{"title":"Therapeutic potential of <i>Nelumbo nucifera</i> Linn. in systemic lupus erythematosus: Network pharmacology and molecular modeling insights.","authors":"Sugandha Jaiswal, Satish Kumar, Biswatrish Sarkar, Rakesh Kumar Sinha","doi":"10.1177/09612033241273074","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in <i>Nelumbo nucifera</i> 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 <i>Nelumbo nucifera</i> as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>In total, 12 active compounds and 1190 targets of <i>N. nucifera's</i> were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of <i>N. nucifera</i> 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.</p><p><strong>Conclusions: </strong>Our study unveiled the potential therapeutic mechanism of <i>N. nucifera</i> in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.</p>","PeriodicalId":18044,"journal":{"name":"Lupus","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09612033241273074","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
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.
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…