Tian Ruifeng, Yang Wenqing, Xue Qiang, Gao Liang, Huo Junli, Ren Dongqing, Chen Xiaoyan
Department of Infectious Disease, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Lin-tong Sanitarium of Land Force, Lanzhou Military Region of PLA, Xi'an 710600, China.
Eur J Pharmacol. 2016 Jan 15;771:84-92. doi: 10.1016/j.ejphar.2015.12.021. Epub 2015 Dec 10.
Rutin exhibits antidiabetic, antioxidant and anti-inflammatory properties, which makes rutin an attractive candidate for diabetic complications. The present study was designed to investigate the potential effect of rutin on diabetic neuropathy. After induction of diabetic neuropathy, rutin (5mg/kg, 25mg/kg and 50mg/kg) were daily given to the diabetic rats for 2 weeks. At the end of rutin administration, rutin produced a significant inhibition of mechanical hyperalgesia, thermal hyperalgesia and cold allodynia, as well as partial restoration of nerve conduction velocities in diabetic rats. Furthermore, rutin significantly increased Na(+), K(+)-ATPase activities in sciatic nerves and decreased caspase-3 expression in dorsal root ganglions (DRG). In addition, rutin significantly decreased plasma glucose, attenuated oxidative stress and neuroinflammation. Further studies showed that rutin significantly increased hydrogen sulfide (H2S) level, up-regulated the expression of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in DRG. The evidences suggest the beneficial effect of rutin on diabetic neuropathy. Additionally, insulin (2 IU) and BG-12 (15mg/kg) were used to investigate the mechanisms underlying the beneficial effect of rutin on diabetic neuropathy. Insulin achieved lower plasma glucose and BG-12 achieved comparable Nrf2 expression than/to rutin (50mg/kg), respectively. In contrast, the beneficial effect of insulin and BG-12 was inferior to that of rutin (50mg/kg), suggesting that both lowered plasma glucose and Nrf2 signaling contribute to the beneficial effect of rutin on diabetic neuropathy. In conclusion, rutin produces significant protection in diabetic neuropathy, which makes it an attractive candidate for the treatment of diabetic neuropathy.
芦丁具有抗糖尿病、抗氧化和抗炎特性，这使得芦丁成为糖尿病并发症的一个有吸引力的候选药物。本研究旨在探讨芦丁对糖尿病神经病变的潜在作用。诱导糖尿病神经病变后，将芦丁（5mg/kg、25mg/kg和50mg/kg）每日给予糖尿病大鼠，持续2周。在芦丁给药结束时，芦丁显著抑制了糖尿病大鼠的机械性痛觉过敏、热痛觉过敏和冷觉异常，同时部分恢复了神经传导速度。此外，芦丁显著增加了坐骨神经中Na(+)、K(+)-ATP酶活性，并降低了背根神经节（DRG）中caspase-3的表达。此外，芦丁显著降低了血糖，减轻了氧化应激和神经炎症。进一步研究表明，芦丁显著提高了DRG中硫化氢（H2S）水平，上调了核因子E2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的表达。这些证据表明芦丁对糖尿病神经病变具有有益作用。此外，使用胰岛素（2 IU）和BG-12（15mg/kg）来研究芦丁对糖尿病神经病变有益作用的潜在机制。胰岛素分别使血糖降低，BG-12使Nrf2表达与芦丁（50mg/kg）相当。相比之下，胰岛素和BG-12的有益作用不如芦丁（50mg/kg），这表明降低血糖和Nrf2信号传导均有助于芦丁对糖尿病神经病变的有益作用。总之，芦丁对糖尿病神经病变具有显著的保护作用，这使其成为治疗糖尿病神经病变的一个有吸引力的候选药物。
