Diabetic neuropathy is a peripheral nervous system disorder affecting both somatic and autonomic components of nervous system. A growing body of evidence have depicted that high glucose levels can induce activation of the Wnt/β‐catenin pathway, however there are no studies targeting this pathway in DN. The intent of the present study was to investigate the effects of isoquercitrin (ISQ), a Wnt/β‐catenin signaling pathway inhibitor, in diabetic neuropathy. Streptozotocin (50 mg/kg, i.p.) was used to induce diabetes in rats. 6‐week diabetic rats were treated intrathecally with ISQ at 10 and 30 μM doses for 3 days. Furthermore, to confirm the results of the intrathecal study, a 2‐week intraperitoneal treatment of ISQ was given to diabetic rats. After 6 weeks, diabetic rats developed neuropathy which was evident from reduced thermal and mechanical hyperalgesia thresholds and significant deterioration in motor nerve conduction velocity (MNCV), nerve blood flow (NBF). Sciatic nerves of diabetic neuropathy rats showed increased expression of Wnt pathway proteins namely β‐catenin, c‐myc and MMP2. Treatment with ISQ, both intrathecally (10 and 30 μM) and intraperitoneally (10 mg/kg), significantly ameliorated the alterations in behavioral pain thresholds and improved functional parameters in diabetic rats. Moreover, ISQ also downregulated the expression of Wnt/β‐catenin pathway proteins significantly in diabetic rats as compared to vehicle‐treated diabetic rats. Results of the present study suggest the neuroprotective potential of ISQ in the treatment of DN via inhibition of Wnt/β‐catenin signaling pathway.

中文翻译：

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异槲皮苷通过Wnt /β-catenin信号通路抑制对糖尿病神经病变的神经保护作用。

糖尿病性神经病是一种周围神经系统疾病，会影响神经系统的躯体和自主神经。越来越多的证据表明，高葡萄糖水平可以诱导Wnt /β-catenin途径的激活，但是目前尚无针对DN的针对该途径的研究。本研究的目的是研究Wnt /β-catenin信号通路抑制剂异槲皮苷（ISQ）在糖尿病性神经病中的作用。链脲佐菌素（50 mg / kg，腹膜内）用于诱导大鼠糖尿病。对6周的糖尿病大鼠进行10到30μM剂量的ISQ鞘内治疗3天。此外，为证实鞘内研究的结果，对糖尿病大鼠进行了为期2周的ISQ腹膜内治疗。6周后 糖尿病大鼠发展为神经病，这可以从降低的热痛觉过敏和机械痛觉过敏阈值以及运动神经传导速度（MNCV），神经血流（NBF）的明显恶化中看出。糖尿病性神经病大鼠的坐骨神经显示出Wnt通路蛋白即β-catenin，c-myc和MMP2的表达增加。鞘内（10和30μM）和腹膜内（10 mg / kg）ISQ的治疗显着改善了糖尿病大鼠行为痛阈值的改变和功能参数的改善。此外，与溶媒治疗的糖尿病大鼠相比，ISQ还显着下调了糖尿病大鼠中Wnt /β-catenin途径蛋白的表达。本研究结果表明，ISQ可通过抑制Wnt /β-catenin信号通路来保护DN。