METHODS: Mice treated by
isoquercitrin were used as a case group, and mice injected with saline was the control group. Sciatic behavioral function was assessed using SFI and CMAPs were measured by electrophysiology. Schwann cells proliferation and migration were tested using EdU staining and Transwell migration chambers respectively. The expression of oxidative stress related factors were detected by qRT-PCR and Western blotting.
RESULTS: In present study, our results demonstrated that
isoquercitrin (20 mg/kg/day) treatment achieved significantly higher SFI and higher amplitude of CMAP, promoted the nerve regeneration and remyelination, increased the production of GAP43, NF200, MAG and PMP22, alleviated target
muscle atrophy and autophagy, and suppressed the expression of ATG7, PINK1 and
Beclin1 in soleus muscles after sciatic nerve crush. In vitro studies found that
isoquercitrin promoted the axonal regeneration of DRGs neurons, the proliferation and migration of Schwann cells, and the expression of
proliferating cell nuclear antigen (
PCNA) in Schwann cells. The administration of
isoquercitrin at 40 and 320 µM showed a dose dependent, and high doses of
isoquercitrin (160 and 320 µM) showed better performance in promoting axonal regeneration of DRGs neurons, and the proliferation and migration of Schwann cells than low dose of
isoquercitrin (40 µM). Furthermore,
isoquercitrin significantly inhibited oxidative stress through reducing the production of Nox4 and
Duox1, and promoting the expression of Nrf2 and SOD2 in soleus muscles after sciatic nerve crush.
CONCLUSIONS: