Planta Med 2023; 89(11): 1052-1062
DOI: 10.1055/a-1728-2249
Biological and Pharmacological Activity
Original Papers

Microbiological and Clinical Effects of a Proanthocyanidin-enriched Extract from Rumex acetosa in Periodontally Healthy Carriers of Porphyromonas gingivalis: a Randomized Controlled Pilot Study

1   Adelaide Dental School, The University of Adelaide, Adelaide, Australia
,
Astrid Klocke
2   Private Practice, Krefeld, Germany
,
Ulrike Peters
3   Department of Periodontics, Preventive and Restorative Dentistry, University Medical Center Eppendorf, Hamburg, Germany
,
Sabine Beckert
4   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
,
Rory Munro Watt
5   Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Peoplesʼ Republic of China
,
Raymond Tong
5   Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Peoplesʼ Republic of China
,
Thomas Frank Flemmig
5   Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, Peoplesʼ Republic of China
,
4   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
,
Thomas Beikler
3   Department of Periodontics, Preventive and Restorative Dentistry, University Medical Center Eppendorf, Hamburg, Germany
› Institutsangaben
Gefördert durch: European Union (ZIEL.2.NRW program) 300262502 to TB
Gefördert durch: European Union (ZIEL.2.NRW program) w1006sb014 to AH

Abstract

Rumex acetosa significantly inhibits the adhesion of Porphyromonas gingivalis (P. g.) to eukaryotic host cells in vitro. The objective of this randomized placebo-controlled pilot-trial was to analyze effects of a mouth rinse containing 0.8% (w/w) of a quantified proanthocyanidin-enriched extract from Rumex acetosa (RA1) on microbiological, clinical, and cytological parameters in systemically healthy individuals without history of periodontitis, harboring P. g. intraorally. 35 subjects received a supragingival debridement (SD) followed by mouth rinsing (3 times daily) with either RA1 mouth rinse solution (test) or placebo (control) for 7 days as adjunct to routine oral hygiene. Supragingival biofilm samples were taken at screening visit, baseline (BL), 2, 4, 7 and 14 days after SD. P. g. and 11 other oral microorganisms were detected and quantified by rtPCR. Changes in the oral microbiota composition of one test and one control subject were assessed via high throughput 16S rRNS gene amplicon sequencing. Approximal Plaque Index (API) and the modified Sulcular Bleeding Index (SBI) were assessed at BL, 7- and 14-days following SD. Brush biopsies were taken at BL and 14 d following SD. Intergroup comparisons revealed no significant microbiological, cytological, and clinical differences at any timepoint. However, a significant reduction in SBI at day 14 (p = 0.003) and API at day 7 (p = 0.02) and day 14 (p = 0.009) was found in the test group by intragroup comparison. No severe adverse events were observed. The results indicate that RA1 mouth rinse is safe but does not seem to inhibit colonization of P. g. or improve periodontal health following SD.

