Mangiferin alleviates experimental peri-implantitis via suppressing interleukin-6 production and Toll-like receptor 2 signaling pathway

BACKGROUND: TLR2 (Toll-like receptor 2) signaling and its downstream proinflammatory cytokines are considered to be important in the progression of peri-implantitis. A natural medicine, mangiferin has exhibited modulatory effect on TLR2 signaling and anti-inflammatory effects on different diseases. The objective of the present study is to investigate the effect of mangiferin on peri-implantitis and the potential mechanisms by administering this drug to an experimental peri-implantitis mouse model. METHODS: Maxillary left first, second, and third molars of mice were extracted, and dental implants were placed in the region of the maxillary left second molars. Then, peri-implantitis was induced by tying ligatures around implants, and mangiferin was given orally to the mice. After 6-week mangiferin treatment, bone loss around the implants was detected using micro-computerized tomography (micro-CT). Alveolar bone and inflammatory infiltrate in peri-implant tissues were examined using hematoxylin and eosin (H&E) staining. Production of interleukin-6 (IL6), a TLR2 downstream proinflammatory cytokine, in the tissue surrounding implants was measured using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. IL6 protein expression and TLR2 signaling pathway activation in peri-implant tissues were detected using western blot analysis. RESULTS: Micro-CT demonstrated reduced bone loss in peri-implantitis upon mangiferin administration. Additionally, H&E staining showed more alveolar bone and less inflammatory infiltrate in peri-implant tissues after mangiferin application. Moreover, qRT-PCR analysis demonstrated lower levels of IL6 gene expression, and western blot analysis showed decreased protein expression of IL6 and TLR2, and suppressed phosphorylation of TLR2 downstream nuclear factor-κB, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase after mangiferin treatment. CONCLUSIONS: These results suggest the suppressive effect of mangiferin on bone damage and inflammatory infiltrate in peri-implantitis. These therapeutic effects may be associated with inhibited IL6 production and reduced TLR2 signaling activation in peri-implant tissues.