EFFECTS OF STREPTOZOTOCIN INDUCED DIABETES MELLITUS TYPE 1 ON THE RAT BRAIN ANTIOXIDANT STATUS AND ACTIVITY OF ACETYL-CHOLINESTERASE: A NOVEL AND POTENTIAL TREATMENT BY VITEX NEGUNDO.
Keywords:Vitex negundo, Diabetes, Acetyl-cholinesterase, Streptozotocin, Antioxidants
Objective: The objective of the present study was to determine the effect of streptozotocin (STZ) induced diabetes type 1 on activity of acetyl-cholinesterase (AChE) in rat brain and on the brain antioxidant status and also that whether supplementation with the aqueous extract of Vitex negundo (AEVN) ameliorates neural degeneration caused by hyperglycemia induced oxidative stress in experimental diabetes.
Methods: Male albino rats weighing 180-200g were made diabetic by the single administration of STZ (45 mg/kg body weight) intraperitoneally. AEVN was administered orally through feeding cannula at a dose of 150 mg/kg body weight daily to STZ-induced diabetic rats for 60 days. On 61st day the rats were sacrificed by cervical dislocation and the effects of the AEVN on fasting blood glucose level. AChE activity and on levels of various oxidant and antioxidant enzyme activity in the brain were appraised.
Results: In the result it is observed that STZ-diabetes caused significant elevation in fasting blood glucose, AChE activity and lipid peroxidase (LPO) level. Whereas activity level of the protective antioxidant enzyme, catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD) exhibited significant decline in STZ-diabetes. Supplementation with AEVN attests significant anti-diabetic and antioxidant potential of it as a prominent decrease in fasting blood glucose level and AChE activity was observed. Similarly, the levels of the protective antioxidant enzymes like SOD, CAT and GSH were increased along with the decrease in the level of oxidant enzyme LPO was observed.
Conclusion: The study emphasizes the involvement of diabetes with neural degeneration and point towards the potential beneficial role of AEVN as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.
Cohen G, Riahi Y, Alpert E, Gruzman A, Sasson S. The roles of hyperglycaemia and oxidative stress in the rise and collapse of the natural protective mechanism against vascular endothelial cell dysfunction in diabetes. Arch Physiol Biochem 2007;113:259â€“67.
Harati Y. Diabetes and the nervous system. Endocrinol Metab Clin North Am 1996;25:325â€“59.
Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 2007;212:167â€“78.
Rahul S, Sanjay K, Abhay KS. Antidiabetic potential of Butea monosperma in rats. Fitoterapia 2006;77:86â€“90.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.
Frode TS, Medeiros YS. Animal models to test drugs with potential antidiabetic activity. J Ethnopharmacol 2008;115:173-83.
Green DA, Lattimer SA. Vascular and metabolic factors in the pathogenesis of experimental diabetic neuropathy in mature rats. Diabetes Met Rev 1988;4:201-21.
Green Tack DA, Takeuchi PR. Nerve microenvironment diabetic neuropathy. Neurochem 1994;117:1395-407.
Sukhwinder LS, Sharma P, Kaur G, Kaur G. Changes in glucose metabolism from discrete regions of rat brain and its relationship to reproductive failure during experimental diabetes. Mol Cell Biochem 1994;141:97-102.
Sen KS. Oxygen toxicity and antioxidants: State of the art. Indian J Physiol Pharmacol 1995;39:179-96.
Galanopoulas E, Lellos V, Papakdis M, Phillippids H, Palailogos G. Effects of fasting and diabetes on some enzyme and transport of glutamate in the cortex slices or synaptosomes form brain. Neurochem Res 1988;13:243-8.
Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gispen WH. Cerebral function in diabetes mellitus. Diabetologia 1994;34:643-50.
Ghareeb DA, Hussen HM. Vanadium improves brain acetylcholinesterase activity in early stage alloxan-diabetic rats. Neurosci Lett 2008;436-47.
