Kanwaljit Chopra

Publications (139)350.4 Total impact

• Article: Protective Effect of Curcumin against Chronic Alcohol-induced Cognitive Deficits and Neuroinflammation in the Adult Rat Brain.

  Vinod Tiwari, Kanwaljit Chopra
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  ABSTRACT: Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in cognitive deficits. In the present study, we investigated the protective effect of curcumin, a potent natural anti-oxidant and anti-inflammatory molecule against chronic alcohol-induced cognitive dysfunction and NF-κβ mediated inflammatory signaling in the brain of rats chronically administered ethanol. Male Wistar rats were given ethanol (10 g/kg; oral gavage) for ten weeks, and treated with curcumin (15, 30 and 60 mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappa β and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with curcumin significantly and dose-dependently prevented all the behavioral, biochemical and molecular alterations in rats chronically administered ethanol. Thus, findings from the current study demonstrates the possible involvement of oxidative-nitrosative stress mediated cytokine release and inflammatory signaling in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of curcumin in preventing cognitive deficits associated with chronic alcohol consumption.
  Neuroscience 04/2013; · 3.38 Impact Factor
• Article: Curcumin loaded solid lipid nanoparticles: an efficient formulation approach for cerebral ischemic reperfusion injury in rats.

  Vandita Kakkar, Sravan Kumar Muppu, Kanwaljit Chopra, Indu Pal Kaur
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  ABSTRACT: SCOPE: To evaluate curcumin loaded solid lipid nanoparticles (C-SLNs) in the experimental paradigm of cerebral ischemia (BCCAO model) in rats. METHODS AND RESULTS: Oral administration of free curcumin and C-SLNs (25 and 50 mg/kg) was started 5 days prior and continued for 3 days after BCCAO. Alleviation in behavioural, oxidative & nitrosative stress, acetylcholinestrase, mitochondrial enzyme complexes and physiological parameters were assessed. Confirmation of effective brain delivery of C-SLNs (p.o) was done using biodistribution studies in mice and confocal microscopy of rat brain section. There was an improvement of 90% in cognition and 52% inhibition of acetylcholinesterase versus cerebral ischemic group (I/R). Neurological scoring improved by 79%. Levels of superoxide dismutase, catalase, glutathione, mitochondrial complex enzyme activities were significantly increased while lipid peroxidation, nitrite and acetylcholinesterase levels decreased (p < 0.05) after C-SLNs administration. It is noteworthy to report the restoration of SOD, GSH, catalase and mitochondrial complex enzyme levels equivalent to sham control values. Gamma-scintigraphic studies show 16.4 and 30 times improvement in brain bioavailability (AUC) upon oral and i.v administration of C-SLNs versus solubilised curcumin (C-S). CONCLUSIONS: Study indicates protective role of curcumin against cerebral ischemic insult; provided it is packaged suitably for improved brain delivery.
  European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 02/2013; · 3.15 Impact Factor
• Article: Resveratrol abrogates alcohol-induced cognitive deficits by attenuating oxidative-nitrosative stress and inflammatory cascade in the adult rat brain.

  Vinod Tiwari, Kanwaljit Chopra
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  ABSTRACT: Chronic alcohol intake is known to induce permanent cognitive deficits along with enhanced oxidative-nitrosative stress and activation of neuroinflammatory cascade. In the present study, we investigated the protective effect of resveratrol, a natural polyphenolic phytoalexin against chronic alcohol-induced cognitive dysfunction and neuroiflammatory cascade in the brain of adult rats chronically administered ethanol. Male Wistar rats were adminstered ethanol (10g/kg; oral gavage) for ten weeks and treated with resveratrol (5, 10 and 20mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappa β and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with resveratrol significantly and dose-dependently prevented all the behavioral, biochemical and molecular deficits. Correlatively, the results of the present study revealed that treatment with resveratrol significantly prevented cognitive deficits induced by chronic ethanol exposure not only by modulating oxido-nitrosative stress but also by attenuating the enhanced levels of pro-inflammatory cytokines (TNF-α and IL-1β), NF-kβ and caspase-3 in different brain regions of ethanol treated rats. Therefore, mechanism underlying the neuroprotective effects of resveratrol observed in our study may be due to its antioxidant, anti-inflammatory and neuromodulating activities.
  Neurochemistry International 02/2013; · 2.86 Impact Factor
• Chapter: Probiotics: Potential pharmaceutical applications.

