木豆叶治疗激素性股骨头坏死作用机制的网络药理学探讨  

A study on the action mechanism of folium cajani on steroid-induced osteonecrosis of femoral head based on network pharmacology

作　　者：王凌汉卿 李可大[1] WANG Linghanqing

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《中医临床研究》2022年第1期32-37,共6页Clinical Journal Of Chinese Medicine

基　　金：辽宁省科学事业公益研究基金项目(2014001010)。

摘　　要：明确木豆叶的活性成分,探讨木豆叶延缓股骨头坏死的作用机制。方法:首先借助Pub Med数据库、Web of Science数据库、CNKI数据库、万方数据库、Swiss Adme对木豆叶的有效成分进行筛选,借助Swiss Target Prediction预测其靶点,与Gene Cards数据库、OMIM数据库中的疾病相关靶点对比。构建"药物-活性成分-潜在靶点"网络图。再通过STRING数据库构建蛋白质-蛋白质相互作用网络,运用Cyto NCA软件对核心靶点进行拓扑分析。使用R语言对核心靶点进行基因本体论(GO)富集分析与京都基因与基因组百科全书(KEGG)通路富集分析。探讨木豆叶治疗激素性股骨头坏死的作用机制。结果:共筛选出13个木豆叶活性成分,149个与激素性股骨头坏死相关的靶点,其中重要成分包括球松素、红车轴草素、芹菜素、染料木素、芒柄花苷、木犀草素、木豆素等;核心靶点包括磷脂酰肌醇-3-激酶催化亚基α(Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha,PIK3CA)、磷酸肌醇3激酶,调控亚基1(Phosphoinositide-3-Kinase Regulatory Subunit 1,PIK3R1)、肉瘤基因(Sarcoma,SRC)、信号转导因子和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、丝裂原活化蛋白激酶1(Mitogen-Activated Protein Kinase 1,MAPK1)、丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、淀粉状蛋白β(A4)前体蛋白(Amyloid Beta Precursor Protein,APP)、丝裂原活化蛋白激酶8(Mitogen-Activated Protein Kinase 8,MAPK8)、Janus激酶2(Janus Kinase 2,JAK2)、凝血因子II(Coagulation Factor II, Thrombin,F2)、雌激素受体1(Estrogen Receptor 1,ESR1)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)等;GO富集分析得到64个细胞组分(CC)、177个分子功能(MF)以及2 202个生物过程(BP);KEGG通路主要富集在磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、脂质和动脉粥样硬化信号通路、晚期Objective: To identify the active components of folium cajani, and explore the action mechanism of folium cajani in delaying femoral head necrosis. Methods: The active components of the folium cajani were screened in PubMed, Web of Science, CNKI,Wanfang data, and Swiss Adme databases. The targets were predicted by Swiss Target Prediction, and were compared to disease-related targets in GeneCards and OMIM databases. The network diagram of “drug-active component-potential target” was constructed. Then,a PPI network was constructed by STRING database, and a topology analysis of core targets was carried out by CytoNCA software. The GO enrichment analysis and KEGG pathway enrichment analysis of the core targets was carried out by the R programming language software. The action mechanism of folium cajani on steroid-induced necrosis of femoral head was investigated. Results: A total of 13 active components and 149 targets related to steroid-induced osteonecrosis of femoral head were identified from folium cajani, among which the important components included pinostrobin, pratensein, apigenin, genistein, ononin, luteolin, cajaninstilbene acid and so on.The core targets included PIK3 CA, PIK3 R1, SRC, STAT3, MAPK1, AKT1, APP, MAPK8, JAK2, F2, ESR1, EGFR and so on. The GO enrichment analysis revealed 64 CC, 177 MF and 2 202 BP. The KEGG pathways mainly enriched in PI3 K/Akt signaling pathway, lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway, insulin resistance signaling pathway, endocrine resistance pathway,and growth hormone synthesis, secretion and action pathway, etc.. Conclusion: Folium cajani may prevent steroid-induced osteonecrosis of femoral head by inhibiting oxidative stress injury, regulating lipid metabolism, improving microcirculation, and regulating inflammatory related factors, which provides new ideas and clues for future medication experiments of folium cajani.

关 键 词：激素性股骨头坏死 网络药理学 木豆叶 中药作用机制 

分 类 号：R274.9[医药卫生—中西医结合]