Efficacy of Proanthocyanidins from Pelargonium sidoides Root Extract in Reducing P. gingivalis Viability While Preserving Oral Commensal S. salivarius

Nijole Savickiene, Aiste Jekabsone, Lina Raudone, Asmaa S Abdelgeliel, Andrea Cochis, Lia Rimondini, Elina Makarova, Solveiga Grinberga, Osvalds Pugovics, Maija Dambrova, Ingrida M Pacauskiene, Nomeda Basevičiene, Pranas Viškelis, Nijole Savickiene, Aiste Jekabsone, Lina Raudone, Asmaa S Abdelgeliel, Andrea Cochis, Lia Rimondini, Elina Makarova, Solveiga Grinberga, Osvalds Pugovics, Maija Dambrova, Ingrida M Pacauskiene, Nomeda Basevičiene, Pranas Viškelis

Abstract

Bacterial resistance to antibiotics and the disruption of beneficial microbiota are key problems in contemporary medicine and make the search for new, more efficient infection treatment strategies among the most important tasks in medicine. Multicomponent plant-derived preparations with mild antibacterial activity created by many simultaneous mechanisms together with anti-inflammatory, innate immune and regenerative capacity-stimulating properties are good candidates for this therapy, and proanthocyanidins are among the most promising compounds of this sort. In this study, we have isolated proanthocyanidins from Pelargonium sidoides DC root extract and characterized and compared the composition, antioxidant properties and antibacterial activity of the proanthocyanidin fraction with those of the whole extract. The results revealed that proanthocyanidins had significantly stronger antioxidant capacity compared to the root extract and exhibited a unique antibacterial action profile that selectively targets Gram-negative keystone periodontal and peri-implant pathogenic strains, such as Porphyromonas gingivalis, while preserving the viability of beneficial oral commensal Streptococcus salivarius. The finding suggests that proanthocyanidins from Pelargonium sidoides root extract are good candidates for the prolonged and harmless treatment of infectious diseases.

Keywords: LC/MS/MS; Pelargonium sidoides root extract; antioxidant activity; bacteriotoxicity; proanthocyanidins.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Content of phenolic compounds (mg/g) determined in Pelargonium sidoides root extract (PSRE).
Figure 2
Figure 2
Antibacterial activity of Pelargonium sidoides root extract (PSRE). The extract at all tested concentrations (expressed as g/mL) induced a significant reduction of P. gingivalis (A) or S. salivarius (B) viability in comparison with the untreated control (p < 0.01, indicated by the *). Values are represented as the mean ± SD of 16 independent measurements.
Figure 3
Figure 3
Antibacterial activity of proanthocyanidins (PACN). A different activity was noticed for various concentrations (expressed as mg/mL). For P. gingivalis (A) only concentrations >0.03 mg/mL were effective in significantly reducing viability (p < 0.01, indicated by the *) with results of approximately 10%. By contrast, PACN had moderate effect on (B) S. salivarius in comparison to P. gingivalis. Values are represented as the mean ± SD of 16 independent measurements.

References

    1. Ventola C.L. The antibiotic resistance crisis: Part 1: Causes and threats. P T. 2015;40:277–283.
    1. Nakatsuji T., Chen T.H., Narala S., Chun K.A., Two A.M., Yun T., Shafiq F., Kotol P.F., Bouslimani A., Melnik A.V., et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl. Med. 2017;9:eaah4680. doi: 10.1126/scitranslmed.aah4680.
    1. Avila M., Ojcius D.M., Yilmaz Ö. The Oral Microbiota: Living with a Permanent Guest. DNA Cell Biol. 2009;28:405–411. doi: 10.1089/dna.2009.0874.
    1. Thursby E., Juge N. Introduction to the human gut microbiota. Biochem. J. 2017;474:1823–1836. doi: 10.1042/BCJ20160510.
    1. Cordell G.A., Colvard M.D. Natural Products and Traditional Medicine: Turning on a Paradigm. J. Nat. Prod. 2012;75:514–525. doi: 10.1021/np200803m.
    1. Taylor P.W. Alternative natural sources for a new generation of antibacterial agents. Int. J. Antimicrob. Agents. 2013;42:195–201. doi: 10.1016/j.ijantimicag.2013.05.004.
    1. Brendler T., van Week B.-E. A historical, scientific and commercial perspective on the medicinal use of Pelargonium sidoides (Geraniaceae) J. Ethnopharmacol. 2008;119:420–433. doi: 10.1016/j.jep.2008.07.037.
    1. Lewu F.B., Grierson D.S., Afolayan A.J. Extracts from Pelargonium sidoides. Inhibit the Growth of Bacteria and Fungi. Pharm. Biol. 2006;44:279–282. doi: 10.1080/13880200600714137.
    1. Lewu F.B., Grierson D.S., Afolayan A.J. The leaves of Pelargonium sidoides may substitute for its roots in the treatment of bacterial infections. Biol. Conserv. 2006;128:582–584. doi: 10.1016/j.biocon.2005.10.018.
    1. Kayser O., Kolodziej H. Antibacterial Activity of Extracts and Constituents of Pelargonium sidoides and Pelargonium reniforme. Planta Med. 1997;63:508–510. doi: 10.1055/s-2006-957752.
    1. Bereznoy V.V., Riley D.S., Wassmer G., Heger M. Efficacy of extract of Pelargonium sidoides in children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis: A randomized, double-blind, placebo-controlled trial. Altern. Ther. Health Med. 2003;9:68–79.
    1. Bachert C., Schapowal A., Funk P., Kieser M. Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: A randomized, double-blind, placebo-controlled trial. Rhinology. 2009;47:51–58.
    1. Matthys H., Eisebitt R., Seith B., Heger M. Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis: A randomised, double-blind, placebo-controlled trial. Phytomedicine. 2003;10:7–17. doi: 10.1078/1433-187X-00308.
    1. Pandey K.B., Rizvi S.I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev. 2009;2:270–278. doi: 10.4161/oxim.2.5.9498.
    1. Yadav M., Jain S., Bhardwaj A., Nagpal R., Puniya M., Tomar R., Singh V., Parkash O., Prasad G.B.K.S., Marotta F., et al. Biological and Medicinal Properties of Grapes and Their Bioactive Constituents: An Update. J. Med. Food. 2009;12:473–484. doi: 10.1089/jmf.2008.0096.
    1. Palaska I., Papathanasiou E., Theoharides C.T. Use of polyphenols in periodontal inflammation. Eur. J. Pharmacol. 2013;720:77–83. doi: 10.1016/j.ejphar.2013.10.047.
    1. La V.D., Howell A.B., Grenier D. Anti-Porphyromonas gingivalis and anti-inflammatory activities of A-type cranberry proanthocyanidins. Antimicrob. Agents Chemother. 2010;54:1778–1784. doi: 10.1128/AAC.01432-09.
    1. Green B., Yao X., Ganguly A., Xu C., Dusevich V., Walker M.P., Wang Y. Grape seed proanthocyanidins increase collagen biodegradation resistance in the dentin/adhesive interface when included in an adhesive. J. Dent. 2010;38:908–915. doi: 10.1016/j.jdent.2010.08.004.
