Vadivelan Ramachandran, Ibrahim Khan, Sudeep Sugumar, Vikash Sundaram
Vadivelan Ramachandran, Ibrahim Khan, Sudeep Sugumar, Vikash Sundaram
Department of Pharmacology, JSS College of Pharmacy JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India.
Volume - 13,
Issue - 10,
Year - 2020
Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of berberine an anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative-nitrosative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic Wistar rats were treated with berberine for 6 weeks at 50 and 100 mg/kg/day. During fifth week of treatment, learning and memory was investigated in single Y-maze and passive avoidance test. At the end of the study biochemical parameters like acetylcholinesterase (AchE) activity, nitrite levels, tumor necrosis factor-alpha (TNF-a) and oxidative stress was measured from cerebral cortex and hippocampus regions of brain. AchE activity was found increased by 56 % in the cerebral cortex of diabetic rat brain. Lipid peroxidation (LPO) levels were increased by 100 % and 95 % in cerebral cortex and hippocampus of diabetic rats, respectively. Nonprotein thiol levels, enzymatic activities of superoxide dismutase and catalase were found decreased in cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in both regions of diabetic brain were increased significantly (P < 0.05) compared to control group. TNF-a, a pro-inflammatory cytokine, was found significantly increased in diabetic rats. Conversely, animal groups treated with significantly attenuated these behavioral and biochemical abnormalities. The results suggest a protective role of berberine against diabetic encephalopathy, which may be sum of its anti-oxidant, anti-cholinesterase, anti-inflammatory and glucose lowering action.
Cite this article:
Vadivelan Ramachandran, Ibrahim Khan, Sudeep Sugumar, Vikash Sundaram. Antioxidant, Anti-inflammatory and Anticholinergic action of berberine attenuates diabetic encephalopathy: Behavioral and Biochemical evidences. Research J. Pharm. and Tech. 2020; 13(10):4550-4556. doi: 10.5958/0974-360X.2020.00802.1
Vadivelan Ramachandran, Ibrahim Khan, Sudeep Sugumar, Vikash Sundaram. Antioxidant, Anti-inflammatory and Anticholinergic action of berberine attenuates diabetic encephalopathy: Behavioral and Biochemical evidences. Research J. Pharm. and Tech. 2020; 13(10):4550-4556. doi: 10.5958/0974-360X.2020.00802.1 Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-10-5
1. Crosby-Nwaobi R, Sivaprasad S, Forbes A, Crosby-Nwaobi R. A systematic review of the association of diabetic retinopathy and cognitive impairment in people with type 2 diabetes. Diabetes Res Clin Pract. 2012; 96:101-10.
2. Bloomgarden, Z.T. 2007. Diabetic Neuropathy. Diabetes Care 30, 1027–1032.
3. Biessels G.J, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006; 5:64-74.
4. Awad N, Gagnon M, Messier C. The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J. Clin. Exp. Neuropsychol. 2004; 26: 1044-1080.
5. Sinclair AJ, Girling J, Bayer AJ. Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study. Diabetes Res. Clin. Pract. 2000; 50:203-212.
6. Mastrocola R, Restivo F, Vercellinatto I, Danni O, Brignardello E, Aragno M, Boccuzzi G. Oxidative and nitrosative stress in brain mitochondria of diabetic rats. J. Endocrinol. 2005; 187: 37-44.
7. Somfai G.M, Knippel B, Ruzicska E, Stadler K, Toth M, Salacz G, Magyar K, Somogyi A. Soluble semicarbazide-sensitive amine oxidase (SSAO) activity is related to oxidative stress and subchronic inflammation in streptozotocin-induced diabetic rats. Neurochem. Int. 2006; 48: 746-752.
8. Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S. Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann. N.Y. Acad. Sci. 2001; 928: 168-175.
9. Tuzcu M, Baydas G.. Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Eur. J. Pharmacol. 2006; 537: 106-110.
10. Ye M, Fu S, Pi R, He F. Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research. J Pharm Pharm Sci. 2009; 61:831-837.
11. Gao F, Gao Y, Liu Y-f, Wang L, Li Y-j. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat. Neuropsychiatr Dis Treat. 2014; 10:2139-2145.
