{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:03:56Z","timestamp":1784880236528,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1600300"],"award-info":[{"award-number":["2022YFD1600300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Patchouli alcohol, a natural tricyclic sesquiterpene isolated from Pogostemon cablin, exhibits promising antimicrobial properties, yet its activity against Streptococcus mutans (S. mutans), a major cariogenic bacterium associated with dental caries, has not been characterized. This study determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of patchouli alcohol against S. mutans to be 40 and 80 \u03bcg\/mL, respectively. A series of phenotypic assays showed that patchouli alcohol delayed bacterial growth and culture acidification, reduced extracellular polysaccharide production, and decreased the biomass and metabolic activity of established S. mutans biofilms. Scanning electron microscopy showed treatment-associated changes in the surface morphology of S. mutans, with more evident deformation at MIC and 2MIC. Real-time quantitative PCR showed that sub-MIC treatment (20 \u03bcg\/mL) significantly downregulated virulence genes associated with adhesion (gbpB and spaP), EPS synthesis (gtfB, gtfC, gtfD, and ftf), acid production (ldh, atpF, and atpD), and the two-component regulatory and quorum sensing systems (vicK, vicR, and luxS). These results suggest that patchouli alcohol may serve as a potential natural anti-cariogenic candidate targeting S. mutans-associated virulence traits under in vitro conditions.<\/jats:p>","DOI":"10.3390\/molecules31152577","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"2577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patchouli Alcohol as a Potential Anti-Cariogenic Compound Targeting Streptococcus mutans"],"prefix":"10.3390","volume":"31","author":[{"given":"Qianying","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-4841","authenticated-orcid":false,"given":"Chong","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3384-2365","authenticated-orcid":false,"given":"Zhimin","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Depo","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Accuramed Technology (Guangzhou) Limited, Guangzhou 510700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/sj.bdj.2012.260","article-title":"Post-brushing rinsing for the control of dental caries: Exploration of the available evidence to establish what advice we should give our patients","volume":"212","author":"Pitts","year":"2012","journal-title":"Br. Dent. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.tim.2014.10.010","article-title":"Solving the etiology of dental caries","volume":"23","author":"Mira","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"GPP3-0051-2018","DOI":"10.1128\/microbiolspec.GPP3-0051-2018","article-title":"The biology of Streptococcus mutans","volume":"7","author":"Lemos","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00897-19","DOI":"10.1128\/IAI.00897-19","article-title":"Contribution of severe dental caries induced by Streptococcus mutans to the pathogenicity of infective endocarditis","volume":"88","author":"Nomura","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Klein, M.I., Hwang, G., Santos, P.H.S., Campanella, O.H., and Koo, H. (2015). Streptococcus mutans-derived extracellular matrix in cariogenic oral biofilms. Front. Cell. Infect. Microbiol., 5.","DOI":"10.3389\/fcimb.2015.00010"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9546","DOI":"10.1038\/s41598-020-66412-z","article-title":"Influence of the long-term use of oral hygiene products containing stannous ions on the salivary microbiome\u2014A randomized controlled trial","volume":"10","author":"Anderson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4103\/jehp.jehp_1297_22","article-title":"A systematic review of medicinal plants and herbal products\u2019 effectiveness in oral health and dental cure with health promotion approach","volume":"12","author":"Amanpour","year":"2023","journal-title":"J. Educ. Health Promot."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105655","DOI":"10.1016\/j.archoralbio.2023.105655","article-title":"Identification of the antibacterial action mechanism of curcumin on Streptococcus mutans through transcriptome profiling","volume":"149","author":"Ke","year":"2023","journal-title":"Arch. Oral Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1080\/08927014.2022.2116320","article-title":"Effects of the green tea catechin epigallocatechin-3-gallate on Streptococcus mutans planktonic cultures and biofilms: Systematic literature review of in vitro studies","volume":"38","author":"Aragao","year":"2022","journal-title":"Biofouling"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1080\/08927014.2013.794456","article-title":"The