Astragalin confers coordinated neuroprotection in Parkinson's disease models through modulation of neurotrophic, anti-inflammatory, and synuclein-related pathways.
Wang Jun, He Jie-Yu, Huang Qin, Ma Hui-Yong, Cao Min-Min, Qin Xiao-Yan, Hu Yang, Lan Rongfeng
Abstract
Parkinson's disease (PD) remains a neurodegenerative disorder without effective disease-modifying therapies, largely due to its multifactorial pathogenesis. We report that the natural flavonoid Astragalin (AST) concurrently addresses three core pathological processes in PD, namely dopaminergic neuron degeneration, α-synucleinopathy, and neuroinflammation, through coordinated modulation of interconnected molecular pathways. In both subacute MPTP- and chronic rotenone-induced murine PD models, AST preserved 85% of nigral tyrosine hydroxylase-positive neurons, fully prevented motor deficits, and suppressed phosphorylated α-synuclein (α-Syn) accumulation and Lewy body-like inclusion formation. Mechanistically, AST activated the BDNF-TrkB/AKT pro-survival pathway, enhanced NRF2-mediated antioxidant defense, and suppressed neuroinflammatory cascades by dual inhibition of Notch1/HES-1 and COP1-C/EBPβ signaling, leading to attenuated microglial and astrocytic activation. These findings position AST as a promising multi-target therapeutic neuroprotective candidate with disease-modifying potential, providing a structural scaffold for developing combination-inspired anti-PD strategies.
Key Findings
- Astragalin preserved 85% of nigral tyrosine hydroxylase-positive neurons in murine Parkinson's disease models.
- Astragalin fully prevented motor deficits and suppressed phosphorylated α-synuclein accumulation and Lewy body-like inclusion formation.
- Astragalin activated the BDNF-TrkB/AKT pro-survival pathway, enhanced NRF2-mediated antioxidant defense, and suppressed neuroinflammatory cascades by inhibiting Notch1/HES-1 and COP1-C/EBPβ signaling.
Clinical Significance
Astragalin shows promise as a multi-target neuroprotective agent with disease-modifying potential for Parkinson's disease, offering a novel therapeutic strategy to address its multifactorial pathology.
Citation
Wang Jun, He Jie-Yu, Huang Qinet al.. Astragalin confers coordinated neuroprotection in Parkinson's disease models through modulation of neurotrophic, anti-inflammatory, and synuclein-related pathways. Free radical biology & medicine. 2026-Aug-20.