Diabetic peripheral neuropathy (DPN) is considered as one of the most important complications of diabetes mellitus. At present, effective treatments that might improve the damaged neurological function in DPN are sorely needed. As myricetin has been proved to possess excellent neuroprotective and antioxidant effects, it might have therapeutic potential for DPN. Therefore, the purpose of our study was to detect the potential beneficial effect of myricetin on DPN. A single dose of 50 mg/kg of streptozotocin was applied in rats for the establishment of diabetic models. Different doses of myricetin (0.5 mg/kg/day, 1.0 mg/kg/day, and 2.0 mg/kg/day) were intraperitoneally injected for 2 weeks from the 21st day after streptozotocin injection. After the final myricetin injection, behavioral, electrophysiological, biochemical, and protein analyses were performed. In the present study, myricetin significantly ameliorated diabetes-induced impairment in sensation, nerve conduction velocities, and nerve blood flow. In addition, myricetin significantly reduced the generation of advanced glycation end-products (AGEs) and reactive oxygen species (ROS), and elevated Na⁺, K⁺-ATPase activity and antioxidant activities in nerves in diabetic animals. Additional studies revealed that myricetin significantly raised the hydrogen sulfide (H₂S) levels, and elevated the expression level of heme oxygenase-1 (HO-1) as well as nuclear factor-E2-related factor-2 (Nrf2) in diabetic rats. In addition, myricetin has the capability of decreasing plasma glucose under diabetic conditions. The findings in our present study collectively indicated that myricetin could restore the impaired motor and sensory functions under diabetic conditions. The Nrf2-dependent antioxidant action and the capability of decreasing plasma glucose might be the underlying mechanisms for the beneficial effect of myricetin on impaired neural functions. Our study showed the therapeutic potential of myricetin in the management of DPN.

In our previous study, metformin was able to promote nerve regeneration after sciatic nerve crushing in rats under diabetic conditions. However, a crush injury also has a strong ability to spontaneously recover. Therefore, in our present study, a model of transection injury of the sciatic nerve in diabetic rats was utilized to detect whether metformin could still promote nerve regeneration. Diabetes was induced via an injection of 50 mg/kg of streptozotocin in rats. After transection injury of the sciatic nerve, the rats were randomly divided into a high-dose metformin group (500 mg/kg/d), mid-dose metformin group (200 mg/kg/d), low-dose metformin group (30 mg/kg/d) and control group (normal saline). The metformin or normal saline was intraperitoneally injected for 4 weeks. Then, behavioral, electrophysiological and morphometric analyses were performed. The results showed that metformin could significantly promote functional restoration and axonal regeneration of the sciatic nerve after transection injury under diabetic conditions. Furthermore, high doses and middle doses of metformin presented more of this ability than a low dose of metformin. In conclusion, metformin is able to accelerate sciatic nerve repair after transection injury under diabetic conditions, showing the therapeutic potential of metformin in the management of nerve injuries during diabetes mellitus.