ABSTRACT
The present study demonstrated the neuroprotective effect of curcuminoids, the active polyphenols of Curcuma longa (L.) rhizomes on mitochondrial dysfunctioning in middle aged and aged female Wistar rat brain. Rats were orally treated with curcuminoids (100 mg/kg) for 3 months and their brain was collected for evaluation of mitochondrial enzymes and complexes activity, ultra structural changes in mitochondria, neuronal nitric oxide synthase (nNOS) protein expression, adenosine triphosphate (ATP) and lipofuscin content. Significant alterations were observed in all the tested parameters in highly aged rat brain when compared with young control. Long term curcuminoids administration prevented this age associated loss of mitochondrial enzymes and complexes activity in middle aged rat brain except for malate dehydrogenase, Complex II and IV activity when compared with young control. Among aged rats, curcuminoids treatment specifically elevated isocitrate and NADH dehydrogenase, cytochrome c oxidase, Complex I and total ATP content. A significant down-regulation of nNOS protein expression along with reduced lipofuscin content was also observed in curucminoids treated middle aged and aged rats. Thus, it was suggested that curcuminoids may act as a putative drug candidate for the prevention of deleterious effects of ageing and age associated neurodegenerative disorders through amelioration of aberrant mitochondrial functioning.
Subject(s)
Aging/physiology , Brain/drug effects , Curcumin/pharmacology , Mitochondria/drug effects , Mitochondria/physiology , Models, Animal , Plant Extracts/pharmacology , Adenosine Triphosphate/metabolism , Administration, Oral , Animals , Brain/metabolism , Brain/physiopathology , Curcumin/administration & dosage , Electron Transport Complex I/metabolism , Electron Transport Complex IV/metabolism , Female , Lipofuscin/metabolism , NADH Dehydrogenase/metabolism , Nitric Oxide Synthase Type I/metabolism , Plant Extracts/administration & dosage , Rats , Rats, WistarABSTRACT
The present study investigated the neuroprotective effect of curcuminoids, the active polyphenols of Curcuma longa (L.) rhizomes against inflammation-mediated dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Male C57BL/6 mice were pre-treated with curcuminoids (150 mg/kg/day) for 1 week, followed by four intra-peritoneal (i.p.) injections of MPTP (20 mg/kg) at 2 h intervals with further administration of curcuminoids or deprenyl (3 mg/kg/day) for 2 weeks. Our results show that oral administration of curcuminoids significantly prevented MPTP-mediated depletion of dopamine and tyrosine hydroxylase (TH) immunoreactivity. In-addition, pre-treatment with curcuminoids reversed glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) protein expression, as well as, reduced pro-inflammatory cytokine and total nitrite generation in the striatum of MPTP-intoxicated mice. Significant improvement in motor performance and gross behavioural activity, as determined by rota-rod and open field tests were also observed. Taken together, our findings suggest that curcuminoids exert a neuroprotective effect against MPTP-induced dopaminergic neurodegeneration through its anti-inflammatory action and thus holds immense potential as a therapeutic candidate for the prevention and management of PD.
Subject(s)
Curcumin/therapeutic use , Dopaminergic Neurons/drug effects , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/physiology , Nerve Degeneration/prevention & control , Neuroprotective Agents/therapeutic use , Parkinsonian Disorders/prevention & control , Animals , Curcuma , Curcumin/isolation & purification , Curcumin/pharmacology , Dopaminergic Neurons/metabolism , Male , Mice , Mice, Inbred C57BL , Nerve Degeneration/metabolism , Neuroprotective Agents/pharmacology , Parkinsonian Disorders/metabolism , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic useABSTRACT
Bacopa monnieri (L.) is a revered medicinal plant of traditional Indian system of medicine effective against cognitive impairment in ageing and SDAT. In our previous study, long term administration of bacosides was found to exhibit remarkable anti ageing effect, ameliorate age associated neurochemical and neurobehavioral deficits and prevent hippocampal neuronal degeneration in middle aged and aged rat brain cortex. In continuation to the previous study, the present study aims to investigate the neuroprotective effect of bacosides against age related chronic neuroinflammation in Wistar rat brain on 3 months treatment. Recently, neuroinflammation has gained considerable interest in age associated neurodegeneration and pathologies like SDAT due to its slow onset and chronic nature. The results of the present study demonstrated the significant attenuation of age dependant elevation of pro inflammatory cytokines, iNOS protein expression, total nitrite and lipofuscin content in middle aged and aged rat brain cortex on long term oral administration of bacosides. Thus, the present results suggest that bacosides possess immense potential to act as a neuroprotective agent due to its pleiotropic action for the prevention of ageing complications and SDAT progression.
