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Peer-reviewedCC BY 4.0Nutrients

Berberine and Berberine-Containing Alkaloid Preparations in Preclinical Models of Endometriosis and Adenomyosis: A Systematic Review

  • Rafał Watrowski1,2
  • Stoyan Kostov3,4
  • Mario Palumbo5
  • Sebastian D. Schäfer6
  • Ingolf Juhasz-Böss7
  • Radmila Sparić8,9
  • Angel Yordanov10
  • Salvatore Giovanni Vitale11
  • Ibrahim Alkatout12
12 affiliations
  1. 1Department of Gynecology, Helios Hospital Müllheim, Teaching Hospital of the University of Freiburg, 79379 Müllheim, Germany
  2. 2Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
  3. 3Department of Gynecology, Hospital “Saint Anna”, 9002 Varna, Bulgaria
  4. 4Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria
  5. 5Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy
  6. 6Department of Gynecology and Obstetrics, Clemenshospital Münster, 48153 Münster, Germany
  7. 7Department of Obstetrics and Gynecology, Medical Center—University Hospital Freiburg, 79106 Freiburg, Germany
  8. 8Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
  9. 9Clinic for Gynecology and Obstetrics, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
  10. 10Department of Gynecologic Oncology, Medical University Pleven, 5800 Pleven, Bulgaria
  11. 11Obstetrics and Gynecology Unit, “Gaspare Rodolico-San Marco” University Hospital, Department of General Surgery and Medical Surgical Specialties, University of Catania, 95124 Catania, Italy
  12. 12Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria
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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.

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Cite

BibTeXRIS
BibTeX
@article{watrowski2026berberine,
  title = {{Berberine and Berberine-Containing Alkaloid Preparations in Preclinical Models of Endometriosis and Adenomyosis: A Systematic Review}},
  author = {Rafał Watrowski and Stoyan Kostov and Mario Palumbo and Sebastian D. Schäfer and Ingolf Juhasz-Böss and Radmila Sparić and Angel Yordanov and Salvatore Giovanni Vitale and Ibrahim Alkatout},
  journal = {Nutrients},
  year = {2026},
  month = nov,
  doi = {10.3390/nu18213647},
  url = {https://www.mdpi.com/2072-6643/18/21/3647},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Berberine and Berberine-Containing Alkaloid Preparations in Preclinical Models of Endometriosis and Adenomyosis: A Systematic Review
AU  - Rafał Watrowski
AU  - Stoyan Kostov
AU  - Mario Palumbo
AU  - Sebastian D. Schäfer
AU  - Ingolf Juhasz-Böss
AU  - Radmila Sparić
AU  - Angel Yordanov
AU  - Salvatore Giovanni Vitale
AU  - Ibrahim Alkatout
PY  - 2026
DA  - 2026/11/02
JO  - Nutrients
DO  - 10.3390/nu18213647
UR  - https://www.mdpi.com/2072-6643/18/21/3647
AB  - 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.
SN  - 2072-6643
ER  -