| 右归丸抗骨质疏松症的中药化合物及靶点网络药理学作用机制 |
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投稿时间：2019-08-19
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| 作者 | Author | 单位 | Address | E-Mail |
| 李敏 |
LI Min |
浙江中医药大学附属第二医院全科医学科, 浙江 杭州 310005 |
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| 史晓林 |
SHI Xiao-lin |
浙江中医药大学附属第二医院骨伤科, 浙江 杭州 310005 |
Department of Orthopaedics, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China |
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| 许超 |
XU Chao |
浙江中医药大学附属第二医院骨伤科, 浙江 杭州 310005 |
Department of Orthopaedics, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China |
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| 吴连国 |
WU Lian-guo |
浙江中医药大学附属第二医院骨伤科, 浙江 杭州 310005 |
Department of Orthopaedics, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China |
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| 何滨 |
HE Bin |
浙江中医药大学附属第二医院骨伤科, 浙江 杭州 310005 |
Department of Orthopaedics, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China |
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| 李琰华 |
LI Yan-hua |
浙江中医药大学附属第二医院全科医学科, 浙江 杭州 310005 |
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| 梁博程 |
LIANG Bo-cheng |
浙江中医药大学附属第二医院骨伤科, 浙江 杭州 310005 |
Department of Orthopaedics, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China |
lbocheng@163.com |
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| 期刊信息：《中国骨伤》2020年，第33卷，第10期，第933-937页 |
| DOI：10.12200/j.issn.1003-0034.2020.10.009 |
| 基金项目:国家自然科学基金青年科学基金项目（编号：81803902）；浙江省中医药科学研究基金计划（编号：2019ZQ026，2016ZA102）；浙江中医药大学科研基金（编号：2018ZD05） |
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中文摘要:
目的：基于中药网络药理学分析右归丸抗骨质疏松症的中药化合物、靶点及其作用机制。
方法：通过中药综合数据库（traditional Chinese medicine integrated database，TCMID）检索右归丸中已知有效化合物；使用中医药分子机制生物信息学分析工具（bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine，BATMAN-TCM）预测各中药化合物的作用靶点；使用DisGeNET和人工文献阅读的方式获取骨质疏松症和骨重建相关靶点；采用Cytoscape 3.7.1软件及其插件BiNGO和ClueGO对相关靶点进行GO基因注释和信号通路的富集分析；并采用课题组基于血清蛋白质组学建立的绝经后骨质疏松症疾病模型中的87个差异表达蛋白对右归丸所有预测靶点进行验证。
结果：在右归丸10味中药中，共检索到392个化合物，分别是君药（附子、肉桂和鹿角胶）83个，臣药（熟地黄、山茱萸、枸杞和山药）127个，佐药（菟丝子、杜仲和当归）182个。其中君药与臣药含有4个相同化合物，君药与佐药含有1个相同化合物，臣药与佐药14个含有相同化合物；共鉴定到2 112个可信靶点，其中君药775个，臣药共1 483个，佐药共1 491个；共筛选出右归丸抗骨质疏松症的靶点227个，主要参与代谢过程、细胞分化和生物学过程调控等20种生物学过程，数据挖掘发现涉及骨重建、骨矿化等的生物学行为；细胞作用位点分布主要包含9种细胞组成；主要具有13种分子功能；KEGG代谢通路富集分析显示，共137个信号通路被显著富集，其中，经典破骨细胞分化信号通路和与绝经后骨质疏松症的密切相关的雌激素调控信号通路在27个信号通路功能组中广泛分布；靶点验证，共筛选出FGA、AGT、P4HB、RAB7A、APOE和DKK3共6个靶点。
结论：（1）初步阐释和明确了右归丸多靶点、多系统相互协同治疗骨质疏松症的特点。（2）右归丸中附子、肉桂、山茱萸、山药、枸杞子、杜仲和当归所含36种化合物靶向FGA、AGT、APOE、DKK3、P4HB和RAB7A共6个靶点发挥抗绝经后骨质疏松症作用。 |
| 【关键词】骨质疏松 中药药理学 中草药 |
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| Mechanism action of Chinese herbal compound and target network pharmacology of Yougui(YG) pill for the treatment of osteoporosis |
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ABSTRACT
Objective: To explore compounds,targets and mechanism of Yougui (YG) pill in treating osteoporosis based on systemic pharmacology of traditional Chinese medicine.
Methods: The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiNGO and ClueGO were used to enrich the GO annotation and pathways of the related targets,and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data.
Results: Totally 392 compounds were retrieved from YG pill,including 83 sovereign drugs(monkshood,cinnamon,deerhorn gelatin),127 ministerial drugs(prepared rehmannia root,dogwood,wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis,eucommia ulmoides and Chinese angelica). Among them,there were 4 same compounds between sovereign drug and ministerial drug,1 same compound between sovereign drug and supplementary drug,and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified,included 775 sovereign drugs,1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis,which participate in nearly 20 process of metabolic process,cell differentiation and biology,and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them,classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Six targets were screened by target validation,such as AGT,FGA,APOE,DKK3,P4HB and RAB7A.
Conclusion: The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified,which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds,and their main action targets include FGA,AGT,APOE,DKK3,P4HB and RAB7A. |
| KEY WORDS Osteoporosis Pharmacology Drugs,Chinese herbal |
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| 引用本文，请按以下格式著录参考文献： |
| 中文格式: | 李敏,史晓林,许超,吴连国,何滨,李琰华,梁博程.右归丸抗骨质疏松症的中药化合物及靶点网络药理学作用机制[J].中国骨伤,2020,33(10):933~937 |
| 英文格式: | LI Min,SHI Xiao-lin,XU Chao,WU Lian-guo,HE Bin,LI Yan-hua,LIANG Bo-cheng.Mechanism action of Chinese herbal compound and target network pharmacology of Yougui(YG) pill for the treatment of osteoporosis[J].zhongguo gu shang / China J Orthop Trauma ,2020,33(10):933~937 |
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