  Indupal Kaur, Anurag Kuhad, Kanwaljit Chopra, Amita Joshi, Amita Garg
  02/2013;
• Article: Attenuation of oxidative stress, neuroinflammation, and apoptosis by curcumin prevents cognitive deficits in rats postnatally exposed to ethanol.

  Vinod Tiwari, Kanwaljit Chopra
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  ABSTRACT: RATIONALE: Clinical and experimental evidence have demonstrated that alcohol consumption during pregnancy can disrupt brain development, leading to a variety of behavioral alterations including hyperactivity, motor dysfunction, and cognitive deficits in offsprings. Alcohol-induced neurocognitive deficits are associated with activation of oxidative-inflammatory cascade coupled with extensive apoptotic neurodegeneration in different brain regions. OBJECTIVES: The present study was designed with an aim to investigate the protective effect of curcumin, a principal curcuminoid present in the Indian spice turmeric, against alcohol-induced cognitive deficits, neuroinflammation, and neuronal apoptosis in rat pups postnatally exposed to ethanol. METHODS AND RESULTS: Male Wistar rat pups were administered ethanol (5 g/kg, 12 % v/v) by intragastric intubation on postnatal days (PD) 7, 8, and 9 and were treated with curcumin (30 and 60 mg/kg) from PD 6 to 28. Performance of ethanol-exposed pups that did not receive curcumin was significantly impaired as evaluated in both Morris water maze and elevated plus maze tasks recorded by using computer tracking. Cognitive deficit was associated with enhanced acetylcholinesterase activity, increased neuroinflammation (oxidative-nitrosative stress, TNF-α, IL-1β, and TGF-β1), and neuronal apoptosis (NF-κβ and caspase 3) in both cerebral cortex and hippocampus of ethanol-exposed pups. Chronic treatment with curcumin significantly ameliorated all the behavioral, biochemical, and molecular alterations in different brain regions of ethanol-exposed pups. CONCLUSIONS: The current study demonstrates the possible involvement of oxidative-inflammatory cascade-mediated apoptotic signaling in cognitive deficits associated with postnatal ethanol exposure and points towards the neuroprotective potential of curcumin in mitigating alcohol-induced behavioral, biochemical, and molecular deficits.
  Psychopharmacologia 07/2012; · 4.08 Impact Factor
• Article: Attenuation of NF-κβ mediated apoptotic signaling by tocotrienol ameliorates cognitive deficits in rats postnatally exposed to ethanol.

  Vinod Tiwari, Vipin Arora, Kanwaljit Chopra
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  ABSTRACT: Ethanol-induced damage in the developing brain may result in cognitive impairment including deficits on neuropsychological tests of learning, memory and executive function, yet the underlying mechanisms remain elusive. In the present study we investigated the protective effect of tocotrienol against cognitive deficit, neuroinflammation and neuronal apoptosis in rat pups postnatally exposed to ethanol. Pups were administered ethanol (5g/kg, 12% v/v) by intragastric intubation on postnatal days 7, 8 and 9. Ethanol-exposed pups showed significant memory impairment in Morris water maze task as evident from increase in escape latency and total distance travelled to reach the hidden platform. Time spent in target quadrant, % total distance traversed in target quadrant and frequency of appearance in target quadrant was also significantly decreased in ethanol exposed pups in probe trial. Poor memory retention was exhibited by ethanol-exposed pups in elevated plus maze test also. Impaired cognition was associated with significantly enhanced acetylcholinesterase activity, increased neuroinflammation (oxidative-nitrosative stress, TNF-α, IL-1β and TGF-β1) and neuronal apoptosis (NF-κβ and Caspase-3) in different brain regions of ethanol-exposed pups. Co-administration with tocotrienol significantly ameliorated all the behavioral, biochemical and molecular alterations in the different brain regions of ethanol exposed pups. The current study thus demonstrates the possible involvement of NF-κβ mediated apoptotic signaling in cognitive deficits associated with postnatal ethanol exposure in rats and points to the potential of tocotrienol in the prevention of cognitive deficits in children with fetal alcohol spectrum disorders (FASDs).
  Neurochemistry International 05/2012; 61(3):310-20. · 2.86 Impact Factor
• Article: Vaccinium myrtillus ameliorates unpredictable chronic mild stress induced depression: possible involvement of nitric oxide pathway.

