Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes

• Published in: Behavioural brain research 2011-06, Vol.220 (1), p.30-41
• Main Authors: Bhutada, Pravinkumar, Mundhada, Yogita, Bansod, Kuldeep, Tawari, Santosh, Patil, Shaktipal, Dixit, Pankaj, Umathe, Sudhir, Mundhada, Dharmendra
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Administration, Oral; Analysis of Variance; Animals; Antioxidants - metabolism; Antioxidants - therapeutic use; Ascorbic Acid - administration & dosage; Behavioral psychophysiology; Berberine; Berberine - administration & dosage; Biological and medical sciences; Blood Glucose - drug effects; Body Weight - drug effects; Brain - drug effects; Brain - metabolism; Cholinesterase Inhibitors - administration & dosage; Cholinesterases - metabolism; Dementia; Diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - pathology; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Donepezil; Dose-Response Relationship, Drug; Drug Interactions; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exploratory Behavior - drug effects; Fundamental and applied biological sciences. Psychology; Glutathione - metabolism; Hypoglycemic Agents - administration & dosage; Indans - administration & dosage; Lipid Peroxidation - drug effects; Male; Maze Learning - drug effects; Medical sciences; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory Disorders - pathology; Metformin; Metformin - administration & dosage; Morris water maze; Neuropharmacology; Oxidative stress; Pharmacology. Drug treatments; Piperidines - administration & dosage; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; Rats; Rats, Wistar; Vitamin C
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2011.01.022

► Berberine protects against cognitive dysfunction induced by streptozotocin in rats. ► Berberine also reverses the streptozotocin induced cognitive dysfunction. ► These protective and curative effects of berberine are multivariate. ► Antidiabetic, antioxidant, and ChE inhibition contributes to effect of berberine. Memory impairment induced by streptozotocin in rats is a consequence of changes in CNS that are secondary to chronic hyperglycemia, impaired oxidative stress, cholinergic dysfunction, and changes in glucagon-like peptide (GLP). Treatment with antihyperglycemics, antioxidants, and cholinergic agonists are reported to produce beneficial effect in this model. Berberine, an isoquinoline alkaloid is reported to exhibit anti-diabetic and antioxidant effect, acetylcholinesterase (AChE) inhibitor, and increases GLP release. However, no report is available on influence of berberine on streptozotocin-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25–100 mg/kg, p.o., twice daily, 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. In another set of experiment, berberine (100 mg/kg) treatment during training trials also improved learning and memory, lowered hyperglycemia, oxidative stress, and ChE activity. Chronic treatment (30 days) with vitamin C or metformin, and donepezil during training trials also improved diabetes-induced memory impairment and reduced oxidative stress and/or choline esterase activity. In conclusion, the present study demonstrates treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in diabetic rats.