Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

Fatani,Amal  Jamil; Al‑Rejaie,Salim  Salih; Abuohashish,Hatem  Mustafa; Al‑Assaf,Abdullah; Parmar,Mihir  Yogeshkumar; Ola,Mohammad  Shamsul; Ahmed,Mohammed  Mahboobuddin

doi:10.3892/etm.2015.2305

Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

Authors:
- Amal Jamil Fatani
- Salim Salih Al‑Rejaie
- Hatem Mustafa Abuohashish
- Abdullah Al‑Assaf
- Mihir Yogeshkumar Parmar
- Mohammad Shamsul Ola
- Mohammed Mahboobuddin Ahmed
View Affiliations

Affiliations: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11544, Saudi Arabia, Department of Biochemistry, College of Science, King Saud University, Riyadh 11544, Saudi Arabia
Published online on: February 20, 2015 https://doi.org/10.3892/etm.2015.2305
Pages: 1670-1678
Copyright: © Fatani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Callaghan BC, Little AA, Feldman EL and Hughes RA: Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 6:CD0075432012.PubMed/NCBI
2	Galer BS, Gianas A and Jensen MP: Painful diabetic polyneuropathy: Epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 47:123–128. 2000. View Article : Google Scholar : PubMed/NCBI
3	Cameron NE and Cotter MA: Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes. Diabetes Res Clin Pract. 45:137–146. 1999. View Article : Google Scholar : PubMed/NCBI
4	Stevens MJ, Obrosova I, Cao X, Van Huysen C and Greene DA: Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes. 49:1006–1015. 2000. View Article : Google Scholar : PubMed/NCBI
5	Calcutt NA: Experimental models of painful diabetic neuropathy. J Neurol Sci. 220:137–139. 2004. View Article : Google Scholar : PubMed/NCBI
6	Sima AA, Zhang W, Xu G, et al: A comparison of diabetic polyneuropathy in type II diabetic BBZDR/Wor rats and in type I diabetic BB/Wor rats. Diabetologia. 43:786–793. 2000. View Article : Google Scholar : PubMed/NCBI
7	Edwards JL, Vincent AM, Cheng HT and Feldman EL: Diabetic neuropathy: Mechanisms to management. Pharmacol Ther. 120:1–34. 2008. View Article : Google Scholar : PubMed/NCBI
8	Ceriello A: Controlling oxidative stress as a novel molecular approach to protecting the vascular wall in diabetes. Curr Opin Lipidol. 17:510–518. 2006. View Article : Google Scholar : PubMed/NCBI
9	Figueroa-Romero C, Sadidi M and Feldman EL: Mechanisms of disease: The oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord. 9:301–314. 2008. View Article : Google Scholar : PubMed/NCBI
10	Zherebitskaya E, Akude E, Smith DR and Fernyhough P: Development of selective axonopathy in adult sensory neurons isolated from diabetic rats: Role of glucose-induced oxidative stress. Diabetes. 58:1356–1364. 2009. View Article : Google Scholar : PubMed/NCBI
11	Cunha JM, Jolivalt CG, Ramos KM, Gregory JA, Calcutt NA and Mizisin AP: Elevated lipid peroxidation and DNA oxidation in nerve from diabetic rats: Effects of aldose reductase inhibition, insulin, and neurotrophic factors. Metabolism. 57:873–881. 2008. View Article : Google Scholar : PubMed/NCBI
12	Yeh GY, Eisenberg DM, Kaptchuk TJ and Phillips RS: Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 26:1277–1294. 2003. View Article : Google Scholar : PubMed/NCBI
13	Kanetkar P, Singhal R and Kamat M: Gymnema sylvestre: A Memoir. J Clin Biochem Nutr. 41:77–81. 2007. View Article : Google Scholar : PubMed/NCBI
14	Daisy P, Eliza J and Mohamed Farook KA: A novel dihydroxy gymnemic triacetate isolated from Gymnema sylvestre possessing normoglycemic and hypolipidemic activity on STZ-induced diabetic rats. J Ethnopharmacol. 126:339–344. 2009. View Article : Google Scholar : PubMed/NCBI
