The Natural Neuroprotective Compounds Used in the 6-Hydroxydopamine-Induced Parkinson’s Disease in Zebrafish: The CurrentApplications and Perspectives

Background and Objective: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of dopamine in the striatum, leading thus to the PD classic movement symptoms: resting tremor, rigidity, and bradykinesia/akinesia. Furthermore, Levodopa’s efficacy declines with long-term use, generating serious motor complications. Neuroprotection implies the use of different agents exhibiting various neuroprotective strategies to prevent brain degeneration and neuron loss. The present review aims to summarize and analyze the natural neuroprotective compounds that have been tested against PD induced by the 6-hydroxydopamine (6-OHDA) in zebrafish. Results: The current study collected 23 different natural substances, divided into five distinct categories, namely herbal extracts, herbal formulations, bioactive compounds, marine products, and marine extracts. They modulate various signaling pathways involved in PD pathogenesis and exhibit specific activities such as an anxiolytic profile, improving locomotor impairment, restoring memory troubles, preventing DNA loss, inhibiting acetylcholinesterase, reducing lipid peroxidation and antiinflammatory activity, and enhancing the brain antioxidant enzymes. Conclusion and Perspectives: This review discusses the most promising natural neuroprotective compounds that have been evaluated for their potential efficiency on the 6-OHDA-induced lesions in the zebrafish model. These natural substances deserve further consideration for determination of their optimum concentrations, bioavailability, and their ability to cross the blood-brain-barrier to exert their effects on PD. Furthermore, a complete understanding of the molecular mechanisms involved in PD and larger epidemiologic and randomized clinical trials in humans is also required.