RESUMO
The TATA-box binding protein associated factor 1 (TAF1) is part of the TFIID complex that plays a key role during the initiation of transcription. Variants of TAF1 are associated with neurodevelopmental disorders. Previously, we found that CRISPR/Cas9 based editing of the TAF1 gene disrupts the morphology of the cerebral cortex and blunts the expression as well as the function of the CaV3.1 (T-type) voltage gated calcium channel. Here, we tested the efficacy of SAK3 (ethyl 8'-methyl-2', 4-dioxo-2-(piperidin-1-yl)-2'H-spiro [cyclopentane-1, 3'-imidazo [1, 2-a] pyridine]-2-ene-3-carboxylate), a T-type calcium channel enhancer, in an animal model of TAF1 intellectual disability (ID) syndrome. At post-natal day 3, rat pups were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 CRISPR/Cas9 viruses. At post-natal day 21, the rat pups were given SAK3 (0.25 mg/kg, p.o.) or vehicle for 14 days (i.e. till post-natal day 35) and then subjected to behavioral, morphological, and molecular studies. Oral administration of SAK3 (0.25 mg/kg, p.o.) significantly rescued locomotion abnormalities associated with TAF1 gene editing. SAK3 treatment prevented the loss of cortical neurons and GFAP-positive astrocytes observed after TAF1 gene editing. In addition, SAK3 protected cells from apoptosis. SAK3 also restored the Brain-derived neurotrophic factor/protein kinase B/Glycogen Synthase Kinase 3 Beta (BDNF/AKT/GSK3ß) signaling axis in TAF1 edited animals. Finally, SAK3 normalized the levels of three GSK3ß substrates - CaV3.1, FOXP2, and CRMP2. We conclude that the T-type calcium channel enhancer SAK3 is beneficial against the deleterious effects of TAF1 gene-editing, in part, by stimulating the BDNF/AKT/GSK3ß signaling pathway.
Assuntos
Canais de Cálcio Tipo T/metabolismo , Modelos Animais de Doenças , Histona Acetiltransferases/deficiência , Imidazóis/administração & dosagem , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/metabolismo , Compostos de Espiro/administração & dosagem , Fatores Associados à Proteína de Ligação a TATA/deficiência , Fator de Transcrição TFIID/deficiência , Animais , Animais Recém-Nascidos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Histona Acetiltransferases/genética , Injeções Intraventriculares , Deficiência Intelectual/genética , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Gravidez , Ratos , Ratos Sprague-Dawley , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genéticaRESUMO
T-type calcium channels, in the central nervous system, are involved in the pathogenesis of many neurodegenerative diseases, including TAF1 intellectual disability syndrome (TAF1 ID syndrome). Here, we evaluated the efficacy of a novel T-type Ca2+ channel enhancer, SAK3 (ethyl 8'-methyl-2', 4-dioxo-2-(piperidin-1-yl)-2'H-spiro [cyclopentane-1, 3'-imidazo [1, 2-a] pyridine]-2-ene-3-carboxylate) in an animal model of TAF1 ID syndrome. At post-natal day 3, rat pups were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 CRISPR/Cas9 viruses. At post-natal day 21 animals were given SAK3 (0.25 mg/kg, p.o.) or vehicle up to post-natal day 35 (i.e. 14 days). Rats were subjected to behavioral, morphological, electrophysiological, and molecular studies. Oral administration of SAK3 (0.25 mg/kg, p.o.) significantly rescued the behavior abnormalities in beam walking test and open field test caused by TAF1 gene editing. We observed an increase in calbindin-positive Purkinje cells and GFAP-positive astrocytes as well as a decrease in IBA1-positive microglia cells in SAK3-treated animals. In addition, SAK3 protected the Purkinje and granule cells from apoptosis induced by TAF-1 gene editing. SAK3 also restored the excitatory post synaptic current (sEPSCs) in TAF1 edited Purkinje cells. Finally, SAK3 normalized the BDNF/AKT signaling axis in TAF1 edited animals. Altogether, these observations suggest that SAK3 could be a novel therapeutic agent for TAF1 ID syndrome.
