Therapeutic potential of Nelumbo nucifera Linn. in systemic lupus erythematosus: Network pharmacology and molecular modeling insights.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI:10.1177/09612033241273074
Sugandha Jaiswal, Satish Kumar, Biswatrish Sarkar, Rakesh Kumar Sinha
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引用次数: 0

Abstract

Background: Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in Nelumbo nucifera have anti-oxidants, anti-inflammatory, and immunomodulatory activities that are essential for managing SLE through natural sources. This study employs network pharmacology to unveil the multi-target and multi-pathway mechanisms of Nelumbo nucifera as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study.

Methods: Active compounds and targets of SLE were obtained from IMPPAT, KNApAcKFamily and SwissTargetPrediction databases. SLE-related targets were retrieved from GeneCards and OMIM databases. A protein-protein interaction (PPI) network was built to screen out the core targets using Cytoscape software. ShinyGO was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and active compounds were assessed by molecular docking and molecular dynamics simulation study.

Results: In total, 12 active compounds and 1190 targets of N. nucifera's were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of N. nucifera are mediated mainly by AGE-RAGE and other associated signalling pathways. Molecular docking indicated favourable binding affinities, particularly leucocianidol exhibiting less than -4.5 kcal/mol for all 10 targets. Subsequent molecular dynamics simulations of the leucocianidol-ESR1 complex aimed to elucidate the optimal binding complex's stability and flexibility.

Conclusions: Our study unveiled the potential therapeutic mechanism of N. nucifera in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.

Nelumbo nucifera Linn.对系统性红斑狼疮的治疗潜力:网络药理学和分子建模见解。
背景:系统性红斑狼疮是一种以多种症状为特征的慢性自身免疫性炎症疾病。绒花中的酚酸类和其他类黄酮具有抗氧化、抗炎和免疫调节活性,是通过天然来源治疗系统性红斑狼疮所必需的。本研究采用网络药理学揭示了作为一种辅助疗法的海绒花的多靶点和多途径机制。研究结果通过分子建模进行了验证,包括分子对接和分子动力学研究:方法:从 IMPPAT、KNApAcKFamily 和 SwissTargetPrediction 数据库中获取系统性红斑狼疮的活性化合物和靶点。从 GeneCards 和 OMIM 数据库中检索了与系统性红斑狼疮相关的靶点。使用 Cytoscape 软件构建了蛋白质-蛋白质相互作用(PPI)网络,以筛选出核心靶标。ShinyGO 用于 GO 和 KEGG 通路富集分析。通过分子对接和分子动力学模拟研究评估了潜在靶点与活性化合物之间的相互作用:结果:共鉴定出 12 种活性化合物和 1190 个 N. nucifera 的靶标。PPI 网络分析发现了 10 个核心靶标。GO 和 KEGG 通路富集分析表明,N. nucifera 的作用主要由 AGE-RAGE 和其他相关信号通路介导。分子对接显示了良好的结合亲和力,尤其是白果杉醇与所有 10 个靶标的结合亲和力均低于-4.5 kcal/mol。随后对leucocianidol-ESR1复合物进行了分子动力学模拟,旨在阐明最佳结合复合物的稳定性和灵活性:我们的研究揭示了 N. nucifera 在治疗系统性红斑狼疮方面的潜在治疗机制。这些发现为后续的实验验证提供了启示,并为该领域的进一步研究开辟了新途径。
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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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