{
  "abstract": "Background\n\nToddalia asiatica is used in Chinese patent medicines for knee osteoarthritis (KOA), but the active constituents and experimental basis remain incompletely defined. This study examined whether dihydrochelerythrine (DHCHE) ameliorates structural and molecular changes in experimental KOA.Methods\n\nActive compounds and candidate targets were screened by network pharmacology and molecular docking. Male Sprague-Dawley rats with monosodium iodoacetate-induced KOA received DHCHE (2.5 or 5 mg/kg) by oral gavage once daily for 28 days, beginning 7 days after model induction. Knee joints were assessed by micro-computed tomography, hematoxylin-eosin staining, Safranin O-fast green staining with positive-area quantification, and Western blotting.Results\n\nNetwork pharmacology prioritized DHCHE, with AKT1, EGFR, and SRC ranking among the core targets. MIA-induced KOA markedly disrupted subchondral bone microarchitecture. BV/TV and BMD were lower than in Sham rats, whereas SMI was higher (all P < 0.001); Tb.N decreased and Tb.Sp increased (both P < 0.01). DHCHE attenuated these changes, and more indices improved at 5 mg/kg. The loss of Safranin O-positive cartilage area in KOA rats was also partially reversed. Western blotting showed a wider response at the higher dose. Treatment with 5 mg/kg DHCHE reduced p-PI3K, p-AKT, and PI3K (all P < 0.001), together with p-EGFR (P = 0.0012) and EGFR (P = 0.0054). At 2.5 mg/kg, p-AKT (P = 0.0037) and PI3K (P < 0.001) were significantly reduced.Conclusion\n\nDHCHE ameliorated subchondral bone microstructural and cartilage pathological changes in MIA-induced KOA rats. The accompanying reductions in phosphorylated EGFR, PI3K, and AKT signals were associated with this signaling axis, but direct target engagement and causality were not established.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Osteoarthrosis, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, People's Republic of China.",
    "Department of Osteoarthrosis, Guizhou Medical University, Guiyang, 561113, People's Republic of China.",
    "Department of Osteoarthrosis, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, 550003, People's Republic of China.",
    "Department of Osteoarthrosis, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, People's Republic of China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yang Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiqi Zha"
    },
    {
      "affs": [
        2
      ],
      "name": "Xue Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunchao Tian"
    },
    {
      "affs": [
        2
      ],
      "name": "Kaide Xia"
    },
    {
      "affs": [
        3
      ],
      "name": "Shuguang Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3c5cfv04ffv4z.bib",
  "cited_by": 0,
  "doi": "10.2147/jir.s620421",
  "fulltext_url": "https://europepmc.org/articles/PMC13682324",
  "id": "3c5cfv04ffv4z",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://europepmc.org/article/MED/42904146",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7222743919",
  "pdf_url": "https://europepmc.org/articles/PMC13682324?pdf=render",
  "pmcid": "PMC13682324",
  "pmid": "42904146",
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3c5cfv04ffv4z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42904146",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42904146"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Network Pharmacology and Experimental Evidence Indicate That Dihydrochelerythrine from Toddalia asiatica Ameliorates Pathological Features of Knee Osteoarthritis in Rats and Is Associated with PI3K/AKT Signaling.",
  "title_text": "Network Pharmacology and Experimental Evidence Indicate That Dihydrochelerythrine from Toddalia asiatica Ameliorates Pathological Features of Knee Osteoarthritis in Rats and Is Associated with PI3K/AKT Signaling.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/3c5cfv04ffv4z",
  "venue": "Journal of inflammation research",
  "versions": []
}