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Inhibition of gingipains and Porphyromonas gingivalis growth and biofilm formation by prenyl flavonoids.
J Periodontal Res. 2017 Feb; 52(1):89-96.JP

Abstract

BACKGROUND AND OBJECTIVE

Porphyromonas gingivalis is considered a major pathogen of chronic periodontitis, which also may be implicated with systemic diseases such as atherosclerosis. Secreted cysteine proteases, gingipains Rgp and Kgp, are essential for P. gingivalis virulence. Some polyphenols and flavonoids are known to inhibit gingipain activity and interfere with biofilm formation by P. gingivalis. Many bioactive compounds have been isolated from Epimedium species, but availability of these compounds on gingipains and P. gingivalis is still unclear. Therefore, the aim of this study was to evaluate natural products from medical plants to develop a new therapeutic agent against periodontal disease.

MATERIAL AND METHODS

Prenylated flavonoids were isolated from Epimedium species plant using column chromatographies. The inhibitory effect of the prenylated flavonoids against protease activity of gingipains were examined using purified gingipains and fluorogenic substrates. Anti-P. gingivalis activity was evaluated to analyze planktonic growth and biofilm formation in brain heart infusion medium in the presence of the prenylated flavonoids.

RESULTS

We isolated 17 prenylated flavonoids (Limonianin, Epimedokoreanin B, etc.) from Epimedium species. We found that some prenylated flavonoids inhibited gingipain activity in a non-competitive manner with Ki values at μm order. The prenylated flavonoids also hindered growth and biofilm formation of P. gingivalis, in a manner independent of gingipain inhibition by the compounds.

CONCLUSION

The results indicated an inhibitory effect of the prenylated flavonoids against P. gingivalis and would provide useful information for future development of periodontitis treatment that suppresses gingipains, P. gingivalis growth and biofilm formation.

Authors+Show Affiliations

Department of Life Science, Shokei University, Kumamoto, Japan.Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.Division of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.Division of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. Department of Oral Immunology and Infectious Disease, University of Louisville, School of Dentistry, Louisville, KY, USA.Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26957413

Citation

Kariu, T, et al. "Inhibition of Gingipains and Porphyromonas Gingivalis Growth and Biofilm Formation By Prenyl Flavonoids." Journal of Periodontal Research, vol. 52, no. 1, 2017, pp. 89-96.
Kariu T, Nakao R, Ikeda T, et al. Inhibition of gingipains and Porphyromonas gingivalis growth and biofilm formation by prenyl flavonoids. J Periodontal Res. 2017;52(1):89-96.
Kariu, T., Nakao, R., Ikeda, T., Nakashima, K., Potempa, J., & Imamura, T. (2017). Inhibition of gingipains and Porphyromonas gingivalis growth and biofilm formation by prenyl flavonoids. Journal of Periodontal Research, 52(1), 89-96. https://doi.org/10.1111/jre.12372
Kariu T, et al. Inhibition of Gingipains and Porphyromonas Gingivalis Growth and Biofilm Formation By Prenyl Flavonoids. J Periodontal Res. 2017;52(1):89-96. PubMed PMID: 26957413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of gingipains and Porphyromonas gingivalis growth and biofilm formation by prenyl flavonoids. AU - Kariu,T, AU - Nakao,R, AU - Ikeda,T, AU - Nakashima,K, AU - Potempa,J, AU - Imamura,T, Y1 - 2016/03/09/ PY - 2016/01/23/accepted PY - 2016/3/10/pubmed PY - 2018/8/21/medline PY - 2016/3/10/entrez KW - Porphyromonas gingivalis growth KW - biofilm KW - gingipains KW - prenylated flavonoids SP - 89 EP - 96 JF - Journal of periodontal research JO - J Periodontal Res VL - 52 IS - 1 N2 - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is considered a major pathogen of chronic periodontitis, which also may be implicated with systemic diseases such as atherosclerosis. Secreted cysteine proteases, gingipains Rgp and Kgp, are essential for P. gingivalis virulence. Some polyphenols and flavonoids are known to inhibit gingipain activity and interfere with biofilm formation by P. gingivalis. Many bioactive compounds have been isolated from Epimedium species, but availability of these compounds on gingipains and P. gingivalis is still unclear. Therefore, the aim of this study was to evaluate natural products from medical plants to develop a new therapeutic agent against periodontal disease. MATERIAL AND METHODS: Prenylated flavonoids were isolated from Epimedium species plant using column chromatographies. The inhibitory effect of the prenylated flavonoids against protease activity of gingipains were examined using purified gingipains and fluorogenic substrates. Anti-P. gingivalis activity was evaluated to analyze planktonic growth and biofilm formation in brain heart infusion medium in the presence of the prenylated flavonoids. RESULTS: We isolated 17 prenylated flavonoids (Limonianin, Epimedokoreanin B, etc.) from Epimedium species. We found that some prenylated flavonoids inhibited gingipain activity in a non-competitive manner with Ki values at μm order. The prenylated flavonoids also hindered growth and biofilm formation of P. gingivalis, in a manner independent of gingipain inhibition by the compounds. CONCLUSION: The results indicated an inhibitory effect of the prenylated flavonoids against P. gingivalis and would provide useful information for future development of periodontitis treatment that suppresses gingipains, P. gingivalis growth and biofilm formation. SN - 1600-0765 UR - https://www.unboundmedicine.com/medline/citation/26957413/Inhibition_of_gingipains_and_Porphyromonas_gingivalis_growth_and_biofilm_formation_by_prenyl_flavonoids_ L2 - https://doi.org/10.1111/jre.12372 DB - PRIME DP - Unbound Medicine ER -