Development of NmeGA, a Dual Scavenger for NO and ROS in Inflammation Treatment

Inflammation, an immune response to external stimuli, can be developed into severe inflammatory diseases if left uncontrolled. This study introduces NmeGA, a novel dual scavenger designed to target both nitric oxide (NO) and reactive oxygen species (ROS), two pivotal factors exacerbating inflammation. NmeGA combines <i>N</i>-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, and gallic acid (GA), a ROS scavenger, through an amide bond. The unique structure of NmeGA yields superior NO and ROS scavenging abilities compared to single scavengers; the amide bond and Nme’s methyl group function as electron donating groups (EDG), enhancing NO reactivity. Meanwhile, GA’s catechol group and the amide bond serve as EDG and electron withdrawing group (EWG), respectively, effectively scavenging ROS. NmeGA’s reduced toxicity and enhanced bioapplication suitability due to increased lipophilicity, indicate its potential for inflammation management. <i>In vitro</i> studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells demonstrate NmeGA’s enhanced NO and ROS scavenging abilities and remarkable anti-inflammatory effects. Moreover, in an LPS-induced peritonitis model, NmeGA significantly reduced mortality rates, NO levels, and inflammatory cytokine levels. This research highlights NmeGA’s promising potential for targeting various inflammatory diseases with minimal toxicity.