계명대학교 의학도서관 Repository

2-Aryl Propionic Acid Amide Modification of Naproxen and Ibuprofen Dimers for Anti-neuroinflammatory Activity in BV2 mouse Microglial Cells

Metadata Downloads
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Keimyung Med J
Issued Date
2022
Volume
41
Issue
2
Keyword
LipopolysaccharideNSAID amide dimerNitric Oxide Synthase Type IIp38 Mitogen-Activated Protein Kinases
Abstract
Inflammation is a common link in the pathophysiology of many neurological illnesses, including Alzheimer’s disease. Activated glial cells contribute to neuroinflammation by producing pro-inflammatory mediators. Naproxen and ibuprofen are nonsteroidal anti-inflammatory drugs with 2-aryl(s) propionic acid as a common pharmacophore. Here we designed a small series of naproxen and ibuprofen amide dimers and tested their effects on the expression of inducible nitric oxide synthase (iNOS), a neuroinflammatory enzyme in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells. Of note, treatment with CNU 019, 020, 021, 023, 024, and 027 at 10 μM markedly inhibited the LPS-induced iNOS expression in BV2 cells. CNU 024 was tested further at different concentrations to regulate the LPS-induced iNOS expression in BV2 cells. Treatment with CNU 024 at 5, 10, or 20 μM dose-dependently suppressed the LPS-induced iNOS protein and mRNA expression levels in BV2 cells, in which maximal inhibition was seen at 20 μM. CNU 024 treatment at doses tested further led to a concentration-dependent inhibition of the LPS-induced phosphorylation (activation) of p38 mitogen-activated protein kinase (MAPK) without influencing its total protein expression in BV2 cells, but it did not affect the LPS-induced activation of c-jun N-terminal kinase-1/2 and extracellular signal-regulated kinases-1/2 in these cells. In summary, our results demonstrate that CNU 024 inhibits the LPS-induced iNOS expression in BV2 cells, partly mediated by the inhibition of p38 MAPK. This work shows that CNU 024 could be a valuable ligand for further development as a potential drug candidate for treating neuroinflammatory pathologies.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2733-5380
Source
https://www.e-kmj.org/journal/view.php?number=2268
DOI
10.46308/kmj.2022.00199
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44492
Appears in Collections:
2. Keimyung Medical Journal (계명의대 학술지) > 2022
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
Authorize & License
  • Authorize공개
Files in This Item:

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.