{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China",
    "School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei Province, PR China",
    "Department 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."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ling Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiayi Hou"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongmei Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenmo Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Di Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Di Huo"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoli Su"
    },
    {
      "affs": [
        0
      ],
      "name": "Xingli Tan"
    },
    {
      "affs": [
        0
      ],
      "name": "Ming Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiling Cheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Jing Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Honglin Feng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/br3hptg51bhd5.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jphs.2026.10.004",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1347861326000605",
  "id": "br3hptg51bhd5",
  "issns": [
    "1347-8613"
  ],
  "landing_url": "https://doi.org/10.1016/j.jphs.2026.10.004",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7223153669",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/br3hptg51bhd5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:57Z",
      "native_id": "b31f3a04e80f42cf83eed5caae85f4ed",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.jphs.2026.10.004"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Amyotrophic Lateral Sclerosis Research",
      "subfield": "neurology"
    }
  ],
  "title": "Combined γ-oryzanol and α-lipoic acid treatment suppresses inflammation and apoptosis in hSOD1",
  "title_text": "Combined γ-oryzanol and α-lipoic acid treatment suppresses inflammation and apoptosis in hSOD1",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:57Z",
  "url": "https://research.draconitic.com/paper/br3hptg51bhd5",
  "venue": "Journal of Pharmacological Sciences",
  "versions": []
}