Supporting Information



Publikationsverlauf

Eingereicht: 24. August 2021

Angenommen nach Revision: 25. Dezember 2021

Accepted Manuscript online:
25. Dezember 2021

Artikel online veröffentlicht:
28. Februar 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Nadkarni MA, Chhour KL, Browne GV, Byun R, Nguyen KA, Chapple CC, Jacques NA, Hunter N. Age-dependent changes in Porphyromonas gingivalis and Prevotella species/phylotypes in healthy gingiva and inflamed/diseased sub-gingival sites. Clin Oral Investig 2015; 19: 911-919 DOI: 10.1007/s00784-014-1301-7.
  • 2 Darveau RP, Hajishengallis G, Curtis MA. Porphyromonas gingivalis as a potential community activist for disease. J Dent Res 2012; 91: 816-820 DOI: 10.1177/0022034512453589.
  • 3 Olsen I, Chen T, Tribble GD. Genetic exchange and reassignment in Porphyromonas gingivalis . J Oral Microbiol 2018; 10: 1457373
  • 4 Thurnheer T, Belibasakis GN, Bostanci N. Colonisation of gingival epithelia by subgingival biofilms in vitro: Role of “red complex” bacteria. Arch Oral Biol 2014; 59: 977-986 DOI: 10.1016/j.archoralbio.2014.05.023.
  • 5 Ximenez-Fyvie LA, Haffajee AD, Som S, Thompson M, Torresyap G, Socransky SS. The effect of repeated professional supragingival plaque removal on the composition of the supra- and subgingival microbiota. J Clin Periodontol 2000; 27: 637-647 DOI: 10.1034/j.1600-051x.2000.027009637.x.
  • 6 Lamont RJ, Jenkinson HF. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis . Microbiol Mol Biol Rev 1998; 62: 1244-1263
  • 7 Bavington C, Page C. Stopping bacterial adhesion: A novel approach to treating infections. Respiration 2005; 72: 335-344 DOI: 10.1159/000086243.
  • 8 Bunte K, Hensel A, Beikler T. Polyphenols in the prevention and treatment of periodontal disease: A systematic review of in vivo, ex vivo and in vitro studies. Fitoterapia 2019; 132: 30-39 DOI: 10.1016/j.fitote.2018.11.012.
  • 9 de la Iglesia R, Milagro FI, Campion J, Boque N, Martinez JA. Healthy properties of proanthocyanidins. Biofactors 2010; 36: 159-168 DOI: 10.1002/biof.79.
  • 10 Palaska I, Papathanasiou E, Theoharides TC. Use of polyphenols in periodontal inflammation. Eur J Pharmacol 2013; 720: 77-83 DOI: 10.1016/j.ejphar.2013.10.047.
  • 11 Fournier-Larente J, Morin MP, Grenier D. Green tea catechins potentiate the effect of antibiotics and modulate adherence and gene expression in Porphyromonas gingivalis. Arch Oral Biol 2016; 65: 35-43 DOI: 10.1016/j.archoralbio.2016.01.014.
  • 12 Löhr G, Beikler T, Podbielski A, Standar K, Redanz S, Hensel A. Polyphenols from Myrothamnus flabellifolia Welw. inhibit in vitro adhesion of Porphyromonas gingivalis and exert anti-inflammatory cytoprotective effects in KB cells. J Clin Periodontol 2011; 38: 457-469 DOI: 10.1111/j.1600-051X.2010.01654.x.
  • 13 Labrecque J, Bodet C, Chandad F, Grenier D. Effects of a high-molecular-weight cranberry fraction on growth, biofilm formation and adherence of Porphyromonas gingivalis . J Antimicrob Chemother 2006; 58: 439-443 DOI: 10.1093/jac/dkl220.
  • 14 Neto CC, Penndorf KA, Feldman M, Meron-Sudai S, Zakay-Rones Z, Steinberg D, Fridman M, Kashman Y, Ginsburg I, Ofek I, Weiss EI. Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral bacteria. Food Funct 2017; 8: 1955-1965 DOI: 10.1039/c7fo00109f.