  Baldeep Kumar, Vipin Arora, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Chronic unpredictable stressors can produce a situation similar to clinical depression and such animal models can be used for the preclinical evaluation of antidepressants. Nitric oxide, a secondary messenger molecule, has been implicated in neurotransmission, synaptic plasticity, learning, aggression and depression. Vaccinium myrtillus (bilberry) extract is a potent inhibitor of reactive oxygen/nitrogen species and cytokine production. The present study investigated the role of nitric oxide in the antidepressant action of Vaccinium myrtillus in unpredictable chronic mild stress-induced depression in mice. Animals were subjected to different stress paradigms daily for a period of 21 days to induce depressive-like behavior. Pretreatment with L-arginine significantly reversed the protective effect of bilberry (500 mg/kg) on chronic stress-induced behavioral (immobility period, sucrose preference) and biochemical (lipid peroxidation and nitrite levels; endogenous antioxidant activities) in stressed mice. Furthermore, L-NAME (10 mg/kg) pretreatment with a sub-effective dose of bilberry (250 mg/kg) significantly potentiated the protective effect of bilberry extract. The study revealed that modulation of the nitric oxide pathway might be involved in antidepressant-like effects of Vaccinium myrtillus in stressed mice.
  Phytotherapy Research 04/2012; 26(4):488-97. · 2.09 Impact Factor
• Article: Neuroprotective Effect of Vitamin E Isoforms Against Chronic Alcohol-induced Peripheral Neurotoxicity: Possible Involvement of Oxidative-Nitrodative Stress.

  Vinod Tiwari, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Small-fiber painful peripheral neuropathy is one of the long-term complications of alcohol for which there is no reliable successful therapy available. The precise mechanisms by which chronic alcohol consumption produces peripheral nerve fiber damage and loss remain unclear. Emerging data from clinical and preclinical studies suggest that increased oxidative-nitrodative stress mediated release of proinflammatory cytokines from damaged neural tissues may play a central role in the pathogenesis of alcoholic neuropathy. The present study investigated the effect of both the isoforms of vitamin E (α-tocopherol and tocotrienol) against chronic alcohol-induced peripheral neuropathy in rats. Ethanol treated rats showed a significant decrease in paw-withdrawal threshold in both Randall-Selitto and von-Frey hair tests along with a significant reduction in tail flick latency in the tail-immersion test. A decreased pain threshold was associated with significant alterations in oxidative-nitrodative stress markers and an increase in proinflammatory cytokines (TNF-α and IL-1β). The 4-week treatment with tocotrienol significantly ameliorated behavioral, biochemical and molecular alterations in alcohol treated rats. However, α-tocopherol failed to produce any protective effect. The results of the present study suggest that oxidative-nitrodative stress mediated cytokine signaling may be responsible for alcohol-induced peripheral neurotoxicity and tocotrienol treatment might be beneficial in chronic alcoholics exhibiting neuropathy. Copyright © 2012 John Wiley & Sons, Ltd.
  Phytotherapy Research 03/2012; 26(11):1738-45. · 2.09 Impact Factor
• Article: Alcoholic neuropathy: possible mechanisms and future treatment possibilities.

  Kanwaljit Chopra, Vinod Tiwari
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  ABSTRACT: Chronic alcohol consumption produces painful peripheral neuropathy for which there is no reliable successful therapy, mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy involves coasting caused by damage to nerves that results from long term excessive drinking of alcohol and is characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism behind alcoholic neuropathy is not well understood, but several explanations have been proposed. These include activation of spinal cord microglia after chronic alcohol consumption, oxidative stress leading to free radical damage to nerves, activation of mGlu5 receptors in the spinal cord and activation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis. Nutritional deficiency (especially thiamine deficiency) and/or the direct toxic effect of alcohol or both have also been implicated in alcohol-induced neuropathic pain. Treatment is directed towards halting further damage to the peripheral nerves and restoring their normal functioning. This can be achieved by alcohol abstinence and a nutritionally balanced diet supplemented by all B vitamins. However, in the setting of ongoing alcohol use, vitamin supplementation alone has not been convincingly shown to be sufficient for improvement in most patients. The present review is focused around the multiple pathways involved in the development of peripheral neuropathy associated with chronic alcohol intake and the different therapeutic agents which may find a place in the therapeutic armamentarium for both prevention and management of alcoholic neuropathy.
  British Journal of Clinical Pharmacology 03/2012; 73(3):348-62. · 2.96 Impact Factor
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  Article: Delivery of sesamol-loaded solid lipid nanoparticles to the brain for menopause-related emotional and cognitive central nervous system derangements.

