Propolis in Wound and Burn Healing

Propolis, a natural substance known for promoting tissue repair and possessing anti-inflammatory, antimicrobial, and antioxidant biological activities, offers distinct advantages in enhancing wound and burn healing.

1. Effects of Propolis on Wound Tissue

Wound healing is influenced by many factors, with the degree of inflammatory response, bacterial infection, and oxidative damage being three critical ones. Consequently, the anti-inflammatory, antimicrobial, and antioxidant properties of propolis are considered key reasons for its ability to promote tissue regeneration and wound repair (de Castro, 2001; Ramos and Miranda, 2007).

Recent studies using rat and pig models for burns and incisions have demonstrated that propolis promotes healing by modulating collagen deposition in the extracellular matrix, accelerating re-epithelialization, and enhancing granulation tissue formation.

•  Propolis and Re-epithelialization

Re-epithelialization is a crucial stage in wound healing, relying on the proliferation, migration, and differentiation of keratinocytes, regulated by factors like growth factors, extracellular matrix, proteases, and integrin receptors. Multiple studies confirm that propolis significantly accelerates wound re-epithelialization.

In a rat full-thickness burn model, Iranian propolis treatment resulted in the mildest inflammation and superior wound contraction and re-epithelialization rates compared to silver sulfadiazine (Khorasgani et al., 2010).

Turkish propolis was noted for its anti-inflammatory effects and its ability to promote re-epithelialization, potentially through anti-inflammatory mechanisms (Han et al., 2005).

In diabetic wound models, propolis improved epithelial closure, suppressed neutrophil infiltration, and normalized macrophage function, linking inflammation modulation to re-epithelialization (McLennan et al., 2008).

Brazilian propolis may stimulate keratinocyte migration directly via caffeic acid derivatives or indirectly by activating macrophages to release fibroblast growth factor (FGF), thereby promoting re-epithelialization (de Almeida et al., 2013).

•  Propolis and Granulation Tissue Formation

Granulation tissue, rich in new capillaries and fibroblasts, fills wounds and combats infection.

Propolis promotes the proliferation of fibroblasts and vascular endothelial cells, enhancing collagen deposition and accelerating granulation tissue formation (Gao Chang, 2009; Kilicoglu et al., 2008; de Almeida et al., 2013).

•  Propolis and Wound Contraction

Wound contraction is primarily mediated by myofibroblasts in granulation tissue via α-smooth muscle actin (α-SMA), regulated by TGF-β and specific extracellular matrix components.

Propolis effectively promotes wound contraction, potentially by upregulating TGF-βexpression and facilitating myofibroblast differentiation (Khorasgani et al., 2010; Iyyam et al., 2010). Flavonoids and polyphenols in propolis are believed to play key roles in this process.

•  Propolis and Extracellular Matrix (ECM) Generation

The ECM provides structural support and regulates cell behavior during healing. Collagen is its primary component.

Propolis promotes the synthesis and orderly deposition of collagen. It can facilitate the replacement of type III collagen with stronger type I collagen, enhancing tissue strength (Albuquerque-Júnior et al., 2009; Pessolato et al., 2011; de Almeida et al., 2013).

Propolis also modulates other ECM components like vitronectin, laminin, and glycosaminoglycans (heparan sulfate, hyaluronic acid), aiding early functional recovery of the ECM (Olczyk et al., 2012, 2013).

Mechanistically, propolis may upregulate key factors like TGF-β (Ansorge et al., 2003), indirectly regulating fibroblast collagen synthesis and ECM secretion.

2. Possible Mechanisms of Propolis in Promoting Wound/Burn Healing

Propolis facilitates healing through a synergistic combination of anti-inflammatory, antioxidant, and antimicrobial actions.

Anti-inflammatory: Flavonoids (e.g., quercetin, galangin) and phenolics (e.g., caffeic acid phenethyl ester, ferulic acid) in propolis (Guimaraes et al., 2012) inhibit the arachidonic acid pathway (Mirzoeva and Calder, 1996), reducing prostaglandin E₂ (PGE₂) production (Tan-No et al., 2006), and interfere with NF-κB signaling (Song et al., 2002), downregulating pro-inflammatory genes. This alleviates excessive inflammation, creating a favorable environment for re-epithelialization and tissue regeneration.

Antioxidant: Oxidative stress in wounds impairs keratinocyte migration. Flavonoids and phenolic acids in propolis scavenge free radicals and enhance endogenous antioxidant enzymes like superoxide dismutase (SOD) (Wang Yuanyuan, 2012), reducing lipid peroxidation and cellular damage, thus supporting re-epithelialization.

Antimicrobial: Propolis exhibits broad-spectrum activity against common wound pathogens like Staphylococcus aureus and Pseudomonas aeruginosa (Breetetta et al., 2012). Components like pinocembrin and caffeic acid work via multiple pathways with a low risk of inducing resistance, effectively controlling infection and reducing secondary inflammation and oxidative damage.

In summary, propolis creates a synergistic regulatory network through its multi-target bioactivities—anti-inflammatory, antioxidant, and antimicrobial—collectively improving the wound microenvironment to promote tissue repair and regeneration.

Reference:

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