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ABSTRACT: Anacyclus pyrethrum (A. pyrethrum) has been reported to exhibit anticonvulsant activity. In the present study, the effect of hydro-alcoholic extract of A. pyrethrum root (HEAP) on pentylenetetrazole (PTZ) induced kindling, spatial memory, oxidative stress and rho kinase (ROCK II) was assessed. Male albino mice (25-30 g) were used in the study. PTZ (35 mg/kg, i.p. on alternate days) was injected to induce kindling and PTZ (70 mg/kg, i.p) challenge was given 7 days post-kindling. HEAP was administered orally daily in the doses of 100, 250 and 500 mg/kg along with PTZ injections during the kindling process and continued till PTZ challenge post kindling. Spatial memory was assessed using Morris water maze test. Oxidative stress parameters [malondialdehyde (MDA) and reduced glutathione (GSH)] and ROCK II expression were estimated in whole brain at the end of the study. Pre-treatment with HEAP (250 and 500 mg/kg) showed significant increase in the myoclonic jerk latency and delay in the development of kindling. A significant decrease in mortality was observed at higher doses of HEAP (250 and 500 mg/kg). Pre-treatment with HEAP significantly increased the number of platform crossings and decreased the escape latency, as opposed to the PTZ group, thus showing protection against memory deficit. HEAP pre-treatment also attenuated the oxidative stress induced by PTZ kindling. PTZ induced kindling increased the ROCK II expression whereas, HEAP pre-treatment attenuated the increase in ROCK II expression. To conclude, HEAP pre-treatment showed antiepileptic effect and also showed protection against cognitive impairment by decreasing oxidative stress and ROCK II expression in PTZ kindled mice.
Neurochemical Research 12/2012; · 2.24 Impact Factor
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ABSTRACT: Obesity is reaching epidemic proportions all over the world yet it lacks adequate treatment. Most of the drugs have failed either due to ineffectiveness or adverse effects. Complementary and alternative system of medicine is being used since ancient times. However, many of them have not been tested for efficacy and safety using modern scientific methods. Therefore, the antiobesity effect of Safoof Mohazzil, a polyherbal formulation, was evaluated in cafeteria diet induced obesity in female Sprague Dawley rats. Animals weighing 100-150 g were divided into four groups (n = 8) i.e. standard pellet diet, cafeteria diet control, cafeteria diet + Safoof Mohazzil and standard pellet diet plus Safoof Mohazzil. The formulation was administered orally at a dose of 1 g/kg/day for 14 weeks. At the end of study, cafeteria diet significantly increased body weight, Lee's index, lipid profile (cholesterol and triglycerides), insulin and leptin levels as compared to standard pellet diet control group. Fourteen week treatment with Safoof Mohazzil significantly prevented the increase in body weight, Lee's index, lipid profile, insulin and leptin levels as compared to cafeteria diet control group without affecting food and water intake. Safoof Mohazzil had no adverse effect on hepatic transaminases, locomotor activity and motor coordination. The study provides evidence for antiobesity effect of Safoof Mohazzil.
Indian journal of experimental biology 11/2012; 50(11):776-84. · 1.29 Impact Factor
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ABSTRACT: The antiepileptic effect of hydroalcoholic extract of Zizyphus jujuba (HEZJ) in experimental seizures was demonstrated earlier. The present study aimed to evaluate the pharmacokinetic and pharmacodynamic interactions of HEZJ with phenytoin (PHT), phenobarbitone (PB), and carbamazepine (CBZ) in maximal electroshock (MES)-induced seizures in male Wistar rats. Maximal electroshock (70mA, 9ms pulse width, 0.2s) was used to induce seizures. Blood samples were collected at two time points for estimation of serum PHT, PB, and CBZ levels using high-pressure liquid chromatography (HPLC). Co-administration of HEZJ with the sub-therapeutic doses of PHT, PB, and CBZ exhibited 66.7, 66.7, and 50.0% protection against tonic hind limb extension as compared to 33.3, 33.3, and 50% protection respectively, in the groups treated with PHT, PB, and CBZ alone in their sub-therapeutic doses. Co-administration of HEZJ with the sub-therapeutic doses of these antiepileptic drugs (AEDs) showed significant improvement in cognitive functions as compared to MES group as well as these AEDs alone. A significant increase in glutathione levels and decrease in malondialdehyde levels were observed with pretreatment of HEZJ with the sub-therapeutic doses of these AEDs. Co-administration of HEZJ with PHT, PB, and CBZ did not cause any significant changes in the serum concentrations of these AEDs. The results of the present study indicate that the co-administration of HEZJ with sub-therapeutic doses of PHT and PB potentiated the antiepileptic effect of PHT and PB in MES-induced seizures with no change found in the antiepileptic effect of CBZ.
