{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:40:31Z","timestamp":1781638831598,"version":"3.54.5"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Streptococcus mutans (S. mutans) is the main cariogenic bacterium with acidophilic properties, in part due to its acid-producing and -resistant properties. As a result of this activity, hard tooth structures may demineralize and form caries. Trans-cinnamaldehyde (TC) is a phytochemical from the cinnamon plant that has established antibacterial properties for Gram-positive and -negative bacteria. This research sought to assess the antibacterial and antibiofilm effects of trans-cinnamaldehyde on S. mutans. TC was diluted to a concentration range of 156.25\u20135000 \u03bcg\/mL in dimethyl sulfoxide (DMSO) 0.03\u20131%, an organic solvent. Antibacterial activity was monitored by testing the range of TC concentrations on 24 h planktonic growth compared with untreated S. mutans. The subminimal bactericidal concentrations (MBCs) were used to evaluate the bacterial distribution and morphology in the biofilms. Our in vitro data established a TC MBC of 2500 \u03bcg\/mL against planktonic S. mutans using a microplate spectrophotometer. Furthermore, the DMSO-only controls showed no antibacterial effect against planktonic S. mutans. Next, the sub-MBC doses exhibited antibiofilm action at TC doses of \u2265625 \u03bcg\/mL on hydroxyapatite discs, as demonstrated through biofilm analysis using spinning-disk confocal microscopy (SDCM) and high-resolution scanning electron microscopy (HR-SEM). Our findings show that TC possesses potent antibacterial and antibiofilm properties against S. mutans. Our data insinuate that the most effective sub-MBC of TC to bestow these activities is 625 \u03bcg\/mL.<\/jats:p>","DOI":"10.3390\/pharmaceutics16010113","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T11:15:01Z","timestamp":1705317301000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Trans-Cinnamaldehyde\u2014Fighting Streptococcus mutans Using Nature"],"prefix":"10.3390","volume":"16","author":[{"given":"Zilefac Brian","family":"Ngokwe","sequence":"first","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"},{"name":"The Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0062-1400","authenticated-orcid":false,"given":"Amit","family":"Wolfoviz-Zilberman","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esi","family":"Sharon","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher","family":"Zabrovsky","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurit","family":"Beyth","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Houri-Haddad","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Kesler-Shvero","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Medical Center, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial biofilms: From the natural environment to infectious diseases","volume":"2","author":"Costerton","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10096-013-1993-7","article-title":"The virulence of Streptococcus mutans and the ability to form biofilms","volume":"33","author":"Jurczak","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1128\/IAI.00422-08","article-title":"Characteristics of biofilm formation by Streptococcus mutans in the presence of saliva","volume":"76","author":"Ahn","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"440","DOI":"10.6026\/97320630005440","article-title":"A proteomic approach for exploring biofilm in Streptococcus mutans","volume":"5","author":"Khan","year":"2011","journal-title":"Bioinformation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wen, Z.T., Yates, D., Ahn, S.J., and Burne, R.A. (2010). Biofilm formation and virulence expression by Streptococcus mutans are altered when grown in dual-species model. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-111"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lemos, J.A., Palmer, S.R., Zeng, L., Wen, Z.T., Kajfasz, J.K., Freires, I.A., Abranches, J., and Brady, L.J. (2019). The Biology of Streptococcus mutans. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.GPP3-0051-2018"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Aqawi, M., Sionov, R.V., Gallily, R., Friedman, M., and Steinberg, D. (2021). Anti-Biofilm Activity of Cannabigerol against. Microorganisms, 9.","DOI":"10.3390\/microorganisms9102031"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"de Sousa, D.L., Lima, R.A., Zanin, I.C., Klein, M.I., Janal, M.N., and Duarte, S. (2015). Effect of Twice-Daily Blue Light Treatment on Matrix-Rich Biofilm Development. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131941"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1128\/JB.01649-09","article-title":"Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms","volume":"192","author":"Koo","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jdsr.2017.08.002","article-title":"Role of Streptococcus mutans surface proteins for biofilm formation","volume":"54","year":"2018","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/prd.12361","article-title":"The dental plaque biofilm matrix","volume":"86","author":"Jakubovics","year":"2021","journal-title":"Periodontology 2000"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4315\/0362-028X.JFP-10-296","article-title":"Effect of trans-cinnamaldehyde on inhibition and inactivation of Cronobacter sakazakii biofilm on abiotic surfaces","volume":"74","author":"Amalaradjou","year":"2011","journal-title":"J. Food Prot."