  Vandita Kakkar, Anil Kumar Mishra, Krishna Chuttani, Kanwaljit Chopra, Indu Pal Kaur
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  ABSTRACT: The physicochemical nature of sesamol (logP 1.29; solubility 38.8 mg/mL) substantially enhances its tissue distribution, minimizing its brain delivery. Sesamol-loaded solid lipid nanoparticles (S-SLNs) with an average particle size of 122 nm and an entrapment efficiency of 75.9 ± 2.91% were developed. Biochemical and behavioral paradigms clearly established the superiority of orally administered S-SLNs. The same was confirmed evidently by scintigraphic images of rabbits administered radiolabeled SLNs and confocal microscopy of brain sections of rats administered similarly prepared SLNs with a fluorescent marker. This study indicates the special importance of using phosphatidylcholine (as co-surfactant) in the preparation of SLNs for improving memory deficits. The aim of the present work was to develop sesamol as a therapeutic agent for central nervous system derangements.
  Rejuvenation Research 12/2011; 14(6):597-604. · 3.83 Impact Factor
• Article: Neoteric pharmacotherapeutic targets in fibromyalgia.

  Kanwaljit Chopra, Anurag Kuhad, Vipin Arora
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  ABSTRACT: INTRODUCTION: Fibromyalgia is a debilitating, chronic pain disorder typically present with allodynia and hyperalgesia. Estimates from the USA suggest that fibromyalgia affects about 5% of women, and is the third most common rheumatic disorder after lower back pain and osteoarthritis. Recent research advances highlighted a role for aberrant central pain processing in fibromyalgia, and consistent with this, the first three drugs (pregabalin, duloxetine and milnacipran) approved by the FDA for fibromyalgia over the past 2 years have a predominantly central mode of action. Despite progress in understanding of fibromyalgia and the long-awaited introduction of three medications for treating it, fibromyalgia continues to pose a significantly unmet medical need, negatively affecting the lives of millions of individuals worldwide in all ethnic groups and all economic classes. AREAS COVERED: Prevailing theories of pathogenesis of fibromyalgia, existing therapies and the potential of current research on novel targets. EXPERT OPINION: Current research on novel sedative-hypnotics, anti-epileptic medications, various reuptake inhibitors, growth hormone agonists, canabinoid agonists, non-opiate analgesics and 5-HT3 antagonists offers hope for the the next generation of therapeutic options for fibromyalgia. With regards to the development of novel pharmacotherapies, there seem to be grounds for increased optimism regarding prospective treatments of the disorder.
  Expert opinion on therapeutic targets 09/2011; 15(11):1267-81. · 3.72 Impact Factor
• Article: Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome.

  Anand Kamal Sachdeva, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by tiredness, difficulty in concentration and memory, and concomitant skeletal and muscular pain, thus affecting both mental and physical domains. The pathogenesis of chronic fatigue syndrome is multifactorial and involves increased oxido-nitrosative stress along with generation of pro-inflammatory cytokines such as TNF-α. In the present study chronic fatigue was produced in rats by plunging a load of 10 ± 2% body weight and subjecting them to forced swim inside a rectangular jar daily for 28 days. Endurance capacity and post-swim fatigue were assessed on 1st, 7th, 14th, 21st and 28th days. EGCG was administered daily by oral gavage 30 min before forced swim session. On the 29th day, after assessment of various behavioral parameters, blood was collected through tail vein, and animals were sacrificed to harvest the brains, spleens and thymus. Chronic fatigue group exhibited significant behavioral alterations along with enhanced oxido-nitrosative stress and serum TNF-α level as compared to naive group. Chronic treatment with EGCG restored all the behavioral and biochemical alterations associated with chronic fatigue syndrome. The present study signifies the therapeutic potential of EGCG for the treatment of chronic fatigue syndrome.
  Brain research bulletin 07/2011; 86(3-4):165-72. · 2.18 Impact Factor
• Article: Involvement of nitric oxide (NO) signalling pathway in the antidepressant activity of essential oil of Valeriana wallichii Patchouli alcohol chemotype.

