1,8-cineole (eucalyptol) mitigates inflammation in amyloid Beta toxicated PC12 cells: relevance to Alzheimer's disease.

Inflammatory process has a fundamental role in the pathogenesis of Alzheimer's disease and insoluble amyloid beta deposits and neurofibrillary tangles provide the obvious stimuli for inflammation. The present study demonstrate the effect of pretreatment of 1,8-cineole (Cin) on inflammation induced by Aß(25-35) in differentiated PC12 cells. The cells were treated with Cin at different doses for 24 h and then replaced by media containing Aß(25-35) for another 24 h. The cell viability was decreased in Aß(25-35) treated cells which was significantly restored by Cin pretreatment. Cin successfully reduced the mitochondrial membrane potential, ROS and NO levels in Aß(25-35) treated cells. Cin also lowered the levels of proinflammatory cytokines TNF-α, IL-1ß and IL-6 in Aß(25-35) treated cells. Moreover, Cin also succeeded in lowering the expression of NOS-2, COX-2 and NF-κB. This study suggests the protective effects of Cin on inflammation and provides additional evidence for its potential beneficial use in therapy as an anti-inflammatory agent in neurodegenerative disease.

Amelioration of cognitive impairment and neurodegeneration by catechin hydrate in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20mg/kgb wt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3mg/kgb wt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1ß levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT).

Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment.

Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment.

Anti-apoptotic and anti-inflammatory effect of Piperine on 6-OHDA induced Parkinson's rat model.

In the present study, we examined the molecular mechanism by which Piperine (bioactive compound of Piper nigrum) inhibits neuronal cell apoptosis. We further investigated the anti-inflammatory effect of Piperine on 6-OHDA induced Parkinson's disease. Consistent with its antioxidant properties, Piperine (10 mg/kg bwt) reduced 6-OHDA-induced lipid peroxidation and stimulated glutathione levels in striatum of rats. Furthermore, Piperine treatment diminished cytochrome-c release from mitochondria and reduced caspase-3 and caspase-9 activation induced by 6-OHDA. Treatment with Piperine markedly inhibited poly(ADP-ribose) polymerase activation, pro-apoptotic Bax levels and elevation of Bcl-2 levels. Piperine reduces contralateral rotations induced by apomorphine. Further narrow beam test and rotarod also showed improvement in motor coordination and balance behavior in rats treated with Piperine. In addition Piperine depletes inflammatory markers, TNF-α and IL-1ß in 6-OHDA-induced Parkinson's rats. We propose that, in addition to its antioxidant properties Piperine exerts a protective effect via anti-apoptotic and anti-inflammatory mechanism on 6-OHDA induced Parkinson's disease.

Naringenin ameliorates Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model.

Oxidative stress is involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) as well as age related cognitive deficit. The present study was designed to investigate the pre-treatment effects of naringenin (NAR), a polyphenolic compound on cognitive dysfunction, oxidative stress in the hippocampus, and hippocampal neuron injury in a rat model of AD-TNDCI. The rats were pre-treated with NAR at a selective dose (50mg/kg, orally) for 2 weeks followed by intracerebroventricular-streptozotocin (ICV-STZ) (3mg/kg; 5µl per site) injection bilaterally. Behavioral alterations were monitored after 2 weeks from the lesion using passive avoidance test and Morris water maze paradigm. Three weeks after the lesion, the rats were sacrificed for measuring non-enzymatic [4-hydroxynonenal (4-HNE), malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), protein carbonyl (PC), reduced glutathione (GSH)] content and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and Na(+)/K(+)-ATPase] activity in the hippocampus, and expression of choline acetyltransferase (ChAT) positive neuron, and histopathology of hippocampal neurons. The non-enzymatic level and enzymatic activity was significantly increased and decreased, respectively, with striking impairments in spatial learning and memory, loss of ChAT positive neuron and severe damage to hippocampal neurons in the rat induced by ICV-STZ. These abnormalities were significantly improved by NAR pre-treatment. The study suggests that NAR can protect against cognitive deficits, neuronal injury and oxidative stress induced by ICV-STZ, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD-TNDCI.

