Extract from Rumex acetosa L. for Prophylaxis of Periodontitis: Inhibition of Bacterial In Vitro Adhesion and of Gingipains of Porphyromonas gingivalis by Epicatechin-3-O-(4β→8)-Epicatechin-3-O-Gallate (Procyanidin-B2-Di-Gallate)

Abstract

BackgroundThe aerial parts of Rumex acetosa L. have been used in traditional European medicine for inflammatory diseases of the mouth epithelial tissue. The following study aimed to investigate the influence of a proanthocyanidin-enriched extract from R. acetosa extract against the adhesion of Porphyromonas gingivalis (P. gingivalis), a pathogen strongly involved in chronic and aggressive periodontitis. A further goal was to define the bioactive lead structures responsible for a potential antiadhesive activity and to characterize the underlying molecular mechanisms of the antiadhesive effects.MethodologyAn extract of R. acetosa (RA1) with a defined mixture of flavan-3-ols, oligomeric proanthocyanidins and flavonoids, was used. Its impact on P. gingivalis adhesion to KB cells was studied by flow cytometry, confocal laser scanning microscopy and in situ adhesion assay using murine buccal tissue. RA1 and its compounds 1 to 15 were further investigated for additional effects on gingipain activity, hemagglutination and gene expression by RT-PCR.Principal FindingsRA1 (5 to 15 μg/mL) reduced P. gingivalis adhesion in a dose-dependent manner to about 90%. Galloylated proanthocyanidins were confirmed to be responsible for this antiadhesive effect with epicatechin-3-O-gallate-(4β,8)-epicatechin-3’-O-gallate (syn. procyanidin B2-di-gallate) being the lead compound. Ungalloylated flavan-3-ols and oligomeric proanthocyanidins were inactive. RA1 and the galloylated proanthocyanidins strongly interact with the bacterial virulence factor Arg-gingipain, while the corresponding Lys-gingipain was hardly influenced. RA1 inhibited also hemagglutination. In silico docking studies indicated that epicatechin-3-O-gallate-(4β,8)-epicatechin-3’-O-gallate interacts with the active side of Arg-gingipain and hemaglutinin from P. gingivalis; the galloylation of the molecule seems to be responsible for fixation of the ligand to the protein. In conclusion, the proanthocyanidin-enriched extract RA1 and its main active constituent procyanidin B2-di-gallate protect cells from P. gingivalis infection by inhibiting bacterial adhesion to the host cell. RA1 and procyanidin B2-di-gallate appear to be promising candidates for future cytoprotective preparations for oral mouth care products.

Punica granatum L. (Pomegranate) Extract: In Vivo Study of Antimicrobial Activity against Porphyromonas gingivalis in Galleria mellonella Model

“…A widely studied medicinal plant is Punica granatum L. (pomegranate) [ 2 ] as it has bactericidal, antifungal properties and can modulate the immune response [ 1 , 6 – 13 ]. In fact, its effects on diseases affecting the human oral cavity (e.g., periodontitis) are currently being evaluated [ 14 , 15 ].…”

“…According to Schmuch et al [ 14 ], most microorganisms which colonize the gingival sulcus or the gingival margin are compatible with periodontal health. However, only a subset of species can cause or contribute to the progression of periodontitis.…”

Hydroalkoholischer Extrakt aus Sauerampferkraut (Rumex acetosa L.) zur Prophylaxe von Mundschleimhauterkrankungen und Periodontitis: Hemmung der bakteriellen Adhäsion und zentraler Virulenzfaktoren von Porphyromonas gingivalis

“…Die vorliegenden Untersuchungen sollten mögliche antiadhäsive Wirkungen der Droge unter In-vitro-Bedingungen prüfen, diese Effekte bestimmten Inhaltsstoffen zuordnen und exakte Struktur-Wirkungsbeziehungen erstellen. Die Details der experimentellen Versuche sind der Originalpublikation zu dieser Zusammenfassung zu entnehmen [38].…”

Quercetin inhibits virulence properties of Porphyromas gingivalis in periodontal disease

“…Periodontal disease is a common chronic inflammatory disease that characterized swelling and bleeding of the gums clinically, and leading to the progressive destruction of tooth-supporting tissues including the gingiva, alveolar bone, periodontal ligament, and cementum. Severe periodontitis can cause periodontal pockets formation, bone resorption, and eventually lead to tooth loss 1 . It has been estimated that nearly 50% of human population worldwide are affected by mild to moderate periodontitis and approximately 11% are severe forms 2 .…”