中国中药杂志

2020, v.45(12) 2932-2937

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基于网络药理学探析滋阴方二至丸抗衰老分子机制研究
Molecular mechanism analysis of Erzhi Wan in treatment of aging based on network pharmacology

单思;王祺;王雯蕾;吴欣宇;严小军;刘红宁;
SHAN Si;WANG Qi;WANG Wen-lei;WU Xin-yu;YAN Xiao-jun;LIU Hong-ning;Jiangxi Province Key Laboratory of Traditional Chinese Medicine Etiopathogenisis, Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory of Jiangxi University of Traditional Chinese Medicine;

摘要(Abstract):

基于网络药理学方法探析滋阴补益肝肾方二至丸抗衰老分子机制。利用中药系统药理学技术平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库获取和筛选二至丸活性成分,PubChem数据库预测二至丸人类靶蛋白。联合运用Gene数据库和HAGR数据库获取衰老相关人类基因,基于生物通路软件Ingenuity Pathway Analysis(IPA)分析二者共同作用的分子网络、生物学通路、共同作用位点,并利用Western blot技术对部分作用位点进行验证。结果显示,利用TCMSP筛选出活性成分12个,PubChem数据库预测出靶蛋白69个,Gene和HAGR数据库获取衰老相关基因148个。IPA对比分析发现,二者分子网络复杂,生物功能多样,共同作用生物通路292条,主要集中于肿瘤相关通路,作用于缺氧诱导因子1α基因(HIF1α)、核因子E2相关因子(Nrf2/NFE2L2)、肿瘤坏死因子(TNF)等位点。Western blot结果表明,二至丸能抑制HIF1α蛋白的表达,且有统计学差异(P<0.05)。由此推论,二至丸可能通过改善机体假性缺氧微环境、炎性状态等方面干预衰老发挥作用。初步揭示了二至丸延缓衰老的分子机制,为二至丸延缓衰老的机制研究奠定了基础,亦为中药复方配伍机制及扩展应用研究提供借鉴。
This present study aimed to explore the molecular mechanism of Erzhi Wan(a prescription of nourishing Yin and toni-fying liver and kidney) in treatment of aging by network pharmacology. The active constituents and target proteins of Erzhi Wan were searched from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and PubChem databases respectively. Aging-related genes were searched from Gene and HAGR databases. Based on the Ingenuity Pathway Analysis(IPA), we analyzed the common molecular network, biological pathway and interaction sites between these two parts, and verified some of them by Western blot. Twelve active constituents of Erzhi Wan were screened by TCMSP databases, 69 protein targets were predicted through PubChem, and 148 aging-related genes were found in Gene and HAGR databases. IPA comparison showed that the molecular networks of these two were complex, with diversity of biological functions. The common pathways involved 292 pathways, mainly related to tumors. They acted on hypoxia inducible factor-1α gene(HIF1α), nuclear factor-E2 related factor(Nrf2/NFE2 L2), tumor necrosis factor(TNF) and other sites. Western blot results suggested that Erzhi Wan could down-regulate the expression of HIF1α, with statistical difference(P<0.05). It was concluded that, Erzhi Wan could intervene aging through improving pseudo-hypoxic microenvironment and inflammation. The molecular mechanism of Erzhi Wan in delaying aging was preliminarily revealed, which laid a foundation for further stu-dying the anti-aging mechanism of Erzhi Wan, and also provided a reference for the compatibility mechanism and extended application of Chinese medicine compounds.

关键词(KeyWords): 网络药理学;衰老;二至丸;IPA
network pharmacology;aging;Erzhi Wan;Ingenuity Pathway Analysis(IPA)

Abstract:

Keywords:

基金项目(Foundation): 江西省卫生健康委中医药科研计划课题(2018A359);; 江西省自然科学基金项目(20192BAB215052);; 江西中医药大学校级科研项目(JXSYLXK-ZHYAO131)

作者(Author): 单思;王祺;王雯蕾;吴欣宇;严小军;刘红宁;
SHAN Si;WANG Qi;WANG Wen-lei;WU Xin-yu;YAN Xiao-jun;LIU Hong-ning;Jiangxi Province Key Laboratory of Traditional Chinese Medicine Etiopathogenisis, Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory of Jiangxi University of Traditional Chinese Medicine;

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