Attenuation of Aß-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress.

Beta-amyloid (Aß) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and compounds that can prevent pathways of Aß-induced neurotoxicity may be potential therapeutic agents for treatment of AD. This study examined the hypothesis that thymoquinone (TQ) would reduce oxidative stress and mitochondrial dysfunction in differentiated pheochromocytoma (PC 12) cells exposed to Aß fragment 25-35 (Aß(25-35)). To test this hypothesis, Aß was used to induce an in vitro model of AD in differentiated PC 12 cell line of rat. After 24 h of exposure with Aß(25-35), a significant reduction in cell viability and mitochondrial membrane potential (MMP) was observed. In addition, a significant elevation in the TBARS content and nitric oxide (NO) and activity of acetylcholine esterase (AChE) was observed which was restored significantly by TQ pretreatment. Furthermore, TQ also ameliorated glutathione and its dependent enzymes (glutathione peroxidase, glutathione reductase) which were depleted by Aß(25-35) in PC 12 cells. These results were supported by the immunocytochemical finding that has shown protection of cells by TQ from noxious effects of Aß(25-35). These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders including AD.

Edaravone ameliorates oxidative stress associated cholinergic dysfunction and limits apoptotic response following focal cerebral ischemia in rat.

Stroke is a life-threatening disease with major cause of mortality and morbidity worldwide. The neuronal damage following cerebral ischemia is a serious risk to stroke patients. Oxidative stress and apoptotic damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The objective of this study was to test the hypothesis that administration of edaravone (Edv) maintains antioxidant status in brain, improves the cholinergic dysfunction and suppresses the progression of apoptosis response in rat. To test this hypothesis, male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) of 2 h followed by reperfusion for 22 h. Edv was administered (10 mg/kg bwt) intraperitoneally 30 min before the onset of ischemia and 1 h after reperfusion. After reperfusion, rats were tested for neurobehavioral activities and were sacrificed for the infarct volume, estimation of oxidative damage markers. Edv treatment significantly reduced ischemic lesion volume, improved neurological deficits, contended oxidative loads, and suppressed apoptotic damage. In conclusion, treatment with Edv ameliorated the neurological and histological outcomes with elevated endogenous anti-oxidants status as well as reduced induction of apoptotic responses in MCA occluded rat. We theorized that Edv is among the pharmacological agents that reduce free radicals and its associated cholinergic dysfunction and apoptotic damage and have been found to limit the extent of brain damage following stroke.

Piperine suppresses cerebral ischemia-reperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-κB in middle cerebral artery occlusion rat model.

The pathophysiological mechanisms leading to neuronal injury in middle cerebral artery occlusion (MCAO) model of cerebral stroke are complex and multifactorial that form the bases of behavioral deficits and inflammation mediated damage. The present study demonstrates the effect of piperine pretreatment (10 mg/kg b wt, once daily p.o. for 15 days) on cerebral ischemia-induced inflammation in male Wistar rats. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 h. A maximum infarct volume (57.80 %) was observed in ischemic MCAO group. However, piperine administration prior to ischemia showed a significant reduction in infarct volume (28.29 %; p < 0.05) and neuronal loss (12.72 %; p < 0.01). As a result of piperine pretreatment, a significant improvement in behavioral outputs of MCAO rats (p < 0.05-0.01) was observed. Piperine successfully reduced the level of proinflammatory cytokines IL-1ß, IL-6 and TNF-α, in ischemic group (p < 0.01). Ischemic group brain has shown edematous morphology with vacuolated architecture and pyknotic nuclei in H & E staining which was successfully ameliorated by piperine administration. Moreover, piperine also succeeded in lowering the expression of COX-2, NOS-2, and NF-κB (p < 0.01). Both cytosolic and nuclear NF-κB were down-regulated in ischemic group pre-administered with piperine (p < 0.01). The present study suggests that piperine is able to salvage the ischemic penumbral zone neurons by virtue of its anti-inflammatory property, thereby limiting ischemic cell death.

