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

Richard L. Jayaraj, Namasivayam Elangovan*, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Musthafa Mohamed Essa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalChemico-Biological Interactions
Volume220
DOIs
Publication statusPublished - Sep 5 2014

Keywords

  • Apoptosis
  • CNB-001
  • Inflammation
  • MPTP
  • Parkinson's disease

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

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