title: Neuroprotective effect of CNB-001, a novel pyrazole derivative of curcumin on biochemical and apoptotic markers against rotenone-induced SK-N-SH cellular model of Parkinson's disease.
abstract: Oxidative stress and mitochondrial dysfunction are underpinned for initiating a cascade of toxic events leading to dopaminergic neuronal death in Parkinson's disease (PD) and identified as vital target for therapeutic intervention. Curcumin, a potent antioxidant has been reported to display diverse neuroprotective properties against various neurodegenerative diseases including PD. In this present study, we investigated the protective effect of CNB-001, a pyrazole derivative of curcumin on rotenone-induced toxicity and its possible mechanisms in neuroblastoma SK-N-SH cells. Rotenone insult significantly reduced cell viability (MTT assay) and resulted in 78 % apoptosis (dual staining) by altering Bcl-2, Bax, caspase-3, and cytochrome C expression. Moreover, rotenone enhanced ROS production and disrupts mitochondrial membrane potential. These resultant phenotypes were distinctly alleviated by CNB-001. Pretreatment with CNB-001(2 μM) 2 h before rotenone exposure (100 nM) increased cell viability, decreased ROS formation, maintained normal physiological mitochondrial membrane potential, and reduced apoptosis. Furthermore, CNB-001 inhibited downstream apoptotic cascade by increasing the expression of vital antiapoptotic protein Bcl-2 and decreased the expression of Bax, caspase-3, and cytochrome C. Collectively, the results suggest that CNB-001 protects neuronal cell against toxicity through antioxidant and antiapoptotic properties through its action on mitochondria. Therefore, it may be concluded that CNB-001 can be further developed as a promising drug for treatment of PD.
authors.affiliation: Department of Biotechnology, Periyar University, Salem, 636011, Tamil Nadu, India.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Jayaraj
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Tamilselvam
authors.forename: Thamilarasan
authors.initials: T
authors.lastname: Manivasagam
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Elangovan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000188:drug therapy; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D012402:Rotenone / Q000633:toxicity
chemical_list: D051017:Apoptosis Regulatory Proteins; C529348:CNB 001; D018696:Neuroprotective Agents; D011720:Pyrazoles; D012402:Rotenone; D003474:Curcumin
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