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yanakiev, S. (2020). Effects of Cinnamon. Molecules, 25.","DOI":"10.3390\/molecules25184184"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"He, Z., Huang, Z., Jiang, W., and Zhou, W. (2019). Antimicrobial Activity of Cinnamaldehyde on. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02241"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1080\/19440049.2017.1419287","article-title":"Selected plant essential oils and their main active components, a promising approach to inhibit aflatoxigenic fungi and aflatoxin production in food","volume":"35","author":"Tarazona","year":"2018","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/08923973.2018.1424902","article-title":"Anti-inflammatory effects of trans-cinnamaldehyde on lipopolysaccharide-stimulated macrophage activation via MAPKs pathway regulation","volume":"40","author":"Kim","year":"2018","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9177108","DOI":"10.1155\/2022\/9177108","article-title":"The Therapeutic Roles of Cinnamaldehyde against Cardiovascular Diseases","volume":"2022","author":"Lu","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Usai, F., and Di Sotto, A. (2023). Cinnamaldehyde as a Novel Candidate to Overcome Bacterial Resistance: An Overview of In Vitro Studies. Antibiotics, 12.","DOI":"10.3390\/antibiotics12020254"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.micpath.2018.04.036","article-title":"Antibacterial mechanisms of cinnamon and its constituents: A review","volume":"120","author":"Vasconcelos","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19124","DOI":"10.1039\/C9RA10820C","article-title":"Characteristics and hazards of the cinnamaldehyde oxidation process","volume":"10","author":"Yu","year":"2020","journal-title":"RSC Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104405","DOI":"10.1016\/j.fitote.2019.104405","article-title":"A review of cinnamaldehyde and its derivatives as antibacterial agents","volume":"139","author":"Doyle","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mu, R., Zhang, H., Zhang, Z., Li, X., Ji, J., Wang, X., Gu, Y., and Qin, X. (2023). Trans-cinnamaldehyde loaded chitosan based nanocapsules display antibacterial and antibiofilm effects against cavity-causing. J. Oral Microbiol., 15.","DOI":"10.1080\/20002297.2023.2243067"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9162","DOI":"10.1021\/acs.chemrev.6b00184","article-title":"Plant Natural Products Targeting Bacterial Virulence Factors","volume":"116","author":"Silva","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1074\/jbc.M114.597906","article-title":"Salivary mucin 19 glycoproteins: Innate immune functions in Streptococcus mutans-induced caries in mice and evidence for expression in human saliva","volume":"290","author":"Culp","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dresser, A.R., Hardy, P.O., and Chaconas, G. (2009). Investigation of the genes involved in antigenic switching at the vlsE locus in Borrelia burgdorferi: An essential role for the RuvAB branch migrase. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000680"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11546","DOI":"10.1038\/s41598-021-91064-y","article-title":"Pure hydroxyapatite synthesis originating from amorphous calcium carbonate","volume":"11","author":"Sawada","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/jam.14794","article-title":"Combinatorial effects of trans-cinnamaldehyde with fluoride and chlorhexidine on Streptococcus mutans","volume":"130","author":"Balasubramanian","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/DER.0000000000000112","article-title":"Cinnamon spice and everything not nice: Many features of intraoral allergy to cinnamic aldehyde","volume":"26","author":"Li","year":"2015","journal-title":"Dermatitis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/cod.14290","article-title":"Cinnamon allergic contact cheilitis","volume":"88","author":"Bernaola","year":"2023","journal-title":"Contact Dermatitis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/DER.0000000000000255","article-title":"Contact Allergy to (Ingredients of) Toothpastes","volume":"28","year":"2017","journal-title":"Dermatitis"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/1\/113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:29Z","timestamp":1760104049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/1\/113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["pharmaceutics16010113"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16010113","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]}}}