Abstract
Parkinson's disease is the most frequent neurodegenerative motor disorder. The clinical syndrome and pathology involve motor disturbance and the degeneration of dopaminergic neurons in the substantia nigra. Root extracts of Withania. somnifera, commonly called Ashwagandha, contain several major chemical constituents known as withanolides. Studies have shown that W. somnifera extracts exhibit numerous therapeutic effects including inflammation and oxidative stress reduction, memory and cognitive function improvement. This study aimed to evaluate the protective effects of KSM-66, W. somnifera root extract, on 6-hydroxydopamine (6-OHDA)-induced toxicity in the human neuroblastoma SH-SY5Y cell line, as well as the associated oxidative response protein expression and redox regulation activity focused on S-glutathionylation. SH-SY5Y cells were treated with 6-OHDA preceded or followed by treatment with the KSM-66 extract. Using KSM-66 concentrations ranging from 0.25 to 1 mg/ml before and after treatment of the cells with 6-OHDA has resulted in an increased viability of SH-SY5Y cells. Interestingly, the extract significantly increased glutathione peroxidase activity and thioltransferase activity upon pre- or post- 6-OHDA treatment. KSM-66 also modulated oxidative response proteins: peroxiredoxin-I, VGF and vimentin proteins upon 6-OHDA pre/post treatments. In addition, the extract controlled redox regulation via S-glutathionylation. Pre-treatment of SH-SY5Y cells with KSM-66 decreased protein-glutathionylation levels in the cells treated with 6-OHDA. The rescue of mitochondria with 0.5 mg/ml KSM-66 extract showed an increase in ATP levels. These findings suggest that W. somnifera root extract acts as a neuroprotectant, thereby introducing a potential agent for the treatment or prevention of neurodegenerative diseases.
Highlights
Parkinson's disease (PD) is the fastest growing neurological disorder in the world
To determine the appropriate concentrations of dopaminergic neurotoxin 6-OHDA and KSM-66 Ashwagandha root extract, SH-SY5Y cells were cultured overnight and were exposed to a series of concentrations from 6-OHDA ranging from 3.9 μM to 2,000 μM whereas KSM-66 concentrations range from 0.25 mg/ml to 10 mg/ml
The results showed that all KSM-66 tested concentrations gave significantly greater cell survival compared to the 6-OHDA treated group at both 30 min and 24 h pre-treatment times (p < 0.05)
Summary
Parkinson's disease (PD) is the fastest growing neurological disorder in the world. In 2016, there were reported over 6 million cases of PD (Collaborators, 2018). Based on systemic analysis of epidemiological studies between 1990-2016, PD caused approximately 200,000 deaths and 3.2 million Disability-adjusted life years (DALYs). The number of people with PD is expected to double again to over 12 million by 2040. Increasing longevity, declining smoking rates and increasing industrialization produce conditions that may increase the burden of disease to over 17 million (Dorsey et al, 2018). The estimated 9.4 million PD global population in 2020 is much greater than the previously reported 6 million PD cases in 2016 (Maserejian et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