Catechin hydrate ameliorates redox imbalance and limits inflammatory response in focal cerebral ischemia.

Epidemiologic studies have shown that foods rich in polyphenols, such as flavonoids, can lower the risk of ischemic disease; however, the mechanism of protection has not been clearly investigated. In this study, we hypothesized that pretreatment effect of catechin hydrate (CH) on functional outcome, neuronal damage and on secondary injuries in the ischemic brain of rats. To test this hypothesis, male Wistar rats were pretreated with CH (20 mg/kg b.wt) for 21 days and then subjected to 2 h middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion. After 2 h MCAO/22 h reperfusion, neurological deficit, infarct sizes, activities of antioxidant enzymes and cytokines level were measured. Immunohistochemistry and western blot were used to analyse the expression of glial fibrillary acidic protein (GFAP), inducible nitric oxide (iNOS) and NF-kB in ischemic brain. The administration of CH showed marked reduction in infarct size, reduced the neurological deficits, suppressed neuronal loss and downregulate the iNOS, GFAP and NF-kB expression in MCAO rats. A significantly depleted activity of antioxidant enzymes and content of glutathione in MCAO group were protected significantly in MCAO group pretreated with CH. Conversely, the elevated level of thiobarbituric acid reactive species and cytokines in MCAO group was attenuated significantly in CH pretreated group when compared with MCAO group. The results indicated that CH protected the brain from damage caused by MCAO, and this effect may be through downregulation of NF-kB expression.

S-allyl cysteine mitigates oxidative damage and improves neurologic deficit in a rat model of focal cerebral ischemia.

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The present study examined the hypothesis that S-allyl cysteine (SAC), organosulfur compounds found in garlic extract, would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). To test this hypothesis, male Wistar rats were subjected to MCAO for 2 hours and 22-hour reperfusion. S-allyl cysteine was administered (100 mg/kg, b.wt.) intraperitoneally 30 minutes before the onset of ischemia and after the ischemia at the interval of 0, 6, and 12 hours. After 24 hours of reperfusion, rats were tested for neurobehavioral activities and were killed for the infarct volume, estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase). S-allyl cysteine treatment significantly reduced ischemic lesion volume, improved neurologic deficits, combated oxidative loads, and suppressed neuronal loss. Behavioral and biochemical alterations observed after MCAO were further associated with an increase in glial fibrillary acidic protein and inducible nitric oxide expression and were markedly inhibited by the treatment with SAC. The results suggest that SAC exhibits exuberant neuroprotective potential in rat ischemia/reperfusion model. Thus, this finding of SAC-induced adaptation to ischemic stress and inflammation could suggest a novel avenue for clinical intervention during ischemia and reperfusion.

Ocimum sanctum attenuates oxidative damage and neurological deficits following focal cerebral ischemia/reperfusion injury in rats.

Stroke is an enormous public health problem with an imperative need for more effective therapy. Free radicals have been reported to play a role in the expansion of ischemic brain lesions, and the effect of free radical scavengers is still under debate. The present study investigated the neuroprotective effect of Ocimum sanctum (OS) to reduce brain injury after middle cerebral artery occlusion (MCAO). Male Wistar rats were subjected to MCAO for 2 h and reperfused for 22 h. The administration of OS (200 mg/kg bwt., orally) once daily for 15 days before MCAO showed marked reduction in infarct size, reduced the neurological deficits, and suppressed neuronal loss in MCAO rats. A significantly depleted activity of antioxidant enzymes and content of glutathione in MCAO group were protected significantly in MCAO group pretreated with OS. Conversely, the elevated level of thiobarbituric acid-reactive substances (TBARS) in MCAO group was attenuated significantly in OS-pretreated group when compared with MCAO group. Consequently, OS pretreatment may reduce the deterioration caused by free radicals, and thus may used to prevent subsequent behavioral, biochemical and histopathological changes that transpire during cerebral ischemia. This finding reflects that supplementation of OS intuitively by reasonable and understandable treatment effectively ameliorates the cerebral ischemia-induced oxidative damage.

