Mitochondrial dysfunction has been implicated as a one of the major factors linked to the development of painful diabetic neuropathy (DN). Several studies have demonstrated that sirtuin (SIRT1) activation recuperates nerve function by activating mitochondrial biogenesis. Polydatin, a resveratrol glycoside, has been explored to improve mitochondrial function via SIRT1 activation. However, the neuroprotective effects of polydatin in DN remain elusive. In this study, polydatin (25 and 50 mg/kg, oral) was administered for last 2 weeks of 8-week study to diabetic Sprague–Dawley rats weighing 250–300 g (post 6-weeks of streptozotocin 55 mg/kg, intraperitoneal). Treatment with polydatin significantly attenuated mechanical and thermal hyperalgesia in diabetic rats. Treated diabetic rats also showed improvement in motor/sensory nerve conduction velocities and nerve blood flow. For in vitro studies, Neuro2a cells were exposed to high-glucose (30 mM) condition to simulate short-term hyperglycemia. Polydatin was evaluated for its role in SIRT1 and Nrf2 activation at a dose of 5, 10, and 20 µM concentrations. Polydatin exposure normalized the mitochondrial superoxides, membrane potentials and improved neurite outgrowth in high-glucose-exposed Neuro2a cells. Increased SIRT1 activation by polydatin resulted in peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) directed mitochondrial biogenesis. SIRT1 activation also facilitated Nrf2-directed antioxidant signaling. Study results inferred that decline in mitochondrial biogenesis and oxidative function in diabetic rats and high-glucose-exposed Neuro2a cells, could be counteracted by polydatin administration, postulated via enhancing SIRT1 and Nrf2 axis.

线粒体功能障碍被认为是与疼痛性糖尿病神经病变 (DN) 发展相关的主要因素之一。几项研究表明，sirtuin (SIRT1) 激活通过激活线粒体生物发生来恢复神经功能。Polydatin 是一种白藜芦醇糖苷，已被探索通过 SIRT1 激活来改善线粒体功能。然而，虎杖苷在 DN 中的神经保护作用仍然难以捉摸。在这项研究中，在为期 8 周的研究的最后 2 周，对体重为 250-300 g 的糖尿病 Sprague-Dawley 大鼠给予虎杖苷（25 和 50 mg/kg，口服）（55 mg/kg 链脲佐菌素 6 周后，腹膜内给药） ）。用虎杖苷治疗可显着减轻糖尿病大鼠的机械和热痛觉过敏。接受治疗的糖尿病大鼠也表现出运动/感觉神经传导速度和神经血流的改善。对于体外研究，Neuro2a 细胞暴露于高葡萄糖 (30 mM) 条件下以模拟短期高血糖。在 5、10 和 20 µM 浓度的剂量下，评估了 Polydatin 在 SIRT1 和 Nrf2 激活中的作用。黄连素暴露使高葡萄糖暴露的 Neuro2a 细胞中的线粒体超氧化物、膜电位和改善的神经突生长正常化。虎杖苷对 SIRT1 的激活增加导致过氧化物酶体增殖物激活受体-γ 共激活因子 1α (PGC-1α) 定向线粒体生物发生。SIRT1 激活也促进了 Nrf2 导向的抗氧化信号。