Isoquercitrin promotes peripheral nerve regeneration through inhibiting oxidative stress following sciatic crush injury in mice

Abstract

Background: Oxidative stress has been recognized to play a crucial role in the pathogenesis of peripheral nerve injury. Isoquercitrin (quercetin-3-glucoside) is a flavonoid that exhibited many biological activities, including antioxidative effect. However, it is unclear whether isoquercitrin has protective effects on peripheral nerve injury.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: Isoquercitrin may promote motor functional recovery and nerve regeneration following peripheral nerve injury though inhibition of oxidative stress, which highlighted the therapeutic values of isoquercitrin as a neuroprotective drug for peripheral nerve repair applications.

<p>Ulinastatin Promotes Regeneration of Peripheral Nerves After Sciatic Nerve Injury by Targeting let-7 microRNAs and Enhancing NGF Expression</p>

“…37,38 For example, isoquercitrin treatment significantly increases the production of GAP43, NF200, MAG, and PMP22, and promotes the nerve regeneration and remyelination. 39 Our results revealed that UTI administration increased the expression of these markers, which suggested that UTI promoted the functional recovery of peripheral nerve by facilitating the axonal outgrowth and remyelination.…”

Isoquercitrin Ameliorates Cisplatin-Induced Nephrotoxicity Via the Inhibition of Apoptosis, Inflammation, and Oxidative Stress

“…First, IQC treatment ameliorated the excessive reactive oxygen species production, and exacerbated the anti-oxygen activity (superoxide dismutase and catalase modulation) in vivo and in vitro after ischemia/reperfusion (Dai et al, 2018). According to a report, IQC promoted peripheral nerve regeneration following nerve injury through suppress of oxidative stress in mice (Qiu et al, 2019). Furthermore, IQC exerted a protective part in apoptosis.…”

Green Tea Polyphenols Promote Functional Recovery from Peripheral Nerve Injury in Rats

“…Interestingly, there are also other agents applied for treatment of PNI. For instance, quercetin induces neurite growth by promoting GAP-43 expression [ 37 ], and isoquercitrin promotes peripheral nerve regeneration and remyelination after sciatic crush injury in mice [ 38 ]. The effects of GTPs on peripheral nerve regeneration and remyelination are similar to those of isoquercitrin.…”