  Sangeeta Pilkhwal Sah, Chandra Shekhar Mathela, Kanwaljit Chopra
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  ABSTRACT: Valeriana wallichii DC (Valerianaceae), popularly named as Indian valerian has been shown to exist as three chemotypes. The present study evaluated the antidepressant like effect of root essential oil of Valeriana wallichii patchouli alcohol chemotype in both acute and chronic treatment study using forced swim test (FST). Mice (n=6 per group) received 10, 20 and 40 mg/kg p.o. doses of test drug. Single administration of oil significantly inhibited the immobility period (57.6% and 46.9%) at doses 20 and 40 mg/kg respectively without changing the motor function (p<0.05). Similarly, daily administration of essential oil (20mg/kg) for 14 days significantly reduced the immobility period (69.9%) in FST (p<0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (29%) and serotonin (19%) (p<0.05) was found at 20mg/kg dose, while no change was observed at 10 and 40 mg/kg doses. The antidepressant-like effect of essential oil (20mg/kg) was prevented by pretreatment of mice with l-arginine (750 mg/kg i.p.) and sildenafil (5mg/kg i.p). On the contrary, pretreatment of mice with l-NAME (10mg/kg i.p.) or methylene blue (10mg/kg i.p.) potentiated the antidepressant action of essential oil (10mg/kg). Taken together, these findings demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.
  Phytomedicine: international journal of phytotherapy and phytopharmacology 07/2011; 18(14):1269-75. · 2.17 Impact Factor
• Article: Effect of quercetin on lipopolysaccharide induced-sickness behavior and oxidative stress in rats.

  Sangeeta Pilkhwal Sah, Naveen Tirkey, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Gram-negative infections and control infusion of recombinant cytokines in human have been shown to induce sickness behavior characterized by fever, prolong sleep, decreased food and water intake, reduced mobility, depression, and anxiety. Therefore, the present study was undertaken to investigate the effect of bioflavonoid quercetin in lipopolysaccharide (LPS)-induced sickness behavior. Wistar albino rats were divided into six groups (n=6). Three groups received vehicle and two doses of quercetin (2 and 25 mg/kg, i.p.) respectively for 2 weeks before being challenged with LPS (1 mg/kg, i.p). One group received vehicle for 2 weeks and was challenged with saline on day 15. The per se effect of quercetin (2 and 25 mg/kg, i.p.) was also seen after 2 weeks of dosing. LPS-induced sickness behavior in rats was quantified by measuring time in social exploration, anxiety, food and water consumption, and weight loss. Levels of cytokines (TNF-α, IL-1β, and IL-6) and oxidative stress in rat brain were also analyzed. Quercetin (2 and 25 mg/kg) administration significantly (P<0.05) attenuated LPS-induced sickness behavior by modulating cytokines production as well inhibiting LPS-induced oxidative stress. Adequate intake of dietary flavonoids (like quercetin) may help promote recovery from sickness behavior.
  Indian Journal of Pharmacology 04/2011; 43(2):192-6. · 0.27 Impact Factor
• Article: Modulation of nitrergic pathway by sesamol prevents cognitive deficits and associated biochemical alterations in intracerebroventricular streptozotocin administered rats.

