Inhibitory Effects of Decursin Derivative against Lipopolysaccharide-Induced Inflammation.

IF 4.3 3区医学 Q2 CHEMISTRY, MEDICINAL

Pharmaceuticals Pub Date : 2024-10-07 DOI:10.3390/ph17101337

Jinhee Lee, Jong-Beom Heo, Sanghee Cho, Chang-Woo Ryu, Hae-Joon Heo, Mi-Young Yun, Gaewon Nam, Gyu-Yong Song, Jong-Sup Bae

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Abstract

Background: This study aims to explore the protective role of JB-V-60-a novel synthetic derivative of decur-sin-against lipopolysaccharide (LPS)-induced inflammation.

Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice.

Results: JB-V-60 enhanced HO-1 levels, inhibited NF-κB activation, reduced COX-2/PGE2 and iNOS/NO concentra-tions, and lowered phosphorylation of signal transducer and activator of transcription 1. It also promoted the translocation of Nrf2 into the nucleus, allowing its binding to antioxidant response elements and resulting in reduced IL-1β in LPS-stimulated HPAECs. The reduction in iNOS/NO levels by JB-V-60 was reversed when HO-1 was inhibited via RNAi. In the animal model, JB-V-60 sig-nificantly decreased iNOS expression in lung tissues and TNF-α levels in bronchoalveolar lavage fluid.

Conclusions: These findings highlight the anti-inflammatory effects of JB-V-60 and its potential as a treat-ment for inflammatory disorders.

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去甲斑蝥素衍生物对脂多糖诱发炎症的抑制作用

背景：本研究旨在探讨JB-V-60--一种新型脱嘌呤衍生物--对脂多糖（LPS）诱导的炎症的保护作用：本研究旨在探讨JB-V-60--一种新合成的脱嘌呤衍生物--对脂多糖（LPS）诱导的炎症的保护作用：我们研究了JB-V-60对LPS激活的人肺动脉内皮细胞（HPAECs）中血红素加氧酶（HO）-1、环氧化酶（COX）-2和诱导型一氧化氮合酶（iNOS）的影响。此外，我们还评估了 JB-V-60 对 LPS 暴露小鼠体内 iNOS、肿瘤坏死因子（TNF）-α 和白细胞介素（IL）-1β 的影响：结果：JB-V-60 提高了 HO-1 的水平，抑制了 NF-κB 的活化，降低了 COX-2/PGE2 和 iNOS/NO 的浓度，并降低了信号转导和转录激活因子 1 的磷酸化。它还能促进 Nrf2 转位至细胞核，使其与抗氧化反应元件结合，从而降低 LPS 刺激的 HPAECs 中的 IL-1β。当通过 RNAi 抑制 HO-1 时，JB-V-60 对 iNOS/NO 水平的降低作用被逆转。在动物模型中，JB-V-60 能显著降低肺组织中 iNOS 的表达和支气管肺泡灌洗液中 TNF-α 的水平：这些发现凸显了 JB-V-60 的抗炎作用及其治疗炎症性疾病的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

6.10

自引率

4.30%

发文量

1332

审稿时长

6 weeks

期刊介绍： Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.