Epilepsy & Behavior 10/2012; 25(3):368-373. · 2.34 Impact Factor
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ABSTRACT: The long term effect of single (day 1) and twice (day 1 and 3) injections of intracerebroventricular (ICV) streptozotocin (STZ) at the doses of 1 and 3 mg/kg on the cognitive functions of male Wistar rats was evaluated. Elevated plus maze, passive avoidance, and Morris water maze tests were used to assess the cognitive functions. A significant cognitive deficit was found at the 2nd week onwards, which persisted up to the 14th week with single and twice ICV-STZ (3 mg/kg) injections, whereas no cognitive impairment was found in ICV-STZ (1 mg/kg) treated groups after 8-10 weeks.
Journal of Alzheimer's disease: JAD 08/2012; · 3.74 Impact Factor
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ABSTRACT: Evolvulus alsinoides, also known as Shankpushapi, is a commonly used traditional medicine for enhancing memory. We evaluated the in vitro free radical scavenging and enzymes [acetylcholinesterase, butyrylcholinestrase, glycogen synthase kinase-3-β (GSK-3-β), rho kinase (ROCK II), prolyl endopeptidase (PEP), catechol-O-methyl transferase (COMT) and lipoxygenase (LOX)] inhibitory activities of aqueous and hydro-alcoholic extracts of E. alsinoides. Hydro-alcoholic extract of E. alsinoides demonstrated more free radical scavenging activity as compared to aqueous extract. Hydro-alcoholic extract also showed higher cholinesterase, GSK-3-β, ROCK II, PEP, COMT and LOX enzyme inhibitory activities as compared to aqueous extract. Phytochemical analysis revealed more flavanoids in hydro-alcoholic extract as compared to aqueous extract but no significant difference in phenolic content of the two extracts was observed. Based on in vitro data, hydro-alcoholic extract (100, 300 and 500mg/kg, p.o.) was selected for in vivo study in intracerebroventricularly injected streptozotocin (STZ) induced cognitive impairment in male Wistar rats. Elevated plus maze, passive avoidance and Morris water maze were used for assessment of cognitive function on 14th, 21st and 28th day after STZ injection. Oxidative stress parameters (malondialdehyde, reduced glutathione, nitric oxide levels and superoxide dismutase activity), cholinergic dysfunction and rho kinase (ROCK II) expression were studied in cerebral cortex and hippocampus of rat brain at the end of the study. Hydro-alcoholic extract of E. alsinoides dose dependently prevented STZ induced cognitive impairment by reducing the oxidative stress, improving cholinergic function and preventing the increase in rho kinase expression. The results suggest an anti-Alzheimer potential of hydro-alcoholic extract of E. alsinoides.
Neurochemistry International 08/2012; · 2.86 Impact Factor
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ABSTRACT: Orchis mascula tuber is used in many polyherbal formulations as a nerve tonic in India.
In the present study, effect of hydroalcholic extract of O. mascula (HEOM) tuber was evaluated against seizures, seizure-induced oxidative stress and cognitive deficit in pentylenetetrazole and maximal electroshock-induced seizures in rats.
HEOM was administered orally 30 min before induction of seizures by pentylenetetrazole (PTZ; 60 mg/kg, i.p) or maximal electroshock (MES; 70 mA). Elevated plus maze and passive avoidance tests were used to assess the learning and memory. Oxidative stress was studied by estimation of reduced glutathione and lipid peroxidation. Whole brain total cholinesterase activity was also evaluated.
