Thongboontho Rungthip, Petcharat Kanoktip, Munkong Narongsuk, Khonthun Chakkraphong, Boondech Atirada, Phromnoi Kanokkarn, Thim-Uam Arthid
Division of Biochemistry, School of Medical Sciences, University of Phayao, Mae Ka 56000, Thailand.
Department of Pathology, School of Medicine, University of Phayao, Mae Ka 56000, Thailand.
Nutr Res Pract. 2023 Oct;17(5):827-843. doi: 10.4162/nrp.2023.17.5.827. Epub 2023 May 26.
BACKGROUND/OBJECTIVES: Mitochondrial DNA leakage leads to inflammatory responses via endosome activation. This study aims to evaluate whether the perennial grass water extract () ameliorate mitochondrial DNA (mtDNA) leakage.
MATERIALS/METHODS: The major bioactive constituents of (PPW) were investigated by high-performance liquid chromatography, after which their antioxidant activities were assessed. In addition, RAW 264.7 macrophages were stimulated with lipopolysaccharide, resulting in mitochondrial damage. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to examine the gene expression and cytokines.
Our results showed that PPW extract-treated activated cells significantly decrease reactive oxygen species and nitric oxide levels by reducing the and expression and lowering cytokine-encoding genes, including , , , and relative to the lipopolysaccharide (LPS)-activated macrophages. Furthermore, we observed that LPS enhanced the mtDNA leaked into the cytoplasm, increasing the transcription of and signaling both /dependent interferon and MyD88/NF-κb p65-dependent inflammatory cytokine mRNA expression but which was alleviated in the presence of PPW extract.
Our data show that PPW extract has antioxidant and anti-inflammatory activities by facilitating mtDNA leakage and lowering the expression and signaling activation.
背景/目的:线粒体DNA泄漏通过内体激活引发炎症反应。本研究旨在评估多年生草本植物水提取物是否能改善线粒体DNA(mtDNA)泄漏。
材料/方法:采用高效液相色谱法研究多年生草本植物水提取物(PPW)的主要生物活性成分,之后评估其抗氧化活性。此外,用脂多糖刺激RAW 264.7巨噬细胞,导致线粒体损伤。采用定量聚合酶链反应和酶联免疫吸附测定法检测基因表达和细胞因子。
我们的结果表明,与脂多糖(LPS)激活的巨噬细胞相比,PPW提取物处理的活化细胞通过降低NLRP3和AIM2表达以及降低包括IL-1β、IL-18、TNF-α、IL-6和IFN-β在内的细胞因子编码基因,显著降低活性氧和一氧化氮水平。此外,我们观察到LPS增强了泄漏到细胞质中的mtDNA,增加了STING和TBK1的转录,并激活了STING/TBK1依赖的干扰素和MyD88/NF-κb p65依赖的炎性细胞因子mRNA表达,但在PPW提取物存在的情况下这种情况得到缓解。
我们的数据表明,PPW提取物通过促进mtDNA泄漏以及降低STING表达和信号激活而具有抗氧化和抗炎活性。