Rehmannioside A alleviates oxidative stress and restores dopaminergic function via the PI3K/Akt pathway in a rotenone-induced Parkinson’s disease model
- 1Mental and Health College, Qiqihar Medical University
Abstract
Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder; available treatments merely relieve symptoms, and no disease-modifying therapies are currently available. This study sought to explore the neuroprotective effects of Rehmannioside A (Re A) in rotenone-induced PD models and clarify its underlying mechanisms.
Methods: A rotenone-induced PD rat model was established for in vivo experiments, with rats administered graded oral doses of Re A. Motor function was assessed via behavioral tests. Striatal oxidative stress markers and neurotransmitters were detected using biochemical assays and ELISA, respectively. HE staining was applied to observe histopathological alterations in the substantia nigra, and immunohistochemistry was used to visualize tyrosine hydroxylase (TH)-positive neurons. Western blotting was performed to measure TH expression and key proteins of the PI3K/Akt pathway in brain tissue. For in vitro experiments, rotenone-challenged PC12 cells were treated with different concentrations of Re A. Cell viability was tested using CCK-8 assay, oxidative stress indicators were quantified, and protein levels were analyzed by Western blot. The PI3K inhibitor LY294002 was used to validate the reliance of protective effects on the PI3K/Akt pathway.
Results: In vivo, Re A significantly rescued weight loss and motor dysfunction, mitigated striatal oxidative stress, and reduced neuronal injury and pyknosis in the substantia nigra, accompanied by an increased number of TH-positive neurons. Re A restored striatal dopamine and its metabolite levels, activated the PI3K/Akt pathway, and upregulated TH protein expression. In vitro, Re A alleviated rotenone-triggered cytotoxicity and oxidative stress, reversed the suppression of PI3K/Akt signaling, and elevated TH expression. These protective effects were partially abolished by LY294002.
Conclusion: Rehmannioside A exerts neuroprotective activity against rotenone-induced PD lesions, possibly via activating the PI3K/Akt signaling pathway, suppressing oxidative stress and preserving dopaminergic function. Re A may serve as a promising therapeutic candidate for PD.
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BibTeX
@article{he2026rehmannioside,
title = {{Rehmannioside A alleviates oxidative stress and restores dopaminergic function via the PI3K/Akt pathway in a rotenone-induced Parkinson’s disease model}},
author = {Yanqi He},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1951721},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1951721/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Rehmannioside A alleviates oxidative stress and restores dopaminergic function via the PI3K/Akt pathway in a rotenone-induced Parkinson’s disease model
AU - Yanqi He
PY - 2026
DA - 2026/10/20
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1951721
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1951721/full
AB - Objective: Parkinson’s disease (PD) is a progressive neurodegenerative disorder; available treatments merely relieve symptoms, and no disease-modifying therapies are currently available. This study sought to explore the neuroprotective effects of Rehmannioside A (Re A) in rotenone-induced PD models and clarify its underlying mechanisms. Methods: A rotenone-induced PD rat model was established for in vivo experiments, with rats administered graded oral doses of Re A. Motor function was assessed via behavioral tests. Striatal oxidative stress markers and neurotransmitters were detected using biochemical assays and ELISA, respectively. HE staining was applied to observe histopathological alterations in the substantia nigra, and immunohistochemistry was used to visualize tyrosine hydroxylase (TH)-positive neurons. Western blotting was performed to measure TH expression and key proteins of the PI3K/Akt pathway in brain tissue. For in vitro experiments, rotenone-challenged PC12 cells were treated with different concentrations of Re A. Cell viability was tested using CCK-8 assay, oxidative stress indicators were quantified, and protein levels were analyzed by Western blot. The PI3K inhibitor LY294002 was used to validate the reliance of protective effects on the PI3K/Akt pathway. Results: In vivo, Re A significantly rescued weight loss and motor dysfunction, mitigated striatal oxidative stress, and reduced neuronal injury and pyknosis in the substantia nigra, accompanied by an increased number of TH-positive neurons. Re A restored striatal dopamine and its metabolite levels, activated the PI3K/Akt pathway, and upregulated TH protein expression. In vitro, Re A alleviated rotenone-triggered cytotoxicity and oxidative stress, reversed the suppression of PI3K/Akt signaling, and elevated TH expression. These protective effects were partially abolished by LY294002. Conclusion: Rehmannioside A exerts neuroprotective activity against rotenone-induced PD lesions, possibly via activating the PI3K/Akt signaling pathway, suppressing oxidative stress and preserving dopaminergic function. Re A may serve as a promising therapeutic candidate for PD.
SN - 1664-2295
ER -