  Shubham Misra, Vinod Tiwari, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Alzheimer's disease is a neurodegenerative disorder characterized by progressive cognitive decline and widespread loss of neurons and their synapses in the cerebral cortex and hippocampus. Increasing evidence indicates that factors such as oxidative-nitrergic stress, glutathione depletion, impaired protein metabolism and cholinergic deficit can interact in a vicious cycle, which is central to Alzheimer's disease pathogenesis. Intracerebroventricular (i.c.v.) streptozotocin induced-cognitive impairment has been widely used as an experimental paradigm to study Alzheimer's disease. In the present study, i.c.v. streptozotocin produced significant cognitive deficits as measured in Morris water maze and elevated plus maze task coupled with increased serum TNF-α levels and marked rise in brain acetylcholinesterase and oxidative-nitrergic stress in female Wistar rats. Sesamol (5-hydroxy-1,3-benzodioxole or 3,4-methylenedioxyphenol), a potent anti-oxidant and anti-inflammatory molecule markedly improved cognitive impairment, reduced acetylcholinesterase activity, TNF-α levels and attenuated oxidative-nitrergic stress in brain of i.c.v.-streptozotocin treated rats. Administration of L-arginine (125 mg/kg i.p), a nitric oxide donor, alone to i.c.v.-streptozotocin treated rats accentuated behavioral and biochemical deficits and also abolished the protective effect of sesamol (8 mg/kg). L-NAME (10 mg/kgi.p.), a non-specific NOS inhibitor significantly restored all the behavioral and biochemical indices in i.c.v.-streptozotocin rats. Moreover, combination of L-NAME with sub-effective dose of sesamol (4 mg/kg) potentiated its protective effect. Our findings demonstrate the effectiveness of sesamol in preventing intracerebroventricular streptozotocin-induced cognitive deficits by modulating nitrergic signaling and oxido-inflammatory cascade.
  European journal of pharmacology 04/2011; 659(2-3):177-86. · 2.59 Impact Factor
• Article: Amelioration of functional, biochemical and molecular deficits by epigallocatechin gallate in experimental model of alcoholic neuropathy.

  Vinod Tiwari, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Long term alcohol consumption leads to decreased nociceptive threshold characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism involved in this pain includes increased oxidative-nitrosative stress, release of pro-inflammatory cytokines and neuronal apoptosis. The present study was designed to explore the protective effect of epigallocatechin-3-gallate against alcoholic neuropathic pain in rats. Rats fed with alcohol (35%) for 10 weeks showed markedly decreased tail flick latency in tail-immersion test (thermal hyperalgesia), vocalization threshold in Randall-Sellito test (mechanical hyperalgesia) and paw-withdrawal threshold in von-Frey hair test (mechanical allodynia) along with enhanced oxidative-nitrosative stress and inflammatory mediators (TNF-α, IL-1β and TGF-β1 levels). Co-administration of epigallocatechin-3-gallate (25-100 mg/kg) significantly and dose-dependently prevented functional, biochemical and molecular changes associated with alcoholic neuropathy. In conclusion, the current findings suggest the neuroprotective potential of epigallocatechin-3-gallate in attenuating the functional, biochemical and molecular alterations associated with alcoholic neuropathy through modulation of oxido-inflammatory cascade.
  European journal of pain (London, England) 03/2011; 15(3):286-92. · 3.37 Impact Factor
• Article: Emblica officinalis corrects functional, biochemical and molecular deficits in experimental diabetic neuropathy by targeting the oxido-nitrosative stress mediated inflammatory cascade.

  Vinod Tiwari, Anurag Kuhad, Kanwaljit Chopra
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  ABSTRACT: Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. Diabetic neuropathic pain is amongst the most difficult types of pain to treat mainly due to the lack of understanding of its etiology and inadequate relief with available drug therapy. The present study targeted oxidative stress mediated nerve damage in diabetic rats using an aqueous extract of Emblica officinalis, a potent natural antioxidant. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test (thermal hyperalgesia) and decreased paw withdrawal threshold in both Randall-Selitto (mechanical hyperalgesia) and von-Frey hair test (mechanical allodynia). A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress, nitrite levels and cytokines (TNF-α, IL-1β and TGF-β1) both in the serum and sciatic nerve of diabetic rats. Treatment with the Emblica officinalis aqueous extract (250, 500 and 1000 mg/kg/day) significantly attenuated all the behavioral, biochemical and molecular alterations in a dose-dependent manner. The major finding of the study is that insulin alone corrected the hyperglycemia and partially reversed the pain response in diabetic rats. However, combination with Emblica officinalis extract not only attenuated the diabetic condition but also reversed neuropathic pain through modulation of oxidative-nitrosative stress in diabetic rats.
  Phytotherapy Research 03/2011; 25(10):1527-36. · 2.09 Impact Factor
• Article: Resveratrol prevents alcohol-induced cognitive deficits and brain damage by blocking inflammatory signaling and cell death cascade in neonatal rat brain.

