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

Rafał Watrowski, Stoyan Kostov, Mario Palumbo, Sebastian Daniel Schäfer, Ingolf Juhasz‐Böss, Radmila Sparić, Angel Yordanov, Salvatore Giovanni Vitale, İbrahim Alkatout
In: Nutrients · 2026 · vol. 18(21) , pp. 3647 · doi:10.3390/nu18213647 · W7225155765
Systematic review / meta-analysis OA: gold CC0
🔓 Open OA copy View on OpenAlex View at publisher

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.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (88)

Source provenance

openalex
last seen: 2026-11-05T06:01:15.807351+00:00
License: CC0 · commercial use OK