Renoprotective effects of Tilianin in diabetic rats through modulation of oxidative stress via Nrf2-Keap1 pathway and inflammation via TLR4/MAPK/NF-κB pathways.

The present study was undertaken to assess the protective effects of Tilianin (TN) on type-2 diabetes-induced renal dysfunction in experimental rats. Diabetes was induced by injecting Nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg) by i.p. and then the rats were treated with TN (10 and 20 mg/kg) daily by oral gavage for 28 days. TN treatment significantly decreases the BUN, creatinine, 24-hour urinary protein, urea, uric acid, and albumin protein levels. The protein of expression of Nrf2, NQO1, and HO-1 was augmented while the expression of Keap-1 decreased significantly. TN also reduces the oxidative/nitrosative status by lowering MDA content, NO, and MPO levels. TN exerted anti-inflammatory effects by suppressing TLR4/NF-κB/MAPK signaling cascades and inhibiting MyD88, TRAF6, IκBα, p38MAPK, JNK, and ERK2 in the diabetic rats. Histopathological findings supported the biochemical and molecular results. The results showed that TN modulated Nrf2-Keap1 and TLR4/MAPK/NF-κB signaling pathways and provided significant protection against diabetes-induced renal dysfunction.