Rutin modulates the TGR5/GLP1 pathway and downregulates proinflammatory cytokine genes in streptozotocin-induced diabetic rats

Abstract

Rutin, a bioactive component of citrus has been used to treat diabetes mellitus, but there is a paucity of information on the mechanism. In this study, rutin's impact on the expression of genes related to inflammation and insulin secretion were examined. Rats induced with streptozotocin (60mg/kg) were grouped into six: normal control, diabetes untreated, metformin and rutin-treated groups (25, 50, and 100mg/kg), for 28 days. The blood glucose were evaluated at 3-day intervals with glucometer. The mRNA expression of PDX-1, TGR-5, GLP-1, DPP4, TNF-α, IL-1β and IL-6 was investigated utilizing RT‒PCR. Schrödinger suites was used to dock rutin with TGR-5, GLP-1 and DPP4. After treatment, the groups administered with rutin had decreased blood glucose levels than the diabetes untreated group. Compared with those in the untreated diabetes group, the expression of PDX-1, TGR-5 (25 and 100mg/kg), and GLP-1 (25 and 100mg/kg) was significantly upregulated, and the expressions of DPP4, IL-1β, TNF-α, and IL-6 were significantly downregulated in the 25mg/kg rutin-treated group. The docking results showed that rutin is a potent ligand of the selected proteins investigated. The antidiabetic effects of rutin could be linked to its potential to downregulate proinflammatory cytokines and modulate the TGR5/GLP-1 signally, leading to normoglycemia.