2-(3-(Chloromethyl)benzoyloxy)benzoic Acid reduces prostaglandin E-2 concentration, NOX2 and NFKB expression, ROS production, and COX-2 expression in lipopolysaccharide-induced mice

Tjahjono, Yudy, Caroline, Caroline and Foe, Kuncoro (2024) 2-(3-(Chloromethyl)benzoyloxy)benzoic Acid reduces prostaglandin E-2 concentration, NOX2 and NFKB expression, ROS production, and COX-2 expression in lipopolysaccharide-induced mice. Prostaglandins and Other Lipid Mediators, 106866. pp. 1-10. ISSN 1098-8823

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Abstract

Introduction: Inflammation is a fundamental response to various insults, including microbial invasion and tissue injury. While aspirin (ASA) has been widely used for its anti-inflammatory properties, its adverse effects and limitations highlight the need for novel therapeutic alternatives. Recently, a novel salicylic acid derivative, 2-((3- (chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl), has emerged as a potential substitute for ASA, offering a simpler, environmentally friendly synthesis and a promising safety profile. Aim of the study: This research aims to evaluate the anti-inflammatory mechanism of 3-CH2Cl in a lipopolysaccharide (LPS)-induced mouse model, focusing on its effects on prostaglandin E-2 (PGE-2) concentration, NOX2 and NFkB expression, ROS production, and COX-2 expression. Material and methods: Utilizing BALB/C mice subjected to LPS-induced inflammation, we investigated the therapeutic potential of 3-CH2Cl. The study included synthesis and tablet preparation, experimental design, peripheral blood plasma PGE-2 measurement, splenocyte isolation and COX-2 expression analysis, nitric oxide and ROS measurement, and immunohistochemical analysis of NOX2 and NFkB expression. Results: 3-CH2Cl significantly reduced PGE-2 levels (p = 0.005), NO concentration in liver homogenates (p = 0.005) and plasma (p = 0.0011), and expression of NOX2 and NFkB in liver (p < 0.0001) and splenocytes (p = 0.0036), demonstrating superior anti-inflammatory activity compared to ASA. Additionally, it showed potential in decreasing COX-2 expression in splenocytes. Conclusion: 3-CH2Cl exhibits potent anti-inflammatory properties, outperforming ASA in several key inflammatory markers in an LPS-induced inflammation model. The reduction of COX-2 expression, alongside the reduction of pro-inflammatory cytokines and oxidative stress markers, suggest it as a promising therapeutic agent for various inflammatory conditions.

Item Type: Article
Uncontrolled Keywords: 3-CH2Cl Anti-inflammation Prostaglandin Cyclooxygenase-2 ROS
Subjects: Pharmacy
Divisions: Journal Publication
Depositing User: F.X. Hadi
Date Deposited: 14 Aug 2024 03:31
Last Modified: 15 Aug 2024 02:50
URI: http://repository.ukwms.ac.id/id/eprint/40831

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