Huang Tianqi, Zhao Dong, Lee Sangbin, Keum Gyochang, Yang Hyun Ok
Division of Bio-Medical Science & Technology, Korea Institute of Science and Technology (KIST) School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea.
Brain Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Biomol Ther (Seoul). 2023 May 1;31(3):276-284. doi: 10.4062/biomolther.2022.092. Epub 2022 Nov 25.
Sinapic acid (SA) is a phenolic acid that is widely distributed in fruits and vegetables, which has various bioactivities, such as antidiabetic, anticancer and anti-inflammatory functions. Over-activated microglial is involved in the development progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The objective of this study was to investigate the effect of SA in microglia neuroinflammation models. Our results demonstrated that SA inhibited secretion of the nitric oxide (NO) and interleukin (IL)-6, reduced the expression of inducible nitric oxide synthase (iNOS) and enhanced the release of IL-10 in a dose-dependent manner. Besides, our further investigation revealed that SA attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, oral administration of SA in mouse regulated the production of inflammation-related cytokines and also suppressed the phosphorylation of MAPK cascades and AKT in the mouse cerebral cortex. These results suggested that SA may be a possible therapy candidate for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.
芥子酸(SA)是一种广泛分布于水果和蔬菜中的酚酸,具有多种生物活性,如抗糖尿病、抗癌和抗炎功能。过度激活的小胶质细胞参与神经退行性疾病(如帕金森病和阿尔茨海默病)的发展进程。本研究的目的是探讨SA在小胶质细胞神经炎症模型中的作用。我们的结果表明,SA以剂量依赖性方式抑制一氧化氮(NO)和白细胞介素(IL)-6的分泌,降低诱导型一氧化氮合酶(iNOS)的表达,并增强IL-10的释放。此外,我们的进一步研究发现,SA可减弱脂多糖诱导的小胶质细胞中AKT和丝裂原活化蛋白激酶(MAPK)级联的磷酸化。同样,给小鼠口服SA可调节炎症相关细胞因子的产生,并抑制小鼠大脑皮层中MAPK级联和AKT的磷酸化。这些结果表明,SA可能是通过靶向AKT/MAPK信号通路发挥抗炎活性的潜在治疗候选物。