Assuntos
Cerebelo/efeitos dos fármacos , Histona Acetiltransferases/genética , Imidazóis/farmacologia , Deficiência Intelectual/fisiopatologia , Neurônios/efeitos dos fármacos , Compostos de Espiro/farmacologia , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Animais , Canais de Cálcio Tipo T/efeitos dos fármacos , Canais de Cálcio Tipo T/metabolismo , Modelos Animais de Doenças , Deficiência Intelectual/genética , Ratos , Ratos Sprague-Dawley , SíndromeRESUMO
TAF1/MRSX33 intellectual disability syndrome is an X-linked disorder caused by loss-of-function mutations in the TAF1 gene. How these mutations cause dysmorphology, hypotonia, intellectual and motor defects is unknown. Mouse models which have embryonically targeted TAF1 have failed, possibly due to TAF1 being essential for viability, preferentially expressed in early brain development, and intolerant of mutation. Novel animal models are valuable tools for understanding neuronal pathology. Here, we report the development and characterization of a novel animal model for TAF1 ID syndrome in which the TAF1 gene is deleted in embryonic rats using clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) technology and somatic brain transgenesis mediated by lentiviral transduction. Rat pups, post-natal day 3, were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 vectors. Rats were subjected to a battery of behavioral tests followed by histopathological analyses of brains at post-natal day 14 and day 35. TAF1-edited rats exhibited behavioral deficits at both the neonatal and juvenile stages of development. Deletion of TAF1 lead to a hypoplasia and loss of the Purkinje cells. We also observed a decreased in GFAP positive astrocytes and an increase in Iba1 positive microglia within the granular layer of the cerebellum in TAF1-edited animals. Immunostaining revealed a reduction in the expression of the CaV3.1â¯T-type calcium channel. Abnormal motor symptoms in TAF1-edited rats were associated with irregular cerebellar output caused by changes in the intrinsic activity of the Purkinje cells due to loss of pre-synaptic CaV3.1. This animal model provides a powerful new tool for studies of neuronal dysfunction in conditions associated with TAF1 abnormalities and should prove useful for developing therapeutic strategies to treat TAF1 ID syndrome.
Assuntos
Sistemas CRISPR-Cas/genética , Cerebelo/patologia , Córtex Cerebral/patologia , Edição de Genes/métodos , Histona Acetiltransferases/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Animais , Animais Recém-Nascidos , Cerebelo/anormalidades , Cerebelo/fisiologia , Córtex Cerebral/anormalidades , Córtex Cerebral/fisiologia , Feminino , Injeções Intraventriculares , Locomoção/fisiologia , Técnicas de Cultura de Órgãos , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND/AIMS: Deregulation of metal ion homeostasis has been assumed as one of the key factors in the progression of neurodegenerative diseases. Aluminium (Al) has been believed as a major risk factor for the cause and progression of Alzheimer's disease (AD). In our lab, we have previously reported that hesperidin, a citrus bioflavonoid reversed memory loss caused by aluminium intoxication through attenuating acetylcholine esterase activity and the expression of Amyloid ß biosynthesis related markers. Al has been reported to cause oxidative stress associated apoptotic neuronal loss in the brain. So in the present study, protective effect of hesperidin against aluminium chloride (AlCl3) induced cognitive impairment, oxidative stress and apoptosis was studied. METHODS: Male Wistar rats were divided into control, AlCl3 treated (100â mg/kg., b.w.), AlCl3 and hesperidin (100â mg/kg., b.w.) co-treated and hesperidin alone treated groups. In control and experimental rats, learning and memory impairment were measured by radial arm maze, elevated plus maze and passive avoidance tests. In addition, oxidative stress and expression of pro and anti-apoptotic markers were also evaluated. RESULTS: Intraperitoneal injection of AlCl3 (100â mg/kg., b.w.) for 60 days significantly enhanced the learning and memory deficits, levels of thiobarbituric acid reactive substances and the expression of Bax and diminished the levels of reduced glutathione, activities of enzymatic antioxidants and the expression of B-cell lymphoma-2 (Bcl-2) as compared to control group in the hippocampus, cortex, and cerebellum. Coadministration of hesperidin (100â mg/kg., b.w. oral) for 60 days prevented the cognitive deficits, biochemical anomalies and apoptosis induced by AlCl3 treatment. CONCLUSION: Results of the present study demonstrated that hesperidin could be a potential therapeutic agent in the treatment of oxidative stress and apoptosis associated neurodegenerative diseases including AD.
Assuntos
Doença de Alzheimer/prevenção & controle , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Modelos Animais de Doenças , Hesperidina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Nootrópicos/uso terapêutico , Cloreto de Alumínio , Compostos de Alumínio , Doença de Alzheimer/metabolismo , Animais , Apoptose , Proteínas Reguladoras de Apoptose/agonistas , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Aprendizagem da Esquiva , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Cloretos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Distribuição Aleatória , Ratos WistarRESUMO
Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD.
Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Benzaldeídos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Rotenona/toxicidade , Animais , Antioxidantes/farmacologia , Apoptose/fisiologia , Benzaldeídos/farmacologia , Relação Dose-Resposta a Droga , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/metabolismo , Estresse Oxidativo/fisiologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Ratos , Ratos WistarRESUMO
The present study was aimed to evaluate the protective effect of hesperidin (Hes) on aluminium chloride (AlCl3) induced neurobehavioral and pathological changes in Alzheimeric rats. Intraperitonial injection of AlCl3 (100 mg/kg body weight) for 60 days significantly elevated the levels of aluminium (Al), activity of acetylcholinesterase (AChE) and protein expressions of amyloid precursor protein (APP), ß amyloid (Aß 1-42), ß and γ secretases as compared to control group in hippocampus and cortex of rat brain. Hes administration orally along with AlCl3 injection for 60 days, significantly revert the Al concentration, AChE activity and Aß synthesis-related molecules in the studied brain regions. Our results showed that aluminum exposure was significantly reduced the spontaneous locomotor and exploratory activities in open field test and enhanced the learning and memory impairments in morris water maze test. The behavioral impairments caused by aluminum were significantly attenuated by Hes. The histopathological studies in the hippocampus and cortex of rat brain also supported that Hes (100 mg/kg) markedly reduced the toxicity of AlCl3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. From these results, it is concluded that hesperidin can reverse memory loss caused by aluminum intoxication through attenuating AChE activity and amyloidogenic pathway.
Assuntos
Compostos de Alumínio/toxicidade , Doença de Alzheimer/prevenção & controle , Cloretos/toxicidade , Hesperidina/farmacologia , Fármacos Neuroprotetores/farmacologia , Cloreto de Alumínio , Doença de Alzheimer/induzido quimicamente , Animais , Comportamento Animal , Masculino , Ratos , Ratos WistarRESUMO
Alzheimer's Disease (AD) is a successive neurodegenerative disorder in the aged population. Many chemicals and phytochemicals are used to treat AD. Polyphenols which occur widely in various fruits, vegetables, beverages, and some other plant sources are gaining importance in AD treatment. Polyphenols comprise various subcategories, such as phenolic acids, lignans, tannins, stilbenes, hydroxybenzoic acid, hydroxycinnamic acid, and flavonoids. These compounds, as sole entities or in combination, can be used for treating AD because they have an abundance of antioxidants that are reported to be effective in free radical scavenging, metal ion chelating, and anti-inflammatory activities. Polyphenols of various plant origins have been studied, and these have been supported by in vitro assays and in vivo studies in rodents. These molecules protect neurons against oxidative stress and deposition of amyloid-ß (Aß) and tau proteins which play a vital role in the pathogenesis of AD. Consumption of wine and other foods rich in polyphenols has a beneficial effect on the neuronal signaling pathways, playing a vital role in shielding neuronal cells from neurodegeneration. Their ability to reduce free radicals and chelate metals are of great advantage. In this review, we highlight the various polyphenols that inhibit neuronal damage and progression of AD while also providing a cure. Some of the polyphenols covered are hesperidin, resveratrol, curcumin, catechin, kaempferol, and quercetin. The mechanisms of the actions of three polyphenols are also elaborated.
Assuntos
Doença de Alzheimer , Humanos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Polifenóis/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismoRESUMO
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder (NDD) associated with the loss of dopaminergic neurons in the substantia nigra and subsequently has an effect on motor function and coordination. The pathology of PD is multifactorial, in which neuroinflammation and oxidative damage are the two of the main protagonists. OBJECTIVES: The present study aims to assess the potential antioxidant and anti-inflammatory effects of demethoxycurcumin (DMC), a natural derivative of curcumin, against rotenone-induced PD in rats. MATERIALS AND METHODS: Rats were randomized and divided into six groups: control, rotenone (0.5 mg/kg/day, intraperitoneal in sunflower oil) treated for 7 days, rotenone and DMC (5, 10, and 20 mg/kg b.w) cotreated, and DMC (20 mg/kg b.w) alone treated groups. RESULTS: Based on the dopamine concentration and biochemical estimations, the effective dose of DMC was selected and the chronic study was performed. At the end of the experimental period, behavioral studies and protein expression patterns of inflammatory markers were analyzed. Rotenone treatment led to motor dysfunctions, neurochemical deficits, and oxidative stress and enhanced expressions of inflammatory markers, whereas oral administration of DMC attenuated all the above. CONCLUSION: Even though further research is needed to prove its efficacy in clinical trial, the results of our study showed that DMC may offer a promising and new therapeutic lead for the treatment of NDDs including PD. SUMMARY: Curcumin and their derivatives have been shown to be potent neuroprotective effectDemethoxycurcumin (DMC) amolerated the rotenone induced behavioural alterationsDMC abrogated the rotenone induced dopamine deficitsDMC attenuated the rotenone induced oxidative stressDMC diminished the rotenone mediated inflammation. Abbreviations used: COX-2: Cyclooxygenase-2; DA: Dopamine; DMC: Demethoxycurcumin; DMRT: Duncan's multiple range test; GSH: Reduced glutathione; GPx: Glutathione peroxidase; IL-1 ß: Interleukin-1 ß; IL-6: Interleukin-6; iNOS: Inducible nitric oxide synthase; PD: Parkinson's disease; SN: Substantia nigra; SOD: Superoxide dismutase; TBARS: Thiobarbituric acid reactive substances; TNF-α: Tumor necrosis factor-α.
