{
  "abstract": "Background/Objectives: Berberine is increasingly promoted through social media and endometriosis-related websites as a non-hormonal supplement, although its disease-specific evidence remains unclear. This PRISMA-compliant systematic review evaluated experimental and clinical evidence for berberine in endometriosis and adenomyosis. Methods: PubMed/MEDLINE, EBSCOhost, BASE, CNKI Overseas, CENTRAL, and Google Scholar were searched from inception to 3 August 2026, supplemented by targeted manual searches. Clinical studies and experimental studies using endometriosis- or adenomyosis-related cellular or animal models were eligible. Purified berberine formed the primary evidence set. Chemically characterized multi-alkaloid preparations containing berberine were analyzed separately. Risk of bias was assessed with SYRCLE for animal studies and a predefined domain-based appraisal for in vitro studies. A structured qualitative assessment examined confidence in the synthesized findings. Contextual evidence from outside endometriosis and adenomyosis concerning steroid signaling, gut microbiota, microbial metabolites, and GLP-1 was discussed separately. Results: Six preclinical studies were included: three on endometriosis and three on adenomyosis, comprising four in vitro and two animal studies. Five investigated purified berberine and one a protoberberine-rich multi-alkaloid fraction. No clinical study was identified. Berberine reduced cell proliferation or viability and, where directly assessed, migration and invasion. It also reduced inflammatory and angiogenesis-related signaling, and, in an adenomyosis mouse model, myometrial infiltration and hyperalgesia. Reduced proliferation or viability recurred in all four cellular studies, with lower IL-6 and VEGF reported across cellular and animal adenomyosis models. Reported molecular effects involved NF-κB, STAT3, TLR4-associated signaling, VEGF, MMPs, TRPV1, COX-2, miR-429, and lncRNA H19. Gut microbiota modulation, short-chain fatty acids, intestinal barrier function, estrogen metabolism, GPER1, and GLP-1/GLP1R signaling remain plausible indirect routes that have not been demonstrated in disease-specific berberine studies. Conclusions: Berberine shows disease-relevant activity across a small and heterogeneous preclinical evidence base. Clinical efficacy, clinically achievable exposure, reproductive safety, and microbiota- or hormone-mediated effects remain unestablished.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gynecology, Helios Hospital Müllheim, Teaching Hospital of the University of Freiburg, 79379 Müllheim, Germany",
    "Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany",
    "Department of Gynecology, Hospital “Saint Anna”, 9002 Varna, Bulgaria",
    "Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria",
    "Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy",
    "Department of Gynecology and Obstetrics, Clemenshospital Münster, 48153 Münster, Germany",
    "Department of Obstetrics and Gynecology, Medical Center—University Hospital Freiburg, 79106 Freiburg, Germany",
    "Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia",
    "Clinic for Gynecology and Obstetrics, University Clinical Centre of Serbia, 11000 Belgrade, Serbia",
    "Department of Gynecologic Oncology, Medical University Pleven, 5800 Pleven, Bulgaria",
    "Obstetrics and Gynecology Unit, “Gaspare Rodolico-San Marco” University Hospital, Department of General Surgery and Medical Surgical Specialties, University of Catania, 95124 Catania, Italy",
    "Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Rafał Watrowski",
      "orcid": "0000-0002-6828-1887"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Stoyan Kostov",
      "orcid": "0000-0002-5279-3095"
    },
    {
      "affs": [
        4
      ],
      "name": "Mario Palumbo",
      "orcid": "0000-0002-0670-2666"
    },
    {
      "affs": [
        5
      ],
      "name": "Sebastian D. Schäfer"
    },
    {
      "affs": [
        6
      ],
      "name": "Ingolf Juhasz-Böss",
      "orcid": "0000-0002-2178-6490"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Radmila Sparić",
      "orcid": "0000-0003-0515-1951"
    },
    {
      "affs": [
        9
      ],
      "name": "Angel Yordanov",
      "orcid": "0000-0002-7719-382X"
    },
    {
      "affs": [
        10
      ],
      "name": "Salvatore Giovanni Vitale"
    },
    {
      "affs": [
        11
      ],
      "name": "Ibrahim Alkatout"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7d1kk83rsw2a7.bib",
  "cited_by": 0,
  "doi": "10.3390/nu18213647",
  "fulltext_url": null,
  "id": "7d1kk83rsw2a7",
  "issns": [
    "2072-6643"
  ],
  "landing_url": "https://www.mdpi.com/2072-6643/18/21/3647",
  "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": "2026-11-02",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7d1kk83rsw2a7.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T00:26:35Z",
      "native_id": "10.3390/nu18213647",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6643/18/21/3647"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6643",
      "subfield": "nutrition"
    }
  ],
  "title": "Berberine and Berberine-Containing Alkaloid Preparations in Preclinical Models of Endometriosis and Adenomyosis: A Systematic Review",
  "title_text": "Berberine and Berberine-Containing Alkaloid Preparations in Preclinical Models of Endometriosis and Adenomyosis: A Systematic Review",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:21:09Z",
  "url": "https://research.draconitic.com/paper/7d1kk83rsw2a7",
  "venue": "Nutrients",
  "versions": []
}