研究动态
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基于网络药理学和分子对接策略探索红景天苷抑制视网膜神经节细胞氧化应激的潜在机制。

Network pharmacology and molecular-docking-based strategy to explore the potential mechanism of salidroside-inhibited oxidative stress in retinal ganglion cell.

发表日期:2024
作者: Peng Zhang, Hongxin Zhao, Xiangping Xia, Hua Xiao, Chong Han, Zhibo You, Junjie Wang, Fang Cao
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

红景天苷(SAL)是红景天提取物的主要成分,是一种黄酮类化合物,具有抗氧化应激、抗炎、降血脂等生物活性。本研究基于体外实验、网络药理学和分子对接技术,探讨SAL抗视网膜神经节细胞(RGC)氧化应激的潜在治疗靶点和机制。检查活性、活性氧(ROS)和细胞凋亡水平的差异。从GeneCards、TCMSP数据库和分析平台中筛选出视紫红质、RGC和氧化应激对应的基因。将三者相交,绘制维恩图。通过STRING数据库、Cytohubba插件和Metascape数据库分析蛋白质相互作用、GO功能富集和KEGG通路富集数据。使用 qRT-PCR 验证了筛选途径中的关键因素。最后利用MOE 2019软件进行分子对接预测,利用Gromacs 2018软件进行分子动力学模拟。在体外RGC氧化应激模型中,SAL处理后细胞活性增强,ROS减少,细胞凋亡减少。共获得SAL RGCs氧化应激的16个潜在靶点,并通过网络拓扑分析筛选出前10个核心靶点。 GO分析表明,SAL视网膜氧化应激治疗主要涉及细胞对应激的反应、转录调节复合物以及DNA结合转录因子的结合。 KEGG分析显示,大多数基因主要富集于多种癌症通路以及糖尿病并发症、非酒精性脂肪肝、脂质和动脉粥样硬化的信号通路。通过PCR、分子对接和分子动力学模拟验证表明,SAL可能通过调节SIRT1、NRF2和NOS3来减轻RGCs的氧化应激并减少细胞凋亡。本研究初步揭示了SAL对RGCs的抗氧化治疗作用和分子机制,为RGCs的抗氧化治疗作用和分子机制提供了理论依据。为后续研究奠定基础。版权所有:© 2024 张等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
Salidroside (SAL), the main component of Rhodiola rosea extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques.RGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software.In the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3.This study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.