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• Several natural neuroprotective compounds have been screened in vivo to manage Parkinson’s disease . • The collected compounds exhibited antioxidant power, reduced neuroinflammation, and lipid peroxidation. • The compounds increased neuronal survivability, reduced dopaminergic neurons’ loss, decreased motor imbalance, and lowered cognitive alterations. • Curcumin, pycnogenol, and berberine are the only ones that have been investigated in clinical trials of Parkinson’s disease. • Further research should be carried out on bioavailability, blood-brain barrier issues, and the applicable doses for clinical uses. Parkinson’s disease (PD) is a progressive neurodegenerative disorder that must be managed judiciously. Multiple phytochemicals have been tested for their neuroprotective or disease-modifying effects in vivo . The present systematic review intends to present an overview of the use of phytochemicals as potent neuroprotective and/or disease-modifying agents against PD induced in rodents by 6-hydroxydopamine. Google Scholar, PubMed, and Scopus were systematically searched following the PRISMA 2020 guidelines. The risk of bias was determined using a scale adapted from the Collaborative Approach for Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES). A total number of 39 phytochemicals were identified from 36 studies, demonstrating antioxidant activity, reduction of neuroinflammation and lipid peroxidation as well as improvements in motor balance, behavior, and cognitive function. Furthermore, they increased neuronal survivability while reducing dopaminergic neuron loss. Of the total phytochemicals that have been found, only curcumin has already been investigated in clinical trials of PD. Phytochemicals are still being used nowadays to treat and prevent PD in vitro, in vivo, and in cellular models. Applying the research to patients is still challenging. Therefore, additional research should focus on bioavailability, blood-brain barrier issues, and determining the optimal doses that might be suitable for clinical use.
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DOI: 10.1016/j.nexres.2025.100473
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