{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:30:43Z","timestamp":1785724243922,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Oils from medicinal plants, including thyme (Thymus vulgaris), cinnamon (Cinnamomum verum), and black seed (Nigella sativa), are recognized for their antibacterial and antioxidant properties. While several studies have investigated individual oils and binary combinations, fewer reports have examined ternary mixtures using systematic optimization approaches. Accordingly, the present study aimed to optimize the antibacterial and antioxidant performance of combinations of these three plant-derived oils using a statistical mixture design strategy supported by in silico exploration. Methods: An Augmented Simplex Centroid Mixture Design was applied to evaluate the individual and combined effects of thyme, cinnamon, and black seed oils. Antibacterial activity was assessed by determining the minimum inhibitory concentrations (MICs) against Escherichia coli and Staphylococcus aureus, while antioxidant activity was measured using the DPPH radical scavenging assay (IC50). The experimental data were fitted to a special cubic model, and model validity was verified through ANOVA parameters, including F-values, R2, and adjusted R2. Multi-response optimization was performed using a desirability function. Potential interactions among oils were further examined using checkerboard assays. Molecular docking and ADMET predictions were conducted as supportive, hypothesis-generating tools. Results: The special cubic model was statistically significant for all responses (p &lt; 0.0001), with R2 values of 0.9763, 0.9944, and 0.9841 for MICE. coli, MICS. aureus, and DPPH IC50, respectively. Response surface analysis and multi-response optimization identified the optimal oil mixture as thyme (41.7%), cinnamon (41.7%), and black seed (16.7%), achieving MIC values of 0.5 \u00b5L\/mL for E. coli and 0.517 \u00b5L\/mL for S. aureus, and a DPPH IC50 of 5.32 \u00b1 0.52 mg\/mL. Checkerboard assays confirmed synergistic interactions for the optimized formulation, with \u03a3FIC values of 0.15 and 0.29 against E. coli and S. aureus, respectively. Cytotoxicity testing of the optimized formulation on WI-38 normal fibroblasts indicated high cell viability (&gt;92%) at all tested concentrations. In silico docking showed favorable binding affinities of major oil constituents with bacterial targets, and ADMET analysis suggested acceptable pharmacokinetic and safety profiles. Conclusions: The study demonstrated that specific combinations of thyme, cinnamon, and black seed oils can synergistically enhance antibacterial and antioxidant activities. The optimized formulation exhibited enhanced antibacterial and antioxidant activities with minimal cytotoxicity, while in silico analyses provided supportive mechanistic insights.<\/jats:p>","DOI":"10.3390\/ph19030372","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimization of Thyme, Cinnamon, and Black Seed Oil Combinations for Enhanced Antibacterial and Antioxidant Efficacy: Mixture Design and In Silico Insights"],"prefix":"10.3390","volume":"19","author":[{"given":"Mahmoud S.","family":"Maher","sequence":"first","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0917-3422","authenticated-orcid":false,"given":"Dina A.","family":"Altwiley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Jeddah, Jeddah 23890, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-4393","authenticated-orcid":false,"given":"Dalal M.","family":"Alkuraythi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Jeddah, Jeddah 23890, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-052X","authenticated-orcid":false,"given":"Mahmoud M. A.","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Genetics and Genetic Engineering Department, Faculty of Agriculture, Benha University, Benha 13736, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary S.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek A. A.","family":"Moussa","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawal","family":"Magdy","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). Global Antimicrobial Resistance and Use Surveillance System (GLASS), WHO. 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