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.
Chang et al. (Thu,) studied this question.