Abstract
This study investigated if the nephroprotective effect of Salidroside T1DM rats involves activation of AMPK/SIRT1. Rats were divided into control or T1DM and treated with vehicle or Salidroside (100 mg/kg) for 56 days. Mesangial cells were cultured in LG or HG media with or without Salidroside (100 mu M/L) for 24 hr. Also, HG + Salidroside-treated cells were pre-incubated with EX-527 or compound C (CC) for 1 hr. With reducing glucose levels, Salidroside improved kidney structure/function in the T1DM rat. It also increased GSH and Bcl-2 levels in control and T1DM rats and inhibited ROS, increased activation of AMPK and nuclear SIRT1, and lowered acetylation of P53 and FOXO-1 in control and T1DM rats and in LG and HG-treated cells. These effects were abolished by EX-527 and CC. Also, CC decreased the nuclear levels of SIRT1. In conclusion, Salidroside attenuates DN in T1DM rats by activation of AMPK and subsequently, SIRT1.
Practical applications This animal and pre-clinical study shows that Salidroside is able to ameliorate DN in T1DM-induced rats and showed that it mainly acts by a hypoglycemic effect and activation of renal AMPK/SIRT1 axis. Given the wide tissue stimulatory effect of AMPK on peripheral glucose utilization, lipogenesis, and other cell signaling pathways, these data are encouraging to investigate the anti-diabetic effect of glycoside in more clinical trials.