From Cardio-Kidney-Metabolic Syndrome to Periodontal Diseases: The Bio-Cellular Role of Propolis

Jia-Feng Chang^1,2, Ting-Yu Yeh³, I-Ta Lee^4,*, Yue-Wen Chen^5,6,*
1 Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, Taiwan
2 Department of Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan
3 Institute of Marine and Environmental Technology, University of Maryland Baltimore County, Baltimore, MD, USA
4 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
5 Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan
6 Research Center of Bees and Bee Products, National Ilan University, Yilan, Taiwan
* Corresponding Author: I-Ta Lee. Email: email ; Yue-Wen Chen. Email: email
(This article belongs to the Special Issue: Unraveling Periodontal Disease: Molecular and Cellular Perspectives)

BIOCELL https://doi.org/10.32604/biocell.2026.080855

Received 16 February 2026; Accepted 23 April 2026; Published online 07 May 2026

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Abstract

Cardio-kidney-metabolic (CKM) syndrome and periodontal diseases are bi-directionally linked pathologies driven by systemic inflammation, oxidative stress, and metabolic dysregulation. Identifying pleiotropic therapeutic agents targeting this axis is a major clinical priority. This review evaluates the bio-cellular role of propolis, a natural resinous hive product, in mitigating CKM syndrome and periodontal disease. Propolis exerts robust protective effects by modulating key intracellular signaling pathways. Specifically, it upregulates nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant defenses, which subsequently interferes with redox-sensitive inflammatory triggers. Concurrently, it antagonizes pro-inflammatory signaling, including nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome cascades. Furthermore, propolis prevents tissue fibrosis and cellular apoptosis by inhibiting transforming growth factor-beta (TGF-β)/suppressor of mothers against decapentaplegic (Smad) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK) pathways. By disrupting this systemic inflammatory-metabolic loop and reducing local periodontal pathogen loads, propolis emerges as a promising adjunctive therapy. Propolis represents a promising candidate adjunctive therapy, although further well-designed and standardized clinical trials are required to validate its efficacy and translational potential.