Flavonoids in propolis acting on mast cell-mediated wound healing

Abstract

Barroso et al. have shown, on the latest issue of Inflammopharmacology, that the topical application of propolis on surgical wounds affected the number of mast cells recruited in these sites, and suggested two well-known antiinflammatory components present in propolis, namely caffeic acid and artepillin C, as possible active molecules (Borrelli et al. 2002; Paulino et al. 2008). It is widely acknowledged that propolis down-regulates type I allergy and inflammation by affecting mast cells, but the effective components of propolis, which cause these effects, remain still unknown. Propolis components vary depending on the area from which they are collected, mainly because of the genetic variability among wild plants in different geographic regions: variability in phenolics composition may result in different biochemical property of the propolis, depending on the main component active in raw propolis or in its extracts. In Chinese propolis, chrysin, kaempferol and its derivative, pinocembrin and galangin were identified as the main flavonoids able to act on mast cell-mediated inflammatory response, while chrysin was shown to inhibit IL-4 and MCP-1 production from antigen-stimulated RBL2H3 basophil/mast cell lines (Nakamura et al. 2010). On the other hand, Brazilian propolis extract contains only small amounts of these flavonoids, which might suggest that variation in propolis components could affect antiallergic and anti-inflammatory properties (Nakamura et al. 2010). Brazilian propolis contains, therefore, major percentage of phenolic acids, such as caffeic acid phenethyl ester (CAPE) and artepillin C (Park et al. 2002). As the activity of propolis, like many natural products, may be due to the synergic effect of several bioactive components, it will be necessary to distinguish between different types of propolis and analyse its complex compositions to guarantee specific biological activities of propolis diffused worldwide (Frankland Sawaya et al. 2011). Furthermore, inflammation by mast cells can be inhibited by several flavonoids present in propolis. Recent evidence was reported showing that chrysin decreased gene expression of pro-inflammatory cytokines, such as TNF-a, IL-1b, IL-4 and IL-6 in mast cells by a nuclear factor-jB (NF-jB) and caspase-1 dependent mechanism (Bae et al. 2011). Genistein modulates NF-jB and TNF-a expression during the early stage of wound healing (Park et al. 2011). CAPE accelerates cutaneous wound healing and it is arguable that propolis with a significant amount of this phenolic acid may exert a wound repairing property (Serarslan et al. 2007). The antiinflammatory property attributed to flavonoids in propolis might suggest that these polyphenols should exert their action toward other newly discovered function of mast cells (Ng 2010), even in association with CAPE or other phenolic acids. Wound healing is a complex process of lysis and reconstitution controlled by a series of cell signaling proteins and involved tissue regeneration and angiogenesis (Hiromatsu and Toda 2003; Nienartowicz et al. 2006). Mast cells have been shown to play a significant role in the early inflammatory stage of wound healing and also influence proliferation and tissue remodeling in skin; according to some authors in wound healing, mast cells are able to modulate only the inflammatory but not the proliferative response in healing and reconstituting damaged tissue (Egozi et al. 2003), while other reports showed that mast cells are involved in tissue remodeling in the late phase of wound healing (Iba et al. 2004), thus expanding S. Chirumbolo (&) Unit of Geriatry, Department of Medicine, University Laboratory of Medical Research, University of Verona, Policlinico GB Rossi piazzale AL Scuro 10, 37134 Verona, Italy e-mail: salvatore.chirumbolo@univr.it Inflammopharmacol (2012) 20:99–101 DOI 10.1007/s10787-012-0125-9 Inflammopharmacology