Subject(s)
Aging/drug effects , Bacopa , Inflammation/drug therapy , Neuroprotective Agents/pharmacology , Saponins/pharmacology , Aging/metabolism , Aging/pathology , Animals , Female , Inflammation/pathology , Inflammation/physiopathology , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/therapeutic use , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Rats, Wistar , Saponins/isolation & purification , Saponins/therapeutic use , Treatment OutcomeABSTRACT
Bacopa monnieri (L.), popularly known as Brahmi, is a revered Ayurvedic medicinal plant used as nerve tonic since time immemorial. The present study aims to investigate the neuroprotective effect of bacosides, the active saponins of Bacopa monnieri (L.) against age associated neurodegeneration and its impact over the prevention of Senile Dementia of Alzheimer's Type (SDAT). The optimum dose of bacosides with no adverse effect was selected by screening its dose dependant activity on ageing biomarker lipofuscin and SDAT biomarker neurotransmitter acetylcholine in the aged female Wistar rat brain. The selected therapeutic dose of bacosides (200 mg/kg) was orally administered for 3 months in middle aged and aged rats and further investigated for its protective action against age associated alterations in neurotransmission system, behavioral paradigms, hippocampal neuronal loss and oxidative stress markers. The results of the present study suggest that bacosides may act as a potential therapeutic intervention in forestalling the deleterious effects of ageing and preventing the age associated pathologies like SDAT.
Subject(s)
Aging , Bacopa , Brain/drug effects , Neurodegenerative Diseases/prevention & control , Neurons/drug effects , Neuroprotective Agents/pharmacology , Saponins/pharmacology , Acetylcholine/metabolism , Acetylcholinesterase/metabolism , Administration, Oral , Age Factors , Aging/metabolism , Animals , Bacopa/chemistry , Behavior, Animal/drug effects , Biogenic Monoamines/metabolism , Biomarkers/metabolism , Brain/metabolism , Brain/pathology , Brain/physiopathology , Cell Death/drug effects , Cognition/drug effects , Dose-Response Relationship, Drug , Female , GPI-Linked Proteins/metabolism , Lipofuscin/metabolism , Memory/drug effects , Motor Activity/drug effects , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/physiopathology , Neurodegenerative Diseases/psychology , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/isolation & purification , Oxidative Stress/drug effects , Rats , Rats, Wistar , Saponins/administration & dosage , Saponins/isolation & purificationABSTRACT
Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage and mitochondrial dysfunction. The aim of the present study is to investigate the effects of curcuminoids, polyphenols of Curcuma longa (L.) on oxidative stress and mitochondrial impairment in the brain of streptozotocin (STZ)-induced diabetic rats. A marked increase in lipid peroxidation and nitrite levels with simultaneous decrease in endogenous antioxidant marker enzymes was observed in the diabetic rat brain, which was restored to normal levels on curcuminoids treatment. Down-regulation of mitochondrial complex I and IV activity caused by STZ induction was also up-regulated on oral administration of curcuminoids. Moreover, curcuminoids administration profoundly elevated the ATP level, which was earlier reduced in the diabetic brain. These results suggest that curcuminoids exhibit a protective effect by accelerating antioxidant defense mechanisms and attenuating mitochondrial dysfunction in the brain of diabetic rats. Curcuminoids thus may be used as a promising therapeutic agent in preventing and/or delaying the progression of diabetic complications in the brain.
