金木汤抗炎和调节炎性小体的作用:综合网络药理学和dss诱导结肠炎模型的实验评价

IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jin Ah Ryuk , Seong Eun Jin , Ami Lee , Seol Jang , Hyunil Ha , Youn-Hwan Hwang
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引用次数: 0

摘要

金木汤(JMT)是一种韩国传统药物,临床上用于治疗炎症性肠病。尽管其长期使用,药理作用机制仍不清楚。本研究采用网络药理学与体内外实验验证相结合的方法,研究JMT对葡聚糖硫酸钠(dextran sulfate sodium, DSS)诱导的溃疡性结肠炎的潜在治疗作用和潜在的信号通路。我们分析了JMT的23个活性化合物,并利用公开数据预测了它们的分子靶点。采用dss诱导的小鼠结肠炎模型,评价JMT的治疗效果。采用组织病理学、免疫组织化学和炎症标志物mRNA表达分析对结肠组织进行检查。采用16S rRNA测序和线性判别分析评估肠道菌群调节。使用Caco-2和J774A.1细胞研究了JMT及其主要化合物的屏障保护作用,以及它们抑制炎性体激活的能力。23种活性化合物的网络药理学分析揭示了炎症相关生物过程的富集,提示了潜在的抗炎机制。组织学、分子和微生物组分析证实,在dss诱导的结肠炎小鼠模型中,JMT显著缓解了疾病症状,降低了炎症细胞因子的表达,并改善了肠道屏障的完整性。J774A.1巨噬细胞的体外实验表明,JMT提取物和代表性化合物可以抑制炎性小体的激活,这可以通过减少IL-1β的产生、LDH的释放和炎性小体相关蛋白的表达来证明。JMT通过靶向炎症相关通路和抑制炎性体激活,对溃疡性结肠炎表现出抗炎作用,表明其作为炎症性肠病多靶点治疗剂的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-inflammatory and inflammasome-modulating effects of Jinmu-Tang, a Korean traditional medicine: Integrated network pharmacology and experimental evaluation in a DSS-induced colitis model
Jinmu-tang (JMT) is a traditional Korean medicine that is clinically used to treat inflammatory bowel conditions. Despite its long-standing use, the pharmacological mechanism of action remains unclear. This study investigated the potential therapeutic effects and underlying signaling pathways of JMT in dextran sulfate sodium (DSS)-induced ulcerative colitis using an integrated approach combining network pharmacology with in vitro and in vivo experimental validation. We analyzed 23 active compounds of JMT and predicted their molecular targets using public datasets. The therapeutic efficacy of JMT was evaluated using a DSS-induced colitis mouse model. Colonic tissues were examined using histopathology, immunohistochemistry, and mRNA expression analysis of inflammatory markers. Gut microbiota modulation was assessed using 16S rRNA sequencing and linear discriminant analysis Effect size. The barrier-protective effects of JMT and its major compounds, along with their ability to inhibit inflammasome activation, were investigated using Caco-2 and J774A.1 cells. Network pharmacology analysis of the 23 active compounds revealed the enrichment of inflammation-related biological processes, suggesting potential anti-inflammatory mechanisms. JMT significantly alleviated disease symptoms, reduced inflammatory cytokine expression, and improved intestinal barrier integrity in a DSS-induced colitis mouse model, as confirmed by histological, molecular, and microbiome analyses. In vitro experiments using J774A.1 macrophages demonstrated that treatment with JMT extract and representative compounds suppressed inflammasome activation, as evidenced by reduced IL-1β production, LDH release, and expression of inflammasome-related proteins. JMT exhibited anti-inflammatory effects against ulcerative colitis by targeting inflammation-related pathways and suppressing inflammasome activation, demonstrating its potential as a multi-target therapeutic agent for inflammatory bowel diseases.
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来源期刊
CiteScore
11.90
自引率
2.70%
发文量
1621
审稿时长
48 days
期刊介绍: Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.
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