Rutin protects dopaminergic neurons from oxidative stress in an animal model of Parkinson's disease.

This study was undertaken to investigate the neuroprotective effects of rutin (vitamin P) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) in rats. Oxidative stress and inflammation is an important event, play a crucial role in neurodegenerative diseases. Rutin has been shown to have antioxidant and anti-inflammatory actions, and thus was tested for its beneficial effects using 6-OHDA-induced PD rat model. Male Wistar rats were pre-treated with rutin (25 mg/kg bwt, orally) for 3 weeks and subjected to unilateral intrastriatal injection of 6-OHDA (10 µg in 0.1% ascorbic acid in normal saline). Three weeks after 6-OHDA infusion, rats were tested for neurobehavioral activity, and were killed after 4 weeks of 6-OHDA infusion for the estimation of thiobarbituric acid reactive substances, glutathione, and its dependent enzymes (glutathione peroxidase and glutathione reductase), dopamine (DA) and its metabolite 3,4-dihydroxyphenyl acetic acid. The increase in 6-OHDA-induced rotations and deficits in locomotor activity and motor coordination and decrease in antioxidant level, DA content and its metabolite and increase in the number of dopaminergic D2 receptors in striatum were protected significantly with lesioned group pre-treated with rutin. These findings were further supported by the histopathological and immunohistochemical findings in the substantia nigra that showed that rutin protected neurons from deleterious effects of 6-OHDA. These results suggest that the consumption of rutin, which is novel vitamin, may have the possibility of protective effect against the neurological disorder such as PD.

Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke.

Incidence of stroke is considered to be a major cause of death throughout the world. The middle cerebral artery occlusion (MCAO) for 2h followed by 22h of reperfusion model was used in male Wistar rats to study the protection of stroke by hesperidin. Hesperidin administration (50mg/kg b.wt.) once daily for 15days has improved the infarct size, reduced the neurological deficits in terms of behaviors, and protected the elevated level of thiobarbituric acid reactive species (TBARS). A significantly depleted activity of antioxidant enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) and content of glutathione (GSH) in MCAO group were protected significantly in MCAO group pretreated with hesperidin. Moreover, inflammatory mediators like TNF-α, IL-1ß levels, expression of iNOS and glial fibrillary acidic protein (GFAP) were significantly attenuated in H+MCAO group as compared to MCAO group. In conclusion, prophylactic treatment with hesperidin ameliorated the functional and histological outcomes with elevated endogenous antioxidants status as well as reduced induction of proinflammatory cytokines in MCA occluded rat. We theorized that hesperidin is among the pharmacological agents that reduce free radicals and its associated inflammation and have been found to limit the extent of brain damage following stroke.

Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and immunohistological study in Wistar rats.

Cerebral stroke is the third largest cause of death and the severe leading cause of disability, thus have astronomical financial and social burden worldwide. Accumulated evidence suggests that ROS can be scavenged through utilizing natural antioxidant compounds present in foods and medicinal plants. In this study, we examined whether silymarin, an antioxidant, present in the milk of thistle can prevent or slowdown neuronal injury in focal cerebral ischemia. Male Wistar rats were pre-treated with silymarin (200mg/kg body weight, dissolved in 0.3 % sodium carboxymethyl cellulose, once orally) for 15 days. On day 16, they underwent a transient 2h suture-occlusion of the middle cerebral artery followed by 22 h of reperfusion. Rats were tested for neurobehavioral activity after 22 h reperfusion. Silymarin was found to be successful in upregulating the antioxidant status and lowering the apoptotic responses, and functional recovery returned close to the baseline. This study revealed that silymarin, a naturally occurring flavone from the milk thistle (Silybum marianum), may be helpful in slowing down the progression of neurodegeneration in focal cerebral ischemia. These results suggest that the neuroprotective potential of silymarin is mediated through its anti-oxidative and anti-apoptotic properties.

