背景:炎症是对各种侮辱的基本反应,包括微生物入侵和组织损伤。虽然阿司匹林(ASA)因其抗炎特性而被广泛使用,其副作用和局限性凸显了对新型治疗替代方案的需求.最近,一种新的水杨酸衍生物,2-((3-(氯甲基)苯甲酰基)氧基)苯甲酸(3-CH2Cl),已经成为ASA的潜在替代品,提供一个更简单的,环保合成和有前途的安全概况。
目的:本研究旨在评估3-CH2Cl在脂多糖(LPS)诱导的小鼠模型中的抗炎机制,关注其对前列腺素E-2(PGE-2)浓度的影响,NOX2和NFkB表达,ROS生产,和COX-2表达。
方法:利用受到LPS诱导的炎症的BALB/C小鼠,我们研究了3-CH2Cl的治疗潜力。该研究包括合成和片剂制备,实验设计,外周血血浆PGE-2测量,脾细胞分离和COX-2表达分析,一氧化氮和ROS测量,和NOX2和NFkB表达的免疫组织化学分析。
结果:3-CH2Cl显着降低了PGE-2水平(p=0.005),肝脏匀浆(p=0.005)和血浆(p=0.0011)中的NO浓度,肝脏(p<0.0001)和脾细胞(p=0.0036)中NOX2和NFkB的表达,与ASA相比,表现出优异的抗炎活性。此外,它显示出降低脾细胞中COX-2表达的潜力。
结论:3-CH2Cl具有有效的抗炎特性,在LPS诱导的炎症模型中,几个关键炎症标志物优于ASA。COX-2表达的减少,随着促炎细胞因子和氧化应激标志物的减少,建议它作为一种有前途的治疗各种炎症的药物。
BACKGROUND: 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.
OBJECTIVE: 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.
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.
CONCLUSIONS: 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.