Ashokkumar N, Pari L, Ramkumar KM. N-Benzoyl-Dphenylalanine attenuates acetylcholinesterase in neonatal steptozotocin-diabetic rats. Basic Clin Pharmacol Toxicol 2006;99:246-50.
Nayeemunnisa, Nawaz R, Jayashree C. Changes in the original protein metabolism in the central nervous system (CNS) of diabetic rat: Protection by Cichorium intybus (Chicory). Phcogmag 2006;2:130-2.
Jiang D, Zhen-Dan H, Ren-Wang J, Wen-Cai Y, Hong-Xi X, Paul PB. Antiviral flavonoids from the root bark of Morus alba L. Phytochemistry 2003;62:1235â€“8.
Pulok KM, Kuntal M, Kakali M, Peter JH. Leads from Indian medicinal plants with hypoglycemic potentials. J Ethanopharmacol 2006;106:1â€“28.
Jia W, Gao W, Tang L. Antidiabetic herbal drugs officially approved in China. Phytother Res 2003;17:1127â€“34.
Khare CP. Indian medicinal plants: an illustrated dictionary. New York: Springer Science and Business Media; 2007. p. 710.
Dev S. A selection of prime Ayurvedic plant drugs: Ancient-modern concordance. New Delhi, India: Anamaya Publishers; 2006. p. 438-9.
Chitra V, Sharma S, Kayande N. Evaluation of anticancer activity of Vitex negundo in experimental animals: an in vitro and in vivo study. Int J Pharm Tech Res 2009;1:1485-9.
Gogte VM. Ayurvedic pharmacology and therapeutic uses of medicinal plants. 3rd ed. Mumbai, India: Bharatiya Vidya Bhavan; 2000. p. 413-4.
Handa SS, Dev DR, Vasisht K. Compendium of medicinal and sromatic plants. Vol II. Italy: ICS-UNIDO; 2006.
Dharmasiri MG, Jayakody J, Galhena G, Liyanage S, Ratnasooriya WD. Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo. J Ethnopharmacol 2003;87:199-206.
Agnelarul JN, Shriram S, Kavithasri LJ, Meenaa V. Gastroprotective role of Vitex negundo Linn. in albino rats with aspirin induced ulcer. J Cell Tissue Res 2010;10:2085-90.
Renuka DP, Krishna KS, Kokilavani C. Effect of Vitex negundo leaf extract on the free radicals scavengers in complete Freundâ€™s adjuvant induced arthritic rats. Indian J Clin Biochem 2007;22:143-7.
Tiwari OP, Tripathi YB. Antioxidant properties of different fractions of Vitex negundo Linn. Food Chem 2007;100:1170-6.
Gupta M, Mazumder UK, Bhawal SR. CNS activity of Vitex negundo Linn. in mice. Indian J Exp Biol 1999;37:143-6.
Tandon VR, Gupta RK. An experimental evaluation of anticonvulsant activity of Vitex negundo. Indian J Physiol Pharmacol 2005a;49:199-205.
Ellman GL, Courtney DK, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-95.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:353-8.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Ind J Biochem Biophys 1984;21:131-2.
Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochem Biophys Acta 1979;582:67-78.
Aebi H. Catalase. In: Bergmeyar (eds). Methods in enzymatic analysis, New York, Academic Press; 1974. p. 674-84.
Aragno M, Parola S, Tamagno E, Brignardello E, Manti R, Danni O, Boccuzzi G. Oxidative derangement in rat synaptosomes induced by hyperglycemia: restorative effect of dehydroepiandrosterone treatment. Biochem Pharmacol 2000;60:389-95.
Liu J, Wang X, Shigenaga MK, Yeo HC, Mori A, Ames BN. Immobilization stress causes oxidative damage to lipid, protein and DNA in the brain of rats. FASEB J 1996;10:1532-8.
Aragno M, Brignardello E, Tamagno O, Boccuzzi G. Dehydroeppiandrosterone administration prevents the oxidative damage induced by acute hyperglycemia in rats. J Endocrinol 1997;155:233-40.
