Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats.

Memory impairment induced by ethanol in rats is a consequence of changes in the CNS that are secondary to impaired oxidative stress and cholinergic dysfunction. Treatment with antioxidants and cholinergic agonists are reported to produce beneficial effects in this model. Berberine, an isoquinoline alkaloid is reported to exhibit antioxidant effect and cholinesterase (ChE) inhibitor activity. However, no report is available on the influence of berberine on ethanol-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in ethanol-induced rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameter of oxidative stress and cholinesterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Forty five days after ethanol treated rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., once a day for 45days) improved cognitive performance, and lowered oxidative stress and ChE activity in ethanol treated rats. In another set of experiments, berberine (100mg/kg) treatment during training trials also improved learning and memory, and lowered oxidative stress and ChE activity. Chronic treatment (45days) with vitamin C, and donepezil during training trials also improved ethanol-induced memory impairment and reduced oxidative stress and/or cholinesterase activity. In conclusion, the present study demonstrates that treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in ethanol treated rats.

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

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 (25-100mg/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 (100mg/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.

Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats.

Diabetes-related cognitive dysfunction is a consequence of changes within the central nervous system that are secondary to chronic hyperglycemia, oxidative stress, and cholinergic dysfunction, and probably therefore anti-diabetics, anti-oxidants, and acetylcholine esterase (AChE) inhibitors were found to have beneficial effects in animal models. Quercetin, a bioflavonoid widely distributed in the plants is reported to be a potent anti-diabetic, anti-oxidant, AChE inhibitor, and memory enhancer. Therefore, we screened its influence against diabetes-induced cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water and elevated plus maze (EPM) paradigms. Thirty days after diabetes induction rats exhibited marked and persistent hyperglycemia, weight loss, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Treatment with quercetin (5-20 mg/kg, p.o., twice daily, 30 days) in streptozotocin-induced diabetic rats prevented the changes in blood glucose, body weight, and performance in Morris water and elevated plus maze tasks. In another set of experiment, quercetin (40 mg/kg, p.o., twice daily) treatment during training trials (31-35 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. This treatment also decreased blood glucose levels, but had no influence on body weights. These effects were comparable to vitamin C (100 mg/kg, twice daily, 30 days) and donepezil (3 mg/kg day 31-day 35, during training trials), and devoid of any motor deficit and anxiety-like effect when tested in open field test. In conclusion, quercetin may provide a new potential option for prevention of the cognitive dysfunction in diabetes.

Electrical Double-Layer Effects on the Brownian Diffusivity and Aggregation Rate of Laponite Clay Particles.

Dynamic light scattering was used to study the Brownian translational diffusion and rate of Brownian aggregation of Laponite (RD) clay particles at low (millimolar) electrolyte concentrations. Laponite is a manufactured clay consisting of monodisperse disk-shaped particles with a 30-nm diameter and a 1-nm thickness. The stability ratio, defined as the ratio of the coagulation rate for Brownian spheres with no particle interactions to the observed coagulation rate, was quite large O(10(5)), suggesting that there was a large potential energy barrier to Brownian aggregation. The apparent potential energy barrier for face-edge aggregation was rationalized on the basis of a calculation of the electrostatic interactions between two disks with negative face charges and positive rim charges. The aggregation rate increased with increasing electrolyte concentration owing to the screening of the electrostatic repulsion associated with the net charge on the particle. The rate decreased with increasing pH because of the decreasing positive charge on the rim. The translational diffusivity of the individual particles before the onset of aggregation exhibited a strong dependence on the electrolyte concentration and was as much as 50% smaller than the diffusivity for an uncharged disk. This effect is attributed to the added drag resulting from the electroviscous effects in the deformed double layer. The electroviscous effect on the diffusion of the disk-like particles is much stronger than that on rods and spheres. Copyright 2001 Academic Press.