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Front Biosci (Schol Ed) ; 10(2): 248-261, 2018 01 01.
Article in English | MEDLINE | ID: mdl-28930531

ABSTRACT

The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. Moreover, ILF attenuated rotenone induced toxicity by down-regulating  Bax, caspases-3, 6, 8 and 9 expression and up-regulating of Bcl-2 expression. Furthermore regulation of p-P13K, p-AKT and p-GSK-3 beta expression by ILF, clearly confirmed its protective effects. Taken together, our results suggested that ILF attenuated rotenone-induced oxidative stress, mitochondrial dysfunction and apoptosis through the regulation of P13K/AKT/GSK-3 beta signaling pathways. However further pre-clinical studies are warranted in rodents to use ILF as a promising therapeutic agent for PD in future.


Subject(s)
Mitochondria/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Rotenone/pharmacology , Sesquiterpenes/pharmacology , Antioxidants/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Interactions , Glycogen Synthase Kinase 3/metabolism , Humans , Lipid Peroxidation/drug effects , Neuroblastoma , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism
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