摘要
目的:通过数据挖掘、网络药理学、分子对接技术探讨中藏药干预高原红细胞增多症组方规律及潜在作用机制。方法:以“高原红细胞增多症”“High Altitude Polycythemia”为主题词,在中国知网、万方医学、PubMed等国内外数据库中检索相关文献,收集汇总药方并对方中使用药物进行频次、聚类、关联分析,选取核心组方;使用网络药理学构建核心组方-活性成分-交集靶点网络图,利用拓扑结构特征值筛选出关键成分和核心靶点,进行分子对接,预测成分与靶点之间相互作用强度;采用基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)富集分析,探讨组方的潜在作用机制。结果:最终纳入131篇文献,筛选出73首方剂,涉及180味中药。在干预高原红细胞增多症方剂中,红花、丹参、黄芪为高频使用药物,药性多温、平,药味多苦、甘,归经多为心经、脾经、肝经,功效多为补虚、活血化瘀;常用配伍是丹参与黄芪、红花与诃子、红花与木香;关联规则分析得到核心组方为木香-红花-肉豆蔻-诃子-余甘子。核心处方的关键成分为山柰酚、槲皮素、诃子次酸、leucodelphinidin、lappadilactone等,核心靶点为白蛋白(ALB)、肿瘤坏死因子(TNF)、丝氨酸/苏氨酸激酶1(Akt1)、缺氧诱导因子-1α(HIF-1α)、基质金属蛋白酶-9(MMP-9)等,涉及信号通路为晚期糖基化终产物及其受体(AGE-RAGE)信号通路、HIF-1信号通路、TNF信号通路等。分子对接结果表明,lappadilactone与TNF、诃子次酸与ALB、槲皮素与MMP9结合稳定。结论:中藏药通过多成分、多靶点、多通路发挥干预高原红细胞增多症的作用,为临床合理用药提供科学依据,为创新药物研发提供数据参考。
Objective:To investigate the formulation patterns and potential mechanisms of Chinese medicine and Tibetan medicine in treating high-altitude polycythemia by data mining,network pharmacology,and molecular docking.Methods:High-altitude polycythemia was taken as a keyword to retrieve the relevant articles from China National Knowledge Infrastructure(CNKI),Wanfang Data,and PubMed.The retrieved articles were systematically reviewed to collect and analyze the frequency,clustering,and correlations of the herbal medicines in the prescriptions.Core prescriptions were identified and subjected to network pharmacological analysis to construct a core prescription-active ingredient-common target network.Topological parameters were employed to identify key ingredients and core targets.Molecular docking was then performed to assess the interaction strengths between key ingredients and core targets.Subsequently,Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to unravel the intricate mechanisms governing the therapeutic effects of these prescriptions.Results:A total of 131 articles were included,from which 73 prescriptions encompassing 180 herbal medicines were screened out.Carthami Flos,Salviae Miltiorrhizae Radix et Rhizoma,and Astragali Radix were frequently utilized,being warm and plain,bitter or sweet,with tropism to the heart,spleen,and liver meridians.These medicines primarily functioned to replenish deficiency,activate blood,and resolve stasis.Prominent herb pairs included Salviae Miltiorrhizae Radix et Rhizoma with Astragali Radix,Carthami Flos with Chebulae Fructus,and Carthami Flos with Aucklandiae Radix.Association rule mining yielded a core combination comprising Aucklandiae Radix,Carthami Flos,Myristicae Semen,Chebulae Fructus,and Phyllanthi Fructus.Key active components in the core prescription encompassed compounds such as kaempferol,quercetin,leucodelphinidin,lappadilactone,and chebulic acid,while core targets included albumin(ALB),tumor necrosis factor(TNF),serine/threonine kinase 1(Akt1),hypoxia-inducible factor-1α(HIF-1α),and matrix metalloprotein-9(MMP-9),which potentially acted on advanced glycation endproducts-receptor for advanced glycation endproducts(AGE-RAGE),HIF-1,and TNF signaling pathways.Molecular docking results revealed stable binding between lappadilactone and TNF,between chebulic acid and ALB,and between quercetin and MMP-9.Conclusion:Chinese medicine and Tibetan medicine can treat high-altitude polycythemia via multiple components,targets,and pathways.The findings furnish a scientific basis for the application of these remedies in clinical practice and offering valuable insights for the development of novel pharmaceuticals.
作者
张彬
孙佑佳
才太吉
贾蔷
吉先才让
杜连平
高燕
赵渤年
ZHANG Bin;SUN Youjia;CAI Taiji;JIA Qiang;Jixiancairang;DU Lianping;GAO Yan;ZHAO Bonian(Institute of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250000,China;Shandong Key Laboratory of Digital Chinese Medicine,Jinan 250000,China;Tibetan Hospital of Qinghai Province,Xining 810007,China;State Key Laboratory of Tibetan Medicine Research and Development,Xining 810016,China)
出处
《中国现代中药》
2025年第7期1312-1320,共9页
Modern Chinese Medicine
基金
青海省十大科技创新平台项目(ZYYSDPT-2023-06)
2023年全国中药特色技术传承人才培训项目(T20234832005)。
关键词
数据挖掘
网络药理学
分子对接
高原红细胞增多症
data mining
network pharmacology
molecular docking
high-altitude polycythemia
