title: Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats.
abstract: 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.
authors.affiliation: Department of Infectious Disease, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Tian
authors.affiliation: Lin-tong Sanitarium of Land Force, Lanzhou Military Region of PLA, Xi'an 710600, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Ultrasonography, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Huo
authors.affiliation: Department of Radiation Medicine and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: dongqingren@163.com.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: xiaoyanchenfmmu@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D003929:Diabetic Neuropathies / Q000097:blood* / Q000188:drug therapy*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D051267:NF-E2-Related Factor 2; D012431:Rutin; D051547:Heme Oxygenase-1; C505410:Casp3 protein, rat; D053148:Caspase 3; D000254:Sodium-Potassium-Exchanging ATPase; D006862:Hydrogen Sulfide
keywords: Diabetic neuropathy; Hydrogen sulfide; Neuroinflammation; Nrf2; Oxidative stress; Rutin