Dose-Dependent Scavenging of Methylglyoxal by Naringenin in Diabetic Mice

Methylglyoxal (MGO) has driven interest as a major precursor of advanced glycation end products due to it being closely implicated in the pathogenesis of diabetic kidney disease (DKD). Therefore, it is critical for seeking active scavenger-targeted MGO to mitigate the development of DKD. Previous studies demonstrated that naringenin (Nar) has a remarkable therapeutic effect on DKD. However, whether Nar could scavenge MGO in diabetic mice remains virtually unknown. This work aims to investigate the effect and mechanism of scavenging MGO by Nar in diabetic mice. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was applied for investigating the scavenging capacity and mechanism of Nar on MGO in diabetic mice. The results indicated that Nar could significantly scavenge MGO in diabetic mice based on the formation of mono-MGO-Nar. In addition, two mono-MGO-Nar nanoparticles were purified, and their structures were deduced as 3-MGO-Nar using LC-MS/MS and NMR spectroscopic analyses. Furthermore, the dose-dependent scavenge effect of Nar on MGO in diabetic mice was elucidated by quantifying mono-MGO-Nar in urine and feces using LC-MS/MS. In summary, our results first demonstrated that targeting the MGO burden may be the new mechanism of Nar combating DKD.