  • 15 Polak D, Naddaf R, Shapira L, Weiss EI, Houri-Haddad Y. Protective potential of non-dialyzable material fraction of cranberry juice on the virulence of P. gingivalis and F. nucleatum mixed infection. J Periodontol 2013; 84: 1019-1025 DOI: 10.1902/jop.2012.120331.
  • 16 Bhadbhade SJ, Acharya AB, Rodrigues SV, Thakur SL. The antiplaque efficacy of pomegranate mouthrinse. Quintessence Int 2011; 42: 29-36
  • 17 Löhr G, Beikler T, Hensel A. Inhibition of in vitro adhesion and virulence of Porphyromonas gingivalis by aqueous extract and polysaccharides from Rhododendron ferrugineum L. A new way for prophylaxis of periodontitis?. Fitoterapia 2015; 107: 105-113 DOI: 10.1016/j.fitote.2015.10.010.
  • 18 de Oliveira Caleare A, Hensel A, Mello JC, Pinha AB, Panizzon GP, Lechtenberg M, Petereit F, Nakamura CV. Flavan-3-ols and proanthocyanidins from Limonium brasiliense inhibit the adhesion of Porphyromonas gingivalis to epithelial host cells by interaction with gingipains. Fitoterapia 2017; 118: 87-93 DOI: 10.1016/j.fitote.2017.03.002.
  • 19 Löhr G. Adhäsion von Porphyromonas gingivalis: Antiadhäsive und zytoprotektive Wirkung proanthocyanidinhaltiger Pflanzenextrakte [PhD thesis]. Münster, Germany: University of Münster; 2010
  • 20 Schmuch J, Beckert S, Brandt S, Lohr G, Hermann F, Schmidt TJ, Beikler T, Hensel A. 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-(4beta→8)-epicatechin-3-O-gallate (procyanidin-B2-Di-gallate). PLoS One 2015; 10: e0120130 DOI: 10.1371/journal.pone.0120130.
  • 21 Gescher K, Hensel A, Hafezi W, Derksen A, Kuhn J. Oligomeric proanthocyanidins from Rumex acetosa L. inhibit the attachment of Herpes simplex virus type-1. Antiviral Res 2011; 89: 9-18 DOI: 10.1016/j.antiviral.2010.10.007.
  • 22 Derksen A, Hensel A, Hafezi W, Herrmann F, Schmidt TJ, Ehrhardt C, Ludwig S, Kuhn J. 3-O-galloylated procyanidins from Rumex acetosa L. inhibit the attachment of influenza A virus. PLoS One 2014; 9: e110089 DOI: 10.1371/journal.pone.0110089.
  • 23 Bicker J, Petereit F, Hensel A. Proanthocyanidins and a phloroglucinol derivative from Rumex acetosa L. Fitoterapia 2009; 80: 483-495 DOI: 10.1016/j.fitote.2009.08.015.
  • 24 Ainamo J, Barmes D, Beagrie G, Cutress T, Martin J, Sardo-Infirri J. Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J 1982; 32: 281-291
  • 25 Teles FR, Teles RP, Uzel NG, Song XQ, Torresyap G, Socransky SS, Haffajee AD. Early microbial succession in redeveloping dental biofilms in periodontal health and disease. J Periodontal Res 2012; 47: 95-104 DOI: 10.1111/j.1600-0765.2011.01409.x.
  • 26 Lo AW, Seers CA, Boyce JD, Dashper SG, Slakeski N, Lissel JP, Reynolds EC. Comparative transcriptomic analysis of Porphyromonas gingivalis biofilm and planktonic cells. BMC Microbiol 2009; 9: 18 DOI: 10.1186/1471-2180-9-18.
  • 27 Haffajee AD, Socransky SS, Patel MR, Song X. Microbial complexes in supragingival plaque. Oral Microbiol Immunol 2008; 23: 196-205 DOI: 10.1111/j.1399-302X.2007.00411.x.
  • 28 Suzuki N, Yoneda M, Hirofuji T. Mixed red-complex bacterial infection in periodontitis. Int J Dent 2013; 2013: 587279 DOI: 10.1155/2013/587279.
  • 29 Yoneda M, Yoshikane T, Motooka N, Yamada K, Hisama K, Naito T, Okada I, Yoshinaga M, Hidaka K, Imaizumi K, Maeda K, Hirofuji T. Stimulation of growth of Porphyromonas gingivalis by cell extracts from Tannerella forsythia . J Periodontal Res 2005; 40: 105-109 DOI: 10.1111/j.1600-0765.2005.00774.x.
