RESUMEN
In the present study, using a human neuroblastoma SK-N-SH cells, we explored antioxidant, mitochondrial protective and antiapoptotic properties of mangiferin against rotenone-mediated cytotoxicity. SK-N-SH cells are divided into four experimental groups based on 3-(4,5-dimethyl2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay-untreated cells, cells incubated with rotenone (100 nM), cells treated with mangiferin (20 µg) (pretreatment 4 h before) + rotenone (100 nM) and mangiferin alone treated. 24 h after treatment with rotenone and 28 h after treatment with mangiferin, levels of ATP thiobarbituricacid reactive substances and reduced glutathione and activities of enzymatic antioxidants including superoxide dismutase, catalase and glutathione peroxidise were measured. Finally mitochondrial transmembrane potential and expressions of apoptotic protein were also analysed. Pre-treatment with mangiferin significantly enhanced cell viability, ameliorated decrease in mitochondrial membrane potential and decreased rotenone-induced apoptosis in the cellular model of Parkinson's disease. Moreover oxidative imbalance induced by rotenone was partially rectified by mangiferin. Our results indicated that anti-apoptotic properties of this natural compound due to its antioxidant and mitochondrial protective function protect rotenone induced cytotoxicity.
Asunto(s)
Apoptosis/fisiología , Mitocondrias/metabolismo , Neuroblastoma/metabolismo , Estrés Oxidativo/fisiología , Rotenona/toxicidad , Xantonas/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Mitocondrias/efectos de los fármacos , Neuroblastoma/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Rotenona/antagonistas & inhibidores , Xantonas/uso terapéuticoRESUMEN
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.