{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:41:48Z","timestamp":1787244108931,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Several studies have demonstrated the possible synergistic effect as an effective strategy to boost the bioactivity of essential oils. Using this framework, this study was conducted to effectively establish the ideal combination of six essential oils from different plants (Origanum compactum, Origanum majorana, Thymus serpyllum, Mentha spicata, Myrtus communis, and Artemisia herba-alba) that would express the best antioxidant activity. Each mixture was optimized using a mixture design approach to generate the most effective blend. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging method was used as a reference method to assess the antioxidant activity. Each essential oil\u2019s composition was identified using the GC\/MS method. The single essential oil activities demonstrated variable antioxidant effects, and following the mixture design approach, the optimal antioxidant blend was revealed, as two mixtures demonstrated the best antiradical activity with 79.46% obtained with the mixture of O. majorana (28%) and M. spicata (71%) and 78.8% obtained with the mixture O. compactum (64%), O. majorana (13%), and T. serpyllum (21%). This study proposes a practical way to elaborate mixtures in the search for a boosting effect that can be oriented for the food or pharmaceutical industry.<\/jats:p>","DOI":"10.3390\/plants10122817","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"2817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Boosted Antioxidant Effect Using a Combinatory Approach with Essential Oils from Origanum compactum, Origanum majorana, Thymus serpyllum, Mentha spicata, Myrtus communis, and Artemisia herba-alba: Mixture Design Optimization"],"prefix":"10.3390","volume":"10","author":[{"given":"Wessal","family":"Ouedrhiri","sequence":"first","affiliation":[{"name":"Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-9089","authenticated-orcid":false,"given":"Hamza","family":"Mechchate","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-3689","authenticated-orcid":false,"given":"Sandrine","family":"Moja","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, UJM-Saint-Etienne, CNRS, BVpam, FRE3727, F-42023 Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi A.","family":"Mothana","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-6381","authenticated-orcid":false,"given":"Omar M.","family":"Noman","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-3676","authenticated-orcid":false,"given":"Andriy","family":"Grafov","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassane","family":"Greche","sequence":"additional","affiliation":[{"name":"National Agency of Medicinal and Aromatic Plants, University Sidi Mohamed Ben Abdellah, Taounate BP 159, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejmech.2015.04.040","article-title":"The Role of Antioxidants in the Chemistry of Oxidative Stress: A Review","volume":"97","author":"Pisoschi","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Togo, H., and Togo, H. (2004). What Are Free Radicals?. Advanced Free Radical Reactions for Organic Synthesis, Elsevier.","DOI":"10.1016\/B978-008044374-4\/50002-5"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10835","DOI":"10.1021\/jf403496k","article-title":"Antioxidant Activity of Essential Oils","volume":"61","author":"Amorati","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ffj.1961","article-title":"Antioxidant Activity of Medicinal and Aromatic Plants. A Review","volume":"2009","author":"Miguel","year":"2010","journal-title":"Antioxidants Oxid. Flavour Fragr. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Es-safi, I., Mechchate, H., Amaghnouje, A., Elbouzidi, A., Bouhrim, M., Bencheikh, N., Hano, C., and Bousta, D. (2021). Assessment of Antidepressant-Like, Anxiolytic Effects and Impact on Memory of Pimpinella Anisum L. Total Extract on Swiss Albino Mice. Plants, 10.","DOI":"10.3390\/plants10081573"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.foodcont.2011.07.031","article-title":"Antioxidant Activity of Essential Oil and Aqueous Extract of Pelargonium Graveolens L\u2019Her","volume":"23","year":"2012","journal-title":"Food Control"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.micres.2013.10.003","article-title":"Antimicrobial and Antioxidative Activity of Extracts and Essential Oils of Myrtus communis L.","volume":"169","author":"Aleksic","year":"2013","journal-title":"Microbiol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF01197931","article-title":"Toxicology of the Synthetic Antioxidants BHA and BHT in Comparison with the Natural Antioxidant Vitamin E","volume":"196","author":"Kahl","year":"1993","journal-title":"Z. Lebensm.-Unters. -Forsch."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e0131321","DOI":"10.1371\/journal.pone.0131321","article-title":"Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination","volume":"10","author":"Bag","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7672","DOI":"10.3390\/molecules16097672","article-title":"Antioxidant and Antiacetylcholinesterase Activities of Some Commercial Essential Oils and Their Major Compounds","volume":"16","author":"Aazza","year":"2011","journal-title":"Molecules"},{"key":"ref_11","first-page":"203","article-title":"Citronellol: A Potential Antioxidant and Aldose Reductase Inhibitor from Cymbopogon Citratus","volume":"7","author":"Jagdale","year":"2015","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_12","first-page":"519","article-title":"An Evaluation of Toxicity in Essential Oils of Geraniol, Geranial Acetate, Gingerol and Eugenol in Rats","volume":"4","author":"Farhath","year":"2012","journal-title":"Int. J. Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3989\/gya.2005.v56.i4.94","article-title":"Inhibition of Lard Oxidation by Fractions of Different Essential Oils","volume":"56","author":"Kulisic","year":"2005","journal-title":"Grasas Aceites"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.indcrop.2016.04.049","article-title":"Mixture Design of Origanum Compactum, Origanum Majorana and Thymus Serpyllum Essential Oils: Optimization of Their Antibacterial Effect","volume":"89","author":"Ouedrhiri","year":"2016","journal-title":"Ind. Crops Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108520","DOI":"10.1016\/j.jnutbio.2020.108520","article-title":"Combination of Catechin, Epicatechin, and Rutin:Optimization of a Novel Complete Antidiabetic Formulation Using a Mixture Design Approach","volume":"88","author":"Mechchate","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3390\/biologics1020009","article-title":"Optimization of a New Antihyperglycemic Formulation Using a Mixture of Linum usitatissimum L., Coriandrum sativum L., and Olea europaea var. sylvestris Flavonoids: A Mixture Design Approach","volume":"1","author":"Mechchate","year":"2021","journal-title":"Biologics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1007\/s13197-014-1278-x","article-title":"Efficacy of Angelica Archangelica Essential Oil, Phenyl Ethyl Alcohol and \u03b1- Terpineol against Isolated Molds from Walnut and Their Antiaflatoxigenic and Antioxidant Activity","volume":"52","author":"Prakash","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_18","first-page":"881","article-title":"Synergistic Antioxidative Effects of Tocopherol and Ascorbic Acid in Fish Oil\/Lecithin\/Water System","volume":"68","author":"Yi","year":"1991","journal-title":"Food Biochem. Lab. Korea Food Res. Inst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1248\/cpb.30.2964","article-title":"Studies on the Antioxidants. XVI. Synergistic Reaction between Butylated Hydroxyanisole and Butylated Hydroxytoluene in Hydrogen Donation to 2,2-Diphenyl-1-Picrylhydrazyl","volume":"30","author":"Kurechi","year":"1982","journal-title":"Chem. Pharm. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/j.fuproc.2011.04.028","article-title":"Study of the Biodiesel B100 Oxidative Stability in Mixture with Antioxidants","volume":"92","author":"Maia","year":"2011","journal-title":"Fuel Process. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.fct.2015.03.030","article-title":"In Vitro Toxicological Evaluation of Essential Oils and Their Main Compounds Used in Active Food Packaging: A Review","volume":"81","author":"Pichardo","year":"2015","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0308-8146(98)00086-7","article-title":"Antioxidant Activity and Mechanism of Action of Thymol and Carvacrol in Two Lipid Systems","volume":"64","author":"Yanishlieva","year":"1999","journal-title":"Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1078\/0944-7113-00380","article-title":"Synergistic Inhibition of Low-Density Lipoprotein Oxidation by Rutin, \u03b3 -Terpinene, and Ascorbic Acid","volume":"11","author":"Milde","year":"2004","journal-title":"Phytomedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.foodchem.2011.08.042","article-title":"Investigation of Antioxidant Synergisms and Antagonisms among Thymol, Carvacrol, Thymoquinone and p-Cymene in a Model System Using the Briggs-Rauscher Oscillating Reaction","volume":"131","author":"Milos","year":"2012","journal-title":"Food Chem."},{"key":"ref_25","first-page":"2717","article-title":"Antioxidative Properties of Procyanidins B-l and B-3 from Azuki Beans in Aqueous Systems1","volume":"52","author":"Ariga","year":"1988","journal-title":"Ratio"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.jff.2013.08.011","article-title":"Green Tea Extract: Chemistry, Antioxidant Properties and Food Applications-A Review","volume":"5","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.mrgentox.2007.01.011","article-title":"Investigation of the Mutagenic and Antimutagenic Effects of Origanum Compactum Essential Oil and Some of Its Constituents","volume":"629","author":"Mezzoug","year":"2007","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_28","first-page":"422","article-title":"Assessment of Bioactive Compounds, Antibacterial Potential and Acute Toxicity of a Volatile Origanum Compactum Extract, an Endemic Plant of Northern Morocco","volume":"7","author":"Rochdi","year":"2021","journal-title":"Arab. J. Med. Aromat. Plants"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4314\/tjpr.v13i1.15","article-title":"Acute Oral Toxicity and Brine Shrimp Lethality of Methanol Extract of Mentha spicata L (Lamiaceae)","volume":"13","author":"Naidu","year":"2014","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bule MH, I.I. (2015). A Comparative Study of the Hypoglycemic Effect of Aqueous and Methanolic Extracts of Myrtus Communis on Alloxan Induced Diabetic Siwis Albino Mice. Med. Aromat. Plants, 4.","DOI":"10.4172\/2167-0412.1000190"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"El Ouahdani, K., Es-safi, I., Mechchate, H., Al-zahrani, M., Qurtam, A.A., Aleissa, M., Bari, A., and Bousta, D. (2021). Thymus Algeriensis and Artemisia Herba-Alba Essential Oils: Chemical Analysis, Antioxidant Potential and In Vivo Anti-Inflammatory, Analgesic Activities, and Acute Toxicity. Molecules, 26.","DOI":"10.3390\/molecules26226780"},{"key":"ref_32","unstructured":"Adams, R.P. (2007). Rober Identification of Essential Oil Components by Gas Chromatography\/Mass Spectrometry, Allured Publishing Corporation. [4th ed.]."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.crci.2009.09.008","article-title":"Antimicrobial and Antioxidant Activities of Artemisia Herba-Alba Essential Oil Cultivated in Tunisian Arid Zone","volume":"13","author":"Mighri","year":"2010","journal-title":"Comptes Rendus Chim."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/10\/12\/2817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:46Z","timestamp":1760168986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/10\/12\/2817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["plants10122817"],"URL":"https:\/\/doi.org\/10.3390\/plants10122817","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}