目的:基于网络药理学方法探讨丹参-牡丹皮配伍治疗膝骨性关节炎(knee osteoarthritis,KOA)的作用机制。方法:在中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCM...目的:基于网络药理学方法探讨丹参-牡丹皮配伍治疗膝骨性关节炎(knee osteoarthritis,KOA)的作用机制。方法:在中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)检索并筛选丹参-牡丹皮活性成分及相关靶点蛋白,利用UniPort数据库进行靶点蛋白名转化。构建丹参-牡丹皮活性成分-靶点网络。在人类基因数据库(the human gene database,GeneCards)、Disgenet数据库、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、药物靶标数据库(therapeutic targetdatabase,TTD)、DrugBank数据库检索KOA疾病相关靶点。筛选丹参-牡丹皮作用于KOA的活性成分靶点。利用Cytoscape 3.7.2软件及其插件Bisogenet、CytoNCA对靶点进行交集分析并构建蛋白-蛋白互作(protein-protein interactions,PPI)网络图。将直接作用靶点输入核心靶基因功能注释数据库(the database for annotation visualization and integrated discovery,DAVID)进行基因本体论(gene ontology,GO)功能和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果:筛选出丹参65个活性成分,牡丹皮11个活性成分。获得丹参靶点蛋白932个,牡丹皮靶点蛋白237个。通过UniPort数据库转化最终获得作用靶点214个。筛选出KOA疾病靶点1207个,得到药物与疾病共同作用靶点97个。IL-6、VEGF、TP53、ESR1、MMP、MYC、CXCL8、FOS、JUN、TNF等可能是丹参-牡丹皮治疗KOA的关键靶点;GO功能富集分析获得349个富集结果,其中包括分子功能、细胞组分、生物过程;KEGG通路富集分析获得90个相关通路。结论:丹参-牡丹皮的有效成分包括槲皮素、木樨草素等,它们通过作用于IL-6、VEGFA、TNF、MMP等靶点,主要介导MAPK信号通路,从而调控软骨细胞的凋亡与退变,减少细胞外基质的降解,抑制骨吸收,介导炎症反应,促进血管新生,加速炎症吸收和代谢分解,最终减缓软骨组织的病损进展,发挥抗KOA的治疗作用。展开更多
Paeonol is a natural phenolic compound found in plants of the Ranunculaceae family,such as Mudanpi(Moutan Cortex)and Shaoyao(Paeoniae Radix).It possesses a wide range of pharmacological activities.Modern research conf...Paeonol is a natural phenolic compound found in plants of the Ranunculaceae family,such as Mudanpi(Moutan Cortex)and Shaoyao(Paeoniae Radix).It possesses a wide range of pharmacological activities.Modern research confirms that paeonol exhibits various pharmacological effects,including anti-inflammatory,antioxidant,antitumor,and immunomodulatory activities,demonstrating unique application value in the treatment of respiratory diseases.With the recent development of nanodelivery systems and derivatives,issues such as low oral bioavailability,poor stability,and short half-life of paeonol have been significantly improved.This article systematically reviews the role and mechanisms of paeonol in treating respiratory diseases such as asthma,pulmonary fibrosis,chronic obstructive pulmonary disease(COPD),lung cancer,allergic rhinitis,and pneumonia,analyzing existing application problems and potential solutions,aiming to provide a theoretical basis for its clinical application and further research and development.展开更多
文摘目的:基于网络药理学方法探讨丹参-牡丹皮配伍治疗膝骨性关节炎(knee osteoarthritis,KOA)的作用机制。方法:在中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)检索并筛选丹参-牡丹皮活性成分及相关靶点蛋白,利用UniPort数据库进行靶点蛋白名转化。构建丹参-牡丹皮活性成分-靶点网络。在人类基因数据库(the human gene database,GeneCards)、Disgenet数据库、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、药物靶标数据库(therapeutic targetdatabase,TTD)、DrugBank数据库检索KOA疾病相关靶点。筛选丹参-牡丹皮作用于KOA的活性成分靶点。利用Cytoscape 3.7.2软件及其插件Bisogenet、CytoNCA对靶点进行交集分析并构建蛋白-蛋白互作(protein-protein interactions,PPI)网络图。将直接作用靶点输入核心靶基因功能注释数据库(the database for annotation visualization and integrated discovery,DAVID)进行基因本体论(gene ontology,GO)功能和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果:筛选出丹参65个活性成分,牡丹皮11个活性成分。获得丹参靶点蛋白932个,牡丹皮靶点蛋白237个。通过UniPort数据库转化最终获得作用靶点214个。筛选出KOA疾病靶点1207个,得到药物与疾病共同作用靶点97个。IL-6、VEGF、TP53、ESR1、MMP、MYC、CXCL8、FOS、JUN、TNF等可能是丹参-牡丹皮治疗KOA的关键靶点;GO功能富集分析获得349个富集结果,其中包括分子功能、细胞组分、生物过程;KEGG通路富集分析获得90个相关通路。结论:丹参-牡丹皮的有效成分包括槲皮素、木樨草素等,它们通过作用于IL-6、VEGFA、TNF、MMP等靶点,主要介导MAPK信号通路,从而调控软骨细胞的凋亡与退变,减少细胞外基质的降解,抑制骨吸收,介导炎症反应,促进血管新生,加速炎症吸收和代谢分解,最终减缓软骨组织的病损进展,发挥抗KOA的治疗作用。
基金National Natural Science Foundation of China(82104662)Natural Science Foundation of Henan Province(252300420126)+1 种基金International Science and Technology Cooperation Project of Henan Province(252102521022)Science and Technology Tackling Project of Henan Province(242102311251).
文摘Paeonol is a natural phenolic compound found in plants of the Ranunculaceae family,such as Mudanpi(Moutan Cortex)and Shaoyao(Paeoniae Radix).It possesses a wide range of pharmacological activities.Modern research confirms that paeonol exhibits various pharmacological effects,including anti-inflammatory,antioxidant,antitumor,and immunomodulatory activities,demonstrating unique application value in the treatment of respiratory diseases.With the recent development of nanodelivery systems and derivatives,issues such as low oral bioavailability,poor stability,and short half-life of paeonol have been significantly improved.This article systematically reviews the role and mechanisms of paeonol in treating respiratory diseases such as asthma,pulmonary fibrosis,chronic obstructive pulmonary disease(COPD),lung cancer,allergic rhinitis,and pneumonia,analyzing existing application problems and potential solutions,aiming to provide a theoretical basis for its clinical application and further research and development.
