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

Abstract

BackgroundChronic 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.MethodsChronic 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.ResultsPropolis 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.ConclusionsThese 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).

Trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model

“…Total soluble collagen was measured in whole sponge homogenates by the Sirius Red reagent based-assay (Lima et al, 2014). Sponge discs from 4 animals per group were homogenized in 1 mL of PBS and 50 μL of the sample mixed with 50 μL of Sirius Red reagent.…”

Evaluation of the Effect of Propolis on Implant Stability by Resonance Frequency Analysis and Removal Torque Test

“…Studies have indicated that propolis is toxic when administered over a concentration of 2000 mg / kg [16]. In a study on rats, propolis administered via oral gavage at 500 mg / kg / day following intraperitoneal implant placement was found to have mitigating effects on inflammation, angiogenesis and fibrogenesis [27]. In a study conducted by Bereket et al, effect of propolis on the consolidation phase was investigated after distraction osteogenesis was performed on rabbits and the applications at oral doses of 100 mg / kg / day and 200 mg / kg / day were compared.…”

“…However, in rats LD50 was found to be 2-7.34 g / kg. The recommended daily dose is 1.4 mg / kg [26,27]. Studies have indicated that propolis is toxic when administered over a concentration of 2000 mg / kg [16].…”

Natural Compounds for Wound Healing

“…Propolis significantly enhanced the production of collagen via the TGF-β1/Smad 2,3 signaling axis in wounded tissues [129]. Brazilian green propolis (from Baccharis dracunculifolia) can suppress an important inflammatory component (cell influx) and reduces the vascular permeability, angiogenesis without compromising the repair process by reducing fibrosis and increasing the pro-inflammatory markers and cytokine (TNF-α) involved in fibrinolytic activity [125,130]. Moreover, propolis has been used in combination with honey in a synergistic effect for wound healing [131], maybe due to the honey's hydrogen peroxide, high osmolality, acidity, nonperoxide factors, nitric oxide, and phenols [132].…”