Network Pharmacology to Reveal the Molecular Mechanisms of Rutaceous Plant-derived Limonin Ameliorating Non-alcoholic Steatohepatitis.

IF 0.8 4区医学 Q4 IMMUNOLOGY

Critical Reviews in Immunology Pub Date : 2023-01-01 DOI:10.1615/CritRevImmunol.2023050080

Wei Wang, Li Yang, Minjie Hu, Yonglin Yang, Qiang Ma, Jiayu Chen

{"title":"Network Pharmacology to Reveal the Molecular Mechanisms of Rutaceous Plant-derived Limonin Ameliorating Non-alcoholic Steatohepatitis.","authors":"Wei Wang, Li Yang, Minjie Hu, Yonglin Yang, Qiang Ma, Jiayu Chen","doi":"10.1615/CritRevImmunol.2023050080","DOIUrl":null,"url":null,"abstract":"Background: Limonin shows promise in alleviating non-alcoholic fatty liver disease. We investigated the mechanisms of limonin against non-alcoholic steatohepatitis (NASH) using network pharmacology and molecular docking.Methods: Public databases provided NASH- and limonin-associated targets. VennDiagram identified potential limonin targets for NASH. Enrichment analysis explored the limonin-NASH relationship. PPI network analysis, CytoHubba models, and bioinformatics identified hub genes for NASH treatment. Molecular docking assessed limonin's binding ability to hub targets.Results: We found 37 potential limonin targets in NASH, involved in oxidative stress, inflammation, and signaling pathways. PPI network analysis revealed seven hub genes (STAT3, NFKBIA, MTOR, TLR4, CASP8, PTGS2, NFKB1) as NASH treatment targets. Molecular docking confirmed limonin's binding to STAT3, CASP8, and PTGS2. Animal experiments on high-fat diet mice showed limonin reduced hepatic steatosis, lipid accumulation, and expression of p-STAT3/STAT3, CASP8, and PTGS2.Conclusion: Limonin's therapeutic effects in NASH may stem from its antioxidant and anti-inflammatory properties. STAT3, CASP8, and PTGS2 are potential key targets for NASH treatment, warranting further investigation.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":0.8000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1615/CritRevImmunol.2023050080","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Limonin shows promise in alleviating non-alcoholic fatty liver disease. We investigated the mechanisms of limonin against non-alcoholic steatohepatitis (NASH) using network pharmacology and molecular docking.

Methods: Public databases provided NASH- and limonin-associated targets. VennDiagram identified potential limonin targets for NASH. Enrichment analysis explored the limonin-NASH relationship. PPI network analysis, CytoHubba models, and bioinformatics identified hub genes for NASH treatment. Molecular docking assessed limonin's binding ability to hub targets.

Results: We found 37 potential limonin targets in NASH, involved in oxidative stress, inflammation, and signaling pathways. PPI network analysis revealed seven hub genes (STAT3, NFKBIA, MTOR, TLR4, CASP8, PTGS2, NFKB1) as NASH treatment targets. Molecular docking confirmed limonin's binding to STAT3, CASP8, and PTGS2. Animal experiments on high-fat diet mice showed limonin reduced hepatic steatosis, lipid accumulation, and expression of p-STAT3/STAT3, CASP8, and PTGS2.

Conclusion: Limonin's therapeutic effects in NASH may stem from its antioxidant and anti-inflammatory properties. STAT3, CASP8, and PTGS2 are potential key targets for NASH treatment, warranting further investigation.

查看原文本刊更多论文

揭示芸香植物来源的Limonin改善非酒精性脂肪性肝炎的分子机制的网络药理学。

背景：利莫宁有望缓解非酒精性脂肪肝。我们利用网络药理学和分子对接研究了柠檬苦素对抗非酒精性脂肪性肝炎（NASH）的机制。方法：公共数据库提供NASH和柠檬苦素相关靶点。VennDiagram确定了NASH的潜在柠檬苦素靶点。富集分析探讨了柠檬苦素与NASH的关系。PPI网络分析、CytoHubba模型和生物信息学鉴定了NASH治疗的中枢基因。分子对接评估了柠檬苦素与中枢靶标的结合能力。结果：我们在NASH中发现了37个潜在的柠檬苦素靶点，涉及氧化应激、炎症和信号通路。PPI网络分析揭示了7个枢纽基因（STAT3、NFKBIA、MTOR、TLR4、CASP8、PTGS2、NFKB1）作为NASH治疗靶点。分子对接证实了柠檬苦素与STAT3、CASP8和PTGS2的结合。在高脂饮食小鼠的动物实验中，柠檬苦素降低了肝脏脂肪变性、脂质积聚以及p-STAT3/STAT3、CASP8和PTGS2的表达。结论：柠檬苦素对NASH的治疗作用可能源于其抗氧化和抗炎特性。STAT3、CASP8和PTGS2是NASH治疗的潜在关键靶点，值得进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Critical Reviews in Immunology 医学-免疫学

CiteScore

2.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Immunology covers a broad spectrum of investigations at the genes, molecular, cellular, organ and system levels to reveal defense mechanisms against pathogens as well as protection against tumors and autoimmune diseases. The great advances in immunology in recent years make this field one of the most dynamic and rapidly growing in medical sciences. Critical ReviewsTM in Immunology (CRI) seeks to present a balanced overview of contemporary adaptive and innate immune responses related to autoimmunity, tumor, microbe, transplantation, neuroimmunology, immune regulation and immunotherapy from basic to translational aspects in health and disease. The articles that appear in CRI are mostly obtained by invitations to active investigators. But the journal will also consider proposals from the scientific community. Interested investigators should send their inquiries to the editor before submitting a manuscript.