{
  "abstract": "Alzheimer's disease (AD) is increasingly recognized as a systemic disorder involving metabolic abnormalities beyond the brain, but links between hepatic alterations and neuroinflammation remain unclear. We integrated behavioral, histopathological, transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses in male mice assigned to WT (n = 15), AD (n = 16), high‐dose HLJDD (n = 16), low‐dose HLJDD (n = 11), and donepezil (n = 10) groups and treated for 10 weeks. Longitudinal behavioral data were analyzed using repeated‐measures models, and omics p‐values were adjusted using the Benjamini–Hochberg FDR procedure. Cognitive impairment, glial activation, and neuroinflammation were accompanied by hepatic metabolic disturbances and alterations in insulin signaling and energy metabolism, implicating PPAR and PI3K/Akt‐related processes. HLJDD, particularly at the high dose, improved behavioral and neuropathological outcomes and shifted abnormalities in TCA‐cycle metabolites, amino acid neurotransmitters, and oxidative balance toward WT levels. To assess hepatocyte contributions to microglial inflammation, we established an AML12–BV2 conditioned‐medium model with hepatocyte PPAR‐γ knockdown. Conditioned medium from LPS/HLJDD‐cotreated AML12 cells elicited lower inflammatory responses in BV2 cells than medium from LPS‐treated hepatocytes. PPAR‐γ knockdown attenuated this effect, supporting a hepatocyte PPAR‐γ‐dependent contribution to microglial regulation and further investigation of hepatic involvement in HLJDD‐associated neuroprotection.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China",
    "Beijing Academy of Traditional Chinese Medicine Beijing University of Chinese Medicine Beijing China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Wenya Gao",
      "orcid": "0000-0002-7324-8723"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Gao",
      "orcid": "0009-0002-7165-9710"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaohui Su"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangying Kong",
      "orcid": "0000-0003-3769-3368"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaolu Wei",
      "orcid": "0000-0002-2337-2208"
    },
    {
      "affs": [
        1
      ],
      "name": "Tunan Ding"
    },
    {
      "affs": [
        1
      ],
      "name": "Tiantian Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuangrong Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanyan Zhou",
      "orcid": "0000-0002-9891-1966"
    },
    {
      "affs": [
        0
      ],
      "name": "Junyi Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyu Zhao",
      "orcid": "0000-0003-0035-1874"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/axn2ncam7v5xk.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78442",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723713/",
  "id": "axn2ncam7v5xk",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78442",
  "language": "en",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7225040586",
  "pdf_url": null,
  "pmcid": "PMC13723713",
  "pmid": "42966893",
  "published": "2026-10-31",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/axn2ncam7v5xk.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:18Z",
      "native_id": "PMC13723713",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78442"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Cross‐Organ Multi‐Omics Profiling of Systemic Alterations in 5xFAD Mice and Changes Associated with Huanglian Jiedu Decoction Treatment",
  "title_text": "Cross‐Organ Multi‐Omics Profiling of Systemic Alterations in 5xFAD Mice and Changes Associated with Huanglian Jiedu Decoction Treatment",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:29Z",
  "url": "https://research.draconitic.com/paper/axn2ncam7v5xk",
  "venue": "Advanced Science",
  "versions": []
}