Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes

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 (IC<sub>50</sub>) across mult...

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Main Authors: Amine Elbouzidi, Mohamed Jeddi, Abdellah Baraich, Mohamed Taibi, Mounir Haddou, Naoufal El Hachlafi, Meryem Idrissi Yahyaoui, Reda Bellaouchi, Bouchra El Guerrouj, Khalid Chaabane, Mohamed Addi
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/7/512
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author Amine Elbouzidi
Mohamed Jeddi
Abdellah Baraich
Mohamed Taibi
Mounir Haddou
Naoufal El Hachlafi
Meryem Idrissi Yahyaoui
Reda Bellaouchi
Bouchra El Guerrouj
Khalid Chaabane
Mohamed Addi
author_facet Amine Elbouzidi
Mohamed Jeddi
Abdellah Baraich
Mohamed Taibi
Mounir Haddou
Naoufal El Hachlafi
Meryem Idrissi Yahyaoui
Reda Bellaouchi
Bouchra El Guerrouj
Khalid Chaabane
Mohamed Addi
author_sort Amine Elbouzidi
collection DOAJ
description 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 (IC<sub>50</sub>) 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 <sub>IC50</sub>, AGI <sub>IC50</sub>, LIP <sub>IC50</sub>, and ALR <sub>IC50</sub> 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 IC<sub>50</sub> values of 10.38 µg/mL (AAI), 62.22 µg/mL (AGI), 3.42 µg/mL (LIP), and 49.58 µg/mL (ALR). The desirability score (0.99) confirmed the effectiveness of the optimized blend. Experimental validation of the optimal mixture resulted in IC<sub>50</sub> values of 11.02 µg/mL (AAI), 60.85 µg/mL (AGI), 3.75 µg/mL (LIP), and 50.12 µg/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.
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spelling doaj-art-5dea64ea837d461490eb892e85eeac4d2025-08-20T03:08:05ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-07-0147751210.3390/cimb47070512Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic EnzymesAmine Elbouzidi0Mohamed Jeddi1Abdellah Baraich2Mohamed Taibi3Mounir Haddou4Naoufal El Hachlafi5Meryem Idrissi Yahyaoui6Reda Bellaouchi7Bouchra El Guerrouj8Khalid Chaabane9Mohamed Addi10Laboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, MoroccoLaboratory of Microbial Biotechnology and Bioactive Molecules, Faculty of Sciences and Technologies, Sidi Mohamed Ben Abdellah University, Imouzzer Road, Fez P.O. Box 2202, MoroccoLaboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Boulevard Mohamed VI, B.P. 717, Oujda 60000, MoroccoLaboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, MoroccoLaboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, MoroccoFaculty of Medicine and Pharmacy, Ibn Zohr University, Guelmim 81000, MoroccoLaboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Boulevard Mohamed VI, B.P. 717, Oujda 60000, MoroccoCentre de l’Oriental des Sciences et Technologies de l’Eau et de l’Environnement (COSTEE), Université Mohammed Premier, Oujda 60000, MoroccoLaboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, MoroccoLaboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, MoroccoLaboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, MoroccoThe 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 (IC<sub>50</sub>) 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 <sub>IC50</sub>, AGI <sub>IC50</sub>, LIP <sub>IC50</sub>, and ALR <sub>IC50</sub> 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 IC<sub>50</sub> values of 10.38 µg/mL (AAI), 62.22 µg/mL (AGI), 3.42 µg/mL (LIP), and 49.58 µg/mL (ALR). The desirability score (0.99) confirmed the effectiveness of the optimized blend. Experimental validation of the optimal mixture resulted in IC<sub>50</sub> values of 11.02 µg/mL (AAI), 60.85 µg/mL (AGI), 3.75 µg/mL (LIP), and 50.12 µg/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.https://www.mdpi.com/1467-3045/47/7/512mixture designeugenolcamphorterpineolbioavailabilityIC<sub>50</sub> optimization
spellingShingle Amine Elbouzidi
Mohamed Jeddi
Abdellah Baraich
Mohamed Taibi
Mounir Haddou
Naoufal El Hachlafi
Meryem Idrissi Yahyaoui
Reda Bellaouchi
Bouchra El Guerrouj
Khalid Chaabane
Mohamed Addi
Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes
Current Issues in Molecular Biology
mixture design
eugenol
camphor
terpineol
bioavailability
IC<sub>50</sub> optimization
title Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes
title_full Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes
title_fullStr Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes
title_full_unstemmed Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes
title_short Optimization of Eugenol, Camphor, and Terpineol Mixture Using Simplex-Centroid Design for Targeted Inhibition of Key Antidiabetic Enzymes
title_sort optimization of eugenol camphor and terpineol mixture using simplex centroid design for targeted inhibition of key antidiabetic enzymes
topic mixture design
eugenol
camphor
terpineol
bioavailability
IC<sub>50</sub> optimization
url https://www.mdpi.com/1467-3045/47/7/512
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