Chen Ming-Ming, Qin Jing, Chen Shu-Jian, Yao Le-Meng, Zhang Lu-Yong, Yin Zhi-Qi, Liao Hong
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
University Medical Center Groningen, University of Groningen, Amsterdam, the Netherlands.
J Nutr Biochem. 2017 Aug;46:57-67. doi: 10.1016/j.jnutbio.2017.04.006. Epub 2017 Apr 17.
Injuries and diseases that occur in the nervous system are common and have few effective treatments. Previous studies have shown that quercetin has a therapeutic effect on nervous system injuries, but its potential effects on and mechanisms of action related to behavioral recovery and axonal regrowth have not been investigated. Here, we showed that quercetin administration promotes behavioral recovery following sciatic nerve-crush injury in mice. Long-term evaluation showed that mice administered 20 mg·kg·day quercetin for 35 days had a greater sensorimotor recovery compared with all other treatment groups. The mechanisms behind these effects were further investigated, and quercetin was found to regulate the expression of genes involved in regeneration and trophic support. Moreover, quercetin increased cyclic adenosine monophosphate expression and downstream pathway activation, which directly leads to neuronal growth activation in peripheral axon regeneration. In addition, quercetin enhanced axon remyelination, motor nerve conduction velocity and plantar muscle function, indicating that the degree of distal portion hypotrophy during the peripheral axon regeneration process was reduced. These results suggest that quercetin accelerates functional recovery by up-regulating neuronal intrinsic growth capacity and postponing distal atrophy. Overall, quercetin triggered multiple effects to promote behavioral recovery following sciatic nerve-crush injury in mice.
神经系统中发生的损伤和疾病很常见，且有效治疗方法很少。先前的研究表明，槲皮素对神经系统损伤具有治疗作用，但其对行为恢复和轴突再生的潜在影响及作用机制尚未得到研究。在此，我们表明给予槲皮素可促进小鼠坐骨神经挤压伤后的行为恢复。长期评估显示，连续35天给予20mg·kg·天槲皮素的小鼠与所有其他治疗组相比，感觉运动恢复更好。我们进一步研究了这些作用背后的机制，发现槲皮素可调节参与再生和营养支持的基因表达。此外，槲皮素增加了环磷酸腺苷的表达并激活了下游通路，这直接导致外周轴突再生中的神经元生长激活。此外，槲皮素增强了轴突髓鞘再生、运动神经传导速度和足底肌肉功能，表明外周轴突再生过程中远端部分萎缩的程度降低。这些结果表明，槲皮素通过上调神经元内在生长能力和延缓远端萎缩来加速功能恢复。总体而言，槲皮素引发了多种效应，以促进小鼠坐骨神经挤压伤后的行为恢复。
