{"title":"治疗炎症的定制小分子:针对一氧化氮和活性氧的双重清除剂。","authors":"","doi":"10.1016/j.jconrel.2024.08.026","DOIUrl":null,"url":null,"abstract":"<div><p>Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates <em>N</em>-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through <em>in vitro</em> studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tailored small molecule for inflammation treatment: Dual scavenger targeting nitric oxide and reactive oxygen species\",\"authors\":\"\",\"doi\":\"10.1016/j.jconrel.2024.08.026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates <em>N</em>-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through <em>in vitro</em> studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases.</p></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.5000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S016836592400573X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S016836592400573X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
与炎症相关的疾病通常以一氧化氮(NO)和活性氧(ROS)水平升高为特征,而一氧化氮和活性氧在炎症的调节中发挥着重要作用。然而,开发能有效控制一氧化氮/活性氧水平的有机材料仍是一项挑战。本研究介绍了一种新型有机化合物 NmeGA,它可以清除 NO 和 ROS。NmeGA 通过酰胺键将 NO 清除剂 N-甲基-1,2,-苯二胺(Nme)与 ROS 清除剂没食子酸(GA)巧妙地结合在一起,使其清除能力比单独的成分更强。这种化合物的毒性降低,亲脂性提高,突出了其生物适用性,并彰显了其作为炎症控制工具的潜力。通过对脂多糖(LPS)刺激的 RAW 264.7 细胞进行体外研究,NmeGA 显示出显著的清除 NO 和 ROS 效能,并具有明显的抗炎作用。在 LPS 诱导的腹膜炎模型中,服用 NmeGA 可大幅降低死亡率、NO 和 ROS 水平以及炎症细胞因子浓度。这些发现凸显了 NmeGA 作为一种治疗剂对各种炎症疾病的多功能性。
Tailored small molecule for inflammation treatment: Dual scavenger targeting nitric oxide and reactive oxygen species
Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates N-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through in vitro studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases.
期刊介绍:
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