Li PA, Gisselsson J, Keuker J, Vogel ML, Kuschinsky SW, Siesjo K. Hyperglycemia-exaggerated ischemic brain damage following 30 min of middle cerebral artery occlusion is not due to capillary obstruction. Brain Res 1998;804:36-44.
Koski RR. Oral antidiabetic agents: a comparative review. J Pharm Pract 2004;17(1):39-48.
Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care 1989;12:553-64.
Twaij HA, Al-Badr AA. Hypoglycemic activity of artemisia herba alba. J Ethnopharmacol 1988;24:123-6.
Kasiviswanath R, Ramesh A, Kumar KE. Hypoglycemic and antihyperglycemic effect of Gmelina asiatica Linn. in normal and in alloxan induced diabetic rats. Biol Pharm Bull 2005;28:729-32.
Dougherty KD, Turchin PI, Walsh TJ. Septocingulate and septohippocampal cholinergic pathways: involvement in working/episodic memory. Brain Res 1998;810(1-2):59-71.
Kwon SH, Kim HC, Lee SY, Jang CG. Loganin improves learning and memory impairments induced by scopolamine in mice. Eur J Pharmacol 2009;619:44-9.
Mount C, Downton C. Alzheimerâ€™s disease: progress or profit? Nat Med 2006;12:780-4.
Kishor VO, Om GB, Rajkumar VS, Chandrakant DU. Effect of hydroalcoholic extract of Vitex negundo Linn. Leaves on learning and memory in normal and cognitive deficit mice. Asian Pacific J Tropical Medicine 2012;2(1):104.
Feillet-Coudray C, Rock E, Coudray C. Lipid peroxidation and antioxidant status in experimental diabetes. Clin Chim Acta 1999;284:31-43.
Hunt J, Dean RT, Wolff SP. Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes and ageing. Biochem J 1988;256:205â€“12.
Pascoe GA, Redd DJ. Cell calcium, vitamin E and the thiol redox system in cystotoxicity. Free Radic Biol Med 1989;6:209-24.
Sen CS. Oxygen toxicity and antioxidants: state of the art. Ind J Physiol Pharmaco 1995;39:177-96.
Gupta A, Hussain M, Chandra R, Kapoor NK. Acetyl homo cysteine Thioactone (Citiolone) protects against restraint stress-induced adverse effects on lipid peroxidation products and catalase activity in the CNS of aged rats. Proc Nat Symposium Quality Ageing 2009;10:29-31.
Lu SC. Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J 1999;13:1169-83.
Nicotera P, Orrenius S. Role of thiols in protection against biological reactive intermediates. Adv Exp Med Biol 1986;197:41-51.
Robinson BH. The role of manganese super oxide dismutase in health and disease. J Inherit Met Dis 1998;21:598-603.
Brioukhanov AL, Netrusov AI. Catalase and superoxide dismutase: distribution, properties, and physiological role in cells of strict anaerobes. Biochem 2004;69:949-62.
Selvam R, Anuradha CV. Effect of oral methionine on blood lipid peroxidation. Nutr Biochem 1990;1:653-65.
Stanely MPP, Menon VP. Antioxidant action of Tinospora cordifolia root extract in alloxan diabetic rats. Phytother Res 2001;15:213-8.
Tahirovic I, Sofic E, Sapcanin A, Gavrankapetanovic I, Bach-Rojecky L, Salkovic-Petrisic M, et al. Reduced brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimerâ€™s disease and diabetes mellitus. Neurochem Res 2007;32:1709-17.
Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH. Ageing and diabetes: implications for brain function. Eur J Pharmacol 2002;441:1-14.
Kumar JS, Menon VP. Effect of diabetes on levels of lipid peroxides and glycolipids in rat brain. Metabolism 1993;42:1435-9.
Ohkuwa T, Sato Y, Naoi M. Hydroxyl radical formation in diabetic rats induced by streptozotocin. Life Sci 1995;56:1789-98.