Effect of a Toothpaste/Mouthwash Containing Carica papaya Leaf Extract on Interdental Gingival Bleeding: A Randomized Controlled Trial

Ina Saliasi, Juan Carlos Llodra, Manuel Bravo, Paul Tramini, Claude Dussart, Stéphane Viennot, Florence Carrouel, Ina Saliasi, Juan Carlos Llodra, Manuel Bravo, Paul Tramini, Claude Dussart, Stéphane Viennot, Florence Carrouel

Abstract

Clinical research on herbal-based dentifrice +/- mouth rinse products is very limited compared with the plethora of research on conventional oral care products under normal oral hygiene conditions. The aim of this study was to determine the anti-inflammatory effects of a novel plant Carica papaya leaf extract (CPLE) on interdental bleeding in healthy subjects. In this randomized, single-blind parallel-design study, the eligible subjects were generally healthy non-smokers, aged 18⁻26, who exhibited healthy periodontal conditions upon study entry. The participants were equally randomized into the following four groups: CPLE dentifrice, CPLE dentifrice and mouthwash, sodium lauryl sulfate (SLS)-free enzyme-containing dentifrice and SLS-free enzyme-containing dentifrice with essential oil (EO) mouthwash. Subjects were instructed to brush their teeth twice a day without changing their other brushing habits. Interdental bleeding (BOIP) was measured from inclusion (T₀) until the fourth week (T₄) of the study. Clinical efficacy was assessed after one, two, three and four weeks of home use. The analyses compared BOIP between groups and were then restricted to participants with ≥70% and then ≥80% bleeding sites at T₀. Pairwise comparisons between groups were performed at T₀ and T₄, and a logistic regression identified correlates of gingival bleeding (T₄). Among 100 subjects (2273 interdental sites), the median percentage of bleeding sites per participant at T₀ was 65%. The bleeding sites dramatically decreased in all groups between T₀ and T₄ (relative variations from -54% to -75%, p < 0.01 for all). Gingival bleeding did not significantly differ between the CPLE dentifrice and the SLS-free dentifrice +/- EO mouthwash groups (from p = 0.05 to p = 0.86), regardless of the baseline risk level. Among the CPLE dentifrice users, fewer bleeding sites were observed when toothpaste and mouthwash were combined compared to bleeding sites in those who used toothpaste alone (21% vs. 32%, p = 0.04). CPLE dentifrice/mouthwash provides an efficacious and natural alternative to SLS-free dentifrice +/-EO-containing mouthwash when used as an adjunct to mechanical oral care to reduce interdental gingival inflammation.

Keywords: Carica papaya; anti-inflammatory; biofilm; essential oils; interdental bleeding; mouthwash; natural dentifrice; sodium lauryl sulfate free dentifrice.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart of the study.
Figure 2
Figure 2
Evolution of interproximal bleeding by group in 2273 interdental sites (100 subjects). Group G: test Carica papaya leaf extract (CPLE) dentifrice; Group G + M: test CPLE dentifrice with CPLE mouthwash; Group Z: control with sodium lauryl sulfate (SLS)-free enzyme-containing dentifrice; Group Z + L: control with SLS-free enzyme-containing dentifrice and alcohol-based essential oil mouthwash; T0: basal; T1: 1 week; T2: 2 weeks; T3: 3 weeks; T4: 4 weeks.

References

    1. Van der Weijden F.A., Slot D.E. Efficacy of homecare regimens for mechanical plaque removal in managing gingivitis a meta review. J. Clin. Periodontol. 2015;42(Suppl. 16):S77–S91. doi: 10.1111/jcpe.12359.
    1. Bernard A., Dornic N., Roudot A., Ficheux A. Probabilistic exposure assessment to face and oral care cosmetic products by the French population. Food Chem. Toxicol. 2018;111:511–524. doi: 10.1016/j.fct.2017.11.056.