HEOM produced 33.3%, 50% and 66.7% protection in PTZ model and 16.7%, 16.7% and 33.3% at 250, 500 and 1000 mg/kg, respectively, in MES-induced seizures. Pre-treatment with HEOM significantly decreased the retention transfer latency in elevated plus maze test, and an increase in the retention latency in passive avoidance test was observed. Oxidative stress induced by seizures was also attenuated as indicated by significant increase in GSH and decrease in MDA levels in HEOM treated groups. PTZ and MES caused a significant decrease in AChE and BChE activities, which was prevented by HEOM.
HEOM thus showed protection against seizures, prevented the associated memory impairment probably by modulating cholinergic status and reducing oxidative stress.
Journal of ethnopharmacology 05/2012; 142(1):23-7. · 2.32 Impact Factor
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ABSTRACT: Stroke is a major cause of mortality and disability worldwide. Presently, recombinant tissue plasminogen activator is the only approved drug for the management of acute ischemic stroke. However, it has limitations like narrow therapeutic window and increased risk of intracranial hemorrhage. In previous studies, immunosuppressive agents such as cyclosporine A and tacrolimus have shown neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. Therefore, the present study was designed to evaluate the effect of mycophenolate mofetil (MMF) on the cerebral ischemic injury in the middle cerebral artery occlusion (MCAo) model in rats. MCAo was carried out in male Wistar rats by inserting an intraluminal thread. One hour after MCAo, the animals were treated with MMF (50, 100, 200mg/kg, i.p.). Reperfusion was done after 2h of occlusion. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of neuroprotective effect of MMF. Twenty four hours after MCAo, motor performance was assessed and the animals were euthanized for estimation of brain malondialdehyde, glutathione, myeloperoxidase and nitric oxide levels. The effect of MMF on apoptosis was also evaluated. MMF significantly attenuated the percent infarct area, apparent diffusion coefficient and signal intensity as compared to a vehicle treated group. Treatment with MMF prevented the motor impairment and significantly reversed the changes in levels of malondialdehyde, glutathione, myeloperoxidase and nitric oxide. MMF treatment significantly reduced the apoptosis. Data of the present study indicate neuroprotective effect of MMF in the experimental model of ischemic stroke.
European journal of pharmacology 04/2012; 684(1-3):71-8. · 2.59 Impact Factor
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ABSTRACT: In Ayurveda, Anacyclus pyrethrum has been used as a brain tonic. The present study evaluates the effect of hydroalcoholic extract of A. pyrethrum (HEAP) root against seizures, seizure-induced oxidative stress and cognitive impairment in experimental models of seizures. Male Wistar rats were used in the study. HEAP was administered in doses of 50, 100, 250, 500 in pentylenetetrazole (PTZ) model and 250, 500 and 1000 mg/kg in maximal electroshock (MES) model. Myoclonic jerk latency and generalized tonic clonic seizures (GTCS) were noted in PTZ whereas occurrence of tonic hind limb extension (THLE) was observed in MES seizures. Cognitive deficit was assessed using elevated plus maze and passive avoidance tests. Whole brain reduced glutathione, malondialdehyde levels and cholinesterase activity were measured. HEAP showed 50, 66.7, 83.3 and 100% protection at 50,100, 250 and 500 mg/kg, respectively against GTCS in PTZ induced seizures. In MES induced seizures, HEAP produced 16.7, 33.3 and 50% protection against THLE at 250, 500 and 1000 mg/kg, respectively. HEAP administration significantly prevented seizure induced oxidative stress and cognitive impairment in a dose-dependent manner. HEAP also normalized the decrease in cholinesterase activity caused by seizures. Thus, HEAP showed protective effect against seizures, seizure-induced oxidative stress and cognitive impairment in rats.
