中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (2): 197-204.doi: 10.12307/2022.033

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

参苓白术散治疗膝骨关节炎作用机制的网络药理学和分子对接技术分析

李安安1,姜  涛2,詹  敏3,蔡宇宁2,宋  敏1,李聪聪1,林文政2,张家媛1,刘文刚2   

  1. 1广州中医药大学,广东省广州市    510405;2广东省第二中医院,广东省广州市    510095;3南方医科大学南方医院,广东省广州市    510515
  • 收稿日期:2020-11-13 修回日期:2020-11-17 接受日期:2021-01-07 出版日期:2022-01-18 发布日期:2021-10-27
  • 通讯作者: 刘文刚,博士,主任中医师,硕士生导师,广东省第二中医院,广东省广州市 510095
  • 作者简介:李安安,男,1996年生,广州中医药大学在读硕士,主要从事中医药治疗骨关节病的研究。
  • 基金资助:
    广东省中医药管理局科研项目(20191021);广东省医学科学技术研究基金项目(A2020071)

Pharmacological mechanism of Shenling Baizhu San in the treatment of knee osteoarthritis based on network pharmacology and molecular docking

Li Anan1, Jiang Tao2, Zhan Min3, Cai Yuning2, Song Min1, Li Congcong1, Lin Wenzheng2, Zhang Jiayuan1, Liu Wengang2   

  1. 1Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 2Guangdong Second Hospital of Traditional Chinese Medicine, Guangzhou 510095, Guangdong Province, China; 3Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong Province, China
  • Received:2020-11-13 Revised:2020-11-17 Accepted:2021-01-07 Online:2022-01-18 Published:2021-10-27
  • Contact: Liu Wengang, MD, Chief physician, Master’s supervisor, Guangdong Second Hospital of Traditional Chinese Medicine, Guangzhou 510095, Guangdong Province, China
  • About author:Li Anan, Master candidate, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    the Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine, No. 20191021; Guangdong Medical Science and Technology Research Fund, No. A2020071

摘要:

文题释义:
膝骨关节炎:是一种好发于中老年人的慢性骨关节退行性疾病,主要临床表现为疼痛、功能障碍,严重者可出现关节畸形肿胀,严重影响患者日常生活。此病属中医“膝痹病”范畴,为中医骨伤科治疗的优势病种。
网络药理学:是一种基于系统生物学理论,利用大数据进行网络分析,选取疾病靶点基因与中药复方活性成分,进行多靶点药物分子设计的新学科。通过强调对信号通路的多途径调节,可提高药物的治疗效果,降低毒副反应,从而提高新药临床试验的成功率,节省药物的研发费用。
背景:参苓白术散是健脾祛湿的代表方之一,具有良好的抗炎及免疫调节效应。近年来课题组在临床实践中发现对早、中期膝骨关节炎患者使用参苓白术散疗效颇丰,但具体的分子机制尚不明确。
目的:通过网络药理学和分子对接探究参苓白术散治疗膝骨关节炎的药理学机制。
方法:使用TCMSP和TCMID数据库搜集参苓白术散活性成分及其作用靶点,使用GenneCards和OMIN-NCBI数据库获取膝骨关节炎靶点,使用STRING与Cytoscape构建药物-活性化学成分-核心靶标网络与PPI蛋白网络互作分析,并进行GO及KEGG分析,使用AutoDockTools将重要活性成分与核心靶点进行分子对接预测。
结果与结论:①共筛选出参苓白术散活性药物化学成分109个,主要成分包含木犀草素、山奈酚和β-谷甾醇等;②其中与疾病交集靶点97个,核心靶点为PTGS2,CASP3,AKT1,MAPK1,MAPK8,TP53和EGFR等;③分子对接结果可见,山奈酚及β-谷甾醇可靶向调控CASP3,AKT1,PTGS2;④GO分析得出苓白术散治疗膝骨关节炎的机制中主要涉及氧化应激、脂多糖、营养水平、肌肉细胞增殖及氧水平等生物过程;⑤KEGG分析结果显示,PI3K-Akt、肿瘤坏死因子、白细胞介素17和Th17细胞通路为苓白术散治疗膝骨关节炎的主要的信号通路;⑥上述结果证实,参苓白术散中木犀草素、山奈酚及β-谷甾醇等活性成分可通过抑制炎症、调控凋亡及降低氧化应激等作用治疗膝骨关节炎。

https://orcid.org/0000-0002-8887-8429 (刘文刚) 

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: 参苓白术散, 膝骨关节炎, 网络药理学, 分子对接, 信号通路, 炎症, 凋亡, 氧化应激

Abstract: BACKGROUND: Shenling Baizhu San is one of the representative prescriptions for strengthening the spleen and removing dampness, which has good anti-inflammatory and immunomodulatory effects. In recent years, we have found positive effect of Shenling Baizhu San in patients with early and mid-stage knee osteoarthritis in clinical practice, but the specific molecular mechanism is still unclear.
OBJECTIVE: To explore the pharmacological mechanism of Shenling Baizhu San in the treatment of knee osteoarthritis through network pharmacology and molecular docking. 
METHODS: The TCMSP and TCMID databases were used to collect the active ingredients and their targets of Shenling Baizhu San. The GenneCards and OMIN-NCBI databases were used to obtain the KOA targets. STRING and Cytoscape were used to construct the drug-active chemical ingredient-core target network and the protein-protein interaction (PPI) analysis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. AutoDockTools was used to predict molecular docking between important active ingredients and core targets. 
RESULTS AND CONCLUSION: A total of 109 active pharmaceutical chemical components of Shenling Baizhu San were screened, and the important components included luteolin, kaempferol, β-sitosterol, etc. Among them, there were 97 intersecting targets with diseases, and the core targets were PTGS2, CASP3, AKT1, MAPK1, MAPK8, TP53, EGFR, etc. The results of molecular docking showed that kaempferol and β-sitosterol could target and regulate CASP3, AKT1, and PTGS2. GO analysis showed that the mechanism mainly involved biological processes such as oxidative stress, lipopolysaccharide, nutritional level, muscle cell proliferation, oxygen level, etc. The results of KEGG analysis showed that PI3K-Akt, tumor necrosis factor, interleukin-17 and Th17 cell pathways were the main signaling pathways. In summary, Luteolin, kaempferol, β-sitosterol, and other active ingredients in Shenling Baizhu San can treat knee osteoarthritis by inhibiting inflammation, regulating apoptosis, and reducing oxidative stress. 

Key words: Shenling Baizhu San, knee osteoarthritis, network pharmacology, molecular docking, signaling pathway, inflammation, apoptosis, oxidative stress

中图分类号: