A water-soluble derivative of propolis augments the cytotoxic activity of natural killer cells

Ethnopharmacological relevance: Propolis, a resinous material collected from numerous plants by honeybees, has historically been used as a health-promoting food. Recently, due to its potential anti-tumor effects, use of propolis has been proposed as an adjuvant therapy to chemotherapy; however, the effects of propolis on immune responses remain unclear. Aim of the study: In this study, we examined the effects of the oral ingestion of propolis on natural killer (NK) cell activity, which is important in immune surveillance against cancer and viral infections. In addition, we assessed the effects of the major components of the water-soluble powder derivative of propolis (WPP). Materials and methods: C57BL/6 (B6) wild-type (WT) and RAG 2-deficient (RAG(-/-)) mice and BALB/c WT, interferon (IFN)-gamma deficient (IFN-gamma(-)/-, IFN-gamma receptor-deficient (IFN-gamma R-/-) and RAG(-/-) mice were orally administered WPP or its major components. NK cell populations and cytotoxic activity were then examined by flow cytometry and Cr-51 release assay, respectively. Results: While the cytotoxic activity of NK cells was increased following administration of 100 mg/kg/day of WPP for 7 days or 200 or 500 mg/kg/day of WPP for 4 days in WT mice, the proportions of NK cell populations were unaltered. Similar activation of NK cell cytotoxicity was observed when RAG(-/-), but not IFN-gamma(-/-) or IFN-gamma R-/-, mice were orally administered 200 mg/kg/day of WPP for 4 days. Oral ingestion of artepillin C or p-coumaric acid, but not drupanin, augmented NK cell cytotoxicity in a manner similar to WPP and to the mixture of these three components. Conclusion: These results suggest that oral ingestion of WPP enhances NK cell cytotoxic activity, but not proliferation, in a manner dependent on IFN-gamma and without the contribution of acquired immune responses. Further, artepillin C or p-coumaric acid, but not drupanin, may be the components responsible for this augmentation of NK cell cytotoxicity. These findings suggest the possible utility of WPP as a therapeutic for prevention of cancer development and against viral infection through NK cell activation.