ABSTRACT
Alzheimer disease (AD) is a widespread neurodegenerative condition that leads to progressive cognitive dysfunction in elderly population. Despite several attempts aimed at molecular determinants of AD, effective disease modifying treatment options are highly limited. Recently, use of natural supplements has gained considerable attention in AD research due to their cost effective and long lasting health beneficial properties. Resveratrol (RSV) is a naturally occurring polyphenolic compound found majorly in grapes. RSV has been shown to exert a plethora of medical benefits due to its anti-oxidant, anti-aging, anti-inflammatory, anti-malignant and neuroprotective properties. In particular, RSV has been shown to increase memory performance. The neuroprotective effect of RSV has strongly been linked to the depolymerization of amyloid ß fibrils. However, the molecular targets of RSV remain the subject of investigation. This review was aimed to comprehend the existing knowledge on the neuroprotective effects of RSV and recent progress made on understanding the role RVS in the regulation of neural plasticity through a molecular target Sirtuin 1, a potential homeostatic regulator in AD.
Subject(s)
Alzheimer Disease/drug therapy , Resveratrol/therapeutic use , Signal Transduction/drug effects , Sirtuin 1/metabolism , Alzheimer Disease/metabolism , Animals , Antioxidants/therapeutic use , Homeostasis/drug effects , Humans , Neuroprotective Agents/therapeutic useABSTRACT
OBJECTIVE: Mitochondrial dysfunction and oxidative stress-mediated apoptosis plays an important role in various neurodegenerative diseases including Huntington's disease, Parkinson's disease (PD) and Alzheimer's disease (AD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the most widely used neurotoxin mimics the symptoms of PD by inhibiting mitochondrial complex I that stimulates excessive intracellular reactive oxygen species (ROS) and finally leads to mitochondrial-dependent apoptosis. Lutein, a carotenoid of xanthophyll family, is found abundantly in leafy green vegetables such as spinach, kale and in egg yolk, animal fat and human eye retinal macula. Increasing evidence indicates that lutein has offers benefits against neuronal damages during diabetic retinopathy, ischemia and AD by virtue of its mitochondrial protective, antioxidant and anti-apoptotic properties. METHODS: Male C57BL/6 mice (23-26 g) were randomized and grouped in to Control, MPTP, and Lutein treated groups. RESULTS: Lutein significantly reversed the loss of nigral dopaminergic neurons by increasing the striatal dopamine level in mice. Moreover, lutein-ameliorated MPTP induced mitochondrial dysfunction, oxidative stress and motor abnormalities. In addition, lutein repressed the MPTP-induced neuronal damage/apoptosis by inhibiting the activation of pro-apoptotic markers (Bax, caspases-3, 8 and 9) and enhancing anti-apoptotic marker (Bcl-2) expressions. DISCUSSION: Our current results revealed that lutein possessed protection on dopaminergic neurons by enhancing antioxidant defense and diminishing mitochondrial dysfunction and apoptotic death, suggesting the potential benefits of lutein for PD treatment.
Subject(s)
Apoptosis , Dietary Supplements , Dopaminergic Neurons/metabolism , Lutein/therapeutic use , Mitochondria/metabolism , Neuroprotective Agents/therapeutic use , Parkinson Disease/prevention & control , Animals , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Antiparkinson Agents/therapeutic use , Apoptosis/drug effects , Apoptosis Regulatory Proteins/agonists , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/metabolism , Behavior, Animal/drug effects , Biomarkers/metabolism , Dietary Supplements/adverse effects , Dopamine/chemistry , Dopamine/metabolism , Dopaminergic Neurons/drug effects , Lutein/administration & dosage , Lutein/adverse effects , MPTP Poisoning/etiology , MPTP Poisoning/metabolism , MPTP Poisoning/physiopathology , Male , Mice, Inbred C57BL , Mitochondria/drug effects , Motor Activity/drug effects , Nerve Tissue Proteins/agonists , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/metabolism , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/adverse effects , Oxidative Stress/drug effects , Parkinson Disease/etiology , Parkinson Disease/metabolism , Random Allocation , Substantia Nigra/drug effects , Substantia Nigra/metabolismABSTRACT
Mangiferin, a polyphenol compound of C-glucoside, is well-known for its anti-inflammatory, antioxidant, anticancer, antidiabetic and cognitive enhancement properties. In this study, we investigated the neuroprotective effect of mangiferin against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), which is most popular and widely used to evaluate therapeutic implications of new protective agents. Male C57BL/6 mice were orally treated with mangiferin (10, 20 and 40 mg/kg body wt.) for 14 days and from 10th day onwards MPTP (30 mg/kg, i.p.) was injected for last 5 days. MPTP treatment leads to enhanced oxidative stress, induction of apoptosis (upregulates the expression of Bax, proapoptotic protein and downregulates the expression of anti-apoptotic marker Bcl-2), and loss of dopominergic neurons which results in motor impairments. Results of our study confirmed that mangiferin prevented MPTP-induced behavioral deficits, oxidative stress, apoptosis, dopaminergic neuronal degeneration and dopamine depletion. Taken together, we conclude that mangiferin attenuates the dopaminergic neurodegeneration mainly through its potent antioxidant and antiapoptotic properties.
