{
  "abstract": "Gastrodin (GAS), a bioactive glycoside from Gastrodia elata, shows anti-inflammatory and neuroprotective activity in preclinical models. This narrative review evaluates whether autophagy, mitochondrial quality control, and NOD-like receptor family pyrin domain containing 3 (NLRP3)-dependent pyroptosis may contribute to its effects on microglia. Studies in microglial cultures and animal models report reduced inflammatory activation and changes in microglial phenotype after GAS treatment. Related studies in endothelial cells, neurons, macrophages, and whole brain tissue associate GAS with AMP-activated protein kinase (AMPK) signaling, mechanistic target of rapamycin (mTOR) inhibition, autophagy or mitophagy markers, and lower inflammasome or pyroptosis markers. These findings support an AMPK/mTOR/NLRP3-centered working model, but the complete causal chain has not been demonstrated in microglia within a single experimental system. We distinguish microglia-specific observations from evidence extrapolated across cell types and disease models, compare GAS with its metabolite p-hydroxybenzyl alcohol, and discuss limitations of inhibitor-based experiments and variation in dose and sampling time. Inducible microglial genetic deletion, flux measurements, target-engagement assays, and matched pharmacokinetic studies are needed to test this model. Human evidence remains insufficient to confirm the proposed microglial mechanism or its clinical relevance.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan",
    "Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan",
    "Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chan-Yen Kuo",
      "orcid": "0000-0002-5702-5730"
    },
    {
      "affs": [
        1
      ],
      "name": "I-Shiang Tzeng",
      "orcid": "0000-0002-9047-8141"
    },
    {
      "affs": [
        2
      ],
      "name": "Yi-Chyan Chen",
      "orcid": "0000-0002-6319-6114"
    },
    {
      "affs": [
        1
      ],
      "name": "Mao-Liang Chen",
      "orcid": "0000-0001-5871-1030"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4t3x82sbvfsvb.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198754",
  "fulltext_url": "https://europepmc.org/articles/PMC13665310",
  "id": "4t3x82sbvfsvb",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/19/8754",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7214998501",
  "pdf_url": "https://europepmc.org/articles/PMC13665310?pdf=render",
  "pmcid": "PMC13665310",
  "pmid": "42883997",
  "published": "2026-09-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/4t3x82sbvfsvb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198754",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8754"
    },
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883997",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883997"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Gastrodin and Microglial Autophagy–Pyroptosis Crosstalk: Evidence and Hypotheses Involving the AMPK/mTOR/NLRP3 Axis",
  "title_text": "Gastrodin and Microglial Autophagy–Pyroptosis Crosstalk: Evidence and Hypotheses Involving the AMPK/mTOR/NLRP3 Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/4t3x82sbvfsvb",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}