[关键词]
[摘要]
目的 系统整理并归纳总结阿尔茨海默病(AD)的中药复方临床用药规律及特点,研究核心中药的潜在作用机制。方法 通过检索中国学术期刊全文数据库(CNKI)、万方数据库(Wanfang Data)、维普生物医学数据库(VIP)、中国生物医学文献数据库(SinoMed)、EMbase、PubMed、Cochrane Library和Web of Science数据库自建库至2024年4月中药复方治疗AD的临床研究,筛选数据并使用Excel建立数据库。运用R Studio软件进行中药频次、频率、剂量、功效、性味、归经、关联规则和层次聚类的分析。利用网络药理学方法预测核心中药的潜在作用靶点和通路,从TCMSP数据库和OMIM等数据库中分别获取中药与AD相关的靶点,取交集靶点后上传至STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,将结果导入Cytoscape 3.9.1软件中,运用CytoNCA工具计算网络拓扑参数并得到关键靶点,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。结果 在纳入的131首方剂中,中药频次以石菖蒲、熟地黄和川芎应用最广。中药功效前3名分别为补虚药、活血化瘀药和安神药。中药四性以温、平居多,五味中甘、苦、辛味为主,归经中以肝、肾和心为主。关联规则分析中支持度≥12%、置信度≥80%时,共得到关联规则19条。高频中药聚类分析得到6类中药。核心中药石菖蒲、熟地黄和川芎与AD的交集靶点124个,经拓扑学分析得到其治疗AD的8个关键靶点,包括丝氨酸/苏氨酸激酶1(AKT1)、肿瘤坏死因子(TNF)、Jun原癌基因(JUN)等。KEGG分析结果提示主要涉及神经营养因子(neurotrophin)、AD、C型凝集素受体(C-type lectin receptor)等信号通路。结论 该研究总结归纳了中药复方治疗AD的用药规律,用药以补益肝肾、活血化瘀和化痰开窍为主。揭示了核心中药通过不同通路治疗AD的多种机制,为后续中药复方临床用药和科学研究提供参考。
[Key word]
[Abstract]
Objective To systematically review and summarize the clinical application patterns and characteristics of traditional Chinese medicine (TCM) formulas in the treatment of Alzheimer's disease (AD) and to investigate the potential mechanisms of action of core Chinese herbs.Methods A comprehensive literature search was conducted in CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library, and Web of Science for clinical studies on TCM formulas for AD from database inception to April 2024. Data were screened and compiled into a database using Excel. R Studio software was employed to analyze the frequency, dose, efficacy, properties, meridian tropism, association rules, and hierarchical clustering of the included Chinese herbs. Network pharmacology was used to predict the potential targets and pathways of core Chinese herbs. Targets related to both the selected herbs and AD were obtained from the TCMSP and OMIM databases, and their intersection was uploaded to the STRING database to construct a protein-protein interaction (PPI) network. The results were then imported into Cytoscape 3.9.1, and key targets were identified through network topology analysis using the CytoNCA tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed.Results Among the 131 included formulas, Acorus Tatarinowii, Rehmannia glutinosai, and Ligusticum chuanxiong were the most frequently used herbs. The three most common therapeutic effects were tonifying deficiency, promoting blood circulation and removing blood stasis, and calming the mind. In terms of the four natures of Chinese medicine, warm and neutral properties were predominant, while the five flavors were mainly sweet, bitter, and pungent. The primary meridian tropisms were the liver, kidney, and heart. Association rule analysis identified 19 rules with a support threshold o f ≥ 12% and a confidence level of ≥80%. High-frequency herbs were clustered into six categories. A total of 124 overlapping targets were identified for the core Chinese herbs (Acorus Tatarinowii, Rehmannia glutinosai, and Ligusticum chuanxiong) in AD treatment, with eight key targets determined through topological analysis, including serine/threonine kinase 1 (AKT1), tumor necrosis factor (TNF), and Jun proto-oncogene (JUN). KEGG pathway analysis indicated that the primary signaling pathways involved neurotrophin, Alzheimer's disease, and C-type lectin receptor pathways.Conclusion This study systematically summarizes the therapeutic patterns of TCM formulas for AD, with an emphasis on tonifying the liver and kidney, promoting blood circulation to remove blood stasis, and resolving phlegm to open orifices. It elucidates the multiple mechanisms by whi ch core Chinese herbs exert therapeutic effects through different pathways, providing valuable references for future clinical applications and scientific research on TCM formulas for AD.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金面上项目(82274616);广东省基础与应用基础研究基金企业联合基金项目(2022A1515220121)