Mechanistic insights into propolis in targeting adipokines including leptin, resistin, and adiponectin: A systematic...

Propolis is a bioactive bee product that may influence adipokines involved in metabolic and inflammatory disorders; however, findings on leptin, adiponectin, and resistin are inconsistent across models and human studies. Current study aimed to systematically synthesize preclinical and clinical evidence on the effects of propolis and propolis-derived compounds on leptin, adiponectin, and resistin, and to summarize proposed mechanistic pathways.

The study protocol was registered in PROSPERO (CRD42024593198). We searched PubMed, Web of Science, Scopus, and Google Scholar to find related articles published between 1900 and 2025. We screened reference lists, and used alert services after the primary search. We included in vitro, animal, and human studies that were published in English language and evaluated propolis/propolis-derived compounds versus a comparator and reporting leptin, adiponectin, and resistin outcomes. Risk of bias was assessed using the CRIS guideline (in vitro), SYRCLE tool (animal), and Cochrane risk-of-bias tool (clinical trials). Findings were synthesized narratively due to heterogeneity.

Twenty-six studies were included (9 in vitro, 11 animals, 6 human). In vitro studies generally reported decreased leptin and resistin expression and increased adiponectin expression following propolis-derived phenolics; one study reported increased leptin mRNA with a Brazilian propolis extract. In animal studies, leptin decreased in 5/8 studies and adiponectin increased in 5/9 studies, while remaining studies reported no change or opposite directions. Human trials showed mixed results: leptin decreased in 1/2 trials and adiponectin increased in 2/5 trials, whereas other trials reported no significant change. Substantial heterogeneity in propolis type/origin, formulation, dose, duration, and participant health status limited comparability.

Preclinical evidence suggests that propolis and selected constituents can modulate adipokines (often lowering leptin/resistin and increasing adiponectin), but clinical evidence is limited and inconsistent. Well-designed, adequately powered trials using standardized propolis preparations are required to clarify efficacy and translational relevance.

The online version contains supplementary material available at 10.1007/s40200-026-01855-1.