{"title":"2-(3-(氯甲基)苯甲酰氧基)苯甲酸可降低脂多糖诱导的小鼠体内前列腺素 E-2 的浓度、NOX2 和 NFKB 的表达、ROS 的产生以及 COX-2 的表达。","authors":"","doi":"10.1016/j.prostaglandins.2024.106866","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>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-CH<sub>2</sub>Cl), has emerged as a potential substitute for ASA, offering a simpler, environmentally friendly synthesis and a promising safety profile.</p></div><div><h3>Aim of the study</h3><p>This research aims to evaluate the anti-inflammatory mechanism of 3-CH<sub>2</sub>Cl 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.</p></div><div><h3>Material and methods</h3><p>Utilizing BALB/C mice subjected to LPS-induced inflammation, we investigated the therapeutic potential of 3-CH<sub>2</sub>Cl. 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.</p></div><div><h3>Results</h3><p>3-CH<sub>2</sub>Cl 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.</p></div><div><h3>Conclusion</h3><p>3-CH<sub>2</sub>Cl 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.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"174 ","pages":"Article 106866"},"PeriodicalIF":2.5000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"\",\"doi\":\"10.1016/j.prostaglandins.2024.106866\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>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-CH<sub>2</sub>Cl), has emerged as a potential substitute for ASA, offering a simpler, environmentally friendly synthesis and a promising safety profile.</p></div><div><h3>Aim of the study</h3><p>This research aims to evaluate the anti-inflammatory mechanism of 3-CH<sub>2</sub>Cl 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.</p></div><div><h3>Material and methods</h3><p>Utilizing BALB/C mice subjected to LPS-induced inflammation, we investigated the therapeutic potential of 3-CH<sub>2</sub>Cl. 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.</p></div><div><h3>Results</h3><p>3-CH<sub>2</sub>Cl 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.</p></div><div><h3>Conclusion</h3><p>3-CH<sub>2</sub>Cl 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.</p></div>\",\"PeriodicalId\":21161,\"journal\":{\"name\":\"Prostaglandins & other lipid mediators\",\"volume\":\"174 \",\"pages\":\"Article 106866\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins & other lipid mediators\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1098882324000601\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins & other lipid mediators","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1098882324000601","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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
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.
期刊介绍：
Prostaglandins & Other Lipid Mediators is the original and foremost journal dealing with prostaglandins and related lipid mediator substances. It includes basic and clinical studies related to the pharmacology, physiology, pathology and biochemistry of lipid mediators.
Prostaglandins & Other Lipid Mediators invites reports of original research, mini-reviews, reviews, and methods articles in the basic and clinical aspects of all areas of lipid mediator research: cell biology, developmental biology, genetics, molecular biology, chemistry, biochemistry, physiology, pharmacology, endocrinology, biology, the medical sciences, and epidemiology.
Prostaglandins & Other Lipid Mediators also accepts proposals for special issue topics. The Editors will make every effort to advise authors of the decision on the submitted manuscript within 3-4 weeks of receipt.
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