{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:03:01Z","timestamp":1775062981574,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T00:00:00Z","timestamp":1484611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and\/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, \u03b2-pinene, eucalyptol, and limonene) and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol\/\u03b2-pinene\/salicylic acid and eugenol\/\u03b2-pinene\/2-phenoxyethanol\/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC) values. The most active antimicrobial combination represented by salycilic acid\/eugenol\/\u03b2-pinene\/2-phenoxyethanol\/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.<\/jats:p>","DOI":"10.3390\/ijms18010175","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T10:00:47Z","timestamp":1484733647000},"page":"175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Development and Sequential Analysis of a New Multi-Agent, Anti-Acne Formulation Based on Plant-Derived Antimicrobial and Anti-Inflammatory Compounds"],"prefix":"10.3390","volume":"18","author":[{"given":"Crina","family":"Saviuc","sequence":"first","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"},{"name":"S.C. SANIMED INTERNATIONAL IMPEX S.R.L., Sos. Bucuresti-Magurele, nr.70, Sector 5, 051434 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-0267","authenticated-orcid":false,"given":"Bianca","family":"Ciubuc\u0103","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"},{"name":"S.C. SANIMED INTERNATIONAL IMPEX S.R.L., Sos. Bucuresti-Magurele, nr.70, Sector 5, 051434 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Dinc\u0103","sequence":"additional","affiliation":[{"name":"S.C. Biotehnos S.A., Gorunului Str. 3-5, 075100 Otopeni, Ilfov, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-338X","authenticated-orcid":false,"given":"Coralia","family":"Bleotu","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"},{"name":"\u015etefan S. Nicolau Institute of Virology, 285 Mihai Bravu Avenue, Sector 3, 030304 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Drumea","sequence":"additional","affiliation":[{"name":"S.C. Biotehnos S.A., Gorunului Str. 3-5, 075100 Otopeni, Ilfov, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-1857","authenticated-orcid":false,"given":"Mariana-Carmen","family":"Chifiriuc","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gratiela","family":"Pircalabioru","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luminita","family":"Marutescu","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Laz\u0103r","sequence":"additional","affiliation":[{"name":"Department of Botany-Microbiology, Research Institute of the University of Bucharest-ICUB, University of Bucharest, Faculty of Biology, SplaiulIndependen\u0163ei 91-95 Sector 5, 76201 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1089\/acm.2013.0137","article-title":"The clinical impact and cost-effectiveness of essential oils and aromatherapy for the treatment of acne vulgaris: A protocol for a randomized controlled trial","volume":"20","author":"Agnew","year":"2014","journal-title":"J. Altern. Complement. Med."},{"key":"ref_2","first-page":"36","article-title":"Moisturizers for Acne: What are their Constituents?","volume":"7","author":"Chularojanamontri","year":"2014","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_3","first-page":"655","article-title":"The development of antimicrobial resistance due to the antibiotic treatment of acne vulgaris: A review","volume":"9","author":"Patel","year":"2010","journal-title":"J. Drugs Dermatol."},{"key":"ref_4","first-page":"519","article-title":"Trends in the treatment of acne vulgaris: Are measures being taken to avoid antimicrobial resistance?","volume":"95","author":"Kinney","year":"2010","journal-title":"J. Drugs Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1529-8019.2008.00175.x","article-title":"New and emerging treatments in dermatology: Acne","volume":"21","author":"Katsambas","year":"2008","journal-title":"Dermatol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.fitote.2012.03.026","article-title":"A review of phytotherapy of acne vulgaris: Perspective of new pharmacological treatments","volume":"83","author":"Azimi","year":"2012","journal-title":"Fitoterapia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/ptr.5125","article-title":"Botanical and phytochemical therapy of acne: A systematic review","volume":"28","author":"Fisk","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijantimicag.2014.10.011","article-title":"Treatment of acne with tea tree oil (melaleuca) products: A review of efficacy, tolerability and potential modes of action","volume":"45","author":"Hammer","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1467-2494.2006.00308.x","article-title":"Evaluation of in vitro antimicrobial activity of Thai basil oils and