  Vinod Tiwari, Kanwaljit Chopra
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  ABSTRACT: Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the 'brain growth spurt' has been associated with significant impairments in attention, learning and memory. Recent studies have shown that administration of ethanol to infant rats during the synaptogenesis period (first 2 weeks after birth) triggers extensive apoptotic neurodegeneration throughout many regions of the developing brain and results in cognitive dysfunctions as the animal matures. The present study was designed with an aim to investigate the effect of resveratrol, a polyphenolic phytoalexin (trans-3,5,4-trihydroxy stilbene) present in red wine on alcohol-induced cognitive deficits and neuronal apoptosis in rat pups postnatally exposed to ethanol. Pups were administered ethanol (5 g/kg, 12% v/v) by intragastric intubation on postnatal days 7, 8, and 9. Ethanol-exposed pups showed impaired memory performance in both Morris water maze elevated plus maze task recorded by using computer tracking with EthoVision software. Behavioral deficit in ethanol-exposed pups was associated with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokine (TNF-α, IL-1β and TGF-β), nuclear factor kappa beta and caspase 3 levels in both cerebral cortex and hippocampus. Chronic treatment with resveratrol (10 and 20 mg/kg) significantly attenuated all the behavioral, biochemical and molecular changes in different brain regions of ethanol administered pups. The major finding of the study is that resveratrol blocks activation of nuclear factor kappa beta pathway and apoptotic signaling and prevents cognitive deficits in rats postnatally exposed to ethanol.
  Journal of Neurochemistry 03/2011; 117(4):678-90. · 4.06 Impact Factor
• Article: Antidepressant effect of Valeriana wallichii patchouli alcohol chemotype in mice: Behavioural and biochemical evidence.

  Sangeeta Pilkhwal Sah, Chandra S Mathela, Kanwaljit Chopra
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  ABSTRACT: Valeriana wallichii DC, an ayurvedic traditional medicine has now been shown to exist chemically as three distinct chemotypes. The study aimed to investigate the antidepressant effect of dichloromethane extract of Valeriana wallichii patchouli alcohol chemotype. Antidepressant effect of dichloromethane extract of Valeriana wallichii (10, 20 and 40mg/kg, p.o.) using forced swim test, was determined in both acute and chronic study. The neurotransmitter levels were estimated in mouse forebrain after two weeks of dosing. Single administration of extract (40mg/kg) significantly inhibited the immobility period in mice (p<0.05). Similarly, chronic administration of extract (20 and 40mg/kg) significantly reduced the immobility period and significantly increased the levels of norepinephrine and dopamine in mouse forebrain (p<0.05). The extract demonstrated antidepressant effect and significantly increased the norepinephrine and dopamine levels in forebrain.
  Journal of ethnopharmacology 02/2011; 135(1):197-200. · 2.32 Impact Factor
• Article: Current perspectives on pharmacotherapy of Alzheimer's disease.

  Kanwaljit Chopra, Shubham Misra, Anurag Kuhad
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  ABSTRACT: INTRODUCTION: Alzheimer's disease (AD) is a daunting public health threat that has prompted the scientific community's ongoing efforts to decipher the underlying disease mechanism, and thereafter, target this therapeutically. Although basic research in AD has made remarkable progress over the past two decades, currently available drugs can only improve cognitive symptoms temporarily; no treatment can reverse, stop, or even slow this inexorable neurodegenerative process. Numerous disease-modifying strategies targeting the production and clearance of Aβ, as well as modulation of abnormal aggregation of tau filaments, are currently in clinical trials . AREAS COVERED: this review provides an overview of a wide array of therapeutic approaches under investigation, and the perspectives developed in the last 10 years. EXPERT OPINION: While it is not possible to predict the success of any individual program, one or more are likely to prove effective. Indeed, it seems reasonable to predict that in the not-too-distant future, a synergistic combination of agents will have the capacity to alter the neurodegenerative cascade and reduce the global impact of this devastating disease. The scientific community must acknowledge that Alzheimer's disease is a complex multifactorial disorder, and thus a single target or pathogenic pathway is unlikely to be identified. The major aim should be to design ligands with pluripotent pharmacological activities.
  Expert Opinion on Pharmacotherapy 02/2011; 12(3):335-50. · 3.20 Impact Factor