摘要
目的:基于肝癌模型小鼠研究复方苦参注射液的血清化学成分,通过网络药理学、血清化学和实验药理学的方法,初步探讨复方苦参注射液对肝癌的作用机制。方法:应用液质联用技术,确定复方苦参注射液血清中的生物碱类化学成分。应用网络药理学的研究思路,将成分-靶点网络与肝癌-靶点网络进行映射,构建成分-肝癌靶点网络。对网络中核心靶点进行代谢通路(KEGG)富集分析。采用H22肝癌荷瘤小鼠模型,观察复方苦参注射液、及复方苦参注射液与环磷酰胺协同给药在肝癌治疗中的作用。结果:共鉴定出10个血清中的生物碱类化学成分如金雀花碱、N-甲基金雀花碱、苦参胺碱、槐胺碱、槐果碱、苦参碱、赝靛叶碱、氧化槐果碱、氧化苦参碱、5α,9α-二羟基苦参碱,可能是通过直接作用于Wnt、Notch、JAK/STAT、PI3K-Akt、ERK等多条通路达到其治疗肝癌作用。复方苦参注射液具有抑瘤作用,与环磷酰胺协同给药可提高环磷酰胺的肿瘤抑制率,并降低肿瘤组织两面神激酶2(JAK2)、信号转导及转录活化因子(STAT3)的蛋白表达。结论:复方苦参注射液中的入血成分多为生物碱类成分,复方苦参注射液可能是通过JAK/STAT信号通路作用于肝癌。
Objective:To study the chemical components of Compound Kushen Injection in the serum of hepatocellular carcinoma mice, and to explore the mechanism of Compound Kushen Injection on hepatocarcinoma by network pharmacology, animal experiments, and serum pharmacochemistry. Methods:LC MS was used to determine the chemical constituents of alkaloids in the serum of Compound Kushen Injection treating mice.Based on the research strategy of network pharmacology,a hepatocarcinoma-target network and a pharmaceutical components-target network were constructed, then the two networks were merged into component-hepatocarcinoma target network. KEGG analysis was performed on the key targets in this network. Mice with transplanted H22 hepatocarcinoma were used to observe the effect of Compound Kushen Injection and Compound Kushen Injection combined with cyclophosphamide in the treatment of liver cancer. Results:A total of 10 alkaloid components in mice serum were identified, such as Cytisine,N-methylcytisine,kuraramine,Sophoridine,Sophocarpine,Matrine,Baptifoline,Oxysophocarpine,oxymatrine,5α and 9α-dihydroxymatrine Oxymatrine. The effect was related to multiple signaling pathways such as Wnt, Notch, JAK/STAT, PI3 K-Akt, and ERK. Compound Kushen Injection showed a tumor-inhibitory effect, while the tumor-inhibitory rate was improved when administered synergistically with cyclophosphamide, it also reduced JAK2 and STAT3 protein expression in tumor tissues. Conclusions:The main components of Compound Kushen Injection in serum were alkaloids,its hepatocellular carcinoma effect may be related to the JAK/STAT signaling pathway.
作者
海丽娜
王佳敏
赵婧
罗虹
王艳
王颖莉
Hai Lina;Wang Jiamin;Zhao Jing;Luo Hong;Wang Yan;Wang Yingli(Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871;Shanxi University of Traditional Chinese Medicine,Jinzhong 030619;Beijing Zhendong Guangming Pharmaceutical Research Institute Limited Company,Beijing 100085)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2020年第4期167-172,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
山西省科技攻关项目(编号:2016ZD0401)。
关键词
复方苦参注射液
血清化学成分
生物碱
网络药理学
肝癌
作用机制
实验验证
Compound Kushen Injection
Serum Chemical Components
Alkaloids
Network Pharmacology
Liver cancer
Mechanism
Experimental verification