    1. Bourgeois D., Weiler D., Carrouel F. Oral Microbiota, Intestinal Microbiota and Inflammatory Bowel Diseases. Res. Rev. Biosci. 2017;12:136.
    1. Rompelberg C., Heringa M.B., van Donkersgoed G., Drijvers J., Roos A., Westenbrink S., Peters R., van Bemmel G., Brand W., Oomen A.G. Oral intake of added titanium dioxide and its nanofraction from food products, food supplements and toothpaste by the Dutch population. Nanotoxicology. 2016;10:1404–1414. doi: 10.1080/17435390.2016.1222457.
    1. Forte M., Mita L., Cobellis L., Merafina V., Specchio R., Rossi S., Mita D.G., Mosca L., Castaldi M.A., De Falco M., et al. Triclosan and bisphenol a affect decidualization of human endometrial stromal cells. Mol. Cell. Endocrinol. 2016;422:74–83. doi: 10.1016/j.mce.2015.11.017.
    1. Heringa M.B., Geraets L., van Eijkeren J.C., Vandebriel R.J., de Jong W.H., Oomen A.G. Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations. Nanotoxicology. 2016;10:1515–1525. doi: 10.1080/17435390.2016.1238113.
    1. Karpuzoglu E., Holladay S.D., Gogal R.M., Jr. Parabens: Potential impact of low-affinity estrogen receptor binding chemicals on human health. J. Toxicol. Environ. Health B Crit. Rev. 2013;16:321–335. doi: 10.1080/10937404.2013.809252.
    1. Sälzer S., Rosema N.A., Martin E.C., Slot D.E., Timmer C.J., Dörfer C.E., van der Weijden G.A. The effectiveness of dentifrices without and with sodium lauryl sulfate on plaque, gingivitis and gingival abrasion-a randomized clinical trial. Clin. Oral Investig. 2016;20:443–450. doi: 10.1007/s00784-015-1535-z.
    1. Searls J.C., Berg C.A. The influence of dentifrice detergents on oral epithelial slough. Dent. Hyg. (Chic) 1986;60:20–23.
    1. Serbiak B., Fourre T., Geonnotti A.R., Gambogi R.J. In vitro efficacy of essential oil mouthrinse versus dentifrices. J. Dent. 2018;69:49–54. doi: 10.1016/j.jdent.2017.08.016.
    1. Zijnge V., van Leeuwen M.B., Degener J.E., Abbas F., Thurnheer T., Gmür R., Harmsen H.J. Oral biofilm architecture on natural teeth. PLoS ONE. 2010;5:e9321. doi: 10.1371/journal.pone.0009321.
    1. Haas A.N., Wagner T.P., Muniz F.W.M.G., Fiorini T., Cavagni J., Celeste R.K. Essential oils-containing mouthwashes for gingivitis and plaque: Meta-analysis and meta-regression. J. Dent. 2016;55:7–15. doi: 10.1016/j.jdent.2016.09.001.
    1. Araujo M.W.B., Charles C.A., Weinstein R.B., McGuire J.A., Parikh-Das A.M., Du Q., Zhang J., Berlin J.A., Gunsolley J.C. Meta-analysis of the effect of an essential oil-containing mouthrinse on gingivitis and plaque. J. Am. Dent. Assoc. 2015;146:610–622. doi: 10.1016/j.adaj.2015.02.011.
    1. Da Costa L.F.N.P., Amaral C.D.S.F., Barbirato D.D.S., Leão A.T.T., Fogacci M.F. Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: A meta-analysis. J. Am. Dent. Assoc. 2017;148:308–318. doi: 10.1016/j.adaj.2017.01.021.
    1. Barbosa M., Prada-López I., Álvarez M., Amaral B., de los Angeles C.D., Tomás I. Post-tooth extraction bacteremia: A randomized clinical trial on the efficacy of chlorhexidine prophylaxis. PLoS ONE. 2015;10:e0124249. doi: 10.1371/journal.pone.0124249.