Epilepsy research 02/2012; 98(2-3):157-65. · 2.48 Impact Factor
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ABSTRACT: Anticonvulsant property of Acorus calamus is known. Since combination therapy can lower the dose of individual drug and dose related toxicities, in this study, the effect of co-administration of hydroalcoholic extract of A. calamus (HAEAC) on conventional antiepileptic drugs (AEDs), sodium valproate and carbamazepine was determined using pentylenetetrazole-induced seizures model in rats. On combining the subanticonvulsant doses of HAEAC with sodium valproate and carbamazepine, greater protection as compared to either drug alone was observed. This was not related to change in levels of the AEDs. Thus, the results further substantiate anticonvulsant effect of HAEAC and suggest a potential for add on therapy with AEDs.
Indian journal of experimental biology 01/2012; 50(1):51-5. · 1.29 Impact Factor
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ABSTRACT: Stroke is a major cause of mortality and disability. The management with thrombolytic therapy has to be initiated within 3-4 h and is associated with limitations like increased risk of intracranial hemorrhage and progression of cerebral injury. Immunophilin inhibitors such as cyclosporine A and tacrolimus have been shown to afford neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. In the present study, the effect of rapamycin in middle cerebral artery occlusion (MCAo) model of ischemic stroke was evaluated. Ischemic stroke was induced in rats by occluding the MCA using the intraluminal thread. After 1 h of MCAo, animals were administered rapamycin (50, 150, 250 μg/kg, i.p.). After 2 h of occlusion, reperfusion was done. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of protective effect of rapamycin. Twenty-four hours after MCAo, motor performance was assessed, the animals were euthanized and the brains were removed for estimation of malondialdehyde, glutathione, nitric oxide and myeloperoxidase. Significant improvement was observed with rapamycin 150 and 250 μg/kg in percent infarct area, apparent diffusion coefficient and signal intensity as compared to vehicle treated group. Rapamycin treatment ameliorated motor impairment associated with MCAo and significantly reversed the changes in levels of malondialdehyde, glutathione, nitric oxide and myeloperoxidase. The results of the present study indicate neuroprotective effect of rapamycin in MCAo model of stroke. Therefore, rapamycin might be considered as a therapeutic strategy for stroke management.
Behavioural brain research 08/2011; 225(2):603-9. · 3.22 Impact Factor
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ABSTRACT: The methylxanthines, e.g., theophylline, are widely used for the treatment of bronchial asthma. Additionally, a pain relieving effect of theophylline has been reported in patients as well as in experimental animals. The mechanism of this antinociceptive action is not clear. In this study, involvement of dopaminergic system in theophylline-induced antinociception was evaluated using tail flick test model. Swiss albino mice, (either sex, weighing 25-30 g) with base line tail flick latencies (TFL) between 2.0 and 3.5 s, were used. TFL was recorded before and at intervals of 15, 30, 45, and 60 min. after drug treatment. The experimental protocol was duly approved by the Institutional Animal Ethics Committee, All India Institute of Medical Sciences, New Delhi, India. To determine the role of dopaminergic system, the mice were pretreated with either D1 or D2 dopaminergic receptor antagonists SCH 23390 and haloperidol, respectively, prior to treatment with theophylline. Another group of animals received apomorphine along with theophylline. The dose of theophylline used, i.e., 10 mg/kg, intraperitoneally (i.p.), had shown a significant increase in TFLs. The theophylline-induced antinociception, 10 mg/kg, i.p., was reversed by pretreatment with both D1 and D2 dopaminergic receptor antagonists SCH 23390 and haloperidol as well as with apomorphine (1 mg/kg) pretreatment. The results suggest that theophylline-induced antinociception is due to release of dopamine.
The International journal of neuroscience 08/2011; 122(1):17-21. · 0.86 Impact Factor
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ABSTRACT: The anticonvulsant effect of the hydroalcoholic extract of Zizyphus jujuba (HEZJ) fruit (100, 250, 500, and 1000 mg/kg, orally) was evaluated in experimental seizure models in rats. The effect of HEZJ on seizure-induced cognitive impairment, oxidative stress, and cholinesterase activity was also investigated. HEZJ (1000 mg/kg) exhibited maximum protection (100%) against generalized tonic-clonic seizures in the pentylenetetrazole (PTZ) seizure model and and 66.7% protection against tonic hindlimb extension in the maximal electroshock (MES) seizure model. Significant impairment in cognitive functions was observed in both PTZ- and MES-challenged rats. Pretreatment with HEZJ resulted in significant improvement in learning and memory. HEZJ also reversed the oxidative stress induced by both PTZ and MES. The significant decrease in cholinesterase activity observed in the PTZ and MES models was significantly reversed by pretreatment with HEZJ. Thus, the present study demonstrates the anticonvulsant effect of HEZJ as well as amelioration of cognitive impairment induced by seizures in rats.