12. Pires ENS, Frozza RL, Hoppe JB, de Melo Menezes B, Salbego CG. Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res. 2014; 1557:26-33.
13. Moghaddam HK, Baluchnejadmojarad T, Roghani M, Khaksari M, Norouzi P, Ahooie M, et al. ameliorate oxidative stress and astrogliosis in the hippocampus of STZinduced diabetic rats. Mol Neurobiol 2014; 49:820-826.
14. Kuhad A, Chopra K. Curcumin attenuates diabetic encephalopathy in rats: Behavioral and biochemical evidences. Eur J Pharmacol. 2007; 576: 34-42.
15. Iwai T, Iinuma Y, Kodani R, Oka J. Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell death in rodents. Neurosci Res. 2008; 61:113-9.
16. Baydas G, Nedzvetskii VS, Nerush PA, Kirichenko SV, Yoldas T. Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin induced diabetes mellitus. Life Sci. 2003; 73: 1907-16.
17. Hasanein P, Shahidi S. Effects of combined treatment with vitamins C and E on passive avoidance learning and memory in diabetic rats. Neurobiol Learn Mem. 2010; 93: 472-8.
18. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7: 88-95.
19. Wills ED. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966; 99: 667-76.
20. Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenze induced liver necrosis: Protective role of glutathione and evidence for 3, 4-bromobenzenoxide as the hepatotoxic intermediate. Pharmacol. 1974; 11:151-69.
21. Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys. 1978; 186:189-95.
22. Claiborne A. Catalase activity. In: Greenwald RA, Raton B, editors. Handbook of methods for oxygen radical research. Florida: CRC Press; 1985. p. 283-4.
23. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem. 1982; 126: 131-8.
24. Roriz-Filho JS, Sa-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves MLF, et al. (Pre) diabetes, brain aging, and cognition. Biochim Biophys Acta. 2009; 1792: 432-43.
25. Sima AAF. Encephalopathies: The emerging diabetic complications. Acta Diabetol. 2010; 47:279-93.
26. Kamboj SS, Chopra K, Sandhir R. Neuroprotective effect of Nacetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes. Metab Brain Dis. 2008; 23:427-43.
27. Bhutada P, Mundhada Y, Bansod K, Tawari S, Patil S, Dixit P, et al. Protection of cholinergic and antioxidant system contributes to the effect of ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav Brain Res. 2011; 220:30-41.
28. Bhutada P, Mundhada Y, Bansod K, Bhutada C, Tawari S, Dixit P, et al. Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats. Neurobiol Learn Mem. 2010; 94:293–302
29. Hong H, Liu LP, Liao JM, Wang TS, Ye FY, Wu J, et al. Downregulation of LPR1 at the blood–brain barrier in streptozotocin-induced diabetic mice. Neuropharmacol. 2009; 56:1054–59.
30. Liu Y, Liu H, Yang J, Liu X, Lu S, Wen T, et al. Increased amyloid β- peptide (1–40) level in brain of streptozotocin-induced diabetic rats. Neuroscience. 2008; 153:796-802.
31. Comin D, Gazarini L, Zanoni JN, Milani H, de Oliveira RMW. Vitamin E improves learning performance and changes the expression of nitric oxide-producing neurons in the brains of diabetic rats. Behav Brain Res. 2010; 210: 38–45.
32. Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RA. Oxidative damage to mitochondrial complex I Due to peroxynitrite. J Biol Chem. 2003; 278:37223–30.
33. Satoh J, Yagihashi S, Toyota T. The possible role of tumor necrosis factor-α in diabetic polyneuropathy. Exp Diabesity Res. 2003; 4:65-71.
34. Brands AMA, Kessels RPC, de Haan EHF, Kappelle LJ, Biessels GJ. Cerebral dysfunction in type 1 diabetes: Effects of insulin, vascular risk factors and blood-glucose levels. Eur J Pharmacol. 2004; 490: 159–68.66.
35. Sharma S, Chopra K, Kulkarni SK. Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF-alpha. Phytother Res. 2007; 21:278–83.