Next Article in Journal
CD86+/CD206+, Diametrically Polarized Tumor-Associated Macrophages, Predict Hepatocellular Carcinoma Patient Prognosis
Previous Article in Journal
Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(3), 315; doi:10.3390/ijms17030315

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

1
Tianjin Key Laboratory of Pulp & Paper, Tianjin University of Science & Technology, Tianjin 300457, China
2
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection/Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian 223300, China
3
Department of Gerontology, Huai’an First People’s Hospital, Nanjing Medical University, Huaian 223300, China
4
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
5
Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
6
State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, Harbin 150040, China
7
Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 8 January 2016 / Revised: 18 February 2016 / Accepted: 25 February 2016 / Published: 1 March 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [1569 KB, uploaded 1 March 2016]   |  

Abstract

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. View Full-Text
Keywords: 5-methoxyl aesculetin; activator protein-1; mitogen-activated protein kinases; inflammation 5-methoxyl aesculetin; activator protein-1; mitogen-activated protein kinases; inflammation
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wu, L.; Li, X.; Wu, H.; Long, W.; Jiang, X.; Shen, T.; Qiang, Q.; Si, C.; Wang, X.; Jiang, Y.; Hu, W. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells. Int. J. Mol. Sci. 2016, 17, 315.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top