昆仙胶囊治疗蛋白尿的“成分-靶点-通路”研究  

Exploration of ‘component-target-pathway’ of Kunxian capsules in treatment of proteinuria

作　　者：荆自伟 马真真[1] 张丁丁 师莹莹 刘丽伟 李卓伦 王晓彤 周霖[1] 贾清泉[1] 孙志[1] 杜书章[1] JING Zi-wei;MA Zhen-zhen;ZHANG Ding-ding;SHI Ying-ying;LIU Li-wei;LI Zhuo-lun';WANG Xiao-tong;ZHOU Lin;JIA Qing-quan;SUN Zhi;DU Shurzhang(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University.Henan Zhengzhou 450052,China;Department of Vas culocardiology.the First Affiliated Hospital of Zhengzhou University,Henan Zhengzhou 450052,China;Henan Health Cadre Collge.Henan Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,河南郑州450052 [2]郑州大学第一附属医院心内科,河南郑州450052 [3]河南卫生健康干部学院,河南郑州450052

出　　处：《中国医院药学杂志》2020年第23期2396-2405,共10页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金(编号:82003956);河南省高等学校重点科研项目(编号:20A350018)。

摘　　要：目的:系统研究昆仙胶囊的主要化学成分,并探讨其治疗蛋白尿的主要作用机制,为其药效物质基础研究提供一定的科学依据。方法:基于UHPLC-Q-Orbitrap HRMS技术对昆仙胶囊中的化学成分进行全面分析,根据化合物的一级、二级质谱信息,并与对照品或参考文献进行比对,以实现对药物的化学信息进行快速、精准识别。在此基础上,采用网络药理学方法对药物的化学成分进行靶标分析、功能富集,初步筛选出药物的主要药效物质,并探讨其作用机制。结果:从昆仙胶囊中共鉴定出51种化学成分,通过OB≥30%和DL≥0.18筛选得到雷公藤红素、淫羊藿苷、朝藿定B、淫羊藿素、儿茶酚、槲皮素、山柰酚、木犀草素、表儿茶素、异鼠李素、儿茶素、甘氨酸等12个主要活性成分;昆仙胶囊靶点220个;尿蛋白靶点2 179个;昆仙胶囊降低尿蛋白靶点115个,主要核心靶点为AKT1、VEGFA、TNF、IL6、TP53、CASP3、MMP9、JUN、MAPK1和EGF;昆仙胶囊降低蛋白尿涉及GO 158条,主要为Inflammatory response等;KEGG通路分析主要得到61条信号通路,主要为PI3K-Akt signaling pathway等。结论:昆仙胶囊可能主要通过对PI3K-Akt、TNF、HIF-1、FoxO、MAPK和TLR等信号通路的干预来发挥治疗蛋白尿的作用,体现了昆仙胶囊多成分、多靶点、多途径的作用特点,为进一步深入揭示昆仙胶囊治疗蛋白尿的作用机制奠定了一定基础。OBJECTIVE To systematically study the main chemical components of Kunxian capsules and explore the main mechanism of its effect of treatment of proteinuria, so as to provide some reference for the research of its pharmacodynamic substance.METHODS The chemical constituents in Kunxian capsules were comprehensively analyzed based on UHPLC-Q-Orbitrap HRMS technique, and the primary and secondary mass spectrometry information of the compounds was compared with the reference substance or reference, so as to realize the rapid and accurate identification of the chemical information of the drugs.On this basis, the network pharmacology method was used to analyze the chemical components of the drug for target analysis and functional enrichment, to preliminarily select the main pharmacodynamic substances of the drug, and to explore its mechanism of action.RESULTS A total of 51 chemical components were identified from Kunxian capsules, and 12 main active components such as celastrol, icariin, Chaohuoding B, patchouli, catechol, mistletoe, catechol, luteolin, epicatechin, isorhamnetin, catechin, and glycine were obtained by OB ≥30% and DL ≥0.18 screening;220 targets of Kunxian capsules;2179 targets of urinary protein;115 targets of urinary protein were reduced by Kunxian capsules, and the main core targets were AKT1, VEGFA, TNF, IL6, TP53, CASP3, MMP9, JUN, MAPK1, and EGF;158 GOs were involved in the reduction of proteinuria by Kunxian capsules, mainly inflammatory response;61 signaling pathways were mainly obtained by KEGG pathway analysis, mainly PI3 K-signaling response.CONCLUSION Kunxian capsule may play a role in the treatment of proteinuria mainly through the intervention of PI3 K-Akt, TNF, HIF-1, FoxO, MAPK and TLR signaling pathways, reflecting the characteristics of multi-component, multi-target and multi-pathway of Kunxian capsules, which lays a foundation for further revealing the mechanism of Kunxian capsules in the treatment of proteinuria.

关 键 词：昆仙胶囊 蛋白尿 UHPLC-Q-Orbitrap HRMS 网络药理学 作用机制 

分 类 号：R284.1[医药卫生—中药学]