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Ginsenoside Rg1 Attenuates Neuroinflammation in Parkinson's Disease Models via Concomitant Modulation of Canonical
Wenshan Li1, Xinlang Yu1, Zhiying Zhang1
1Department of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing210022, China.
Abstract:
Microglial-mediated neuroinflammation is a core driver of brain disorders. Thus, modulating microglial activity is a critical therapeutic goal. In this study, we explored how Ginsenoside Rg1 (Rg1) protects against the inflammation seen in Parkinson's disease (PD). Our experiments utilized MPTP-challenged mice and lipopolysaccharide (LPS)-stimulated BV2 cells. Our data show that Rg1 restores motor function and preserves dopaminergic neurons in the substantia nigra. Notably, Rg1 treatment reconfigures the neuroinflammatory milieu, characterized by the targeted suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and a reciprocal elevation of the anti-inflammatory marker (IL-10). This effect stems from a precise rebalancing of Wnt signaling. Rg1 activates the Wnt3a/β-catenin pathway while suppressing the Wnt5a/ROR2/JNK axis. Such regulation promotes the transition of microglia to a protective M2 phenotype. When we knocked down Wnt3a and ROR2 using siRNA, the benefits of Rg1 were largely lost. In short, Rg1 alleviates neuroinflammation by recalibrating Wnt signals, offering a potential strategy for PD intervention.
Insights
Ginsenoside Rg1 (Rg1) reduces neuroinflammation in Parkinson's disease models by rebalancing Wnt signaling pathways. This modulation shifts microglia to a protective state, restoring motor function and preserving neurons.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Microglial activation drives neuroinflammation, a key factor in neurodegenerative diseases like Parkinson's disease (PD).
- Targeting microglial activity presents a promising therapeutic avenue for PD treatment.
Purpose of the Study:
- To investigate the neuroprotective effects of Ginsenoside Rg1 (Rg1) in Parkinson's disease models.
- To elucidate the underlying mechanisms of Rg1's anti-inflammatory action, focusing on Wnt signaling pathways.
Main Methods:
- Utilized MPTP-induced Parkinson's disease mouse models and lipopolysaccharide (LPS)-stimulated BV2 microglial cells.
- Assessed motor function, dopaminergic neuron survival, cytokine levels (TNF-α, IL-1β, IL-6, IL-10), and Wnt pathway components (Wnt3a, β-catenin, Wnt5a, ROR2, JNK).
- Employed siRNA to knockdown key Wnt signaling molecules (Wnt3a, ROR2) to confirm their role in Rg1's effects.
Main Results:
- Rg1 treatment significantly restored motor function and protected dopaminergic neurons in MPTP-challenged mice.
- Rg1 suppressed pro-inflammatory cytokines while increasing anti-inflammatory IL-10, indicating a shift in the neuroinflammatory environment.
- Rg1 modulated Wnt signaling by activating the Wnt3a/β-catenin pathway and suppressing the Wnt5a/ROR2/JNK axis.
- Knockdown of Wnt3a or ROR2 diminished the neuroprotective and anti-inflammatory benefits of Rg1.
Conclusions:
- Ginsenoside Rg1 effectively alleviates neuroinflammation and neurodegeneration in Parkinson's disease models.
- Rg1 exerts its protective effects by rebalancing Wnt signaling, promoting a shift towards a protective M2 microglial phenotype.
- Rg1 represents a potential therapeutic agent for Parkinson's disease intervention through its immunomodulatory properties.
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