Salidroside protects against diabetes mellitus-induced kidney injury and renal fibrosis by attenuating TGF-β1 and Wnt1/3a/β-catenin signalling.

This study evaluated if the nephroprotective effect of Salidroside in type 1 diabetes mellitus (T1DM) involves modulation of Wnt/β-catenin signalling pathways. Control or Streptozotocin (STZ, 50 mg/kg, iv)-induced T1DM adult male Wister rats were treated with the vehicle and Salidroside (100 mg/kg, orally) for 8 weeks daily. As compared to T1DM-induced rats, Salidroside improved kidney structure, reduced urinary protein and albumin level, increased creatinine clearance, and suppressed renal fibrosis. It also decreased mRNA and protein levels of Wnt1, Wnt3, and TGF-β1, phosphorylation of Smad-3, total and nuclear levels of β-catenin, and levels and activities of cleaved caspase-3. Concomitantly, Salidroside significantly increased the levels of p-β-catenin (Ser33/37 /Thr41 ) and suppressed protein levels of Axin-2, fibronectin, and, mRNA and protein levels of collagen IIIa, the main targets of β-catenin. In both control and T1DM rats, Salidroside significantly lowered fasting glucose levels and reduced renal levels of reactive oxygen species (ROS) p-and GS3Kβ (Ser9) but significantly increased levels of SOD and GSH. In conclusion, Salidroside protected the kidney of rats against T1DM-induced injury and fibrosis by activating GS3Kβ-induced inhibition of Wnt1/Wnt3a β-catenin. This was associated with hypoglycaemic and antioxidant effects.