| 乐纯琰,杨国蓉,傅杭杰,高天问,丁滨,季巾君.基于网络药理学预测芹菜素治疗系统性红斑狼疮的机制[J].浙江中西医结合杂志,2022,32(6): |
| 基于网络药理学预测芹菜素治疗系统性红斑狼疮的机制 |
| Network pharmacology-based prediction of potential mechanisms of apigenin for application on systemic lupus erythematosus treatment |
| 投稿时间：2021-10-31 修订日期：2022-04-18 |
| DOI： |
| 中文关键词: 网络药理学 芹菜素 系统性红斑狼疮 作用机制 |
| 英文关键词:Network pharmacology Apigenin Systemic lupus erythematosus Mechanism |
| 基金项目: |
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| 中文摘要: |
| 摘 要 目的 以积雪草为组分的解毒祛瘀滋阴方治疗系统性红斑狼疮（Systemic lupus erythematosus, SLE）的疗效已经在临床得到证实，但有关核心靶点和潜在机制尚不清楚。前期研究表明积雪草中的芹菜素可能在治疗SLE中发挥作用。本研究通过网络药理学预测芹菜素治疗SLE的潜在靶点以及涉及的信号通路。方法 通过SwissTargetPrediction 及Pharm Mapper数据库预测芹菜素的潜在靶点，用OMIM、GeneCards、DrugBank和PharmGKB等数据库收集SLE疾病相关靶点。从STRING数据库获取蛋白质-蛋白质相互作用关系，并运用Cytoscape 3.8.2软件绘制芹菜素-SLE的蛋白互作关系图（PPI），并筛选核心靶点。基于DAVID数据库和Bioconductor生物信息软件包对共同靶点进行GO功能和KEGG通路富集分析。通过双荧光素酶报告基因实验验证芹菜素对所筛选通路的调控作用。结果 共筛选出芹菜素潜在靶点77个，SLE相关靶点1016个，芹菜素-SLE共同靶点共21个，其中核心靶点3个：ALB、HSP90AA1、ESR1；GO分析结果包括37条生物学功能、12条细胞组成过程和26条分子功能过程；KEGG通路分析显示与12条通路相关，主要涉及雌激素信号通路（Estrogen signaling pathway）、NF-κB信号通路（NF-κB signaling pathway）、精氨酸和脯氨酸代谢通路（Arginine and proline metabolism）等经典通路。双荧光素酶报告基因实验结果显示芹菜素可抑制ERα、ERβ和NF-κB的转录。结论 网络药理学的研究结果提示芹菜素治疗SLE有多靶点，多途径的特点，可以通过调控雌激素信号通路和NF-κB信号通路，从而抑制下游基因及炎症因子的表达，改善SLE。 |
| 英文摘要: |
| ABSTRACT Objective The clinical effect of Jieduquyuziyin Prescription (JP), with Centella asiatica (L.) Urban. (CA) as one composition, application on systemic lupus erythematosus (SLE) treatment has been demonstrated previously. However, the key targets and the potential mechanism are still unclear. The publications indicated that the apigenin in CA maybe one of functional ingredients. In this study, the key targets and potential mechanism of apigenin on SLE treatment have been predicted with network pharmacology methods. Methods The SwissTargetPrediction and Pharm Mapper databases were applied to predict potential targets. And the SLE disease-related targets were collected by screening databases, OMIM, GeneCards, DrugBank and PharmGKB. The protein-protein interaction relationship was obtained by using of the STRING database, and shown as protein interaction diagram (PPI) with Cytoscape 3.8.2 software. The GO function and KEGG pathway enrichment analysis of the targets were performed based on the DAVID database and Bioconductor bioinformatics software package. The dual luciferase reporter gene experiment was engaged to verify the regulatory effect of apigenin on the selected pathways. Results A total of 77 potential targets of apigenin and 1016 SLE-related targets were collected; 21 proteins should be the targets of ingredients-disease, of which the top 3 key molecular, ALB, HSP90AA1, ESR1, were selected with PPI analysis; 37 biological functions, 12 cell composition processes and 26 molecular functional processes were significantly focused with GO analysis; and the KEGG pathway analysis showed that 12 signaling pathways may be involved, such as the estrogen signaling pathway, NF-κB signaling pathway, arginine and proline metabolism pathway. The results of dual luciferase reporter gene experiments showed that apigenin can inhibit the transcriptional activity of ERα, ERβ and NF-κB. Conclusion Based on the analysis of network pharmacology, the characteristics of apigenin's multi-target and multi-channel treatment of SLE was in shown. Apigenin may ameliorate SLE through the estrogen signaling pathway and the NF-κB signaling pathway, thereby attenuating the expression of downstream genes and inflammatory factors. |
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