Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) ; Mangiferin is a polyphenol compound obtained from mango and has been reported to possess antioxidant and anti-inflammatory properties.Aim: We propose to evaluate the influence of mangiferin in preventing and treating experimental peri-odontitis induced in Wistar rats.Main methods: Periodontitis was induced in rats by applying a ligature around the lower right first molar. After ligature, groups of animals were submitted orally to the following treatments: saline 10 mL/kg, piroxicam 20 mg/kg or mangiferin 100 mg/kg. on days 1, 4 or 7 after ligature application the alveolar bone loss (ABL) was determined. We evaluated the effect of mangiferin on ABL by histological techniques (alveolar bone loss and cellularity), enzyme immunoassay (lipoxin A(4)), intravital microscopy (rolling leukocytes and endothelial-leukocyte adhesion), zymographic analyses (metalloproteinases MMPs 2 and, 9), immunohistochemistry (PCNA, COX-2 and CXCR4) and toxicology.Key findings: Oral administration of mangiferin significantly reduced ABL We also observed the reduction of cellularity in mangiferin-treated rats. Treatment with mangiferin inhibited COX-2 expression and the rolling and adhesion of leukocytes, while maintaining normal lipoxin A4 levels. The mangiferin did not interfere in the activity of MMP-2 or -9. The mangiferin-treated rats presented an earlier peak of cell proliferation and augmented angiogenesis in the injured region.Significance: Our results have demonstrated promising therapeutic potential of mangiferin both in the prevention and treatment of periodontitis. Published by Elsevier B.V.