  • 30 Inagaki S, Onishi S, Kuramitsu HK, Sharma A. Porphyromonas gingivalis vesicles enhance attachment, and the leucine-rich repeat BspA protein is required for invasion of epithelial cells by Tannerella forsythia . Infect Immun 2006; 74: 5023-5028 DOI: 10.1128/IAI.00062-06.
  • 31 Savickiene N, Jekabsone A, Raudone L, Abdelgeliel AS, Cochis A, Rimondini L, Makarova E, Grinberga S, Pugovics O, Dambrova M, Pacauskiene IM, Baseviciene N, Viskelis P. Efficacy of proanthocyanidins from Pelargonium sidoides root extract in reducing P. gingivalis viability while preserving oral commensal S. salivarius . Materials 2018; 11: 1499 DOI: 10.3390/ma11091499.
  • 32 Polonyi M, Prenninger N, Arweiler NB, Haririan H, Winklehner P, Kierstein S. Assessment of viable periodontal pathogens by reverse transcription quantitative polymerase chain reaction. J Periodontal Res 2013; 48: 671-676 DOI: 10.1111/jre.12052.
  • 33 Uzel NG, Teles FR, Teles RP, Song XQ, Torresyap G, Socransky SS, Haffajee AD. Microbial shifts during dental biofilm re-development in the absence of oral hygiene in periodontal health and disease. J Clin Periodontol 2011; 38: 612-620 DOI: 10.1111/j.1600-051X.2011.01730.x.
  • 34 Ooshima T, Minami T, Aono W, Tamura Y, Hamada S. Reduction of dental plaque deposition in humans by oolong tea extract. Caries Res 1994; 28: 146-149
  • 35 Weiss EI, Kozlovsky A, Steinberg D, Lev-Dor R, Bar Ness Greenstein R, Feldman M, Sharon N, Ofek I. A high molecular mass cranberry constituent reduces mutans streptococci level in saliva and inhibits in vitro adhesion to hydroxyapatite. FEMS Microbiol Lett 2004; 232: 89-92 DOI: 10.1016/s0378-1097(04)00035-7.
  • 36 Zhou M, Meng HX, Zhao YB, Chen ZB. Changes of four proinflammatory proteins in whole saliva during experimental gingivitis. Chin J Dent Res 2012; 15: 121-127
  • 37 Matthews CR, Joshi V, de Jager M, Aspiras M, Kumar PS. Host-bacterial interactions during induction and resolution of experimental gingivitis in current smokers. J Periodontol 2013; 84: 32-40 DOI: 10.1902/jop.2012.110662.
  • 38 Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem Toxicol 2002; 40: 599-607 DOI: 10.1016/s0278-6915(02)00006-6.
  • 39 Carlin V, Matsumoto MA, Saraiva PP, Artioli A, Oshima CT, Ribeiro DA. Cytogenetic damage induced by mouthrinses formulations in vivo and in vitro . Clin Oral Investig 2012; 16: 813-820 DOI: 10.1007/s00784-011-0559-2.
  • 40 Velleuer E, Dietrich R, Pomjanski N, de Santana Almeida Araujo IK, Silva de Araujo BE, Sroka I, Biesterfeld S, Bocking A, Schramm M. Diagnostic accuracy of brush biopsy-based cytology for the early detection of oral cancer and precursors in Fanconi anemia. Cancer Cytopathol 2020; 128: 403-413 DOI: 10.1002/cncy.22249.
  • 41 Soares S, Brandao E, Guerreiro C, Mateus N, de Freitas V, Soares S. Development of a new cell-based oral model to study the interaction of oral constituents with food polyphenols. J Agric Food Chem 2019; 67: 12833-12843 DOI: 10.1021/acs.jafc.9b05575.
  • 42 Lange DE, Plagmann HC, Eenboom A, Promesberger A. [Clinical methods for the objective evaluation of oral hygiene]. Dtsch Zahnarztl Z 1977; 32: 44-47
  • 43 Lange DE. The use of indices in the diagnosis of periodontal diseases. Dtsch Zahnarztl Z 1978; 33: 8-11
  • 44 Bocking A. Standardization of cytopathologic diagnosis. Pathologe 1998; 19: 236-241
  • 45 Bell ML, Kenward MG, Fairclough DL, Horton NJ. Differential dropout and bias in randomised controlled trials: when it matters and when it may not. BMJ 2013; 346: e8668 DOI: 10.1136/bmj.e8668.