Yudy Tjahjono, Caroline, Kuncoro Foe, Hendy Wijaya, Bernadette Dian Novita Dewi, Srikanth Karnati, Senny Yesery Esar, Philipus Karel, Fransiskus Regis Partana, Michelle Angelina Henrikus, Claritta Angelina Wiyanto, Yufita Ratnasari Wilianto, Wuryanto Hadinugroho, Jusak Nugraha, Dwi Aris Agung Nugrahaningsih, Dwi Liliek Kusindarta, Hevi Wihadmadyatami
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. © 2024 Elsevier Inc.
Faculty of Pharmacy, Widya Mandala Catholic University Surabaya, Jalan Kalisari Selatan 1, East Java, Surabaya, 60237, Indonesia; Faculty of Medicine, Widya Mandala Catholic University Surabaya, Jalan Kalisari Selatan 1, East Java, Surabaya, 60237, Indonesia; Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, Würzburg, Germany; Study Program of Veterinary Science, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Jalan Fauna No.2 Karangmalang, Yogyakarta, 55281, Indonesia; Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Jl. Mayjen Prof. Dr. Moestopo No.47, Surabaya, 60132, Indonesia; Department of Pharmacology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Jalan Fauna No.2 Karangmalang, Yogyakarta, 55281, Indonesia; Authors contributed equally.