槐黄酮G通过抑制RAW 264.7巨噬细胞中丝裂原活化蛋白激酶(MAPK)介导的信号通路,阻止变形链球菌表面抗原I/II诱导的一氧化氮(NO)和前列腺素E2(PGE2)的产生。
Sophoraflavanone G prevents Streptococcus mutans surface antigen I/II-induced production of NO and PGE2 by inhibiting MAPK-mediated pathways in RAW 264.7 macrophages.
作者信息
Cha Su-Mi, Cha Jeong-Dan, Jang Eun-Jin, Kim Gi-Ug, Lee Kyung-Yeol
机构信息
Department of Oral Microbiology and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, South Korea.
Department of Efficacy Research, Institute of Jinan red ginseng, Jinan 567-801, South Korea.
出版信息
Arch Oral Biol. 2016 Aug;68:97-104. doi: 10.1016/j.archoralbio.2016.04.001. Epub 2016 Apr 4.
BACKGROUND
Sophora flavescens AITON (Leguminosae) is a typical traditional Korean medical herb considered to exhibit antibacterial, anti-inflammatory, and antipyretic effects, and is also used for the treatment of skin and mucosal ulcers, sores, diarrhea, gastrointestinal hemorrhage, arrhythmia, and eczema.
OBJECTIVE AND DESIGN
This study examined the inhibitory effects of sophoraflavanone G (SF) of S. flavescens on the bacterial fibrillar protein, Antigen I/II (AgI/II)-N recombinant protein isolated from Streptococcus mutans(rAg I/II)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). The investigation was focused on whether SF could inhibit the production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin (PG) E2 as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-a, interleukin (IL)-6, nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) in rAgI/II-stimulated RAW 264.7 cells using Griess reagent, Enzyme linked immunosorbent assay (ELISA), and Western blotting analysis.
RESULTS
SG significantly inhibited the production of NO and PGE2 and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α in Ag I/II-N-stimulated RAW264.7 cells, which were mediated by the down-regulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. The SF inhibited the phosphorylation of IκB-α, nuclear translocation of p65, and subsequent activation of NF- κB in the rAgI/II-stimulated cells. In addition, the SF suppressed the rAgI/II-stimulated activation of ERK MAPK as well as the MAPK inhibitor significantly reduced the rAgI/II-induced production of NO and PGE2.
CONCLUSION
Collectively, we suggest that the SF inhibits the expression and production of inflammatory mediators by blocking the ERK MAPK mediated pathway and inhibiting the activation of NF-κB.
背景
苦参(豆科)是一种典型的韩国传统草药,被认为具有抗菌、抗炎和解热作用,还用于治疗皮肤和黏膜溃疡、疮、腹泻、胃肠道出血、心律失常和湿疹。
目的与设计
本研究检测了苦参中的槐黄酮G(SF)对变形链球菌诱导产生的一氧化氮(NO)和前列腺素E2(PGE2)的细菌纤维状蛋白、抗原I/II(AgI/II)-N重组蛋白的抑制作用。研究重点在于SF是否能抑制促炎介质如NO和前列腺素(PG)E2的产生,以及在rAgI/II刺激的RAW 264.7细胞中诱导型一氧化氮合酶(iNOS)、环氧化酶(COX)-2、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、核因子(NF)-κB和丝裂原活化蛋白激酶(MAPKs)的表达,采用格里斯试剂、酶联免疫吸附测定(ELISA)和蛋白质免疫印迹分析。
结果
SG显著抑制了Ag I/II-N刺激的RAW264.7细胞中NO和PGE2以及促炎细胞因子如白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α的产生,这是通过诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)表达的下调介导的。SF抑制了rAgI/II刺激细胞中IκB-α的磷酸化、p65的核转位以及随后NF-κB的激活。此外,SF抑制了rAgI/II刺激的ERK MAPK激活,并且MAPK抑制剂显著降低了rAgI/II诱导的NO和PGE2的产生。
结论
总体而言,我们认为SF通过阻断ERK MAPK介导的途径并抑制NF-κB的激活来抑制炎症介质的表达和产生。