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

Abstract

Inulin has been widely recognized for reducing glucose levels in diabetes mellitus, but rarely reported on concurrent diabetic encephalopathy. In this study, the type 2 diabetic KK-Ay mice were administrated by inulin with different molecular weight for 10 weeks. Intriguingly, it was noted that a significant decrease in the level of inflammatory factors IL-1β and Aβ protein deposition occurring in brain tissue by immunofluorescence analysis, when treated by inulin with different molecular weight, especially in H (5-10 kDa) group, illustrating inulin was benefit for ameliorating intracerebral neuroinflammation. The RNA-seq analysis indicated that it might be related to the inactivation of RAGE-mediated inflammatory pathway. Employed by ELISA and Western blot analysis, inulin in H group significantly decreased AGEs content, and down-regulated the expression of RAGE as well as downstream NFκB and its phosphorylation, which qualified above speculation. Tracing the reason, it was attributed to the fact that inulin possessed excellent scavenging of AGEs intermediate dicarbonyl compounds to block the glycation reaction, according to the in vitro BSA-FRU model analysis. And the gut microbes such as Desulfovibrionaceae, etc. also volunteered the degradation of AGEs in vivo. To sum up, this study highlighted a new perspective of inulin applied in diabetic complications.