Verification of the mechanism of action of isoliquiritigenin derivatives on LPS-induced FLS cells in rheumatoid arthritis based on network pharmacology

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-04-16 DOI:10.1016/j.bmc.2025.118199

Qing Ma, Zhiwei Liu, Dan Wang, Chi Liu, Xinyue Liu, Enbo Cai, Fengyan Su

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Abstract

Isoliquiritigenin (ISL), which has a chalcone parent structure, has a variety of pharmacological effects. In this study, ISL was structurally modified to create 16 bromate derivatives of ISL. The structures of these derivatives were determined using ¹H NMR and ¹³C NMR. An in vitro rheumatoid arthritis inflammation model was established using LPS-induced fibroblast-like synoviocytes (FLS). The survival, NO content and viability of derivatives bound to LPS were determined by Elisa assay of the expression of the relevant inflammatory factors TNF-α, IL-1 and IL-1β. Network pharmacology predicted the relevant targets and pathways of action of ISL in rheumatoid arthritis, which were experimentally validated by RT-PCR method and Western Blot method. The results showed that ISL-6 exerted anti-rheumatoid arthritis effects by reducing the expression of inflammatory factors TNF-α, IL-1 and IL-1β, activating the PI3K/AKT pathway, promoting AKT phosphorylation, and then affecting the expression of the downstream signaling molecule FOXO1, which is associated with inflammation.

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基于网络药理学的异尿酸原素衍生物对脂多糖诱导的类风湿关节炎FLS细胞作用机制的验证

异异黄酮原（ISL）具有查尔酮母体结构，具有多种药理作用。在本研究中，对ISL进行了结构修饰，得到了16个ISL的溴酸盐衍生物。这些衍生物的结构通过1H NMR和13C NMR进行了表征。采用脂多糖诱导的成纤维细胞样滑膜细胞（FLS）建立体外类风湿关节炎炎症模型。通过Elisa法检测相关炎症因子TNF-α、IL-1和IL-1β的表达，检测LPS结合衍生物的存活率、NO含量和活力。网络药理学预测了ISL在类风湿关节炎中的相关靶点和作用途径，并通过RT-PCR方法和Western Blot方法进行了实验验证。结果表明，il -6通过降低炎症因子TNF-α、IL-1和IL-1β的表达，激活PI3K/AKT通路，促进AKT磷酸化，进而影响与炎症相关的下游信号分子FOXO1的表达，从而发挥抗类风湿关节炎的作用。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.