TY - JOUR
T1 - 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
AU - Jayaraj, Richard L.
AU - Elangovan, Namasivayam
AU - Dhanalakshmi, Chinnasamy
AU - Manivasagam, Thamilarasan
AU - Essa, Musthafa Mohamed
PY - 2014/9/5
Y1 - 2014/9/5
N2 - 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.
AB - 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.
KW - Apoptosis
KW - CNB-001
KW - Inflammation
KW - MPTP
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84904568487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904568487&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2014.06.022
DO - 10.1016/j.cbi.2014.06.022
M3 - Article
C2 - 24995576
AN - SCOPUS:84904568487
SN - 0009-2797
VL - 220
SP - 149
EP - 157
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -