Tailored small molecule for inflammation treatment: Dual scavenger targeting nitric oxide and reactive oxygen species

Abstract

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.