specific degree-of-polymerization of A-type proanthocyanidin oligomers impacts Streptococcus mutans glucan-mediated adhesion and transcriptome responses within biofilms","volume":"29","author":"Feng","year":"2013","journal-title":"Biofouling"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107056","DOI":"10.1016\/j.intimp.2020.107056","article-title":"Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review","volume":"89","author":"Lee","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104929","DOI":"10.1016\/j.phrs.2020.104929","article-title":"A review of therapeutic agents and Chinese herbal medicines against SARS-CoV-2 (COVID-19)","volume":"158","author":"Huang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_13","first-page":"307","article-title":"Evaluation of the antibacterial activity of patchouli oil","volume":"12","author":"Yang","year":"2013","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.intimp.2018.12.044","article-title":"Effect of patchouli alcohol on Helicobacter pylori-induced neutrophil recruitment and activation","volume":"68","author":"Ren","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, S.W., Zhang, T.T., Li, Z.J., Wang, Y., Liu, L., and Song, Z.B. (2023). Antibacterial mechanism of areca nut essential oils against Streptococcus mutans by targeting the biofilm and the cell membrane. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1140689"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bloch, S., Hager-Mair, F.F., Andrukhov, O., and Sch\u00e4ffer, C. (2024). Oral streptococci: Modulators of health and disease. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1357631"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41368-022-00167-3","article-title":"Expert consensus on dental caries management","volume":"14","author":"Cheng","year":"2022","journal-title":"Int. J. Oral Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.4103\/ijdr.ijdr_404_21","article-title":"Comparative effectiveness of herbal and conventional toothpaste on prevention of dental caries: Systematic review and meta-analysis","volume":"33","author":"Kengadaran","year":"2022","journal-title":"Indian J. Dent. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11655-016-2452-y","article-title":"In vitro and in vivo antibacterial activity of patchouli alcohol from Pogostemon cablin","volume":"27","author":"Wan","year":"2021","journal-title":"Chin. J. Integr. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1128\/IAI.73.4.2245-2252.2005","article-title":"Fluid- or surface-phase human salivary scavenger protein gp340 exposes different bacterial recognition properties","volume":"73","author":"Loimaranta","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1574-6968.1997.tb12608.x","article-title":"The N-terminal half part of the oral streptococcal antigen I\/IIf contains two distinct binding domains","volume":"153","author":"Sciotti","year":"1997","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_22","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":"Krzysciak","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1348-0421.2003.tb03389.x","article-title":"The role of glucan-binding proteins in the cariogenicity of Streptococcus mutans","volume":"47","author":"Matsumura","year":"2003","journal-title":"Microbiol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1399-302X.2007.00351.x","article-title":"Biological functions of glucan-binding protein B of Streptococcus mutans","volume":"22","author":"Fujita","year":"2007","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/iai.53.3.587-594.1986","article-title":"Cloning of a Streptococcus mutans glucosyltransferase gene coding for insoluble glucan synthesis","volume":"53","author":"Aoki","year":"1986","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000324598","article-title":"Biology of Streptococcus mutans-derived glucosyltransferases: Role in extracellular matrix formation of cariogenic biofilms","volume":"45","author":"Bowen","year":"2011","journal-title":"Caries Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1128\/MMBR.70.1.157-176.2006","article-title":"Structure-function relationships of glucansucrase and fructansucrase enzymes from lactic acid bacteria","volume":"70","author":"Kralj","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1128\/iai.56.8.1999-2005.1988","article-title":"Isolation and characterization of the Streptococcus mutans gtfC gene, coding for synthesis of both soluble and insoluble glucans","volume":"56","author":"Hanada","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1128\/iai.57.7.2079-2085.1989","article-title":"Isolation and characterization of the Streptococcus mutans gtfD gene, coding for primer-dependent soluble glucan synthesis","volume":"57","author":"Hanada","year":"1989","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1128\/jb.170.2.810-816.1988","article-title":"Sequence