{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:44:34Z","timestamp":1790948674773,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Red onion wastes (ROW) are valuable sources of bioactive metabolites with promising antimicrobial effects. Methicillin-resistant Staphylococcus aureus (MRSA) infections are a growing risk in hospitals and communities. This study aims to investigate the in vitro and in vivo antibiofilm activities of the acidified ethanolic extract of red onion scales (RO-T) and its fractions against an MRSA vaginal colonization model. The RO-T extract, as well as its anthocyanin-rich fraction (RO-P) and flavonoid-rich fraction (RO-S), recorded a promising antibacterial activity against highly virulent strains of bacteria (MRSA, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa). RO-S showed the highest antibacterial activity (MBC of 0.33 \u00b1 0.11 mg\/mL) against MRSA USA300 and significantly eradicated its biofilm formation with an IC50 of 0.003. Using a rat model, in vivo assessment on all samples, which were formulated as a hydrogel, revealed a significant reduction of MRSA bacterial load recovered from an infected vagina compared to that of the negative control group (NCG). RO-T extract and vancomycin groups recorded the highest antibacterial activity with a bacterial load 2.998 and 3.358 logs lower than the NCG, respectively. The histopathological investigation confirmed our findings. RO-T and RO-S were standardized for their quercetin content. Finally, ROW offers a new potent antibiofilm agent mostly due to its high quercetin content.<\/jats:p>","DOI":"10.3390\/molecules28010355","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:08:59Z","timestamp":1672628939000},"page":"355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["In Vitro and In Vivo Antibiofilm Activity of Red Onion Scales: An Agro-Food Waste"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6170-6301","authenticated-orcid":false,"given":"Nermeen B.","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3179-3352","authenticated-orcid":false,"given":"Riham A.","family":"El-Shiekh","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4277-2693","authenticated-orcid":false,"given":"Rehab M.","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabah H.","family":"El-Gayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, 6th October University, Cairo 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0617-1420","authenticated-orcid":false,"given":"Essam","family":"Abdel-Sattar","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-9827","authenticated-orcid":false,"given":"Mariam","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala City, Suez 43511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,1]]},"reference":[{"key":"ref_1","first-page":"435","article-title":"Antioxidant, radical scavenging and antimicrobial activities of red onion (Allium cepa L.) skin and edible part extracts","volume":"23","author":"Bezjak","year":"2009","journal-title":"Chem. Biochem. Eng. Q."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112327","DOI":"10.1016\/j.fct.2021.112327","article-title":"Spiraeoside extracted from red onion skin ameliorates apoptosis and exerts potent antitumor, antioxidant and enzyme inhibitory effects","volume":"154","author":"Nile","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pagano, C., Marinozzi, M., Baiocchi, C., Beccari, T., Calarco, P., Ceccarini, M.R., Chielli, M., Orabona, C., Orecchini, E., and Ortenzi, R. (2020). Bioadhesive polymeric films based on red onion skins extract for wound treatment: An innovative and eco-friendly formulation. Molecules, 25.","DOI":"10.3390\/molecules25020318"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fredotovi\u0107, \u017d., Puizina, J., Nazli\u0107, M., Maravi\u0107, A., Ljubenkov, I., Soldo, B., Vuko, E., and Baji\u0107, D. (2021). Phytochemical characterization and screening of antioxidant, antimicrobial and antiproliferative properties of Allium\u00d7 cornutum clementi and two varieties of Allium cepa L. peel extracts. Plants, 10.","DOI":"10.3390\/plants10050832"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e05478","DOI":"10.1016\/j.heliyon.2020.e05478","article-title":"Antimicrobial assessment of polyphenolic extracts from onion (Allium cepa L.) skin of fifteen cultivars by sonication-assisted extraction method","volume":"6","author":"Sagar","year":"2020","journal-title":"Heliyon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11274-019-2719-5","article-title":"An overview on anti-biofilm properties of quercetin against bacterial pathogens","volume":"35","author":"Memariani","year":"2019","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13756-021-00897-9","article-title":"Vaginal colonization with antimicrobial-resistant bacteria among women in labor in central Uganda: Prevalence and associated factors","volume":"10","author":"Tumuhamye","year":"2021","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_8","first-page":"4953","article-title":"Inhibition of methicillin resistant Staphylococcus aureus (MRSA) with underutilized medicinal plants extracts","volume":"28","author":"Coolborn","year":"2021","journal-title":"J Int Med Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113895","DOI":"10.1016\/j.jep.2021.113895","article-title":"Ginkgo biloba exocarp extracts inhibit S. aureus and MRSA by disrupting biofilms and affecting gene expression","volume":"271","author":"Wang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","first-page":"49","article-title":"Phytochemical composition, antimicrobial and cytotoxic activities of red onion peel extracts prepared using different methods","volume":"15","author":"Chiew","year":"2014","journal-title":"Int. J. Integr. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"631058","DOI":"10.3389\/fmicb.2021.631058","article-title":"Quercetin inhibits biofilm formation by decreasing the production of EPS and altering the composition of EPS in Staphylococcus epidermidis","volume":"12","author":"Mu","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_12","first-page":"266213","article-title":"Antibacterial and antibiofilm activities of quercetin against clinical isolates of Staphyloccocus aureus and Staphylococcus saprophyticus with resistance profile","volume":"3","author":"Pereira","year":"2018","journal-title":"Int. J. Environ. Agric. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1007\/s13197-020-04277-w","article-title":"Quantification of flavonoids, total phenols and antioxidant properties of onion skin: A comparative study of fifteen Indian cultivars","volume":"57","author":"Sagar","year":"2020","journal-title":"J. Food Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.postharvbio.2009.05.005","article-title":"Effect of curing at different temperatures on biochemical composition of onion (Allium cepa L.) skin from three freshly cured and cold stored UK-grown onion cultivars","volume":"54","author":"Downes","year":"2009","journal-title":"Postharvest Biol. Technol."},{"key":"ref_15","first-page":"48","article-title":"Study of bioactive compound content in different onion sections","volume":"66","author":"Downes","year":"2011","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nguyen, T.L.A., and Bhattacharya, D. (2022). Antimicrobial Activity of Quercetin: An Approach to Its Mechanistic Principle. Molecules, 27.","DOI":"10.3390\/molecules27082494"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sousa, L.G., Castro, J., and Cerca, N. (2020). The Utilization of Essential Oils to Treat Biofilm-Associated Vaginal Infections. Microbial Biofilms, CRC Press.","DOI":"10.1201\/9780367415075-23"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1021\/jf051264d","article-title":"Antioxidative compounds from the outer scales of onion","volume":"53","author":"Ly","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.fct.2009.02.004","article-title":"Polyphenolics from various extracts\/fractions of red onion (Allium cepa) peel with potent antioxidant and antimutagenic activities","volume":"47","author":"Singh","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.diabres.2018.03.042","article-title":"Red onion scales ameliorated streptozotocin-induced diabetes and diabetic nephropathy in Wistar rats in relation to their metabolite fingerprint","volume":"140","author":"Abouzed","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Roy, P.K., Song, M.G., and Park, S.Y. (2022). The inhibitory effect of quercetin on biofilm formation of Listeria monocytogenes mixed culture and repression of virulence. Antioxidants, 11.","DOI":"10.3390\/antiox11091733"},{"key":"ref_22","first-page":"1","article-title":"Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids","volume":"10","author":"Gil","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Roy, P.K., Park, S.-H., Song, M.G., and Park, S.Y. (2022). Antimicrobial Efficacy of Quercetin against Vibrio parahaemolyticus biofilm on food surfaces and downregulation of virulence genes. Polymers, 14.","DOI":"10.3390\/polym14183847"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.foodchem.2007.09.053","article-title":"Flavonol glucosides in Allium species: A comparative study by means of HPLC\u2013DAD\u2013ESI-MS\u2013MS","volume":"107","author":"Bonaccorsi","year":"2008","journal-title":"Food Chem."},{"key":"ref_25","first-page":"1934578X1501000120","article-title":"Anthocyanins of Hibiscus sabdiffera calyces from Sudan","volume":"10","author":"Ali","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sedeek, M.S., Afifi, S.M., Mansour, M.K., Hassan, M., Mehaya, F.M., Naguib, I.A., Abourehab, M.A.S., and Farag, M.A. (2022). Unveiling Antimicrobial and Antioxidant Compositional Differences between Dukkah and Za&rsquo;atar via SPME-GCMS and HPLC-DAD. Molecules, 27.","DOI":"10.3390\/molecules27196471"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114021","DOI":"10.1016\/j.ejmech.2021.114021","article-title":"Design and synthesis of ciprofloxacin-sulfonamide hybrids to manipulate ciprofloxacin pharmacological qualities: Potency and side effects","volume":"228","author":"Ibrahim","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ismail, M.M., Hassan, M., Moawad, S.S., Okba, M.M., Ashour, R.M., Fayek, N.M., and Saber, F.R. (2021). Exploring the Antivirulence Activity of Pulverulentone A, a Phloroglucinol-Derivative from Callistemon citrinus Leaf Extract, against Multi-Drug Resistant Pseudomonas aeruginosa. Antibiotics, 10.","DOI":"10.3390\/antibiotics10080907"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"El-Shiekh, R.A., Hassan, M., Hashem, R.A., and Abdel-Sattar, E. (2021). Bioguided Isolation of Antibiofilm and Antibacterial Pregnane Glycosides from Caralluma quadrangula: Disarming Multidrug-Resistant Pathogens. Antibiotics, 10.","DOI":"10.3390\/antibiotics10070811"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e01934-17","DOI":"10.1128\/JCM.01934-17","article-title":"CLSI Methods Development and Standardization Working Group Best Practices for Evaluation of Antimicrobial Susceptibility Tests","volume":"56","author":"Humphries","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2147\/IDR.S285940","article-title":"In vivo Antibacterial Activity of Star Anise (Illicium verum Hook.) Extract Using Murine MRSA Skin Infection Model in Relation to Its Metabolite Profile","volume":"14","author":"Salem","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5247","DOI":"10.2147\/IJN.S316326","article-title":"Tailoring Terpesomes and Leciplex for the Effective Ocular Conveyance of Moxifloxacin Hydrochloride (Comparative Assessment): In-vitro, Ex-vivo, and In-vivo Evaluation","volume":"16","author":"Albash","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s40005-019-00427-1","article-title":"Development and investigation of timolol maleate niosomal formulations for the treatment of glaucoma","volume":"50","author":"Ramadan","year":"2020","journal-title":"J. Pharm. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e02321-19","DOI":"10.1128\/mBio.02321-19","article-title":"Identification of Key Determinants of Staphylococcus aureus Vaginal Colonization","volume":"10","author":"Deng","year":"2019","journal-title":"mBio"},{"key":"ref_35","first-page":"e54708","article-title":"A Murine Model of Group B Streptococcus Vaginal Colonization","volume":"117","year":"2016","journal-title":"JoVE"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/1\/355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:55:38Z","timestamp":1760118938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/1\/355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["molecules28010355"],"URL":"https:\/\/doi.org\/10.3390\/molecules28010355","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,1]]}}}