Anti-inflammatory and macrophage polarization effects of Cranberry Proanthocyanidins (PACs) for periodontal and peri-implant disease therapy

Background and objective: Macrophages' cytokine expression and polarization play a substantial role in the host's "destructive" inflammatory response to periodontal and peri-implant pathogens. This study aimed to evaluate cell viability, anti-inflammatory activity, and macrophage polarization properties of different cranberry concentrates.

Methods: THP-1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB-G cell line), osteosarcoma-derived osteoblasts (SAOS-2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti-inflammatory analysis, induced macrophages exposed to cranberry concentrates (A-type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)-8, IL-1 ß, IL-6, and IL-10 expression of LPS-stimulated macrophages, and macrophage polarization markers were evaluated through determination of live-cell protease activity, enzyme-linked immunosorbent assay, and immunofluorescence staining semi-quantification.

Results: Cranberry concentrates (A-type PACs) did not reduce HGF, SAOS-2, and macrophage viability after 24 hours of exposure. Pro-inflammatory cytokine expression (ie IL-8 and IL-6) was downregulated in LPS-stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti-inflammatory IL-10 expression was significantly upregulated in LPS-stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS-stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS-stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours.

Conclusion: Cranberry-derived proanthocyanidins may have the potential to act as an anti-inflammatory component in the therapy of periodontal and peri-implant diseases.

Keywords: anti-inflammatory agents; cranberry; interleukins; macrophage polarization; peri-implantitis; periodontitis; proanthocyanidin.