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2'-Hydroxyflavanone prevents LPS-induced inflammatory response and cytotoxicity in murine macrophages.
Toxicology in Vitro ( IF 2.6 ) Pub Date : 2020-08-13 , DOI: 10.1016/j.tiv.2020.104966
Himangshu Sonowal 1 , Kota V Ramana 1
Affiliation  

2′-Hydroxyflavanone (2-HF) is a natural flavonoid isolated from citrus fruits. Multiple studies have demonstrated that 2-HF with its anti-proliferative and pro-apoptotic effects prevent the growth of various cancers. Although 2-HF is a well known anti-oxidative and chemopreventive agent, its role as an anti-inflammatory agent is not well established. In this study, we examined the effect of 2-HF on LPS-induced cytotoxicity and inflammatory response in murine RAW 264.7 macrophages. Flow cytometry analysis showed that pre-treatment of RAW 264.7 macrophages with 2-HF significantly prevented LPS-induced macrophage apoptosis. 2-HF also prevented LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) production, lipid peroxidation, and loss of mitochondrial membrane potential in murine macrophages. Most importantly, the release of multiple inflammatory cytokines and chemokines such as eotaxin, IL-2, IL-10, IL-12p40, LIX, IL-15, IL-17, MCP-1, and TNF-α induced by LPS in the macrophages was inhibited by 2-HF. 2-HF also prevented LPS-induced activation of protein kinases p38MAPK and SAPK/JNK. Apart from this, LPS-induced phosphorylation, nuclear translocation, and DNA-binding of the redox transcription factor, NF-κB, was prevented by 2-HF. Our results demonstrate that 2-HF by regulating ROS/MAPK/NF-κB prevents LPS-induced inflammatory response and cytotoxicity in murine macrophages suggesting that the need of potential development of 2-HF as an anti-inflammatory agent to ameliorate various inflammatory complications.



中文翻译:


2'-Hydroxyflavanone 可防止 LPS 诱导的小鼠巨噬细胞炎症反应和细胞毒性。



2'-羟基黄烷酮 (2-HF) 是从柑橘类水果中分离出来的天然黄酮类化合物。多项研究表明,2-HF 具有抗增殖和促凋亡作用,可预防各种癌症的生长。尽管 2-HF 是一种众所周知的抗氧化和化学预防剂,但其作为抗炎剂的作用尚不明确。在本研究中,我们研究了 2-HF 对 LPS 诱导的小鼠 RAW 264.7 巨噬细胞的细胞毒性和炎症反应的影响。流式细胞术分析表明,用 2-HF 预处理 RAW 264.7 巨噬细胞可显着阻止 LPS 诱导的巨噬细胞凋亡。 2-HF 还可以防止 LPS 诱导的活性氧 (ROS) 和一氧化氮 (NO) 产生、脂质过氧化以及小鼠巨噬细胞中线粒体膜电位的丧失。最重要的是,LPS 诱导多种炎症细胞因子和趋化因子的释放,如嗜酸细胞趋化因子、IL-2、IL-10、IL-12p40、LIX、IL-15、IL-17、MCP-1 和 TNF-α。巨噬细胞被2-HF抑制。 2-HF 还可以阻止 LPS 诱导的蛋白激酶 p38MAPK 和 SAPK/JNK 的激活。除此之外,2-HF 还可阻止 LPS 诱导的氧化还原转录因子 NF-κB 的磷酸化、核转位和 DNA 结合。我们的结果表明,2-HF 通过调节 ROS/MAPK/NF-κB 来预防 LPS 诱导的小鼠巨噬细胞炎症反应和细胞毒性,这表明需要开发 2-HF 作为抗炎剂来改善各种炎症并发症。

更新日期:2020-08-20
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