15	Ramkumar KM, Ponmanickam P, Velayuthaprabhu S, Archunan G and Rajaguru P: Protective effect of Gymnema montanum against renal damage in experimental diabetic rats. Food Chem Toxicol. 47:2516–2521. 2009. View Article : Google Scholar : PubMed/NCBI
16	Grover JK, Yadav S and Vats V: Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol. 81:81–100. 2002. View Article : Google Scholar : PubMed/NCBI
17	Ye WC, Zhang QW, Liu X, Che CT and Zhao SX: Oleanane saponins from Gymnema sylvestre. Phytochemistry. 53:893–899. 2000. View Article : Google Scholar : PubMed/NCBI
18	Surveswaran S, Cai YZ, Xing J, Corke H and Sun M: Antioxidant properties and principal phenolic phytochemicals of Indian medicinal plants from Asclepiadoideae and Periplocoideae. Nat Prod Res. 24:206–221. 2010. View Article : Google Scholar : PubMed/NCBI
19	Al-Rejaie SS, Abuohashish HM, Ahmed MM, Aleisa AM and Alkhamees O: Possible biochemical effects following inhibition of ethanol-induced gastric mucosa damage by Gymnema sylvestre in male Wistar albino rats. Pharm Biol. 50:1542–1550. 2012. View Article : Google Scholar : PubMed/NCBI
20	Aleisa AM, Al-Rejaie SS, Abuohashish HM, Ola MS, Parmar MY and Ahmed MM: Pretreatment of Gymnema sylvestre revealed the protection against acetic acid-induced ulcerative colitis in rats. BMC Complement Altern Med. 14:492014. View Article : Google Scholar : PubMed/NCBI
21	Sedlak J and Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellmans reagent. Anal Biochem. 25:192–205. 1968. View Article : Google Scholar : PubMed/NCBI
22	Kono Y: Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys. 186:189–195. 1978. View Article : Google Scholar : PubMed/NCBI
23	Aebi H: CatalaseMethods in Enzymatic Analysis. Bergmeyer: New York: pp. 674–684. 1974
24	Kamboj SS, Vasishta RK and Sandhir R: N-acetylcysteine inhibits hyperglycemia-induced oxidative stress and apoptosis markers in diabetic neuropathy. J Neurochem. 112:77–91. 2010. View Article : Google Scholar : PubMed/NCBI
25	Al Sharari SD, Al-Rejaie SS, Abuohashish HM, Aleisa AM, Parmar MY and Ahmed MM: Ameliorative potential of morin in streptozotocin-induced neuropathic pain in rats. Trop J Pharm Res. 13:1429–1436. 2014. View Article : Google Scholar
26	El Shafey AAM, El-Ezabi MM, Seliem MME, Ouda HHM and Ibrahim DS: Effect of Gymnema sylvestre R. Br. leaves extract on certain physiological parameters of diabetic rats. Journal of King Saud University – Science. 25:135–141. 2013. View Article : Google Scholar
27	Verma N, Shakya VK and Saxena RC: Antidiabetic activity of glycoside isolated from Gymnema sylvestre in streptozotocin induced diabetic rats. Asian J Chem. 20:5033–5036. 2008.
28	Yoshioka S: Inhibitory effects of gymnemic acid and an extract from the leaves of Ziziphus jujuba on glucose absorption in the rat small intestine. J Yonago Med Assoc. 37:142–154. 1986.
29	Fushiki T, Kojima A, Imoto T, Inoue K and Sugimoto E: An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucose-stimulated gastric inhibitory peptide secretion in rats. J Nutr. 122:2367–2373. 1992.PubMed/NCBI
30	Sahu NP, Mahato SB, Sarkar SK and Poddar G: Triterpenoid saponins from Gymnema sylvestre. Phytochemistry. 41:1181–1185. 1996. View Article : Google Scholar : PubMed/NCBI
31	Bolajoko EB, Mossanda KS, Adeniyi F, Akinosun O, Fasanmade A and Moropane M: Antioxidant and oxidative stress status in type 2 diabetes and diabetic foot ulcer. S Afr Med J. 98:614–617. 2008.PubMed/NCBI