Quercetin protects against oxidative stress associated damages in a rat model of transient focal cerebral ischemia and reperfusion.

Experimental studies have demonstrated that oxidative stress and apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The purpose of this study was to determine whether the quercetin dihydrate (Q) protects against cerebral ischemia neuronal damage. Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and reperfused for 72 h. Quercetin (30 mg/kg, i.p) was administrated 30 min before the onset of ischemia and after the ischemia at interval of 0, 24, 48, and 72 h. The administration of Q showed marked reduction in infarct size, reduced the neurological deficits in terms of behaviors, suppressed neuronal loss and diminished the p53 expression in MCAO rats. Q was found to be successful in upregulating the antioxidant status and lowering the TBARS level. Conversely, the elevated activity of poly (ADP-ribose) polymerase (PARP), and activity of caspase-3 in MCAO group was attenuated significantly in Q treated group when compared with MCAO group. Our study reveals that Q, as a powerful antioxidant, could prevent free radicals associated oxidative damage and morphological changes in the MCAO rats. Thus, it may have a therapeutic value for the treatment of stroke.

S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type.

S-allyl cysteine (SAC), a sulfur containing amino acid derived from garlic, has been reported to have antioxidant, anti-cancer, antihepatotoxic and neurotrophic activity. This study was designed to examine the pre-treatment effects of SAC on cognitive deficits and oxidative damage in the hippocampus of intracerebroventricular streptozotocin (ICV-STZ)-infused mice. Mice pre-treated with SAC (30mg/kg) and vehicle (intraperitoneal; once daily for 15days) were bilaterally injected with ICV-STZ (2.57mg/kg body weight), whereas sham rats received the same volume of vehicle. The pre-treatment of this drug to Swiss albino mice has prevented the cognitive and neurobehavioral impairments. An increased latency and path length were observed in lesion, i.e. streptozotocin (STZ) group as compared to sham group and these were protected significantly in STZ group pre-treated with SAC. Levels of reduced glutathione (GSH) and its dependent enzymes (Glutathione peroxidase [GPx] and glutathione reductase [GR]) were decreased in STZ group as compared to sham group and pre-treatment of STZ group with SAC has protected their activities significantly. Conversely, the elevated level of thiobarbituric acid reactive substances (TBARS) in STZ group was attenuated significantly in SAC pre-treated group when compared with STZ lesioned group. Apoptotic parameters like DNA fragmentation, expression of Bcl2 and p53 were protected by the pre-treatment of SAC against STZ induced cognitive impairment. This study concludes that intervention of SAC could prevent free radicals associated deterioration of cognitive functions and neurobehavioral activities.

Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical and immunohistochemical studies.

Curcumin, the active principle of turmeric used in Indian curry is known for its antitumor, antioxidant, antiarthritic, anti-ischemic and anti-inflammatory properties and might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients. A Parkinsonian model in rats was developed by giving 6-hydroxydopamine (10 µg/2 µl in 0.1% ascorbic acid-saline) in the right striatum. After 3 weeks of lesioning, the behavior activities (rotarod, narrow beam test, grip test and contra-lateral rotations) were increased in a lesioned group as compared to a sham group and these activities were protected significantly with the pretreatment of curcumin. A significant protection on lipid peroxidation, glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, tyrosine hydroxylase and D(2) receptor binding was observed in the striatum of lesioned group animals pretreated with 80 mg/kg body weight of curcumin for 21 days as compared to lesion group animals. No significant alterations on behavior and biochemical parameters were observed in sham group animals and the animals of sham group pretreated with curcumin. This study indicates that curcumin, which is an important ingredient of diet in India and also used in various systems of indigenous medicine, is helpful in preventing Parkinsonism and has therapeutic potential in combating this devastating neurologic disorder.

Synergistic effect of selenium and melatonin on neuroprotection in cerebral ischemia in rats.

