| 摘要: |
| 目的：基于网络药理学结合分子对接技术系统分析消痛散外用治疗膝骨关节炎（knee osteoarthritis，KOA）的作用机制。方法：检索数据库并筛选消痛散的活性成分，结合外用药物经皮渗透、局部起效特点，以皮肤渗透系数（Log Kp）为关键指标进一步筛选；收集KOA疾病靶点，与药物靶点取交集，获得潜在治疗靶点；构建中药-成分-靶点网络、蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络，筛选核心靶点；进行基因本体（gene ontology， GO）功能注释和京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes， KEGG）通路富集分析；采用AutoDock Vina软件对核心成分与核心靶点进行分子对接验证。结果：共筛选得到消痛散有效成分85种，核心成分为槲皮素、鞣花酸、山柰酚、杨梅素、芹菜素等；消痛散治疗KOA的核心靶点包括肿瘤坏死因子（tumor necrosis factor，TNF）、 AKT丝氨酸/苏氨酸激酶1（AKT serine/threonine kinase 1，AKT1）、表皮生长因子受体（epidermal growth factor receptor，EGFR）、Src酪氨酸蛋白激酶（Src tyrosine kinase，SRC）、基质金属蛋白酶9（matrix metallopeptidase 9，MMP9）等；GO功能富集分析涉及细胞应答、炎症反应等生物过程，KEGG通路富集分析显示涉及磷脂酰肌醇3激酶/蛋白激酶B （phosphatidylinositol 3-kinase/protein kinase B，PI3K-Akt）、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）、Ras信号通路等多条通路；分子对接结果显示，核心成分与核心靶点结合活性良好。结论：消痛散可通过多成分、多靶点、多通路发挥治疗KOA的作用，其机制可能与抑制炎症因子表达、调控PI3K-Akt及MAPK等信号通路以改善炎症反应和软骨代谢相关。 |
| 关键词: 膝骨关节炎 消痛散 外用制剂 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of Xiaotong powder in treatment of knee osteoarthritis: A study based on network pharmacology and molecular docking |
| BI Huaizhong,ZHANG Hanwen,BAI Liqun |
| (Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China) |
| Abstract: |
| Objective: To investigate the mechanism of action of the external application of Xiaotong powder in the treatment of knee osteoarthritis （KOA） based on network pharmacology and molecular docking. Methods: The active components of Xiaotong powder were obtained and further screened based on the features of transdermal permeation and local effect and the key indicator of skin permeability coefficient （Log Kp）. The disease targets of KOA were obtained and intersected with the targets of Xiaotong powder to obtain potential therapeutic targets. A traditional Chinese medicine （TCM）-component-target network and a protein-protein interaction network were constructed to identify core targets. The gene ontology （GO） functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed, and AutoDock Vina was used to perform molecular docking between core components and core targets. Results: A total of 85 active components were obtained for Xiaotong powder, with the core components of quercetin, ellagic acid, kaempferol, myricetin, and apigenin, and the core targets of Xiaotong powder in the treatment of KOA included tumor necrosis factor, AKT serine/threonine kinase 1, epidermal growth factor receptor, src tyrosine kinase, and matrix metallopeptidase 9. The GO functional enrichment analysis involved the biological processes such as cell response and inflammatory response, and the KEGG pathway enrichment analysis involved multiple pathways such as the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway, the mitogen-activated protein kinase （MAPK） signaling pathway, and the Ras signaling pathway. Molecular docking showed good binding activities between the core components and the core targets. Conclusion: Xiaotong powder exerts a therapeutic effect on KOA through multiple components, targets, and pathways, possibly by inhibiting the expression of inflammatory factors and regulating the signaling pathways including PI3K-Akt and MAPK to improve inflammatory response and cartilage metabolism. |
| Key words: knee osteoarthritis Xiaotong powder external preparation network pharmacology molecular docking |
