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

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 salic...

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Published in:	Prostaglandins & other lipid mediators Vol. 174; p. 106866
Main Authors:	Tjahjono, Yudy, Caroline, Foe, Kuncoro, Wijaya, Hendy, Dewi, Bernadette Dian Novita, Karnati, Srikanth, Esar, Senny Yesery, Karel, Philipus, Partana, Fransiskus Regis, Henrikus, Michelle Angelina, Wiyanto, Claritta Angelina, Wilianto, Yufita Ratnasari, Hadinugroho, Wuryanto, Nugraha, Jusak, Nugrahaningsih, Dwi Aris Agung, Kusindarta, Dwi Liliek, Wihadmadyatami, Hevi
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-10-2024
Subjects:	3-CH2Cl Animals Anti-inflammation Anti-Inflammatory Agents - pharmacology Cyclooxygenase 2 - metabolism Cyclooxygenase-2 Dinoprostone - biosynthesis Dinoprostone - metabolism Inflammation - chemically induced Inflammation - drug therapy Inflammation - metabolism Inflammation - pathology Lipopolysaccharides - pharmacology Male Mice Mice, Inbred BALB C NADPH Oxidase 2 - metabolism NF-kappa B - metabolism Prostaglandin Reactive Oxygen Species - metabolism ROS Cyclooxygenase-2 Prostaglandin 3-CH2Cl Anti-inflammation ROS 3-CHCl
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Summary:	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. 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. 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. 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. 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. [Display omitted] •3-CH2Cl reduces PGE-2, NOX2, NFkB, and ROS levels.•3-CH2Cl decreases endogenous COX-2 expression.•Outperforms ASA in LPS-induced inflammation model.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1098-8823
DOI:	10.1016/j.prostaglandins.2024.106866