Effect comparison of inulin with different molecular weights ameliorating intracerebral neuroinflammation induced by advanced glycation end products (AGEs) in diabetic mice

Inulin is widely recognized for reducing glucose levels in diabetes mellitus, but its role in concurrent diabetic encephalopathy has rarely been reported. In this study, type 2 diabetic KK-Ay mice were administered inulin with different molecular weights for 10 weeks. Intriguingly, a significant decrease in the level of inflammatory factors IL-1β and Aβ protein deposition occurred in brain tissue based on immunofluorescence analysis when the mice were treated with inulin with different molecular weights, especially in the H (5-10 kDa) group, indicating that inulin was beneficial for ameliorating intracerebral neuroinflammation. RNA-seq analysis indicated that this effect might be related to the inactivation of the RAGE-mediated inflammatory pathway. Based on ELISA and western blot analysis, inulin in the H group significantly decreased AGEs content and downregulated the expression of RAGE as well as downstream NFκB and its phosphorylation, validating the above speculation. This was attributed to the fact that inulin has excellent scavenging ability of AGEs intermediate dicarbonyl compounds to block the glycation reaction, according to the <i>in vitro</i> BSA-FRU model analysis. Gut microbes such as <i>Desulfovibrionaceae</i> also contributed to the degradation of AGEs <i>in vivo</i>. In conclusion, this study highlighted a new application perspective of inulin in the treatment of diabetic complications.