RESUMO
Depression is frequently encountered during Parkinson's disease (PD) as a non-motor feature, which has been reported to cause and exaggerate motor deficits and neurodegenerative events in experimental PD models. We studied the effect of chronic mild stress (CMS) (pre, post and pre & post) exposure mediated depression on motor and non-motor symptoms, oxidative stress, inflammation and brain derived neurotrophic factor (BDNF) levels and its related signalling molecules against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced neurotoxicity in mice. CMS and MPTP/p-coexposed C57BL/6 mice exhibited low neuromuscular strength and stride length with enhanced oxidative stress and inflammation as compared to CMS or MPTP/p alone exposed mice. Coexposure diminished the levels of BDNF and expressions of p-TrkB, p-ERK/ERK, p-AKT/AKT and p-CREB in nigrostriatal regions as compared to those of the alone exposure. CMS alone exposed mice showed more anxiety related behaviour with diminished expression of serotonin transporter as compared to MPTP/p alone injected group. Post-stress exposure to MPTP/p mice exhibited lowest motor and reflecting higher anxiety state with greatest enhancement in inflammation and reduction in the protein expression of stress and cell signalling markers as compared to pre and pre & post stress exposed PD mice. However, pre- and pre & post CMS exposed PD animals are more vulnerable to oxidative stress as compared with post-stress experienced MPTP/p mice. CMS mediated depression exacerbates motor/non-motor symptoms in MPTP/p-PD animals by modulating oxidative stress and various signalling molecules. Our results suggested that stress induced NMS can accelerate neurodegenerative processes in the PD in a progressive or expedited manner.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Transtornos Parkinsonianos/fisiopatologia , Estresse Psicológico/fisiopatologia , Adjuvantes Farmacêuticos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Força Muscular/efeitos dos fármacos , Probenecid/toxicidade , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tiobarbitúricos/toxicidade , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Parkinson's disease (PD) is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic) neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS) such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS), a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks) of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor) impairments, levels and expressions of dopamine (DA), serotonin (5-HT), DAergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporters-2 (VMAT 2) and α-synuclein in nigrostriatal (striatum (ST) and substantia nigra (SN)) and extra-nigrostriatal (hippocampus, cortex and cerebellum) tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.
Assuntos
Encéfalo/metabolismo , Intoxicação por MPTP/metabolismo , Estresse Psicológico/metabolismo , Animais , Comportamento Animal , Encéfalo/fisiologia , Dopamina/metabolismo , Locomoção , Intoxicação por MPTP/complicações , Intoxicação por MPTP/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Probenecid/toxicidade , Serotonina/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , alfa-Sinucleína/metabolismoRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disorder that mainly affects the movement of the aged populations. Lycopene is a carotenoid with unique pharmacological properties and its efficacy on experimental Hunginton's disease and brain ischemia has shown intense neuroprotective effects. The present study was aimed to explore the neuroprotective effect of lycopene against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mice. Administration of lycopene (5, 10 and 20 mg/kg/day orally) protected MPTP induced depletion of striatal dopamine (DA) and its metabolites in a dose dependent manner. It also attenuated MPTP-induced oxidative stress and motor abnormalities seen in PD mice. Our western blot studies showed that treatment with lycopene reversed MPTP induced apoptosis may be due to its antioxidant and antiapoptotic properties. As to conclude, lycopene reverses neurochemical deficts, oxidative stress, apoptosis and physiological abnormalities in PD mice and offer promise strategy in the treatment of this neurodegenerative disease.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Carotenoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Carotenoides/uso terapêutico , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Citocromos c/metabolismo , Dopamina/metabolismo , Força da Mão , Licopeno , Masculino , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/etiologia , Doença de Parkinson/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismoRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder that results mainly due to the death of dopaminergic neurons in the substantia nigra (SN), and subsequently has an effect on one's motor function and coordination. The current investigation explored the neuroprotective potential of escin, a natural triterpene-saponin on chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced mouse model of PD. Administration of MPTP led to the depleted striatal dopamine content, impaired patterns of behavior, enhanced oxidative stress and diminished expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2). The expressions of interleukin-6 and -10, glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (IBA-1), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in SN were also enhanced. Oral treatment of escin significantly attenuated MPTP/p induced dopaminergic markers depletion, physiological abnormalities, oxidative stress and inhibit neuroinflammatory cytokine expressions in SN. The result of our study confirmed that escin mediated its protection against experimental PD through its antioxidant and anti-inflammatory properties.