    1. How K.Y., Song K.P., Chan K.G. Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line. Front. Microbiol. 2016;7 doi: 10.3389/fmicb.2016.00053.
    1. Mysak J., Podzimek S., Sommerova P., Lyuya-Mi Y., Bartova J., Janatova T., Prochazkova J., Duskova J. Porphyromonas gingivalis: Major periodontopathic pathogen overview. J. Immunol. Res. 2014 doi: 10.1155/2014/476068.
    1. Kolenbrander P.E., Palmer R.J., Periasamy S., Jakubovics N.S. Oral multispecies biofilm development and the key role of cell-cell distance. Nat. Rev. Microbiol. 2010;8:471–480. doi: 10.1038/nrmicro2381.
    1. Mahato N., Wu X., Wang L. Management of peri-implantitis: A systematic review, 2010–2015. Springerplus. 2016;5 doi: 10.1186/s40064-016-1735-2.
    1. Hellström J., Sinkkonen J., Karonen M., Mattila P. Isolation and structure elucidation of procyanidin oligomers from Saskatoon berries (Amelanchier alnifolia) J. Agric. Food Chem. 2007;55:157–164. doi: 10.1021/jf062441t.
    1. Porter L.J., Hrstich L.N., Chan B.G. The conversion of procyanidins and prodelphinidins to cyanidin and delphinidin. Phytochemistry. 1985;25:223–230. doi: 10.1016/S0031-9422(00)94533-3.
    1. Schötz K., Nöldner M. Mass spectroscopic characterisation of oligomeric proanthocyanidins derived from an extract of Pelargonium sidoides roots (EPs® 7630) and pharmacological screening in CNS models. Phytomedicine. 2007;14:32–39. doi: 10.1016/j.phymed.2006.11.019.
    1. Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 1999;26:1231–1237. doi: 10.1016/S0891-5849(98)00315-3.
    1. Benzie I.F.F., Strain J.J. Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol. 1998;299:15–27.
    1. Amarowicz R., Pegg R.B. Content of proanthocyanidins in selected plant extracts as determined via n-butanol/HCl hydrolysis and a colorimetric assay or by HPLC—A short report. Pol. J. Food Nutr. Sci. 2006;15:319–322.
    1. Fu Y., Qiao L., Cao Y., Zhou X., Liu Y., Ye X. Structural Elucidation and Antioxidant Activities of Proanthocyanidins from Chinese Bayberry (Myrica rubra Sieb. et Zucc.) Leaves. PLoS ONE. 2014;9:e096162. doi: 10.1371/journal.pone.0096162.
    1. Taamalli A., Iswaldi I., Arráez-Román D., Segura-Carretero A., Fernández-Gutiérrez A., Zarrouk M. UPLC-QTOF/MS for a rapid characterisation of phenolic compounds from leaves of Myrtus communis L. Phytochem. Anal. 2014;25:89–96. doi: 10.1002/pca.2475.
    1. Pereira A., Bester M., Soundy P., Apostolides Z. Activity-guided isolation and identification of the major antioxidant and anticancer compounds from a commercial Pelargonium sidoides tincture. Med. Chem. Res. 2015;24 doi: 10.1007/s00044-015-1425-6.
    1. Engström M.T., Pälijärvi M., Fryganas C., Grabber J.H., Mueller-Harvey I., Salminen J.-P. Rapid Qualitative and Quantitative Analyses of Proanthocyanidin Oligomers and Polymers by UPLC-MS/MS. J. Agric. Food Chem. 2014;62:3390–3399. doi: 10.1021/jf500745y.
    1. Kolodziej H., Burmeister A., Trun W., Radtke O.A., Kiderlen A.F., Ito H., Hatano T., Yoshida T., Lai Y.F. Tannins and related compounds induce nitric oxide synthase and cytokines gene expressions in Leishmania major-infected macrophage-like RAW 264.7 cells. Bioorg. Med. Chem. 2005;13:6470–6476. doi: 10.1016/j.bmc.2005.07.012.
    1. Kolodziej H. Fascinating metabolic pools of Pelargonium sidoides and Pelargonium reniforme, traditional and phytomedicinal sources of the herbal medicine Umckaloabo®. Phytomedicine. 2007;14:9–17. doi: 10.1016/j.phymed.2006.11.021.
