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

Galárraga-Vinueza, María Elisa; Dohle, Eva; Ramanauskaitė, Aušra; Al-Maawi, Sara; Obreja, Karina; Magini, Ricardo de Souza; Sader, Robert; Ghanaati, Shahram; Schwarz, Frank

doi:10.1111/jre.12773

Cited by 27 publications

(28 citation statements)

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“…Conferring to the mentioned immunological processes, several studies have shown that M1 polarization is in fact associated with osteolytic processes [17,28,30]. Moreover, some studies have also implied that macrophage switch from M1 to M2 phenotype plays a central role to decrease chronic inflammation and osteolytic effects [9,28,30].…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies have shown that pro-inflammatory reactions at host tissues can be induced by bacteria sub-products (i.e., lipopolysaccharides) or interferon (IFN)-g which subsequently activate M1 phenotype promoting inflammation [10,28]. In chronic inflammatory diseases, CD4-T-cell-centered processes stimulate T-helper cells to promote or counteract inflammation and osteolysis, playing a pivotal role on macrophage polarization [1,9,29]. In this scenario, Th1 and Th17 cells are associated to disease progression, upregulating inflammation, and osteolytic effects.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, Th2 cells and Tregs have been described to reduce disease progression and to decrease inflammation. The Th conversion from Th1 to Th2/Tregs has been related to M2 polarization and the prevention of disease [9,29]. Conferring to the mentioned immunological processes, several studies have shown that M1 polarization is in fact associated with osteolytic processes [17,28,30].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, certain mechanisms like epigenetic deregulations, disruption of the periodontium/peri-implant tissue homeostasis, and a dysfunctional immunological response to bacterial endotoxins can trigger inflammatory responses at tooth and implant sites [6,7]. The initiation or resolution of inflammation might be governed by macrophage phenotype alternation which is dependent on different environmental signals [8,9]. Accordingly, macrophages activated by bacteria sub-products (i.e., lipopolysaccharides) or interferon (IFN)-g present a M1 phenotype and are associated with proinflammatory responses, phagocytosis, tissue destruction, and interleukin (IL)-6 and IL-1β production.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage polarization in peri-implantitis lesions

et al. 2020

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Objectives To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites. Materials and methods A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses. Results Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4-17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9-9.4) and 5.22% (95% CI 3.8-6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1-12-1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values. Conclusion The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression. Clinical relevance Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host's immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis' underlying pathogenesis.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macrophage polarization in peri-implantitis lesions

et al. 2020

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“…(Galarra ga-Vinueza et al 2020) [12] Unverified commercial proanthocyanidin (PA) purchased at ChemFace, with molecular weight =594.52 and untypical structure.…”

Section: Influence On Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

Proanthocyanidins and Flavan-3-ols in the Prevention and Treatment of Periodontitis - Immunomodulatory Effects, Animal and Clinical Studies

Nawrot-Hadzik

Matkowski

Kubasiewicz−Ross

et al. 2020

Preprint

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This paper continues the review study on antimicrobial properties relevant to the periodontal diseases. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response has been covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies has been analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there is still much less studies using animal models and only a few clinical studies. Most of the studies, regardless of the used model indicated efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontitis is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.

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Ibero‐Panamerican Federation of Periodontics Delphi study on the trends in diagnosis and treatment of peri‐implant diseases and conditions: A Latin American consensus

Alarcón

Sanz‐Sánchez

López-Pacheco

et al. 2021

Journal of Periodontology

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

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 27 publications

References 43 publications

Macrophage polarization in peri-implantitis lesions

Macrophage polarization in peri-implantitis lesions

Proanthocyanidins and Flavan-3-ols in the Prevention and Treatment of Periodontitis - Immunomodulatory Effects, Animal and Clinical Studies

Ibero‐Panamerican Federation of Periodontics Delphi study on the trends in diagnosis and treatment of peri‐implant diseases and conditions: A Latin American consensus

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