{
  "abstract": "Ferulic acid (FA), a principal phenolic constituent of Angelica sinensis, attenuates hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). Here, we employed an integrated approach combining network pharmacology, transcriptomics, molecular dynamics (MD), single-cell RNA-seq (scRNA-seq) pseudobulk analysis, and in vitro validation in a PA/OA-induced HepG2 model. External validation revealed consistent upregulation of FADS2 across cohorts, whereas PTGS2 exhibited cohort-dependent directionality. Single-cell pseudobulk analysis suggested a hepatocyte-intrinsic trend for FADS2 and PPARG, although donor-level significance was not reached (p = 0.29 and p = 0.10, respectively). Molecular docking predicted favorable binding of FA to FADS2 (−8.539 kcal/mol), PTGS2 (−7.146 kcal/mol), and PPARG (−5.882 kcal/mol). In vitro, FA dose-dependently reduced lipid accumulation (Oil Red O and TC/TG) without cytotoxicity (confirmed by CCK-8). qPCR revealed that FA suppressed lipogenic genes (SREBP-1c, FASN, ACC1) and the desaturase SCD, while restoring the expression of the fatty acid oxidation marker CPT1A and the hepatocyte-intrinsic desaturase FADS2. Western blot confirmed FA suppressed PTGS2 and PPARG protein expression. The coordinated suppression of lipogenesis and restoration of FADS2 expression is consistent with a ‘lipid remodeling’ hypothesis—FA may shift lipid flux toward less toxic, highly desaturated species—which warrants dedicated mechanistic validation. We identify FADS2 as a novel transcriptional signature of FA, with PTGS2 and PPARG as supported candidate targets.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Lin Zang"
    },
    {
      "name": "Chen Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4y7kp8h32fq9t.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1996455",
  "fulltext_url": null,
  "id": "4y7kp8h32fq9t",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1996455",
  "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": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-11",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4y7kp8h32fq9t.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T06:20:44Z",
      "native_id": "10.3389/fphar.2026.1996455",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1996455"
    },
    {
      "first_seen": "2026-11-11T12:26:20Z",
      "native_id": "10.3389/fphar.2026.1996455",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1996455/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Ferulic acid attenuates hepatic steatosis and modulates PTGS2, PPARG, and FADS2 expression: an integrated network pharmacology, molecular dynamics, and experimental study",
  "title_text": "Ferulic acid attenuates hepatic steatosis and modulates PTGS2, PPARG, and FADS2 expression: an integrated network pharmacology, molecular dynamics, and experimental study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T00:21:26Z",
  "url": "https://research.draconitic.com/paper/4y7kp8h32fq9t",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}