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新型姜黄素衍生物 FM0807 通过 ROS/JNK/p53 通路对 RAW264.7 细胞脂多糖诱导的炎症因子释放的影响。

Effects of FM0807, a novel curcumin derivative, on lipopolysaccharide-induced inflammatory factor release via the ROS/JNK/p53 pathway in RAW264.7 cells.

机构信息

The Graduate School of Fujian Medical University, Fuzhou, P.R. China.

The School of Clinical Medicine,Fujian Medical University, Fuzhou, P.R.China.

出版信息

Biosci Rep. 2018 Oct 17;38(5). doi: 10.1042/BSR20180849. Print 2018 Oct 31.

DOI:10.1042/BSR20180849
PMID:30249753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6200701/
Abstract

Sepsis is a systemic inflammatory response caused by infection. Curcumin is known to have antioxidant and anti-inflammatory activities. FM0807, a curcumin derivative, was investigated in the present study to determine its effect on cytokines and the possible molecular mechanism. The experiments were carried out in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cell viability was measured by MTT assay. ELISA, Griess assays, fluorescence-based quantitative PCR, flow cytometric analysis, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) experiments, and Western blotting were carried out to assess the potential effects of FM0807 on LPS-induced RAW 264.7 cells. FM0807 had no cytotoxic effects on RAW 264.7 cells. Furthermore, pretreatment with FM0807 inhibited the inflammatory factor tumor necrosis factor-α (TNF-α), interleukin (IL) 1β (IL-1β), IL-6, and inducible nitric oxide synthase (iNOS) at the protein and gene levels. FM0807 also inhibited the production of reactive oxygen species (ROS) and apoptosis. In addition, the activation of the ROS/JNK (c-jun NH-terminal kinase)/p53 signaling pathway was inhibited by FM0807 in RAW 264.7 cells FM0807 has anti-inflammatory activity , which suggests a potential clinical application in sepsis. The anti-inflammatory activity of FM0807 may be mediated by the ROS/JNK/p53 signaling pathway.

摘要

脓毒症是一种由感染引起的全身炎症反应。姜黄素具有抗氧化和抗炎活性。本研究旨在研究姜黄素衍生物 FM0807 对细胞因子的影响及其可能的分子机制。该实验在脂多糖(LPS)诱导的 RAW 264.7 细胞中进行。通过 MTT 法测定细胞活力。通过 ELISA、Griess 测定、荧光定量 PCR、流式细胞术分析、2',7'-二氯二氢荧光素二乙酸酯(DCFH-DA)实验和 Western blot 分析评估 FM0807 对 LPS 诱导的 RAW 264.7 细胞的潜在影响。FM0807 对 RAW 264.7 细胞没有细胞毒性作用。此外,FM0807 预处理可抑制炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)1β(IL-1β)、IL-6 和诱导型一氧化氮合酶(iNOS)在蛋白和基因水平上的表达。FM0807 还抑制活性氧(ROS)和细胞凋亡的产生。此外,FM0807 还抑制了 RAW 264.7 细胞中 ROS/JNK(c-jun NH2-末端激酶)/p53 信号通路的激活。FM0807 具有抗炎活性,这表明其在脓毒症中具有潜在的临床应用价值。FM0807 的抗炎活性可能是通过 ROS/JNK/p53 信号通路介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/71b883667fb3/bsr-38-bsr20180849-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/59e18b6437e1/bsr-38-bsr20180849-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/f0d405036c5d/bsr-38-bsr20180849-g2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/f1ac50b9ea3f/bsr-38-bsr20180849-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/71b883667fb3/bsr-38-bsr20180849-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/59e18b6437e1/bsr-38-bsr20180849-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/f0d405036c5d/bsr-38-bsr20180849-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/c83d5d898502/bsr-38-bsr20180849-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17b/6200701/f1ac50b9ea3f/bsr-38-bsr20180849-g4.jpg
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