摘要
目的:系统阐明附子和熟地黄药对的化学成分组成,并初步探索治疗慢性阻塞性肺疾病(COPD)的有效成分和作用机制。方法:网络药理学分析"附子-熟地黄"治疗COPD过程中起作用的化学成分及起调控作用的靶点和通路;采用高分辨质谱技术(UPLC-Q-TOF-MS/MS)对"附子-熟地黄"水煎剂(FZSD)进行分析,验证药物水煎剂中起作用的活性成分,以A549炎症细胞为模型,通过ELISA和Western blot分析方法对KEGG分析中的通路进行验证。结果:经蛋白互作分析及网络拓扑分析后,获得核心靶标23个,活性成分45个,涉及20条信号通路(P<0.05)。高分辨质谱分析验证网络药理学中的8个成分,可通过调节体内炎症反应、肿瘤坏死因子(TNF-α)信号通路、小细胞肺癌、IL-17信号通路、细胞凋亡、NF-κB信号通路等生物过程来发挥治疗COPD的作用。结论:FZSD可通过多途径多靶点多通路共同发挥作用,其中对炎症通路上的IL-17、TNF-α、MAPK8、AKT1蛋白表达的抑制,最终达到抑制肺部细胞的炎症反应从而起到治疗COPD的作用。
Objective:To systematically elucidate the chemical composition of Fuzi and Shudihuang,and to initially explore the effective composition and mechanism of action for the treatment of chronic obstructive pulmonary disease(COPD).Methods:Network pharmacological analysis of the chemical components that played a role in the treatment of COPD in"Fuzi-Shudihuang"and the regulatory targets and pathways.Ultra-high liquid phase-tandem quadrupole time-of-flight mass spectrometer technology(UPLC-QTOF-MS/MS)was used to verify the active ingredients in"Fuzi-Shudihuang"decoction(FZSD),and using A549 inflammatory cells as a model,the pathways in the KEGG analysis were verified by ELISA and Western blot analysis methods.Results:After protein interaction analysis and network topology analysis,23 core targets and 45 active ingredients were obtained,involving 20 signal pathways(P<0.05).Network pharmacology prediction combined with high-resolution mass spectrometry analysis confirmed 8 components,which could regulate inflammation in the body,tumor necrosis factor(TNF-α)signaling pathway,small cell lung cancer,IL-17 signaling pathway,apoptosis,NF-κB signal pathways and other biological processes played a role in the treatment of COPD.Conclusion:FZSD can play a role through multiple pathways,multiple targets and multiple path,in which it inhibits the expression of IL-17,TNF-α,MAPK8 and AKT1 proteins on the inflammatory pathway,and ultimately inhibits the inflammatory response of lung cells to play a role in the treatment of COPD.
作者
汪景
位佳琳
何蕊
赵东凯
初洪波
位鸿(指导)
WANG Jing;WEI Jialin;HE Rui;ZHAO Dongkai;CHU Hongbo;WEI Hong(Changchun University of Chinese Medicine,Changchun 130117,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2022年第4期419-426,共8页
Chinese Journal of Immunology
基金
吉林省科技发展计划项目(20200404066YY)。
