Naringenin Inhibits the Formation of N ^ε ‐Carboxymethyllysine and Ameliorates Inflammation Induced by it in RAW 264.7 Cells

Utilizing active ingredients to inhibit the formation of N^ε-carboxymethyllysine (CML) and alleviate CML-induced inflammation damage is crucial for treating diabetic nephropathy caused by CML. In the present study, we aimed to investigate the inhibitory effect and mechanism of naringenin (Nar) on the formation of CML and CML-induced inflammation damage in RAW 264.7 cells. The results indicated that Nar could dose-dependently inhibit the formation of CML in the system of L-lysine and glyoxal (GO) by producing mono-GO-Nar, as evidenced by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Furthermore, CML-induced inflammatory injury in RAW 264.7 cells was alleviated by Nar through the reduction of gene expression levels of TNF-α and IL-6. Further mechanistic studies suggested that Nar inhibited inflammatory injury via the AGEs/RAGE/NF-κB pathway. In summary, our results initially demonstrated that Nar could inhibit the formation of CML and alleviate CML-induced inflammation, which might represent a novel mechanism by which Nar combats chronic diseases where CML plays a significant role.