    1. Lynch M.C., Cortelli S.C., McGuire J.A., Zhang J., Ricci-Nittel D., Mordas C.J., Aquino D.R., Cortelli J.R. The effects of essential oil mouthrinses with or without alcohol on plaque and gingivitis: A randomized controlled clinical study. BMC Oral Health. 2018;18:6. doi: 10.1186/s12903-017-0454-6.
    1. Elkerbout T.A., Slot D.E., Bakker E.W., Van der Weijden G.A. Chlorhexidine mouthwash and sodium lauryl sulphate dentifrice: Do they mix effectively or interfere? Int. J. Dent. Hyg. 2016;14:42–52. doi: 10.1111/idh.12125.
    1. Enioutina E.Y., Salis E.R., Job K.M., Gubarev M.I., Krepkova L.V., Sherwin C.M. Herbal Medicines: Challenges in the modern world. Part 5. Status and current directions of complementary and alternative herbal medicine worldwide. Expert Rev. Clin. Pharmacol. 2017;10:327–338. doi: 10.1080/17512433.2017.1268917.
    1. Tartaglia G.M., Kumar S., Fornari C.D., Corti E., Connelly S.T. Mouthwashes in the 21st century: A narrative review about active molecules and effectiveness on the periodontal outcomes. Expert Opin. Drug Deliv. 2017;14:973–982. doi: 10.1080/17425247.2017.1260118.
    1. Mishra R., Tandon S., Rathore M., Banerjee M. Antimicrobial Efficacy of Probiotic and Herbal Oral Rinses against Candida albicans in Children: A Randomized Clinical Trial. Int. J. Clin. Pediatr. Dent. 2016;9:25–30. doi: 10.5005/jp-journals-10005-1328.
    1. Kouidhi B., Al Qurashi Y.M., Chaieb K. Drug resistance of bacterial dental biofilm and the potential use of natural compounds as alternative for prevention and treatment. Microb. Pathog. 2015;80:39–49. doi: 10.1016/j.micpath.2015.02.007.
    1. Varghese J., Tumkur V.K., Ballal V., Bhat G.S. Antimicrobial effect of Anacardium occidentale leaf extract against pathogens causing periodontal disease. Adv. Biosci. Biotechnol. 2013;4:15–18. doi: 10.4236/abb.2013.48A2003.
    1. Palombo E.A. Traditional Medicinal Plant Extracts and Natural Products with Activity against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases. Evid. Based Complement. Altern. Med. 2011;2011:680354. doi: 10.1093/ecam/nep067.
    1. Singh A., Purohit B. Tooth brushing; oil pulling and tissue regeneration: A review of holistic approaches to oral health. J. Ayurveda Integr. Med. 2011;2:64–68. doi: 10.4103/0975-9476.82525.
    1. Karygianni L., Al-Ahmad A., Argyropoulou A., Hellwig E., Anderson A.C., Skaltsounis A.L. Natural Antimicrobials and Oral Microorganisms: A Systematic Review on Herbal Interventions for the Eradication of Multispecies Oral Biofilms. Front. Microbiol. 2016;6:1529. doi: 10.3389/fmicb.2015.01529.
    1. Chandra Shekar B.R., Nagarajappa R., Suma S., Thakur R. Herbal extracts in oral health care—A review of the current scenario and its future needs. Pharmacogn. Rev. 2015;9:87–92. doi: 10.4103/0973-7847.162101.
    1. Bhat S.S., Hegde S.K., Ratheesh M.S. Comparison of Antimicrobial Potential of Various Herbal Dentifrices. Int. J. Dent. Med. Res. 2014;1:41–45.
    1. Jayashankar S., Panagoda G.J., Amaratunga E.A., Perera K., Rajapakse P.S. A randomised double-blind placebo-controlled study on the effects of a herbal toothpaste on gingival bleeding, oral hygiene and microbial variables. Ceylon Med. J. 2011;56:5–9. doi: 10.4038/cmj.v56i1.2887.
