Work

Stigmasterol exerts antioxidant effects through activation of the Keap1/Nrf2 signaling pathway in Parkinson’s disease model

Year: 2025

Type: article

Abstract: BACKGROUND: Given that there is not yet a fully effective treatment for Parkinson's disease (PD), further research into therapeutic agents is necessary to enhance PD patients' clinical performance and quality of life. Stigmasterol (ST) exerts some pharmacological effects on the nervous system, such as antioxidant, anti-apoptosis, anti-inflammation, and modulation of autophagy, but its potential effects on PD are unclear. This study aimed to determine whether ST exerted neuroprotective benefits in a PD model and to clarify the underlying molecular mechanism. METHODS: )-induced PD cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model to evaluate the impacts of ST on dyskinesia, the degree of dopaminergic neuron degeneration, and the prooxidant-antioxidant system, as well as the signaling pathways underlying its neuroprotective actions. RESULTS: We found that ST in the PD model activated the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway and promoted the Nrf2 nuclear translocation. Additionally, it increased the antioxidant enzymes expression, thereby attenuating reactive oxygen species (ROS)-induced oxidative stress, which in turn, slowed the dopaminergic neuron loss by inhibiting apoptotic pathways, and improved the tyrosine hydroxylase (TH) protein expression, and helped reduce motor impairments in the PD mouse model. CONCLUSIONS: Our results indicate that ST has an antioxidant role in the PD model through activating the Keap1/Nrf2 signaling pathway, offering a theoretical foundation for its potential therapeutic use in PD treatment.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-025-07502-2

Authors: Yanfei Tong, Qi Qu, Zhiting Wan, Qi Luo, Ren-He Xu, Shaogang Qu

Institutions: Nanfang Hospital, Southern Medical University, University of Macau

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,890