中国中药杂志

2021, v.46(10) 2489-2500

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UHPLC-Q-TOF-MS整合网络药理学研究升陷汤有效成分及其治疗慢性心力衰竭的作用机制
Effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure based on UHPLC-Q-TOF-MS integrated with network pharmacology

马颖;王博龙;王亮;黄翠云;孙美;焦广洋;张凤;陈万生;
MA Ying;WANG Bo-long;WANG Liang;HUANG Cui-yun;SUN Mei;JIAO Guang-yang;ZHANG Feng;CHEN Wan-sheng;Department of Pharmacy, Changzheng Hospital, Second Military Medical University;Chemistry and Biological Engineering College, Yichun University;Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine;

摘要(Abstract):

基于UHPLC-Q-TOF-MS技术阐明升陷汤方剂的主要入血成分,并结合网络药理学探讨其治疗慢性心力衰竭的作用机制。首先采用超高效液相色谱-四极杆-飞行时间串联质谱(UHPLC-Q-TOF-MS)技术来鉴定和推测升陷汤在大鼠血清中的主要移行成分;在此基础上,采用TCMSP数据库、SwissTargetPrediction数据平台对鉴定得到的入血成分进行靶点预测,并运用网络可视化软件Cytoscape 3.6.1绘制关联网络图,最后对核心靶基因进行GO富集分析和KEGG通路富集分析。该研究从大鼠含药血清中共鉴定出升陷汤方剂所含18个原型成分,来自黄芪、升麻、柴胡、知母和桔梗的化合物分别为5,4,4,4,1个。上述化合物作用于13个关键靶点包括炎症因子IL6,IL1B,TNF,PTGS2,IL10;氧化还原反应酶CAT,HMOX1,MPO;心血管靶点VEGFA,NOS3,NOS2;跨膜蛋白CAV1以及INS;调节HIF-1,PI3K-Akt, cGMP-PKG,cAMP和TNF等信号通路。该系列研究初步明确了升陷汤的入血成分及潜在作用机制,为筛选其药效成分及深入阐明作用机制提供了科学的理论依据。
This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.

关键词(KeyWords): UHPLC-Q-TOF-MS;升陷汤;血清药物化学;慢性心力衰竭;信号通路;网络药理学
UHPLC-Q-TOF-MS;Shengxian Decoction;serum pharmacochemistry;chronic heart failure;signaling pathways;network pharmacology

Abstract:

Keywords:

基金项目(Foundation): 上海市科委项目(18401931600);; 上海市卫健委项目(ZYCC2019018);; 国家自然科学基金重点项目(81830109);; 金字塔人才项目(1016)

作者(Author): 马颖;王博龙;王亮;黄翠云;孙美;焦广洋;张凤;陈万生;
MA Ying;WANG Bo-long;WANG Liang;HUANG Cui-yun;SUN Mei;JIAO Guang-yang;ZHANG Feng;CHEN Wan-sheng;Department of Pharmacy, Changzheng Hospital, Second Military Medical University;Chemistry and Biological Engineering College, Yichun University;Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine;

Email:

DOI: 10.19540/j.cnki.cjcmm.20200915.201

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