{
  "abstract": "Pulmonary arterial hypertension (PAH) is a progressive and fatal cardiopulmonary disease characterized by pulmonary vascular remodeling, endothelial dysfunction, inflammation, and increased pulmonary vascular resistance. Despite advances in targeted therapies, effective treatment options remain limited. This study investigated the molecular mechanisms underlying the therapeutic effects of Panax notoginseng against PAH through integrated computational and experimental validation. Network pharmacology was employed to identify the bioactive compounds and therapeutic targets of Panax notoginseng. Functional enrichment, protein-protein interaction network analysis, transcriptomic validation, molecular docking, surface plasmon resonance (SPR), molecular dynamics simulation, and MM/PBSA analyses were performed to characterize representative target-compound interactions. Experimental validation to predict the therapeutic mechanism was performed using RAW264.7 macrophages, pulmonary artery smooth muscle cells (PASMCs), and a Sugen5416/hypoxia-induced murine model of PAH. A total of 67 overlapping therapeutic targets were identified, with enrichment analyses highlighting inflammation, oxidative stress, apoptosis, vascular remodeling, and the PI3K/AKT signaling pathway. AKT1 was identified as a central hub gene and was significantly upregulated under hypoxic conditions. Quercetin and Liquiritigenin (DFV)exhibited stable interactions with AKT1, with quercetin demonstrating stronger binding affinity (-11.10 kcal/mol) than liquiritigenin (-9.33 kcal/mol). Consistent with these computational predictions, Panax notoginseng reduced AKT1 expression and phosphorylation, attenuated oxidative stress and inflammatory cytokine production, inhibited PASMC proliferation and migration, and significantly improved pulmonary hemodynamics, right ventricular hypertrophy, and pulmonary vascular remodeling in vivo. Collectively, these findings identify AKT1 as a key molecular target through which Panax notoginseng exerts therapeutic effects against PAH in vivo.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Central Laboratory Wuxi Key Laboratory of Biomaterials for Clinical Application, Jiangyin Clinical College of Xuzhou Medical University Wuxi P. R. China.",
    "Shanghai Public Health Clinical Center (Fudan University) Jinshan Shanghai China.",
    "Department of Thoracic and Cardiovascular Surgery The Affiliated Jiangyin Hospital of Nantong University Wuxi Jiangsu China.",
    "Department of Cardiology The Second Affiliated Hospital of Soochow University Suzhou China.",
    "Department of Cardiothoracic Surgery The Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "YiFan Sheng"
    },
    {
      "affs": [
        1
      ],
      "name": "ZhiMeng Lu"
    },
    {
      "affs": [
        2
      ],
      "name": "TianYu Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "HuiLin Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "XinYao Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "ZhiHao Zhao"
    },
    {
      "affs": [
        4
      ],
      "name": "Praise Audax Rukonge"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "GuiPing Yu",
      "orcid": "0000-0002-6806-513X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8ccq2aycggfaz.bib",
  "cited_by": 0,
  "doi": "10.1002/pul2.70435",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717484/?tool=EBI",
  "id": "8ccq2aycggfaz",
  "issns": [
    "2045-8932",
    "2045-8940"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13717484",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2740|Pulmonary Hypertension Research and Treatments"
    ]
  ],
  "openalex": "W7224427281",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717484/pdf/?tool=EBI",
  "pmcid": "PMC13717484",
  "pmid": "42959756",
  "published": "2026-10-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/8ccq2aycggfaz.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:39Z",
      "native_id": "PMC:PMC13717484",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13717484"
    },
    {
      "first_seen": "2026-10-31T12:21:46Z",
      "native_id": "MED:42959756",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959756"
    },
    {
      "first_seen": "2026-11-02T12:21:47Z",
      "native_id": "PMC13717484",
      "source": "pmc",
      "url": "https://doi.org/10.1002/pul2.70435"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Pulmonary Hypertension Research and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Integrated Network Pharmacology and Experimental Validation Implicate AKT1‐Associated Signaling in the Protective Effects of Panax notoginseng Against Pulmonary Arterial Hypertension",
  "title_text": "Integrated Network Pharmacology and Experimental Validation Implicate AKT1‐Associated Signaling in the Protective Effects of Panax notoginseng Against Pulmonary Arterial Hypertension",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:47Z",
  "url": "https://research.draconitic.com/paper/8ccq2aycggfaz",
  "venue": "Pulmonary circulation",
  "versions": []
}