title: Neuroprotective effects ofGymnema sylvestreon streptozotocin-induced diabetic neuropathy in rats.
abstract: The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia.
authors.forename: Amal Jamil
authors.initials: AJ
authors.lastname: Fatani
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia.
authors.forename: Salim Salih
authors.initials: SS
authors.lastname: Al-Rejaie
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia ; Department of Biomedical Dental Sciences, College of Dentistry, University of Dammam, Dammam, Eastern Province 31441, Saudi Arabia.
authors.forename: Hatem Mustafa
authors.initials: HM
authors.lastname: Abuohashish
authors.affiliation: Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11544, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Assaf
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia.
authors.forename: Mihir Yogeshkumar
authors.initials: MY
authors.lastname: Parmar
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11544, Saudi Arabia.
authors.forename: Mohammad Shamsul
authors.initials: MS
authors.lastname: Ola
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia.
authors.forename: Mohammed Mahboobuddin
authors.initials: MM
authors.lastname: Ahmed
keywords: Gymnema sylvestre; hyperglycemic neuropathy; inflammation; oxidative stress