中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (5): 772-778.doi: 10.3969/j.issn.2095-4344.3014

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    下一篇

丹参干预骨质疏松症:网络药理学解释的作用机制

肖方骏1,陈树东2,栾继耀1,侯  宇2,何  坤1,林定坤2   

  1. 1广州中医药大学第二临床医学院,广东省广州市   510006;2广州中医药大学第二附属医院/广东省中医院,广东省广州市   510120
  • 收稿日期:2020-02-10 修回日期:2020-02-18 接受日期:2020-03-18 出版日期:2021-02-18 发布日期:2020-12-01
  • 通讯作者: 林定坤,博士生导师,主任医师,广州中医药大学第二附属医院/广东省中医院,广东省广州市 510120
  • 作者简介:肖方骏,男,1994年生,湖南省永州市人,汉族,广州中医药大学第二临床医学院在读硕士,医师,主要从事脊柱骨科方向的研究。

An insight into the mechanism of Salvia miltiorrhiza intervention on osteoporosis based on network pharmacology

Xiao Fangjun1, Chen Shudong2, Luan Jiyao1, Hou Yu2, He Kun1, Lin Dingkun2   

  1. 1Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China; 2Second Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
  • Received:2020-02-10 Revised:2020-02-18 Accepted:2020-03-18 Online:2021-02-18 Published:2020-12-01
  • Contact: Lin Dingkun, Doctoral supervisor, Chief physician, Second Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
  • About author:Xiao Fangjun, Master candidate, Physician, Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China

摘要:

文题释义:
丹参:是唇形科植物丹参的干燥根及根茎,味苦性微寒,归心、肝经,具有活血祛瘀、通经止痛、清心除烦,凉血消痈的作用,为祛瘀要药,近年来被广泛地应用于骨质疏松症的治疗。
网络药理学:是基于系统生物学和多项药理学的理论,对生物系统网络进行整体分析,预测及阐明药物在人体的作用机制,探索药物、靶点、疾病之间相关性的一门新兴学科。

背景:丹参近年来被广泛地应用于骨质疏松症的治疗,但其在人体的作用机制尚不明确。
目的:通过网络药理学的方法,筛选中药丹参中主要活性成分及其相应靶点,构建中药活性成分-作用靶点-疾病网络,探究丹参治疗骨质疏松症的作用机制。
方法:首先,在中药系统药理学数据库和分析平台(TCMSP)中基于药代动力学特征筛选出丹参的主要活性成分及其相关作用靶标,然后从人类孟德尔遗传数据库(OMIM)和GeneCards数据库,筛选出骨质疏松症已知的治疗靶标,将丹参靶标和骨质疏松症靶标取交集,得到中药-疾病共同靶标,并利用Cytoscape软件拓扑出中药-活性成分-靶标-疾病调控网络,利用String数据库构建中药-疾病靶标的蛋白互作网络(PPI)和条形图,筛选核心靶标。最后对中药-疾病靶标进行GO功能富集分析和KEGG通路富集分析。
结果与结论:筛选得到丹参的活性成分65个、相关靶标932个、疾病靶标3 264个,中药-疾病共同作用靶标74个。通过网络药理学方法发现,丹参治疗骨质疏松症的潜在有效成分主要包扩木犀草素、丹参酮IIa、隐丹参酮等,这些成分可通过激活AKT1、白细胞介素6、血管内皮生长因子A、MAPK1等靶标蛋白,活化PI3K-Akt 信号通路、白细胞介素17信号通路、低氧诱导因子1信号通路、糖尿病并发症中的AGE-RAGE信号通路等通路直接或间接参与细胞分化和凋亡、代谢、氧化应激、炎症反应等途径发挥治疗骨质疏松症的作用,进一步证实了丹参可多成分、多靶标、多系统地作用于骨质疏松症,但上述结论及具体作用调节机制仍需进一步研究来验证。
https://orcid.org/0000-0002-3945-5526 (肖方骏) 

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 丹参, 骨质疏松症, 网络药理学, 作用机制

Abstract: BACKGROUND: Salvia miltiorrhiza has been widely used in the treatment of osteoporosis in recent years, but its mechanism in human body is not clear.
OBJECTIVE: To screen the main active components of Salvia miltiorrhiza and their corresponding targets by the method of network pharmacology, to construct the active components-action target-disease network of traditional Chinese medicine, and to explore the mechanism of Salvia miltiorrhiza in the treatment of osteoporosis. 
METHODS: Firstly, the main active components and related targets of Salvia miltiorrhiza were selected based on the characteristics of pharmacokinetics in the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and then the known therapeutic targets of osteoporosis were screened from the Online Mendelian Inheritance in Man (OMIM) and GeneCards database. The Salvia miltiorrhiza target and osteoporosis target were intersected to obtain the common target of traditional Chinese medicine and disease. The traditional Chinese medicine-active ingredient-target-disease regulation network was topologically constructed by using Cytoscape software, and the protein-protein interaction network and bar graph of traditional Chinese medicine-disease target were constructed by using String database to screen the core targets. Finally, the traditional Chinese medicine-disease target was analyzed by GO functional enrichment analysis and KEGG pathway enrichment analysis.
RESULTS AND CONCLUSION: A total of 65 active ingredients of Salvia miltiorrhiza, 932 related targets, 3 264 disease targets, and 74 Chinese medicine-disease interaction targets were obtained through screening. The analysis based on network pharmacology indicated that the potential active ingredients of Salvia miltiorrhiza in treating osteoporosis mainly include luteolin, tanshinone IIa, cryptotanshinone, etc. These components can activate target proteins such as AKT1, interleukin-6, vascular endothelial growth factor A, and MAPK1 to activate PI3K-Akt, interleukin-17, hypoxia-inducible factor-1, AGE-RAGE signaling pathway in diabetic complications. These activated signaling pathways can directly or indirectly participate in cell differentiation and apoptosis, metabolism, oxidative stress, and inflammatory response in the treatment of osteoporosis. The role of Salvia miltiorrhiza can be further confirmed by its multi-component, multi-target, and multi-system effects on osteoporosis. However, the above conclusions and specific mechanism of action need to be further studied.

Key words: Salvia miltiorrhiza, osteoporosis, network pharmacology, action mechanism

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