    1. Lee S.S., Zhang W., Li Y. The antimicrobial potential of 14 natural herbal dentifrices: Results of an in vitro diffusion method study. J. Am. Dent. Assoc. 2004;135:1133–1141. doi: 10.14219/jada.archive.2004.0372.
    1. Smith C. Pasting the competition. AGD Impact. 1996;24:16.
    1. Carrouel F., Llodra J.C., Viennot S., Santamaria J., Bravo M., Bourgeois D. Access to Interdental Brushing in Periodontal Healthy Young Adults: A Cross-Sectional Study. PLoS ONE. 2016;11:e0155467. doi: 10.1371/journal.pone.0155467.
    1. Bourgeois D., Carrouel F., Llodra J.C., Bravo M., Viennot S. A Colorimetric Interdental Probe as a Standard Method to Evaluate Interdental Efficiency of Interdental Brush. Open Dent. J. 2015;9:431–437. doi: 10.2174/1874210601509010431.
    1. Cugini M., Thompson M., Warren P.R. Correlations between two plaque indices in assessment of toothbrush effectiveness. J. Contemp. Dent. Pract. 2006;7:1–9.
    1. Dubey S.D., Lehnhoff R.W., Radike A.W. A statistical confidence interval for true per cent reduction in caries-incidence studies. J. Dent. Res. 1965;44:921–923. doi: 10.1177/00220345650440052801.
    1. Adams S.E., Arnold D., Murphy B., Carroll P., Green A.K., Smith A.M., Marsh P.D., Chen T., Marriott R.E., Brading M.G. A randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology. Sci. Rep. 2017;7:43344. doi: 10.1038/srep43344.
    1. Bassolé I.H., Juliani H.R. Essential oils in combination and their antimicrobial properties. Molecules. 2012;17:3989–4006. doi: 10.3390/molecules17043989.
    1. Baskaran C., Bai V.R., Velu S., Kumaran K. The efficacy of Carica papaya leaf extract on some bacterial and a fungal strain by well diffusion method. Asian Pac. J. Trop. Dis. 2012;2:S658–S662. doi: 10.1016/S2222-1808(12)60239-4.
    1. Zunjar V., Mammen D., Trivedi B., Daniel M. Pharmacognostic, physicochemical and phytochemical studies on Carica papaya Linn. leaves. Pharmacogn. J. 2011;3:5–8. doi: 10.5530/pj.2011.20.2.
    1. Gogna N., Hamid N., Dorai K. Metabolomic profiling of the phytomedicinal constituents of Carica papaya L. leaves and seeds by 1H NMR spectroscopy and multivariate statistical analysis. J. Pharm. Biomed. Anal. 2015;115:74–85. doi: 10.1016/j.jpba.2015.06.035.
    1. Akhila S., Vijayalakshmi N.G. Phytochemical studies on Carica papaya leaf juice. Int. J. Pharm. Sci. Res. 2015;6:880–883.
    1. Igwe O. Chemical constituents of the leaf essential oil of Carica papaya from sout east Nigeria and its antmicrobial activity. [(accessed on 29 May 2015)];IJRPC. 2015 5:77–83. Available online: .
    1. Chávez-Quintal P., González-Flores T., Rodríguez-Buenfil I., Gallegos-Tintoré S. Antifungal activity in ethanolic extracts of Carica papaya L. cv. maradol leaves and seeds. Indian J. Microbiol. 2011;51:54–60. doi: 10.1007/s12088-011-0086-5.
    1. Zuhrotun N.F., Astuti M., Murdiati A., Mubarika H.S. Anti-proliferation and Apoptosis Induction of Aqueous Leaf Extract of Carica papaya L. on Human Breast Cancer Cells MCF-7. Pakistan J. Biol. Sci. 2017;20:36–41. doi: 10.3923/pjbs.2017.36.41.
