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

Abstract

This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. 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 are 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 is 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 are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the 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 periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.

Keywords: Camellia sinensis; condensed tannins; cranberry; flavan-3-ols; gingivitis; gum disease; immunomodulatory; natural compounds; natural substances; periodontitis; polyphenols; proanthocyanidins.

Figure 1

Schematic picture illustrating immunomodulatory activities of flavan-3-ols and proanthocyanidins in periodontitis. Some of the more important cytokines are shown in the figure. The figure was created using BioRender.com. Abbreviations shown in the figure: IL, interleukin; TNF-α, tumor necrosis factor α; MMP, matrix metalloproteinases; ROS, reactive oxygen species; PGE₂, prostaglandin E₂; CCL, C-C motif chemokine ligand; CXCL, C-X-C motif chemokine ligand; LPS, lipopolysaccharide; LtxA, Leukotoxin released by A. actinomycetemcomitans.

Figure 2

Flowchart of the article search strategy, exclusion criteria, study selection, and data management process. Of all 65 considered references, 50 are reviewed in this paper and 31 in [1], of which 16 references are included in both reviews.

Figure 3

Structure of untypical proanthocyanidins isolated from fruits of Vitis vinifera used in the study of Huang et al. [13].