title: CNB-001, a novel pyrazole derivative mitigates motor impairments associated with neurodegeneration via suppression of neuroinflammatory and apoptotic response in experimental Parkinson's disease mice.
abstract: Parkinson's disease (PD) is characterized by the progressive degeneration via apoptosis of nigrostriatal dopaminergic neurons associated with inflammation, resulting in behavioral anomalies. Therefore, an anti-apoptotic and anti-inflammatory regimen may be useful in treatment of PD. CNB-001, a novel pyrazole derivative of curcumin and cyclohexyl bisphenol A has superior biological properties than its parental compounds. The present study utilizes a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate anti-inflammatory and anti-apoptotic mediated neuroprotection of CNB-001. The administration of MPTP (30 mg/kg for four successive days) significantly induced motor impairments as determined by behavioral studies (narrow beam test, catalepsy and akinesia), lowered dopamine levels and up-regulated the expressions of the inflammatory and apoptotic markers (tumor necrosis factor-alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase, glial fibrillary acidic protein, cyclooxygenase-2 and Bax). Moreover, MPTP treatment attenuated Bcl-2 and nigrostriatal dopamine transporter expression and also increased total nitrite and citrulline levels in comparison to the control group. However, co-treatment with CNB-001 significantly attenuated motor impairments and pathological changes caused by MPTP administration. Collectively, our results demonstrate that CNB-001 is neuroprotective through its anti-inflammatory and anti-apoptotic properties. Thus, CNB-001 has potential to be further developed as a therapeutic candidate 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.affiliation: Department of Biotechnology, Periyar University, Salem 636011, Tamil Nadu, India. Electronic address: elangovannn@gmail.com.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Elangovan
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608 002 Tamil Nadu, India.
authors.forename: Chinnasamy
authors.initials: C
authors.lastname: Dhanalakshmi
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608 002 Tamil Nadu, India.
authors.forename: Thamilarasan
authors.initials: T
authors.lastname: Manivasagam
authors.affiliation: Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman.
authors.forename: Musthafa Mohamed
authors.initials: MM
authors.lastname: Essa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy*; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; C529348:CNB 001; D011720:Pyrazoles; D003474:Curcumin
keywords: Apoptosis; CNB-001; Inflammation; MPTP; Parkinson’s disease