{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:34:42Z","timestamp":1790350482459,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The optimization of bioactive compound mixtures is critical for enhancing pharmacological efficacy. This study investigates, for the first time, the combined effects of eugenol, camphor, and terpineol, focusing on their half-maximal inhibitory concentrations (IC50) across multiple biological responses related to diabetes management. Using a mixture design approach, the objective was to determine the optimal formulation that maximizes bioactivity and validate the findings experimentally. A simplex-centroid design was applied to evaluate the combined effects of eugenol, camphor, and terpineol on AAI IC50, AGI IC50, LIP IC50, and ALR IC50 responses. The desirability function was used to determine the ideal composition. The optimized formulation was experimentally validated using in vitro assays, and IC50 values were measured for each response using standard protocols. Results: The optimal formulation identified was 44% eugenol, 0.19% camphor, and 37% terpineol, yielding IC50 values of 10.38 \u00b5g\/mL (AAI), 62.22 \u00b5g\/mL (AGI), 3.42 \u00b5g\/mL (LIP), and 49.58 \u00b5g\/mL (ALR). The desirability score (0.99) confirmed the effectiveness of the optimized blend. Experimental validation of the optimal mixture resulted in IC50 values of 11.02 \u00b5g\/mL (AAI), 60.85 \u00b5g\/mL (AGI), 3.75 \u00b5g\/mL (LIP), and 50.12 \u00b5g\/mL (ALR), showing less than 10% deviation from predicted values, indicating high model accuracy. This study confirms the combined potential of eugenol, camphor, and terpineol, with eugenol and terpineol significantly enhancing bioactivity. The validated formulation demonstrates potential for pharmaceutical and cosmeceutical applications. Future research should explore mechanistic interactions, bioavailability, and in vivo efficacy to support the development of optimized natural compound-based therapies.<\/jats:p>","DOI":"10.3390\/cimb47070512","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T09:08:44Z","timestamp":1751447324000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0314-8484","authenticated-orcid":false,"given":"Amine","family":"Elbouzidi","sequence":"first","affiliation":[{"name":"Laboratoire d\u2019Am\u00e9lioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Facult\u00e9 des Sciences, Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-1842","authenticated-orcid":false,"given":"Mohamed","family":"Jeddi","sequence":"additional","affiliation":[{"name":"Laboratory of Microbial Biotechnology and Bioactive Molecules, Faculty of Sciences and Technologies, Sidi Mohamed Ben Abdellah University, Imouzzer Road, Fez P.O. Box 2202, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-6738","authenticated-orcid":false,"given":"Abdellah","family":"Baraich","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Boulevard Mohamed VI, B.P. 717, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-3538","authenticated-orcid":false,"given":"Mohamed","family":"Taibi","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Am\u00e9lioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Facult\u00e9 des Sciences, Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"},{"name":"Centre de l\u2019Oriental des Sciences et Technologies de l\u2019Eau et de l\u2019Environnement (COSTEE), Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4366-843X","authenticated-orcid":false,"given":"Mounir","family":"Haddou","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Am\u00e9lioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Facult\u00e9 des Sciences, Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-5914","authenticated-orcid":false,"given":"Naoufal","family":"El Hachlafi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Ibn Zohr University, Guelmim 81000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2721-7854","authenticated-orcid":false,"given":"Meryem Idrissi","family":"Yahyaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Boulevard Mohamed VI, B.P. 717, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda","family":"Bellaouchi","sequence":"additional","affiliation":[{"name":"Centre de l\u2019Oriental des Sciences et Technologies de l\u2019Eau et de l\u2019Environnement (COSTEE), Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"El Guerrouj","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Am\u00e9lioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Facult\u00e9 des Sciences, Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"},{"name":"Centre de l\u2019Oriental des Sciences et Technologies de l\u2019Eau et de l\u2019Environnement (COSTEE), Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Chaabane","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Am\u00e9lioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Facult\u00e9 des Sciences, Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-6694","authenticated-orcid":false,"given":"Mohamed","family":"Addi","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Am\u00e9lioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Facult\u00e9 des Sciences, Universit\u00e9 Mohammed Premier, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K., Ostolaza, H., and Mart\u00edn, C. 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