their micro-emulsion formulas against Propionibacterium acnes","volume":"28","author":"Viyoch","year":"2006","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"723","DOI":"10.3109\/10717544.2014.903010","article-title":"Development and characterization of a novel antiacne niosomal gel of rosmarinic acid","volume":"22","author":"Budhiraja","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_11","first-page":"125","article-title":"Effectiveness of antimicrobial formulations for acne based on orange (Citrus sinensis) and sweet basil (Ocimum basilicum L) essential oils","volume":"32","author":"Matiz","year":"2012","journal-title":"Biomedica"},{"key":"ref_12","first-page":"30","article-title":"Synergy and its clinical reievance in topical acne therapy","volume":"4","author":"Kircik","year":"2011","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1155\/2014\/301304","article-title":"New perspectives on antiacne plant drugs: Contribution to modern therapeutics","volume":"2014","author":"Sinha","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_14","unstructured":"US Pharmacopeia for Antimicrobial Effectiveness Testing. Available online: http:\/\/www.pharmacopeia.cn\/v29240\/usp29nf24s0_c51.html."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2165\/00128071-200304040-00005","article-title":"Treatment of gram-negative folliculitis in patients with acne","volume":"4","author":"Nehrhoff","year":"2003","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1046\/j.1365-4362.1999.00688.x","article-title":"Bacteriologic and immunologic aspects of gram-negative folliculitis: A study of 46 patients","volume":"38","author":"Neubert","year":"1999","journal-title":"Int. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.jaad.2015.11.025","article-title":"Staphylococcus aureus carriage rates and antibiotic resistance patterns in patients with acne vulgaris","volume":"74","author":"Delost","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1346-8138.2010.01109.x","article-title":"Antibiotic susceptibility of Propionibacterium acnes isolated from acne vulgaris in Korea","volume":"38","author":"Song","year":"2011","journal-title":"J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3892\/etm.2014.1498","article-title":"In vitro anti-MRSA activity of carvone with gentamicin","volume":"7","author":"Mun","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/2049-632X.12033","article-title":"Pseudomonas aeruginosa: New insights into pathogenesis and host defenses","volume":"67","author":"Gellatly","year":"2013","journal-title":"Pathog. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ramos, J.-L., and Filloux, A. (2007). Pseudomonas\u2014A Model System in Biology, Springer.","DOI":"10.1007\/978-1-4020-6097-7"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hauser, A.R., and Rello, J. (2003). Severe Infections Caused by Pseudomonas aeruginosa, Springer Science, Business Media, LLC.","DOI":"10.1007\/978-1-4615-0433-7"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.2174\/1874285801307010072","article-title":"A simple method for assessment of MDR bacteria for over-expressed efflux pumps","volume":"7","author":"Martins","year":"2013","journal-title":"Open Microbiol. J."},{"key":"ref_24","unstructured":"Wu, W.H., Jin, Y.X., Bai, F., and Jin, S.G. (2015). Molecular Medical Microbiology, Elsevier."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fmicb.2011.00155","article-title":"Protein secretion systems in Pseudomonas aeruginosa: An essay on diversity, evolution, and function","volume":"2","author":"Filloux","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_26","unstructured":"(2005). European Pharmacopoeia 5.0, Council of Europe."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14651","DOI":"10.3390\/molecules181214651","article-title":"Anti- and pro-lipase activity of selected medicinal, herbal and aquatic plants, and structure elucidation of an anti-lipase compound","volume":"18","author":"Ado","year":"2013","journal-title":"Molecules"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.intimp.2015.03.026","article-title":"Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status","volume":"26","author":"Huang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","unstructured":"Cheryll, W. (2010). Medicinal Plants in Australia, Rosenberg Publishing."},{"key":"ref_30","unstructured":"Raja, K.S., Jared, R., Jagdeo, P.E., and Howard, I.M. (2015). Cosmeceuticals and Active Cosmetics, Taylor and Francis. [3rd ed.]."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Singh, S., Das, S.S., Singh, G., Schuff, C., de Lampasona, M.P., and Catal\u00e1n, C.A.N. (2014). Composition, in vitro antioxidant and antimicrobial activities of essential oil and oleoresins obtained from black cumin seeds (Nigella sativa L.). BioMed Res. 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