Combined γ-oryzanol and α-lipoic acid treatment suppresses inflammation and apoptosis in hSOD1
- 1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China
- 2School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei Province, PR China
- 3Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China; Corresponding author. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, PR China.
Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex pathogenic mechanisms, and the efficacy of single-target interventions remains limited. γ-Oryzanol (Orz) and α-lipoic acid (ALA) exert neuroprotective effects individually, yet their combined effects and molecular mechanisms in ALS remain unclear. Aim: To investigate the therapeutic effects and mechanisms of combined Orz and ALA treatment in ALS. Methods: Network pharmacology was used to identify potential targets shared by the compounds and ALS. Core targets and pathways were identified through protein-protein interaction (PPI) network analysis, molecular docking, and functional enrichment analysis, followed by experimental validation in hSOD1 G93A cell and transgenic mouse models. Results: Six core targets (EGFR, AKT1, HSP90AA1, BCL2, SRC, HSP90AB1) were identified. In hSOD1 G93A cells, combined treatment modulated mRNA expression and protein phosphorylation of the core targets and attenuated cellular injury. In hSOD1 G93A transgenic mice, the combination delayed disease progression, prolonged survival, improved motor function, and reduced motor neuron loss. This combination alleviated inflammation and apoptosis by activating the AKT/GSK3β pathway. Conclusion: Combined Orz and ALA treatment modulates core targets, activates the AKT/GSK3β pathway, and suppresses inflammation and apoptosis. This combination represents a promising therapeutic strategy for ALS.
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BibTeX
@article{han2026combined,
title = {{Combined γ-oryzanol and α-lipoic acid treatment suppresses inflammation and apoptosis in hSOD1}},
author = {Ling Han and Jiayi Hou and Dongmei Zhang and Wenmo Zhang and Di Wang and Di Huo and Xiaoli Su and Xingli Tan and Ming Wang and Jing Xu and Jiling Cheng and Jing Wang and Honglin Feng},
journal = {Journal of Pharmacological Sciences},
year = {2026},
month = oct,
doi = {10.1016/j.jphs.2026.10.004},
url = {https://doi.org/10.1016/j.jphs.2026.10.004},
note = {CC BY},
}
RIS
TY - JOUR
TI - Combined γ-oryzanol and α-lipoic acid treatment suppresses inflammation and apoptosis in hSOD1
AU - Ling Han
AU - Jiayi Hou
AU - Dongmei Zhang
AU - Wenmo Zhang
AU - Di Wang
AU - Di Huo
AU - Xiaoli Su
AU - Xingli Tan
AU - Ming Wang
AU - Jing Xu
AU - Jiling Cheng
AU - Jing Wang
AU - Honglin Feng
PY - 2026
DA - 2026/10/30
JO - Journal of Pharmacological Sciences
DO - 10.1016/j.jphs.2026.10.004
UR - https://doi.org/10.1016/j.jphs.2026.10.004
AB - Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex pathogenic mechanisms, and the efficacy of single-target interventions remains limited. γ-Oryzanol (Orz) and α-lipoic acid (ALA) exert neuroprotective effects individually, yet their combined effects and molecular mechanisms in ALS remain unclear. Aim: To investigate the therapeutic effects and mechanisms of combined Orz and ALA treatment in ALS. Methods: Network pharmacology was used to identify potential targets shared by the compounds and ALS. Core targets and pathways were identified through protein-protein interaction (PPI) network analysis, molecular docking, and functional enrichment analysis, followed by experimental validation in hSOD1 G93A cell and transgenic mouse models. Results: Six core targets (EGFR, AKT1, HSP90AA1, BCL2, SRC, HSP90AB1) were identified. In hSOD1 G93A cells, combined treatment modulated mRNA expression and protein phosphorylation of the core targets and attenuated cellular injury. In hSOD1 G93A transgenic mice, the combination delayed disease progression, prolonged survival, improved motor function, and reduced motor neuron loss. This combination alleviated inflammation and apoptosis by activating the AKT/GSK3β pathway. Conclusion: Combined Orz and ALA treatment modulates core targets, activates the AKT/GSK3β pathway, and suppresses inflammation and apoptosis. This combination represents a promising therapeutic strategy for ALS.
SN - 1347-8613
ER -