    1. Inam A., Shahzad M., Shabbir A., Shahid H., Shahid K., Javeed A. Carica papaya ameliorates allergic asthma via down regulation of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS levels. Phytomedicine. 2017;32:1–7. doi: 10.1016/j.phymed.2017.04.009.
    1. Zhang K., Zuo Y. GC-MS determination of flavonoids and phenolic and benzoic acids in human plasma after consumption of cranberry juice. J. Agric. Food Chem. 2004;52:222–227. doi: 10.1021/jf035073r.
    1. Chen H., Zuo Y., Deng Y. Separation and determination of flavonoids and other phenolic compounds in cranberry juice by high-performance liquid chromatography. J. Chromatogr. A. 2001;913:387–395. doi: 10.1016/S0021-9673(00)01030-X.
    1. Nguyen T.T.T., Shaw P.N., Parat M.O., Hewavitharana A.K. Anticancer activity of Carica papaya: A review. Mol. Nutr. Food Res. 2013;57:153–164. doi: 10.1002/mnfr.201200388.
    1. Fauziya S., Krishnamurthy R. Papaya (Carica papaya): Source material for anticancer. CIBTech J. Pharm. Sci. 2013;2:25–34.
    1. Anjum V., Arora P., Ansari S.H., Najmi A.K., Ahmad S. Antithrombocytopenic and immunomodulatory potential of metabolically characterized aqueous extract of Carica papaya leaves. Pharm. Biol. 2017;55:2043–2056. doi: 10.1080/13880209.2017.1346690.
    1. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr. Res. 2004;24:851–874. doi: 10.1016/j.nutres.2004.07.005.
    1. Li Y., Yao J., Han C., Yang J., Tabassum Chaudhry M., Wang S., Liu H., Yin Y. Quercetin, inflammation and immunity. Nutrients. 2016;8:167. doi: 10.3390/nu8030167.
    1. Parthiban P., Siddha M.D., Clinic K.S.M.S., Road K.M. Analysis of phytochemical constituents and Antimicrobial activity of Carica papaya. Int. J. Adv. Res. Biol. Sci. 2016;3:329–334.
    1. Kuete V., Simo I.K., Ngameni B., Bigoga J.D., Watchueng J., Nzesse Kapguep R., Etoa F.X., Ngadjui Tchaleu B., Penlap Beng V. Antimicrobial activity of the methanolic extract, fractions and four flavonoids from the twigs of Dorstenia angusticornis Engl. (Moraceae) J. Ethnopharmacol. 2007;112:271–277. doi: 10.1016/j.jep.2007.03.008.
    1. Li Z.Y., Wang Y., Shen W.T., Zhou P. Content determination of benzyl glucosinolate and anti-cancer activity of its hydrolysis product in Carica papaya L. Asian Pac. J. Trop. Med. 2012;5:231–233. doi: 10.1016/S1995-7645(12)60030-3.
    1. Otsuki N., Dang N.H., Kumagai E., Kondo A., Iwata S., Morimoto C. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J. Ethnopharmacol. 2010;127:760–767. doi: 10.1016/j.jep.2009.11.024.
    1. Zhang Z.-S., Wang X.-M., Han Z.-P., Zhao M.-X., Yin L. Purification, antioxidant and moisture-preserving activities of polysaccharides from papaya. Carbohydr. Polym. 2012;87:2332–2337. doi: 10.1016/j.carbpol.2011.10.067.
    1. Singh O., Ali M. Phytochemical and antifungal profiles of the seeds of Carica papaya L. Indian J. Pharm. Sci. 2011;73:447–451. doi: 10.4103/0250-474X.95648.
    1. Julianti T., Oufir M., Hamburger M. Quantification of the antiplasmodial alkaloid carpaine in papaya (Carica papaya) leaves. Planta Med. 2014;80:1138–1142. doi: 10.1055/s-0034-1382948.