analysis of the Streptococcus mutans fructosyltransferase gene and flanking regions","volume":"170","author":"Shiroza","year":"1988","journal-title":"J. Bacteriol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0003-9969(79)90175-4","article-title":"Structure of extracellular water-soluble polysaccharides synthesized from sucrose by oral strains of Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis and Actinomyces viscosus","volume":"24","author":"Birkhed","year":"1979","journal-title":"Arch. Oral Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1177\/00220345960750080801","article-title":"Cariogenicity of Streptococcus mutans strains with defects in fructan metabolism assessed in a program-fed specific-pathogen-free rat model","volume":"75","author":"Burne","year":"1996","journal-title":"J. Dent. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1128\/JB.181.9.2863-2871.1999","article-title":"Regulation of expression of the fructan hydrolase gene of Streptococcus mutans GS-5 by induction and carbon catabolite repression","volume":"181","author":"Burne","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1574-6968.2001.tb10522.x","article-title":"The role of fructans on dental biofilm formation by Streptococcus sobrinus, Streptococcus mutans, Streptococcus gordonii and Actinomyces viscosus","volume":"195","author":"Rozen","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.11620\/IJOB.2019.44.2.31","article-title":"Virulence genes of Streptococcus mutans and dental caries","volume":"44","author":"You","year":"2019","journal-title":"Int. J. Oral Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1099\/mic.0.26888-0","article-title":"Proteome analysis of Streptococcus mutans metabolic phenotype during acid tolerance","volume":"150","author":"Len","year":"2004","journal-title":"Microbiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1099\/mic.0.2008\/023770-0","article-title":"A model of efficiency: Stress tolerance by Streptococcus mutans","volume":"154","author":"Lemos","year":"2008","journal-title":"Microbiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1128\/AAC.01016-10","article-title":"The tea catechin epigallocatechin gallate suppresses cariogenic virulence factors of Streptococcus mutans","volume":"55","author":"Xu","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.mib.2006.01.005","article-title":"Regulation of bacterial virulence by two-component systems","volume":"9","author":"Beier","year":"2006","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.21775\/cimb.032.167","article-title":"The VicRK two-component system regulates Streptococcus mutans virulence","volume":"32","author":"Lei","year":"2019","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Stipp, R.N., Boisvert, H., Smith, D.J., H\u00f6fling, J.F., Duncan, M.J., and Mattos-Graner, R.O. (2013). CovR and VicRK regulate cell surface biogenesis genes required for biofilm formation in Streptococcus mutans. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058271"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1128\/JB.00793-09","article-title":"Inactivation of VicK affects acid production and acid survival of Streptococcus mutans","volume":"191","author":"Senadheera","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1177\/0022034520979798","article-title":"Dissecting the role of VicK phosphatase in aggregation and biofilm formation of Streptococcus mutans","volume":"100","author":"Wang","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-3-540-75418-3_4","article-title":"Quorum sensing and microbial biofilms","volume":"Volume 322","author":"Romeo","year":"2008","journal-title":"Bacterial Biofilms"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1039\/b702781h","article-title":"Interspecies and interkingdom communication mediated by bacterial quorum sensing","volume":"37","author":"Lowery","year":"2008","journal-title":"Chem. Soc. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1128\/AEM.71.5.2372-2380.2005","article-title":"LuxS-based signaling affects Streptococcus mutans biofilm formation","volume":"71","author":"Yoshida","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s00284-013-0403-9","article-title":"Screening of Actinobacillus pleuropneumoniae LuxS inhibitors","volume":"67","author":"Li","year":"2013","journal-title":"Curr. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/15\/2577\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:42Z","timestamp":1784878602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/15\/2577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":47,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["molecules31152577"],"URL":"https:\/\/doi.org\/10.3390\/molecules31152577","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}