Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Toxicol In Vitro. 2020 Dec;69:104966. doi: 10.1016/j.tiv.2020.104966. Epub 2020 Aug 13.
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.
2'-羟基黄烷酮(2-HF)是一种从柑橘类水果中分离出来的天然类黄酮。多项研究表明,具有抗增殖和促凋亡作用的 2-HF 可阻止多种癌症的生长。尽管 2-HF 是一种众所周知的抗氧化和化学预防剂,但它作为抗炎剂的作用尚未得到充分证实。在这项研究中,我们研究了 2-HF 对 LPS 诱导的鼠 RAW264.7 巨噬细胞细胞毒性和炎症反应的影响。流式细胞术分析表明,2-HF 预处理 RAW264.7 巨噬细胞可显著预防 LPS 诱导的巨噬细胞凋亡。2-HF 还可预防 LPS 诱导的活性氧(ROS)和一氧化氮(NO)产生、脂质过氧化以及鼠巨噬细胞中线粒体膜电位的丧失。最重要的是,2-HF 抑制了 LPS 诱导的多种炎症细胞因子和趋化因子的释放,如嗜酸性粒细胞趋化因子、IL-2、IL-10、IL-12p40、LIX、IL-15、IL-17、MCP-1 和 TNF-α。2-HF 还可预防 LPS 诱导的丝裂原活化蛋白激酶 p38MAPK 和应激活化蛋白激酶 SAPK/JNK 的激活。除此之外,2-HF 还可防止 LPS 诱导的氧化还原转录因子 NF-κB 的磷酸化、核易位和 DNA 结合。我们的研究结果表明,2-HF 通过调节 ROS/MAPK/NF-κB 可预防 LPS 诱导的鼠巨噬细胞炎症反应和细胞毒性,提示需要将 2-HF 作为抗炎剂开发以改善各种炎症并发症。