Department of Rheumatology, Henan province hospital of traditional Chinese medicine (The second affiliated hospital of Henan university of traditional Chinese medicine), Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Biomed Pharmacother. 2021 Jun;138:111413. doi: 10.1016/j.biopha.2021.111413. Epub 2021 Mar 4.
BACKGROUND: Monosodium urate (MSU)-mediated inflammatory response is a crucial inducing factor in gouty arthritis. Here, we explored the underlying mechanism of total glucosides of paeony (TGP) in MSU-induced inflammation of THP-1 macrophages in gouty arthritis. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine RNA and protein expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to confirm the interaction between miR-876-5p and MALAT1 or NLR family pyrin domain containing 3 (NLRP3). RESULTS: MSU-induced damage and inflammatory response in THP-1 macrophages were alleviated by the treatment of TGP in a dose-dependent manner. Overexpression of NLRP3 or MALAT1 reversed the protective effects of TGP in MSU-induced THP-1 macrophages. The binding relation between miR-876-5p and MALAT1 or NLRP3 was identified in THP-1 macrophages. MALAT1 up-regulated the expression of NLRP3 by sponging miR-876-5p in THP-1 macrophages. TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis. TGP suppressed MSU-induced activation of TLR4/MyD88/NF-κB pathway through regulating MALAT1/miR-876-5p/NLRP3 axis. CONCLUSION: In conclusion, TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis and TLR4/MyD88/NF-κB pathway, suggesting that TGP was a promising active ingredient for gouty arthritis treatment.
背景：单钠尿酸盐（MSU）介导的炎症反应是痛风性关节炎的关键诱导因素。在这里，我们探讨了白芍总苷（TGP）在 MSU 诱导的痛风性关节炎 THP-1 巨噬细胞炎症中的作用机制。
方法：采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法检测细胞活力。酶联免疫吸附试验（ELISA）法检测白细胞介素 1β（IL-1β）和肿瘤坏死因子 α（TNF-α）的产生。实时定量聚合酶链反应（RT-qPCR）和 Western blot 法检测 RNA 和蛋白表达。双荧光素酶报告基因实验、RNA 免疫沉淀（RIP）实验和 RNA 下拉实验用于证实 miR-876-5p 与 MALAT1 或 NLR 家族含pyrin 结构域 3（NLRP3）之间的相互作用。
结果：TGP 以剂量依赖的方式减轻了 MSU 诱导的 THP-1 巨噬细胞损伤和炎症反应。NLRP3 或 MALAT1 的过表达逆转了 TGP 在 MSU 诱导的 THP-1 巨噬细胞中的保护作用。在 THP-1 巨噬细胞中鉴定到 miR-876-5p 与 MALAT1 或 NLRP3 之间的结合关系。MALAT1 通过海绵吸附 miR-876-5p 上调 THP-1 巨噬细胞中 NLRP3 的表达。TGP 通过调节 MALAT1/miR-876-5p/NLRP3 轴抑制 MSU 诱导的 THP-1 巨噬细胞炎症。TGP 通过调节 MALAT1/miR-876-5p/NLRP3 轴抑制 MSU 诱导的 TLR4/MyD88/NF-κB 通路激活。
结论：综上所述，TGP 通过调节 MALAT1/miR-876-5p/NLRP3 轴和 TLR4/MyD88/NF-κB 通路抑制 MSU 诱导的 THP-1 巨噬细胞炎症，提示 TGP 是治疗痛风性关节炎的一种有前途的活性成分。
J Ethnopharmacol. 2024-1-30
Curr Pharm Des. 2025
Naunyn Schmiedebergs Arch Pharmacol. 2025-4
Comb Chem High Throughput Screen. 2024
Front Immunol. 2023
Signal Transduct Target Ther. 2023-3-2
Front Endocrinol (Lausanne). 2022
Front Pharmacol. 2022-10-20
Zotero 插件