The Therapeutic Potential of Propolis for Anxiety and Depression: A Systematic Review of Preclinical and Clinical Evidence

Document Type : Review Paper

Authors

1 Research Center for Evidence-based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Medical Microbiology, Sarab Faculty of Medical Sciences, Sarab, Iran

3 Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

5 Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

6 Department of Clinical Sciences, TaMS.C., Islamic Azad University, Tabriz, Iran

7 Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Anxiety and depression are highly prevalent neuropsychiatric disorders, often comorbid with chronic physical illnesses. Given the limitations of conventional treatments, there is growing interest in natural adjunctive therapies. Propolis, a resinous bee product enriched with flavonoids and phenolic acids, has emerged as a candidate due to its reported antioxidant, anti-inflammatory, and neuroprotective properties. This systematic review synthesizes the available evidence on the efficacy of propolis for symptoms of anxiety, depression, and stress. This review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, EMBASE, Web of Science, Scopus, and Google Scholar was performed from inception to June 2025. We included preclinical studies and randomized controlled trials (RCTs) that assessed behavioral or clinical outcomes related to anxiety, depression, or stress following propolis administration. Fourteen studies (10 preclinical, 4 RCTs) were included. Preclinical studies (doses 10–200 mg/kg) consistently demonstrated anxiolytic, antidepressant, and anti-stress effects, associated with increased BDNF, reduced cortisol, and attenuated oxidative stress. In clinical trials (doses 500–1500 mg/day), propolis significantly reduced anxiety scores in three RCTs (e.g., a 59.8% reduction in menopausal women, p < 0.01) and depressive symptoms in two RCTs (e.g., a 54.2% reduction, p < 0.01). Stress-related outcomes were inconsistent. Proposed mechanisms include antioxidant and anti-inflammatory activities, neuroprotection, and gut-brain axis modulation. Current evidence indicates that propolis is a promising adjunctive intervention for anxiety and depression. However, clinical heterogeneity and limited data on stress outcomes necessitate further validation. Future research should prioritize standardized preparations, dose-response studies, and large-scale RCTs to firmly establish efficacy, safety, and mechanistic pathways.

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References

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Journal of Medicinal plants and By-products
Volume 15, Issue 6
November and December 2026
Pages 631-638

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