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

Research output: Contribution to journalArticle

11 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

Fingerprint

Parkinsonian Disorders
Parkinson Disease
Derivatives
Anti-Inflammatory Agents
Catalepsy
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Citrulline
Dopamine Plasma Membrane Transport Proteins
Curcumin
Dopaminergic Neurons
Glial Fibrillary Acidic Protein
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Nitrites
Interleukin-1
Neurons
Interleukin-6
Dopamine
Tumor Necrosis Factor-alpha
pyrazole

Keywords

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

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

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

In: Chemico-Biological Interactions, Vol. 220, 05.09.2014, p. 149-157.

Research output: Contribution to journalArticle

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