Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice

BACKGROUND: Chronic inflammatory processes in the peritoneal cavity develop as a result of ischemia, foreign body reaction, and trauma. Brazilian green propolis, a beeswax product, has been shown to exhibit multiple actions on inflammation and tissue repair. Our aim was to investigate the effects of this natural product on the inflammatory, angiogenic, and fibrogenic components of the peritoneal fibroproliferative tissue induced by a synthetic matrix. METHODS: Chronic inflammation was induced by placing polyether-polyurethane sponge discs in the abdominal cavity of anesthetized Swiss mice. Oral administration of propolis (500/mg/kg/day) by gavage started 24 hours after injury for four days. The effect of propolis on peritoneal permeability was evaluated through fluorescein diffusion rate 4 days post implantation. The effects of propolis on the inflammatory (myeloperoxidase and n-acetyl-β-D-glucosaminidase activities and TNF-α levels), angiogenic (hemoglobin content-Hb), and fibrogenic (TGF-β1 and collagen deposition) components of the fibrovascular tissue in the implants were determined 5 days after the injury. RESULTS: Propolis was able to decrease intraperitoneal permeability. The time taken for fluorescence to peak in the systemic circulation was 20 ± 1 min in the treated group in contrast with 15 ± 1 min in the control group. In addition, the treatment was shown to down-regulate angiogenesis (Hb content) and fibrosis by decreasing TGF-β1 levels and collagen deposition in fibroproliferative tissue induced by the synthetic implants. Conversely, the treatment up-regulated inflammatory enzyme activities, TNF-α levels and gene expression of NOS2 and IFN-γ (23 and 7 fold, respectively), and of FIZZ1 and YM1 (8 and 2 fold) when compared with the untreated group. CONCLUSIONS: These observations show for the first time the effects of propolis modulating intraperitoneal inflammatory angiogenesis in mice and disclose important action mechanisms of the compound (downregulation of angiogenic components and activation of murine macrophage pathways).