    1. Kovendan K., Murugan K., Panneerselvam C., Aarthia N., Mahesh Kumar P., Subramaniama J., Amerasan D., Kalimuthu K., Vincent S. Antimalarial activity of Carica papaya (Family: Caricaceae) leaf extract against Plasmodium falciparum. Asian Pac. J. Trop. Dis. 2012;2:S306–S311. doi: 10.1016/S2222-1808(12)60171-6.
    1. Wabo Poné J., Ngankam Ntemah J.D., Bilong Bilong C.F., Mbida M. A comparative study of the ovicidal and larvicidal activities of aqueous and ethanolic extracts of pawpaw seeds Carica papaya (Caricaceae) on Heligmosomoides bakeri. Asian Pac. J. Trop. Med. 2011;4:447–450. doi: 10.1016/S1995-7645(11)60123-5.
    1. Melariri P., Campbell W., Etusim P., Smith P. Antiplasmodial properties and bioassay-guided fractionation of ethyl acetate extracts from Carica papaya leaves. J. Parasitol. Res. 2011;2011:104954. doi: 10.1155/2011/104954.
    1. Ayanfemi A.A., Bukola A.O. Antibacterial Activity of Carica Papaya Leaves and Seeds Extracts on Some Bacteria and their Phytochemical Characterization. Int. J. Bot. Res. 2015;5:15–22.
    1. Akujobi C.N., Ofodeme C.N., Enweani C.A. Determination of antibacterial activity of Carica papaya (pawpaw) extracts. Niger. J. Clin. Pract. 2010;13:55–57.
    1. Vieira R.H.S.D.F., Rodrigues D.D.P., Gonçalves F.A., De Menezes F.G.R., Aragão J.S., Sousa O.V. Microbicidal effect of medicinal plant extracts (Psidium guajava Linn. and Carica papaya Linn.) upon bacteria isolated from fish muscle and known to induce diarrhea in children. Rev. Inst. Med. Trop. Sao Paulo. 2001;43:145–148. doi: 10.1590/S0036-46652001000300005.
    1. Emeruwa A.C. Antibacterial substance from Carica papaya fruit extract. J. Nat. Prod. 1982;45:123–127. doi: 10.1021/np50020a002.
    1. Joseph B., Sankarganesh P., Ichiyama K., Yamamoto N. In vitro study on cytotoxic effect and anti-DENV2 activity of Carica papaya L. leaf. Front. Life Sci. 2014;8:18–22. doi: 10.1080/21553769.2014.924080.
    1. Ahmad N., Fazal H., Ayaz M., Abbasi B.H., Mohammad I., Fazal L. Dengue fever treatment with Carica papaya leaves extracts. Asian Pac. J. Trop. Biomed. 2011;1:330–333. doi: 10.1016/S2221-1691(11)60055-5.
    1. Amazu L., Azikiwe C., Njoku C., Osuala F.N., Nwosu P.J.C., Ajugwo A.O., Enye J.C. Antiinflammatory activity of the methanolic extract of the seeds of Carica papaya in experimental animals. Asian Pac. J. Trop. Med. 2010;3:884–886. doi: 10.1016/S1995-7645(10)60212-X.
    1. Owoyele B.V., Adebukola O.M., Funmilayo A.A., Soladoye A.O. Anti-inflammatory activities of ethanolic extract of Carica papaya leaves. Inflammopharmacology. 2008;16:168–173. doi: 10.1007/s10787-008-7008-0.
    1. Vlachojannis C., Chrubasik-Hausmann S., Hellwig E., Al-Ahmad A. A Preliminary Investigation on the Antimicrobial Activity of Listerine, Its Components, and of Mixtures Thereof. Phytother. Res. 2015;29:1590–1594. doi: 10.1002/ptr.5399.

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