
关键词
网络药理学
黄芪
厚朴
前列腺癌
分子对接
GO/KEGG富集分析
Network pharmacology
Astragalus
Magnolia officinallis
Prostatic cancer
Molecular docking
GO/KEGG enrichment analysis
作者简介
任李玥(1985-),女,哈尼族,云南普洱人,理学硕士,主管药师,主要从事中药质量标准研究和质量标准提高的研究工作;通信作者:刘家佳,E-mail:441603928@qq.com。