The synergistic scavenger effects of selenium and melatonin collectively we called Se-Mel was studied on the prevention of neuronal injury induced by ischemia/reperfusion. Male Wistar rats were treated with sodium selenite (0.1 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) 30 min before the middle carotid artery occlusion (MCAO) and immediately after MCAO to male Wistar rats and was continued for 3 days once daily at the interval of 24 h. Behavioral activity (spontaneous motor activity and motor deficit) was improved in Se-Mel-treated rats as compared to MCAO group rats. The level of glutathione and the activity of antioxidant enzymes was depleted significantly while the content of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide radical (NO(·)) was increased significantly in MCAO group. Systemic administration of Se-Mel ameliorated oxidative stress and improves ischemia/reperfusion-induced focal cerebral ischemia. Se-Mel also inhibited inducible nitric oxide synthase expression in Se-Mel+MCAO group as compared to MCAO group rats. Thus, Se-Mel has shown an excellent neuroprotective effect against ischemia/reperfusion injury through an anti-ischemic pathway. In conclusion, we demonstrated that the pretreatment with Se-Mel at the onset of reperfusion, reduced post-ischemic damage, and improved neurological outcome following transient focal cerebral ischemia in male Wistar rat.

Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease.

The present study was undertaken to investigate the neuroprotective effects of resveratrol (RES) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) in rats. PD is an age-related neurodegenerative disorder in which the role of reactive oxygen species (ROS) is strongly implicated. RES, a polyphenolic antioxidant compound enriched in grapes, has been shown to have antioxidant and anti-inflammatory actions and thus was tested for its beneficial effects using 6-OHDA-induced PD rat model. Male Wistar rats were pretreated with RES (20mg/kg body weight i.p.) once daily for 15 days and subjected to unilateral intrastriatal injection of 6-OHDA (10 microg in 0.1% ascorbic acid in normal saline). Three weeks after 6-OHDA infusion, rats were tested for neurobehavioral activity and were killed after 4 weeks of 6-OHDA infusion for the estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase [GPx], glutathione reductase [GR], catalase [CAT], and superoxide dismutase [SOD]. RES was found to be successful in upregulating the antioxidant status and lowering the dopamine loss. Conversely, the elevated level of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC), and activity of phospholipase A2 in 6-OHDA group was attenuated significantly in RES-pretreated group when compared with 6-OHDA-lesioned group. These results were supported by the immunohistochemical findings in the substantia nigra that has shown the protection of neurons by RES from deleterious effects of 6-OHDA. Thus, RES may be used to reduce the deterioration caused by free radicals thereby preventing subsequent behavioral, biochemical, and histopathological changes that occur during PD.

Sesamin attenuates behavioral, biochemical and histological alterations induced by reversible middle cerebral artery occlusion in the rats.

Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species (ROS) with consequent reperfusion injury. ROS cause lipid peroxidation, protein oxidation, and DNA damage, all of which are deleterious to cells. So diminishing the production of free radicals and scavenging them may be a successful therapeutic strategy for the protection of brain tissue in cerebral stroke. The present study investigated the neuroprotective effect of sesamin (Sn) to reduce brain injury after middle cerebral artery occlusion (MCAO). The middle cerebral artery (MCA) of adult male Wistar rat was occluded for 2h and reperfused for 22h. Sesamin is the most abundant lignan in sesame seed oil is a potent antioxidant. Sesamin (30 mg/kg) was given orally twice, 30 min before the onset of ischemia and 12h after reperfusion. The initial investigations revealed that sesamin reduced the neurological deficits in terms of behavior and reduced the level of thiobarbituric acid reactive species (TBARS), and protein carbonyl (PC) in the different areas of the brain when compared with the MCAO group. A significantly depleted level of glutathione and its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) in MCAO group were protected significantly in MCAO group treated with sesamin. The present study suggests that sesamin may be able to attenuate the ischemic cell death and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the rat brain. Thus, sesamin may be a potential compound in stroke therapy.