Neurosupportive Role of Vanillin, a Natural Phenolic Compound, on Rotenone Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

Chinnasamy Dhanalakshmi,Thamilarasan Manivasagam,Jagatheesan Nataraj,Musthafa Mohamed Essa,Arokiasamy Justin Thenmozhi

doi:10.1155/2015/626028

Abstract

Vanillin, a phenolic compound, has been reported to offer neuroprotection against experimental Huntington's disease and global ischemia by virtue of its antioxidant, anti-inflammatory, and antiapoptotic properties. The present study aims to elucidate the underlying neuroprotective mechanism of vanillin in rotenone induced neurotoxicity. Cell viability was assessed by exposing SH-SY5Y cells to various concentrations of rotenone (5–200 nM) for 24 h. The therapeutic effectiveness of vanillin against rotenone was measured by pretreatment of vanillin at various concentrations (5–200 nM) and then incubation with rotenone (100 nM). Using effective dose of vanillin (100 nM), mitochondrial membrane potential, levels of reactive oxygen species (ROS), and expression patterns of apoptotic markers were assessed. Toxicity of rotenone was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, release of cyt-c, and enhanced expressions of proapoptotic and downregulation of antiapoptotic indices via the upregulation of p38 and JNK-MAPK pathway proteins. Our results indicated that the pretreatment of vanillin attenuated rotenone induced mitochondrial dysfunction, oxidative stress, and apoptosis. Thus, vanillin may serve as a potent therapeutic agent in the future by virtue of its multiple pharmacological properties in the treatment of neurodegenerative diseases including PD.

Highlights

Parkinson’s disease (PD) is one of the most common, progressive, and age-related neurodegenerative diseases, that is, raised by the selective loss of dopaminergic (DA) neurons in substantia nigra pars compacta and resulting in striatal dopamine depletion leading to movement disorder [1]
Vanillin, 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT), 2-7-diacetyl dichlorofluorescein (DCFH-DA), rhodamine 123 (Rh-123), heat-inactivated fetal bovine serum (FBS), Dulbecco’s modified Eagle’s medium (DMEM), antibiotic/antimycotic, EDTA, and Trypsin-EDTA were procured from Sigma Chemicals Co
A dosedependent cytotoxic effect of rotenone was evaluated by MTT assay in SH-SY5Y human neuroblastoma cells, which measures mitochondrial function or integrity with a dose of 10 nM vanillin + rotenone (100 nM) which caused ∼50% of cell death as compared with controls and was taken as inhibitory dose (Figures 2(a) and 2(b))

Summary

Introduction

Parkinson’s disease (PD) is one of the most common, progressive, and age-related neurodegenerative diseases, that is, raised by the selective loss of dopaminergic (DA) neurons in substantia nigra pars compacta and resulting in striatal dopamine depletion leading to movement disorder [1]. Could access the cytoplasm of dopaminergic neurons [3] It could enter into mitochondria and inhibit mitochondrial complex I activity. Since current therapies are ineffective in preventing degeneration of dopaminergic neurons, it is imperative to identify novel drugs that delay the progression of PD Phytoconstituents, those of a dietary origin especially present in fruits, vegetables, and spices, have been a subject of intense investigation in recent years for their therapeutic potential in a multitude of age-related chronic ailments such as cardiovascular, endocrine, neoplastic, and neurodegenerative diseases [10,11,12,13]. The present study was designed to find out the protective effects of vanillin on the mitochondrial dysfunction, oxidative stress, and apoptotic damage produced in rotenone exposed SH-SY5Y neuroblastoma cells

Materials and Methods

Results

Discussion

Conclusion