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基于“成分-靶点-通路”网络模式探讨淫羊藿治疗骨性关节炎的分子机制
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| 篇名： | 基于“成分-靶点-通路”网络模式探讨淫羊藿治疗骨性关节炎的分子机制 |
| TITLE： | |
| 摘要： | 目的：基于“成分-靶点-通路”网络模式探讨淫羊藿治疗骨性关节炎可能的分子机制。方法：通过中药系统药理学数据库和分析平台，筛选和预测淫羊藿可能的入血活性成分[以药物动力学参数中的口服药物生物利用度（OB）≥30％和类药性（DL）≥0.18进行筛选]和靶点，挖掘疾病相关数据库中骨性关节炎的作用靶点，采用拓扑分析工具筛选淫羊藿治疗骨性关节炎的关键靶点，采用ClueGo插件分析其可能的分子机制。结果：检索出淫羊藿相关成分130个，根据OB和DL值筛选出23个活性成分，同时预测出102个可能的作用靶点，构建了“入血活性成分-疾病靶点”相互关系网络图；通过疾病相关数据库检索出168个骨性关节炎相关靶点，拓扑分析筛选出185个关键节点；ClueGo分析结果显示，淫羊藿作用于骨性关节炎的关键节点涉及的信号通路主要被富集在细胞周期、炎症及癌症相关等68条信号通路中；其可能的控制疾病进展的作用机制不仅包括直接参与软骨细胞的增殖、凋亡及分化，调节骨代谢平衡，还可以通过调节炎症、免疫等干预和影响骨与软骨微环境。结论：淫羊藿治疗骨性关节炎具有多系统、多成分、多靶点的特点；预测、筛选出的机制与目前治疗骨性关节炎的作用机制相符合。 |
| ABSTRACT： | OBJECTIVE： To investigate the potential molecular mechanism of Epimedium brevicornu in the treatment of osteoarthritis based on “ingredient-target-pathway” network mode. METHODS： The potential active components in blood [pharmacokinetic parameters as oral drug bioavailability （OB）≥30％ and drug-likeness （DL）≥0.18] and target spots of E. brevicornu were screened and predicted by TCM system pharmacology database and analysis platform. The target spots of osteoarthritis were excavated from disease-related database， and key target spots of E. brevicornu in the treatment of osteoarthritis were screened by Topology analysis. The potential molecular mechanism of it was analyzed by using ClueGo analysis. RESULTS： A total of 130 corresponding compounds of E. brevicornu were retrieved in the study； 23 active compounds were screened according to OB and DL value， which predicted 102 potential target spots， the relationship networks of “the active components in blood-disease target” was structured. A total of 168 targets spots related to osteoarthritis were retrieved from disease-related database， and 185 key nodes were screened out by topological analysis. ClueGo analysis showed that signaling pathways involved in the action of E. brevicornu on osteoarthritis were mainly enriched in 68 signaling pathways such as cell cycle， inflammation and cancer related signaling pathways. The potential mechanism is that control the progress of disease to participate in the proliferation， apoptosis and differentiation of cartilage cells directly， regulate bone metabolism balance， and regulate the inflammation system， immune system and etc. to interfere with and influence bone and cartilage microenvironment. CONCLUSIONS： For osteoarthritis， E. brevicornu has the characteristics of multiple systems， multiple targets and multiple components. It is consistent with the current mechanism of osteoarthritis treatment. |
| 期刊： | 2018年第29卷第15期 |
| 作者： | 骆帝，许波，李刚，梁学振，盖帅帅，李嘉程，阎博昭，夏聪敏 |
| AUTHORS： | LUO Di，XU Bo，LI Gang，LIANG Xuezhen，GAI Shuaishuai，LI Jiacheng，YAN Bozhao，XIA Congmin |
| 关键字： | 淫羊藿；骨性关节炎；网络药理学；靶点；分子机制；信号通路 |
| KEYWORDS： | Epimedium brevicornu； Osteoarthritis； Network pharmacology； Target spot； Molecular mechanisms； Signaling pathway |
| 阅读数： | 1036 次 |
| 本月下载数： | 10 次 |
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