Neuroprotective potential of solanesol against tramadol induced zebrafish model of Parkinson’s disease: insights from neurobehavioral, molecular, and neurochemical evidence

Abstract

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum. Solanesol, an alcohol that acts as a precursor to coenzyme Q10, possesses potential applications in managing neurological disorders with antioxidant, anti-inflammatory, and neuromodulatory potential. In this study, a zebrafish model was employed to investigate the effects of solanesol in tramadol induced PD like symptoms. Zebrafish were administered tramadol injections (50 mg/kg) over a 20-day period. Solanesol was administered at doses of 25, 50, and 100 mg/kg, three hours prior to tramadol administration from day 11 to day 20. Behavioral tests assessing motor coordination were conducted on a weekly basis using open field and novel diving tank apparatus. On day 21, the zebrafish were euthanized, and brain tissues were examined for markers of oxidative stress, inflammation, and neurotransmitters level. Chronic tramadol treatment resulted in motor impairment, reduced antioxidant enzyme levels, enhanced release of proinflammatory cytokines in the striatum, and disrupted neurotransmitter balance. However, solanesol administration mitigated these effects and exhibited a neuroprotective effect against neurodegenerative alterations in the zebrafish model of PD. This was evident through improvements in behavior, modulation of biochemical markers, attenuation of neuroinflammation, restoration of neurotransmitters level, and enhancement of mitochondrial activity. The histopathological study also confirmed that solanesol dose dependently restored neuronal cell density which confirmed its neuroprotective potential. Further investigations are required to elucidate the underlying mechanisms of solanesol neuroprotective effects and evaluate its efficacy in human patients.

Highlights

• Neuroprotective effects: Solanesol has shown significant neuroprotective effects in a zebrafish model of Parkinson’s disease induced by chronic tramadol usage.

• Improved behavioral performance: Administration of solanesol resulted in improved motor coordination in the open field test (OFT) and novel diving apparatus in the tramadol-induced zebrafish model of PD.

• Decreased inflammation: Solanesol treatment significantly reduced pro-inflammatory cytokine levels in the tramadol-induced zebrafish model of PD, indicating its anti-inflammatory properties.

• Restored oxidative parameters: Solanesol administration restored oxidative stress parameters, as well as catecholamine and neurotransmitter levels in the tramadol-induced zebrafish model of PD.

• Histopathological improvement: Solanesol administration prevented histopathological alterations induced by tramadol, indicating its ability to protect against neuronal damage in the zebrafish model of PD.

Keywords:

• Parkinson’s disease
• neurodegenerative disorder
• dopaminergic neurons
• solanesol
• coenzyme Q10
• neuroprotective effects
• tramadol

Acknowledgements

Authors pay deep sense of gratitude to Prof. (Dr.) Y.K. Gupta (MD, PhD) President AIIMS Bhopal and Jammu and Chairman Research Advisory Committee ISF College of Pharmacy, Moga 142001, Punjab, India and further highly thankful to management and chairman Sh. Parveen Sir, ISF College of Pharmacy, Moga 142001, Punjab, India and all those scientists who published lot of advanced research in the field of neuropharmacology.

Author contributions

Md Reyaz Alam wrote the manuscript, manuscript reading, data collection, and data contribution. Shamsher Singh contributed as designed review paper, data analysis, manuscript reading, and final approval.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data and material are already provided with the manuscript.

Additional information

Funding

No funding is associated with this work.