摘要
目的:以补骨脂-三七药对为例,从整合药理学角度探索补肾活血法治疗骨质疏松症的作用机制。方法:基于整合药理学平台(TCMIP),收集补骨脂、三七的化学成分信息,以"osteoporosis"作为疾病关键词,得到骨质疏松症全部靶标。通过TCMIP的蛋白质-蛋白质相互作用信息(PPI)数据库,获得补骨脂-三七作用靶标与骨质疏松疾病靶标之间的PPI,构建药对与疾病间的关键靶标网络,基于基因本体和京都基因与基因组百科全书数据库,确定靶标基因、蛋白质分子功能、细胞内定位及其所参与的生物学反应和通路。结果:两药共有靶标34个;作用机制可能与Smad蛋白磷酸化,Smad蛋白导入细胞核和维生素D应答元件结合等生物过程有关;并与破骨细胞分化、氧化磷酸化、过氧化物酶体增殖物激活受体信号通路、内分泌和其他因子调节钙重吸收等生物途径有关。结论:补骨脂-三七药对参与Smad蛋白调控及其信号转导过程,可为补肾活血制剂参与调控Smad蛋白,进而影响Runt相关转录因子2等转录因子、胞外信号调节激酶等信号通路,实现防治骨质疏松症提供一定思路。
Objective: Taking couplet medicines of Psoraleae Fructus and Notoginseng Radix et Rhizoma as an example,the mechanism of tonifying kidney and promoting blood circulation in treatment of osteoporosis was explored from the perspective of integrated pharmacology. Method: Based on the Integrated Pharmacology Platform( TCMIP),the chemical constituents of Psoraleae Fructus and Notoginseng Radix et Rhizoma were collected,and all targets of osteoporosis were obtained by taking "osteoporosis"as a key word of disease. Through the proteinprotein interaction( PPI) database in TCMIP,the PPI between the targets of Psoraleae Fructus-Notoginseng Radix et Rhizoma and the targets of osteoporosis was obtained,a key target network between drug pairs and diseases was established,and the target genes, protein molecular function, intracellular localization, and the biological reactions and pathways were determined based on gene ontology( GO) and Kyoto Encyclopedia of Genes and Genomes( KEGG) database. Result: Psoraleae Fructus and Notoginseng Radix et Rhizoma had a total of 34 targets. The mechanism may be related to biological processes, such as phosphorylation of Smad protein,introduction of Smad protein into the nucleus,vitamin D reaction element binding,etc; and it was associated with osteoclast differentiation,oxidative phosphorylation,peroxisome proliferator-activated receptor signaling pathway,endocrine and other factors regulating calcium resorption and other biological pathways. Conclusion: Psoraleae Fructus and Notoginseng Radix et Rhizoma can participate in the regulation of Smad protein and its signal transduction process. It can provide some ideas for tonifying kidney and promoting blood circulation preparations to achieve the prevention and treatment of osteoporosis by regulating the Smad protein,thereby affecting Runt related transcription factor 2 and other transcription factors, and extracellular signal-regulated kinase and other signal pathways.
作者
章轶立
魏戌
谢雁鸣
唐彬
姜俊杰
申浩
支英杰
ZHANG Yi-li;WEI Xu;XIE Yan-ming;TANG Bin;JIANG Jun-jie;SHEN Hao;ZHI Ying-jie(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China;Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China;Changxindian Community Health Service Center,Beijing 100072,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第21期163-169,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金青年基金项目(81704102,81603517)
中华中医药学会(2017—2019年度)青年人才托举工程项目(CACM-2017-QNRC2-A03)
关键词
整合药理学
补骨脂
三七
骨质疏松症
靶点
信号通路
基因本体
integrated pharmacology
Psoraleae Fructus
Notoginseng Radix et Rhizoma
osteoporosis
targets
signal pathway
gene ontology