{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:17:20Z","timestamp":1790648240677,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    This study explores the antimicrobial activity of three principal bioactive constituents of\n                    <jats:italic>Crocus sativus<\/jats:italic>\n                    L.\u2014safranal, crocin, and crocetin\u2014using a simplex-centroid mixture design to evaluate their individual and synergistic effects. Twelve formulations were tested against\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ,\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , and\n                    <jats:italic>Geotrichum candidum<\/jats:italic>\n                    . Minimum inhibitory concentrations (MICs) were determined via microdilution assays, and the results were fitted using special cubic regression models. The models exhibited strong predictive accuracy (R\n                    <jats:sup>2<\/jats:sup>\n                    = 0.97\u20130.99). Safranal showed the highest individual activity against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    (\u03c3\n                    <jats:sub>1<\/jats:sub>\n                    = 169.77,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0053), while crocin exerted the strongest effect on\n                    <jats:italic>E. coli<\/jats:italic>\n                    (\u03c3\n                    <jats:sub>2<\/jats:sub>\n                    = 166.63,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.0001). Significant synergistic interactions were observed between crocin and crocetin for both bacterial strains (\u03c3\n                    <jats:sub>23<\/jats:sub>\n                    = \u2212290.34 for\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ; \u2212170.28 for\n                    <jats:italic>E. coli<\/jats:italic>\n                    ). Ternary mixtures displayed superior efficacy compared to single compounds, producing the lowest MIC values across all pathogens. The optimal antibacterial formulation\u201433.31% safranal, 33.29% crocin, and 33.39% crocetin\u2014yielded MICs of 41.14%\n                    <jats:italic>(v\/v)<\/jats:italic>\n                    (predicted) and 39.5% \u00b1 0.75%\n                    <jats:italic>(v\/v)<\/jats:italic>\n                    (experimental) against\n                    <jats:italic>E. coli<\/jats:italic>\n                    . Against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , a blend of 27% safranal, 33% crocin, and 38% crocetin resulted in a predicted MIC of 42.15%\n                    <jats:italic>(v\/v)<\/jats:italic>\n                    , confirmed experimentally at 38.13% \u00b1 1.33%\n                    <jats:italic>(v\/v)<\/jats:italic>\n                    . For\n                    <jats:italic>G. candidum<\/jats:italic>\n                    , the optimized mixture reached MIC values of 9.13%\n                    <jats:italic>(v\/v)<\/jats:italic>\n                    (predicted) and 10.24% \u00b1 2.05%\n                    <jats:italic>(v\/v)<\/jats:italic>\n                    (observed). These findings demonstrate that synergistic combinations of saffron-derived metabolites markedly enhance antimicrobial potency. Moreover, mixture design modeling emerges as an effective predictive and optimization strategy for developing reproducible, plant-based antimicrobial formulations targeting antibiotic resistance.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1734075","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:33:43Z","timestamp":1770989623000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Promising synergistic interactions and mixture optimization of safranal, crocin, and crocetin from Moroccan Crocus sativus L. with enhanced antimicrobial activity"],"prefix":"10.3389","volume":"17","author":[{"given":"Abdellah","family":"Baraich","sequence":"first","affiliation":[{"name":"Laboratoire de Bioressources, Biotechnologie, Ethnopharmacologie et Sant\u00e9 (LBBES), Facult\u00e9 des Sciences d\u2019Oujda (FSO), Universit\u00e9 Mohammed Premier (UMP)","place":["Oujda, 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Biotechnologie, Ethnopharmacologie et Sant\u00e9 (LBBES), Facult\u00e9 des Sciences d\u2019Oujda (FSO), Universit\u00e9 Mohammed Premier (UMP)","place":["Oujda, Morocco"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer M.","family":"Almarfadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi A.","family":"Mothana","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed F.","family":"Hawwal","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University","place":["Riyadh, Saudi 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