Epilepsy & Behavior 06/2011; 21(4):356-63. · 2.34 Impact Factor
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ABSTRACT: The present study investigates the interaction of curcumin with four antiepileptic drugs (AEDs) in male Wistar rats. In the first protocol, seizures were induced using pentylenetetrazole (PTZ) and valproate was injected intraperitoneally (i.p.) in therapeutic and sub-therapeutic doses 30min before PTZ administration. Curcumin was co-administered with sub-therapeutic dose of valproate 60min before PTZ injection. In the second protocol, seizures were induced by maximal-electroshock. Phenytoin, phenobarbitone and carbamazepine were injected in their therapeutic and sub-therapeutic doses 120, 60 and 30min, respectively, before seizure induction. Curcumin was administered along with sub-therapeutic doses of phenytoin, phenobarbitone and carbamazepine, 60min before induction of seizures. Behavioral parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were assessed and the serum levels of the AEDs were estimated. The AEDs in their therapeutic doses produced complete protection against seizures. However, sub-therapeutic doses of these AEDs failed to completely protect against seizures. Co-administration of curcumin with sub-therapeutic dose of valproate significantly increased the latency to myoclonic jerks. The percentage protection against seizures with sub-therapeutic doses of valproate, phenytoin, phenobarbitone and carbamazepine was also enhanced by concomitant curcumin administration. Both PTZ and MES induced seizures caused significant impairment of cognitive functions. Co-administration of curcumin with these AEDs in their sub-therapeutic doses prevented the impairment of learning and memory due to seizures whereas no such improvement was observed in the groups administered the sub-therapeutic doses of the AEDs alone. Additionally, curcumin reversed the oxidative stress due to seizures. However, curcumin co-administration did not cause any significant alteration in the serum levels of the AEDs. The results thus suggest the potential of curcumin as an adjunct to these AEDs in epilepsy with the advantage of increasing the efficacy, reducing the dose and side effects of the AEDs.
Pharmacology Biochemistry and Behavior 05/2011; 99(3):399-407. · 2.53 Impact Factor
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ABSTRACT: Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methyl-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.
The Indian journal of medical research 01/2011; 133:15-26. · 1.84 Impact Factor
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ABSTRACT: This study evaluates the anti-arthritic effect of Terminalia chebula hydroalcoholic extract (TCHE) in experimental models and attempts to correlate the effect of treatment on macrophage-derived pro-inflammatory cytokine expression and extent of disease activity.
Arthritis was induced in rats by subplantar administration of either formaldehyde or complete Freund's adjuvant (CFA). Joint size was measured at regular intervals by using a micrometer screw gauge. Serum and ankle joints of rats immunized with CFA were collected and subjected to ELISA for estimation of TNF-α level and immuno-histochemistry for detection of IL-1β, IL-6 and TNF-R1, respectively. An acute and 28-day oral toxicity study was carried out to evaluate the safety of the test drug.
TCHE produced a significant inhibition of joint swelling as compared with control in both formaldehyde-induced and CFA-induced arthritis. TCHE treatment also reduced serum TNF-α level and synovial expression of TNF-R1, IL-6 and IL-1β. Results of acute toxicity study showed that the oral LD50 of TCHE was >2000 mg/kg. Chronic administration also did not produce any significant physiological changes as compared with normal rats.
Results indicate that the anti-arthritic activity of TCHE was at least in part due to its modulatory effect on pro-inflammatory cytokine expression in the synovium. We believe that TCHE has the potential to be used as a disease-modifying agent in treatment of rheumatoid arthritis.
