5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

International Journal of Molecular Sciences

卷:17

Chuanling Si¹  Yunyao Jiang¹  Xueqin Li²  Haifeng Wu³  Wei Long⁴  Ting Shen⁵  Qian Qiang⁶  Xinfeng Wang⁶  Weicheng Hu⁶  Xiaojian Jiang⁷  Lei Wu⁸ 

[1] Environmental Protection/Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian 223300, China;

[2] Paper, Tianjin University of Science &

[3] Technology, Tianjin 300457, China;

[4] Department of Gerontology, Huai’an First People’s Hospital, Nanjing Medical University, Huaian 223300, China;

[5] Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China;

[6] Jiangsu Collaborative Innovation Center of Regional Modern Agriculture &

[7] Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China;

[8] Tianjin Key Laboratory of Pulp &

关键词: 5-methoxyl aesculetin;    activator protein-1;    mitogen-activated protein kinases;    inflammation;   

DOI  :  10.3390/ijms17030315

来源: DOAJ

【 摘 要 】

For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.

【 授权许可】

Unknown