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

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

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;(4)GO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;(5)KEGG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。

BACKGROUND:Shenling Baizhu San is one of the representative prescriptions for strengthening the spleen and removing dampness,which has good antiinflammatory 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 OMINNCBI 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 andβ-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 PI3 K-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.