32	Julius U, Drel VR, Grässler J and Obrosova IG: Nitrosylated proteins in monocytes as a new marker of oxidative-nitrosative stress in diabetic subjects with macroangiopathy. Exp Clin Endocrinol Diabetes. 117:72–77. 2009. View Article : Google Scholar : PubMed/NCBI
33	Bonnefont-Rousselot D: Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care. 5:561–568. 2002. View Article : Google Scholar : PubMed/NCBI
34	Halliwell B: Drug antioxidant effects. A basis for drug selection? Drugs. 42:569–605. 1991. View Article : Google Scholar : PubMed/NCBI
35	Preuss HG, Jarrell ST, Scheckenbach R, Lieberman S and Anderson RA: Comparative effects of chromium, vanadium and Gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr. 17:116–123. 1998. View Article : Google Scholar : PubMed/NCBI
36	Kang MH, Lee MS, Choi MK, Min KS and Shibamoto T: Hypoglycemic activity of Gymnema sylvestre extracts on oxidative stress and antioxidant status in diabetic rats. J Agric Food Chem. 60:2517–2524. 2012. View Article : Google Scholar : PubMed/NCBI
37	Kumar V, Bhandari U, Tripathi CD and Khanna G: Evaluation of antiobesity and cardioprotective effect of Gymnema sylvestre extract in murine model. Indian J Pharmacol. 44:607–613. 2012. View Article : Google Scholar : PubMed/NCBI
38	Sharma K, Singh U, Vats S, Priyadarsini K, Bhatia A and Kamal R: Evaluation of evidenced-based radioprotective efficacy of Gymnema sylvestre leaves in mice brain. J Environ Pathol Toxicol Oncol. 28:311–323. 2009. View Article : Google Scholar : PubMed/NCBI
39	Rachh PR, Patel SR, Hirpara HV, et al: In vitro evaluation of antioxidant activity of Gymnema sylvestre R. BR. leaf extract. Rom J Biol. 54:141–148. 2009.
40	Brownlee M: The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 54:1615–1625. 2005. View Article : Google Scholar : PubMed/NCBI
41	Navarro-González JF and Mora-Fernández C: The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 19:433–442. 2008. View Article : Google Scholar : PubMed/NCBI
42	Li J, Wei GH, Huang H, Lan YP, Liu B, Liu H, Zhang W and Zuo YX: Nerve injury-related autoimmunity activation leads to chronic inflammation and chronic neuropathic pain. Anesthesiology. 118:416–429. 2013. View Article : Google Scholar : PubMed/NCBI
43	Djordjevic A, Bursać B, Veličković N, Vasiljević A and Matić G: The impact of different fructose loads on insulin sensitivity, inflammation, and PSA-NCAM-mediated plasticity in the hippocampus of fructose-fed male rats. Nutr Neurosci. 18:66–75. 2015. View Article : Google Scholar : PubMed/NCBI
44	Diwan PV, Margaret I and Ramakrishna S: Influence of Gymnema sylvestre on inflammation. Inflammopharmacology. 3:271–277. 1995. View Article : Google Scholar
45	Jitender KM, Manvi F, Alagawadi K and Noolvi M: Evaluation of anti-inflammatory activity of Gymnema sylvestre leaves extract in rats. IJGP. 2:114–115. 2008.
46	Yasukawa K, Okuda S and Nobushi Y: Inhibitory effects of Gymnema (Gymnema sylvestre) leaves on tumour promotion in two-stage mouse skin carcinogenesis. Evid Based Complement Alternat Med. 2014:3286842014. View Article : Google Scholar : PubMed/NCBI
47	Scarth JP: Modulation of the growth hormone-insulin-like growth factor (GH-IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: An emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review. Xenobiotica. 36:119–218. 2006. View Article : Google Scholar
48	Freeman RS, Burch RL, Crowder RJ, Lomb DJ, Schoell MC, Straub JA and Xie L: NGF deprivation-induced gene expression: After ten years, where do we stand? Prog Brain Res. 146:111–126. 2004. View Article : Google Scholar : PubMed/NCBI