    1. Janecki A., Conrad A., Engels I., Frank U., Kolodziej H. Evaluation of an aqueous-ethanolic extract from Pelargonium sidoides (EPs® 7630) for its activity against group A-streptococci adhesion to human HEp-2 epithelial cells. J. Ethnopharmacol. 2011;133:147–152. doi: 10.1016/j.jep.2010.09.018.
    1. Kolodziej H. Antimicrobial, antiviral and immunomodulatory activity studies of Pelargonium sidoides (EPs® 7630) in the context of health promotion. Pharmaceuticals. 2011;4:1295–1314. doi: 10.3390/ph4101295.
    1. Schoetz K., Erdelmeier C., Germer S., Hauer H. A Detailed View on the Constituents of EPs® 7630. Planta Med. 2008;74:667–674. doi: 10.1055/s-2008-1074515.
    1. Plumb G.W., de Pascual-Teresa S., Santos-Buelga C., Rivas-Gonzalo J.C., Williamson G. Antioxidant properties of gallocatechin and prodelphinidins from pomegranate peel. Redox Rep. 2002;7:41–46. doi: 10.1179/135100002125000172.
    1. Xia E.-Q., Deng G.-F., Guo Y.-J., Li H.-B. Biological activities of polyphenols from grapes. Int. J. Mol. Sci. 2010;11:622–646. doi: 10.3390/ijms11020622.
    1. Taguri T., Tanaka T., Kouno I. Antimicrobial Activity of 10 Different Plant Polyphenols against Bacteria Causing Food-Borne Disease. Biol. Pharm. Bull. 2004;27:1965–1969. doi: 10.1248/bpb.27.1965.
    1. Pham-Huy L.A., He H., Pham-Huy C. Free radicals, antioxidants in disease and health. Int. J. Biomed. Sci. 2008;4:89–96.
    1. Goncalves C., Dinis T., Batista M. Antioxidant properties of proanthocyanidins of bark decoction: A mechanism for anti-inflammatory activity. Phytochemistry. 2005;66:89–98. doi: 10.1016/j.phytochem.2004.10.025.
    1. Pinent M., Castell-Auví A., Genovese M.I., Serrano J., Casanova A., Blay M., Ardévol A. Antioxidant effects of proanthocyanidin-rich natural extracts from grape seed and cupuassu on gastrointestinal mucosa. J. Sci. Food Agric. 2016;96:178–182. doi: 10.1002/jsfa.7079.
    1. Arulselvan P., Fard M.T., Tan W.S., Gothai S., Fakurazi S., Norhaizan M.E., Kumar S.S. Role of Antioxidants and Natural Products in Inflammation. Oxid. Med. Cell. Longev. 2016 doi: 10.1155/2016/5276130.
    1. Silva N., Abusleme L., Bravo D., Dutzan N., Garcia-Sesnich J., Vernal R., Hernández M., Gamonal J. Host response mechanisms in periodontal diseases. J. Appl. Oral Sci. 2015;23:329–355. doi: 10.1590/1678-775720140259.
    1. Masdea L., Kulik E.M., Hauser-Gerspach I., Ramseier A.M., Filippi A., Waltimo T. Antimicrobial activity of Streptococcus salivarius K12 on bacteria involved in oral malodour. Arch. Oral Biol. 2012;57:1041–1047. doi: 10.1016/j.archoralbio.2012.02.011.
    1. Sliepen I., Van Damme J., Van Essche M., Loozen G., Quirynen M., Teughels W. Microbial Interactions Influence Inflammatory Host Cell Responses. J. Dent. Res. 2009;88:1026–1030. doi: 10.1177/0022034509347296.
    1. Ulrey R.K., Barksdale S.M., Zhou W., van Hoek M.L. Cranberry proanthocyanidins have anti-biofilm properties against Pseudomonas aeruginosa. BMC Complement. Altern. Med. 2014;14:499. doi: 10.1186/1472-6882-14-499.
    1. Maisuria V.B., Los Santos Y.L., Tufenkji N., Déziel E. Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa. Sci. Rep. 2016;6:30169. doi: 10.1038/srep30169.
    1. Krachler A.M., Orth K. Targeting the bacteria-host interface: Strategies in anti-adhesion therapy. Virulence. 2013;4:284–294. doi: 10.4161/viru.24606.
    1. 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.

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