The Anti-inflammatory Effects of 4-((5-Bromo-3-chloro-2-hydroxybenzyl) amino)-2-hydroxybenzoic Acid in Lipopolysaccharide-Activated Primary Microglial Cells

AbstractOver-activated microglial cells are known to be implicated in various neurological diseases, such as Alzheimer ’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis. Our previous reports have shown that ZL006, a compound with a hydrophobic ring A and a hydrophilic ring B with a carboxyl group, exhibited stronger neuroprotective activityin vitro andin vivo. However, the directly anti-inflammatory effects of these compounds in the central nervous system (CNS) have not been elucidated. In the present study, as a part of our ongoing screening experiment to evaluate the anti-inflammatory effects of new compounds, a newly synthesized 4-((5-bromo-3-chloro-2-hydroxybenzyl) amino)-2-hydroxybenzoic acid (LX007) was used to examine whether it could reduce the inflammatory responses of activated microglia. Our results indicated that LX007 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) expression, as well as their regulatory gene-inducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2) in LPS-treated primary microglia. LPS-induced production from microglia of interleukin (IL)-1 β, IL-6, and tumor necrosis factor (TNF-α) was also significantly attenuated by LX007. Mechanistically, LX007 potently suppressed phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) p65 nuclear translocation in LPS-induced microglia. We therefore conclu de that LX007 exhibits anti-inflammatory effec...
Source: Inflammation - Category: Allergy & Immunology Source Type: research