TY - JOUR
T1 - Thymoquinone prevents neurodegeneration against MPTP in vivo and modulates α-synuclein aggregation in vitro
AU - Ardah, Mustafa T.
AU - Merghani, Madiha Mohieldin
AU - Haque, M. Emdadul
N1 - Funding Information:
There are no patents, products in development, or marketed products to declare. This study was supported by grant from the College of Medicine & Health Sciences, UAE University, UAE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
This work was supported by a research grant (grant code: 31M332 ) from the College of Medicine and Health Sciences, United Arab Emirates University to MEH.
Funding Information:
This work was supported by a research grant (grant code: 31M332) from the College of Medicine and Health Sciences, United Arab Emirates University to MEH. We thank Mahmoud Hag Ali, the Animal Research Facility controller for his help with animal care and welfare.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/9
Y1 - 2019/9
N2 - Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive dopaminergic neurodegeneration with a concomitant increase in oxidative stress and neuroinflammation in the substantia nigra pars compacta (SNc). Recent studies have focused on targeting neuroinflammation and oxidative stress to effectively treat PD. The present study evaluated the neuroprotective effect of thymoquinone (TQ) against 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced oxidative stress and neuroinflammation in a PD mouse model. TQ (10 mg/kg body weight [b. wt.]) was administered for 1 week prior to MPTP (25 mg/kg b. wt.). MPTP administration caused oxidative stress as evidenced by decreased activities of superoxide dismutase and catalase, a depletion of reduced glutathione, and a concomitant rise in malondialdehyde. It also significantly increased pro-inflammatory cytokines and elevated inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Immunohistochemical analysis revealed dopamine neuron loss in the SNc and decreased dopamine transporters in the striatum following MPTP administration; however, these were rescued by TQ treatment. TQ treatment further restored antioxidant enzymes, prevented glutathione depletion, inhibited lipid peroxidation, and attenuated pro-inflammatory cytokines. TQ also decreased the raised levels of inflammatory mediators, such as COX-2 and iNOS. Therefore, TQ is thought to protect against MPTP-induced PD and the observed neuroprotective effects are attributed to its potent antioxidant and anti-inflammatory properties. Moreover, the in vitro analysis found that TQ significantly inhibited α-synuclein aggregation and prevented cell death induced by pre-formed fibrils. Thus, TQ not only scavenges the MPTP-induced toxicity but also prevents α-synuclein-fibril formation and its associated toxicity.
AB - Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive dopaminergic neurodegeneration with a concomitant increase in oxidative stress and neuroinflammation in the substantia nigra pars compacta (SNc). Recent studies have focused on targeting neuroinflammation and oxidative stress to effectively treat PD. The present study evaluated the neuroprotective effect of thymoquinone (TQ) against 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced oxidative stress and neuroinflammation in a PD mouse model. TQ (10 mg/kg body weight [b. wt.]) was administered for 1 week prior to MPTP (25 mg/kg b. wt.). MPTP administration caused oxidative stress as evidenced by decreased activities of superoxide dismutase and catalase, a depletion of reduced glutathione, and a concomitant rise in malondialdehyde. It also significantly increased pro-inflammatory cytokines and elevated inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Immunohistochemical analysis revealed dopamine neuron loss in the SNc and decreased dopamine transporters in the striatum following MPTP administration; however, these were rescued by TQ treatment. TQ treatment further restored antioxidant enzymes, prevented glutathione depletion, inhibited lipid peroxidation, and attenuated pro-inflammatory cytokines. TQ also decreased the raised levels of inflammatory mediators, such as COX-2 and iNOS. Therefore, TQ is thought to protect against MPTP-induced PD and the observed neuroprotective effects are attributed to its potent antioxidant and anti-inflammatory properties. Moreover, the in vitro analysis found that TQ significantly inhibited α-synuclein aggregation and prevented cell death induced by pre-formed fibrils. Thus, TQ not only scavenges the MPTP-induced toxicity but also prevents α-synuclein-fibril formation and its associated toxicity.
KW - MPTP
KW - Neurodegeneration
KW - Neurotoxicity
KW - Parkinson's disease
KW - Thymoquinone
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=85064606383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064606383&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2019.04.014
DO - 10.1016/j.neuint.2019.04.014
M3 - Article
C2 - 31028778
AN - SCOPUS:85064606383
SN - 0197-0186
VL - 128
SP - 115
EP - 126
JO - Neurochemistry International
JF - Neurochemistry International
ER -