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1.400038 重庆,陆军军医大学(第三军医大学)第一附属医院药剂科
2.400042 重庆,陆军军医大学(第三军医大学)大坪医院药剂科
[夏培元,E-mail:peiyuan_xia2013@163.com XIA Peiyuan, E-mail:peiyuan_xia2013@163.com
收稿:2019-07-07,
修回:2019-08-13,
纸质出版:2019-11-30
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刘芳, 刘耀, 詹世鹏, 等. 基于网络药理学探讨藏药诃子治疗类风湿性关节炎的作用机制[J]. 第三军医大学学报, 2019,41(22):2238-2245.
Fang LIU, Yao LIU, Shipeng ZHAN, et al. Mechanism of Tibetan medicine
刘芳, 刘耀, 詹世鹏, 等. 基于网络药理学探讨藏药诃子治疗类风湿性关节炎的作用机制[J]. 第三军医大学学报, 2019,41(22):2238-2245. DOI: 10.16016/j.1000-5404.201907047.
Fang LIU, Yao LIU, Shipeng ZHAN, et al. Mechanism of Tibetan medicine
目的
2
运用网络药理学方法探讨藏药诃子治疗类风湿性关节炎(rheumatoid arthritis
RA)的活性成分-靶点及相关通路。
方法
2
利用中药系统药理学技术平台(TCMSP)查找诃子中的活性成分,利用反向分子对接服务器(DRAR-CPI)对活性成分的药理作用靶点进行预测,从美国国家生物技术信息中心(NCBI)数据库和Genecards数据库获取类风湿性关节炎的相关靶点基因;借助STRING平台构建靶蛋白相互作用网络,并通过生物学信息注释数据库(DAVID)对靶点基因本体(GO)生物过程及京都基因与基因组百科全书(KEGG)中的代谢通路进行分析,随后通过Cytoscape 3.6.1软件构建诃子活性成分-靶点-通路网络。
结果
2
通过TCMSP数据库和文献补充,从诃子中共筛选出10个活性成分,主要为酚酸类和生物碱两大类。经DRAR-CPI对接预测,共预测出47个RA靶点,其中TP53、PTGS2、TNF、IL-6、HSP90B等为关键靶点。GO富集分析和KEGG通路分析结果显示:诃子主要参与凋亡、炎症抑制以及免疫调节等生物过程,通过调控细胞凋亡和NLR、TLR、JAK-STAT和MAPK信号通路等为主的54条信号通路发挥多途径治疗RA的作用。
结论
2
诃子中的酚酸类成分(如鞣花酸)和生物碱成分(如玫瑰树碱)可能参与细胞凋亡、炎症、免疫调节等生物学过程,调控细胞凋亡通路和TLR、JAK-STAT和MAPK信号通路,发挥治疗RA的作用。
Objective
2
To investigate the mechanism of Tibetan herb
Terminalia chebula Retz
in the treatment of rheumatoid arthritis (RA) by using network pharmacology.
Methods
2
The active components and relative targets of
Terminalia chebula Retz
were searched by using TCMSP database; the potential targets were predicted by using DRAR-CPI platform; the relevant target genes for RA were obtained from NCBI database and Genecards database. Then the protein-protein interaction network was conducted by STRING platform
the enriched gene ontology (GO) and metabolic pathways of the Kyoto encyclopedia of genes and genomes (KEGG) were analyzed through the DAVID database. The active components-targets-pathway network was created by Cytoscape 3.6.1 software.
Results
2
According to the searching results of TCMSP database as well as literature supplement
10 active compounds were screen out as the main compounds of
Terminalia chebula Retz
. They are mainly phenolic acids and alkaloids. A total of 47 key targets including TP53
PTGS2
TNF
IL-6 and HSP90B had been predicted as
Terminalia chebula Retz
related RA targets; GO and KEGG analyses showed that active compounds of
Terminalia chebula Retz
may be involved in the processes of inflammation suppression
immune-modification and apoptosis
and regulate 54 relative KEGG pathways
such as apoptosis
NOD like receptor (NLR) signal pathway
Toll-like receptor (TRL) signal pathway
JAK-STAT signal pathway and
MAPK signal pathway in the treatment of RA.
Conclusion
2
Phenolic acids (such as ellagic acid) and alkaloids (such as ellipticine) isolated from
Terminalia chebula Retz
can treat RA by being involued in the processes of apoptosis
inflammation
and immune-modification
and through regulating apoptosis pathway
NLR signal pathway
TLR signal pathway
JAK-STAT signal pathway and MAPK signal pathway.
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