Review of flavonoids shows preclinical neuroprotective potential in Parkinson's disease models

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Frontiers in Medicine Published April 18, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Note preclinical neuroprotective mechanisms of flavonoids in Parkinson's disease models with translational limitations.

This narrative review examines the potential of specific flavonoids, including baicalein, quercetin, apigenin, luteolin, and EGCG, within the context of Parkinson's disease. The scope is restricted to preclinical and experimental findings rather than clinical trials involving human populations. No sample size or specific patient population data are reported for these observations.

The authors synthesize arguments suggesting these compounds exert neuroprotective effects by preserving dopaminergic neurons, attenuating alpha-synuclein pathology, modulating monoamine metabolism, and suppressing glutamate-driven excitability. Additional mechanisms described include antioxidant effects, anti-inflammatory effects, and influence on intracellular signaling pathways and mitochondrial activity. No effect sizes, absolute numbers, or p-values are reported for these outcomes.

The review acknowledges significant limitations, specifically pharmacokinetic limitations and translational challenges that hinder direct application to clinical practice. Safety data regarding adverse events or tolerability are not reported for the human context, though the text notes advantageous safety characteristics in the experimental context. The authors caution that these findings represent preclinical evidence and experimental findings that require further validation before influencing clinical management.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Parkinson’s disease (PD) is recognized as the second most common neurodegenerative disorder worldwide, and it stands out as one of the neurological conditions exhibiting the fastest rise in prevalence, disability, and economic consequences. While the degeneration of dopaminergic neurons and the depletion of striatal dopamine are fundamental to the classic motor symptoms of PD, growing evidence suggests that PD is a multifaceted multisystem disorder marked by extensive impairment across various neurotransmitter systems. Beyond dopaminergic impairment, serotonergic, glutamatergic, γ-aminobutyric acid (GABA)ergic and cholinergic pathways are profoundly disrupted during disease progression, contributing to motor and non-motor symptoms that respond poorly to dopamine-centred therapies. These limitations underscore an unmet need for multi-target therapeutic strategies capable of restoring broader neurotransmitter homeostasis. Flavonoids represent a varied group of polyphenolic compounds sourced from plants and have been recognized as potential neuropharmacological candidates due to their multifaceted biological activities and advantageous safety characteristics. Flavonoids not only possess antioxidant and anti-inflammatory characteristics, but they also influence intracellular signaling pathways, mitochondrial activity, neuroinflammation, and synaptic plasticity. Additionally, many of these compounds have the ability to traverse the blood-brain barrier. A growing body of preclinical evidence suggests that representative flavonoids—including baicalein, quercetin, apigenin, luteolin and EGCG—exert neuroprotective effects in experimental PD models by preserving dopaminergic neurons, attenuating α-synuclein pathology, modulating monoamine metabolism and suppressing glutamate-driven excitability.In this Review, we synthesize current evidence that flavonoids can ameliorate neurotransmitter dysfunction in PD. Focusing on dopamine, serotonin, glutamate and acetylcholine, we integrate experimental findings to highlight the multi-target regulatory capacity of flavonoids. We also discuss key pharmacokinetic limitations, nanodelivery strategies, toxicological considerations and translational challenges.