The Journal of pharmacy and pharmacology. 12/2010; 62(12):1801-6.
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ABSTRACT: Epilepsy as well as chronic use of most antiepileptic drugs predisposes to cognitive impairment. Curcumin has been reported to possess antioxidant, anticonvulsant as well as neuroprotective potential. Hence, this study was conducted to evaluate the effect of curcumin against seizures, cognitive impairment and oxidative stress in pentylenetetrazole-induced kindling in rats.
The effect of pretreatment with curcumin (100, 200 and 300 mg/kg, orally) on pentylenetetrazole (PTZ)-induced kindling, kindling-induced cognitive impairment and oxidative stress was evaluated. Male Wistar rats were injected PTZ (30 mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Cognitive impairment was assessed using elevated plus maze and passive avoidance test while the oxidative stress parameters (malondialdehyde and glutathione) were estimated in the whole brain at the end of experiments.
PTZ, 30 mg/kg, induced kindling in rats after 31.0±1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with curcumin in a dose-dependent manner.
The results indicate that pretreatment with curcumin ameliorates seizures, oxidative stress and cognitive impairment in PTZ induced kindling in rats. These results thus suggest the potential of curcumin as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure induced memory impairment.
Life sciences 11/2010; 87(19-22):596-603. · 2.56 Impact Factor
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European Journal of Clinical Pharmacology 11/2010; 67(5):537-8. · 2.85 Impact Factor
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ABSTRACT: The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.
European journal of pharmacology 10/2010; 644(1-3):106-12. · 2.59 Impact Factor
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ABSTRACT: In the present study we investigated the anti-amnesic activity of Vitex negundo in scopolamine induced amnesia in rats. Wistar rats (180-200 g) were trained on active avoidance task. Each animal received session of 15 trials with inter trial duration of 15 s for 5 days. Scopolamine (3 mg/kg, i.p) was administered at different time periods on the basis of stages of memory i.e acquisition, consolidation and retention in different groups (n = 6). Effect of Vitex negundo extract was evaluated and compared to a standard drug, Donepezil. Significant (p < 0.05) increase in the avoidance response on the 5th session has been observed as compared to 1st session in control group. Scopolamine treatment significantly (p < 0.05) reduced the avoidance response compared to control. Extract treated groups shown significant (p < 0.05) increase in number of avoidance responses as compared to scopolamine treated groups. Increased oxidative stress in brain after scopolamine treatment, as observed by increase in MDA & decrease in GSH & SOD, was lowered in the groups treated with extracts. AChE activity was also improved after V. negundo treatment. Results of the study have shown that V. negundo treated groups decrease the phenomenon of amnesia by increasing learning of memory through antioxidant effect and decreasing AChE activity.
Pharmacology & Pharmacy. 01/2010; 1:1-8.
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ABSTRACT: The present study investigates the effect of chronic curcumin administration on phenytoin-induced cognitive impairment and oxidative stress in rats. Male Wistar rats were administered drugs/vehicle for 21 days. Learning and memory was evaluated using the passive avoidance paradigm and the elevated plus maze. On day 21, serum phenytoin concentrations and whole brain malondialdehyde (MDA) and glutathione (GSH) levels were estimated. Phenytoin (75 mg/kg, i.p.) produced significant deficits in learning/memory as indicated by the significant increase in retention transfer latency in elevated plus maze test and a significant decrease in retention latency in the passive avoidance paradigm. Chronic administration of phenytoin also produced significant elevations in brain MDA and reduction of brain GSH levels. Curcumin (100, 200 and 300 mg/kg, orally), when administered with phenytoin, significantly prevented phenytoin-induced cognitive impairment and oxidative stress in a dose-dependent manner. There were no significant differences in the serum levels of phenytoin in any of the treatment groups. This study demonstrates that curcumin is effective in preventing phenytoin-induced cognitive impairment and oxidative stress in rats without altering the serum phenytoin levels. This suggests the potential of adjuvant curcumin therapy in ameliorating cognitive impairment caused by chronic phenytoin therapy.
Brain research 09/2009; 1301:52-60. · 2.46 Impact Factor
