{
  "abstract": "Pulmonary arterial hypertension (PAH) remains a progressive disease with limited therapies. As part of our continuing study to identify effective agents for PAH from natural herbal medicines, we analyzed the chemical constituents of an empirically validated herbal formula named Guilou Tongluo formula (GLTL) by UHPLC-Q-Exactive MS, retrieved its putative blood-absorbed constituents from databases, and integrated them with lung RNA-sequencing data to discover potential active constituents against PAH. A compound–disease network was constructed; drug–disease intersection genes underwent functional enrichment analysis, whereas hub targets were prioritized by protein–protein interaction analysis. Immune infiltration and single-cell RNA sequencing were used to analyze the vascular microenvironment, while nomogram and decision curve analyses exploratorily assessed the association of candidate targets with disease status at the tissue level. Target engagement was predicted by molecular docking and molecular dynamics simulation and supported by cellular thermal shift and drug affinity target stability assays; the mechanism of the constituents was then examined. The results showed that GLTL attenuated proliferation and promoted apoptosis in PDGF-BB-stimulated pulmonary arterial smooth muscle cells (PASMCs), an effect associated with IGF1R/PI3K/AKT signaling in smooth muscle cells, with IGF1R identified as a key candidate target. Molecular docking and dynamics simulation predicted that naringenin and luteolin could bind IGF1R, and CETSA and DARTS provided experimental support for IGF1R engagement. Both compounds engaged IGF1R and suppressed IGF-1/IGF1R signaling, thereby reducing PI3K/AKT phosphorylation and the expression of Cyclin D1, BCL2, PCNA, and Ki67. In summary, luteolin and naringenin are potential active constituents of GLTL that suppress proliferation and promote apoptosis in PDGF-BB-stimulated PASMCs in vitro, an effect associated with suppression of IGF1R/PI3K/AKT signaling.",
  "abstract_shown": true,
  "affiliations": [
    "Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China",
    "Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hanghang Gou"
    },
    {
      "affs": [
        0
      ],
      "name": "Liping Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Chengxun He"
    },
    {
      "affs": [
        0
      ],
      "name": "Qi Liang"
    },
    {
      "affs": [
        1
      ],
      "name": "Ke Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yi Zhu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiuli Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Peng",
      "orcid": "0000-0003-0511-9564"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c8ks8nsb92ht0.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms272110018",
  "fulltext_url": null,
  "id": "c8ks8nsb92ht0",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/10018",
  "language": null,
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-08",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/c8ks8nsb92ht0.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:39Z",
      "native_id": "10.3390/ijms272110018",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/10018"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Luteolin and Naringenin from Herbal Medicines Suppress Pulmonary Arterial Smooth Muscle Cell Hyperproliferation in Pulmonary Arterial Hypertension by Modulating IGF1R/PI3K/AKT Signaling",
  "title_text": "Luteolin and Naringenin from Herbal Medicines Suppress Pulmonary Arterial Smooth Muscle Cell Hyperproliferation in Pulmonary Arterial Hypertension by Modulating IGF1R/PI3K/AKT Signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:39Z",
  "url": "https://research.draconitic.com/paper/c8ks8nsb92ht0",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}