# Aesculus hippocastanum Extract Exerts Neuroprotective Effects in an MPP+‐Induced Parkinson's Disease Model via PPARγ Activation

## TL;DR

Horse chestnut extract protects brain cells in a lab model of Parkinson's disease by reducing inflammation and stress through a specific receptor called PPARγ.

## Contribution

This study identifies PPARγ as the key mechanism through which horse chestnut extract exerts neuroprotective effects in Parkinson's disease models.

## Key findings

- HCE at 31.2 and 62.5 μg/mL improved cell viability after MPP+ toxicity.
- HCE reduced Parkinson's markers like α-syn and restored tyrosine hydroxylase levels.
- PPARγ activation by HCE reduced inflammation and stress, and silencing PPARγ removed these benefits.

## Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the neuroprotective and anti‐inflammatory potential of
Aesculus hippocastanum
(horse chestnut extract, HCE) in an in vitro model of PD. Human neuroblastoma SH‐SY5Y cells were treated with the neurotoxin 1‐methyl‐4‐phenylpyridinium (MPP+) (1 mM) and/or in combination with HCE at the concentrations of 15.6, 31.2 and 62.5 μg/mL for 24 h. After 24 h, several analyses have been performed. Treatment with HCE at the concentrations of 31.2 and 62.5 μg/mL significantly improved cell viability following MPP+‐induced neurotoxicity. Furthermore, HCE effectively modulated key Parkinsonian markers by restoring tyrosine hydroxylase (TH) and reducing the number of α‐syn‐positive cells. At the same concentrations, HCE also attenuated NF‐κB signalling pathway activation and diminished the release of pro‐inflammatory cytokines IL‐1β, IL‐17, and TNF‐α. Notably, HCE promoted the activation of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ), known for its neuroprotective properties, and reduced both oxidative and nitrosative stress. Crucially, silencing of PPARγ abolished the beneficial effects of HCE, indicating that its neuroprotective actions are mediated specifically through PPARγ activation. Thus, these findings suggest that HCE confers neuroprotection in vitro by regulating inflammation and oxidative stress primarily via PPARγ modulation.