{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:15Z","timestamp":1787027595812,"version":"build-2736575974"},"reference-count":94,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babe\u0219\u201d University of Medicine and Pharmacy Timi;oara, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Rosacea is a chronic inflammatory skin disorder characterized by oxidative stress, innate immune dysregulation, vascular instability, and microbiome-related triggers. Glycyrrhiza glabra (Gg, licorice) root contains phenolics and triterpenoids with antioxidant, anti-inflammatory, antimicrobial, and anti-angiogenic properties that may benefit rosacea-prone skin. Xanthan-gum hydrogels containing 2% methanolic Gg extract (S1, S2) were prepared and characterized. Rheology, in vitro release, and in vitro permeation were evaluated, with the aim of assessing their suitability as topical formulations for rosacea-prone skin. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Antimicrobial effects were tested against S. pyogenes, S. aureus, and C. acnes. Safety and bioactivity were examined through HaCaT keratinocyte assays (MTT, Neutral Red, LDH), the HET-CAM irritation test, and the CAM angiogenesis assay. Immunocytochemistry was performed on rosacea-related inflammatory markers. Both hydrogels showed suitable rheology, sustained release, and preserved strong antioxidant activity. Moderate antimicrobial effects were observed, particularly against S. pyogenes and C. acnes. HaCaT cell viability remained above 84% for the S2 formulation at the highest concentration (200 \u00b5g\/mL), indicating improved cytocompatibility compared with formulation S1. The hydrogels were non-irritant in the HET-CAM model and reduced neovascularization in the CAM assay, with a more sustained effect observed for formulation S2. Immunohistochemistry supported potential modulation of inflammatory pathways relevant to rosacea, evidencing suppressed VEGF expression and preserved CD44-mediated integrity, particularly in the Labrasol-based formulation (S2), while Caspase-3 staining indicated a controlled apoptotic profile. Overall, Gg hydrogels are safe, biocompatible, non-irritant, and exhibit antioxidant, antimicrobial, and anti-angiogenic activities, supporting their potential as biocompatible topical formulations with antioxidant and pathway-modulating properties relevant to the biological features associated with rosacea, while underscoring the importance of formulation design.<\/jats:p>","DOI":"10.3390\/antiox15020158","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T13:55:34Z","timestamp":1769176534000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Formulation and Biological Evaluation of Glycyrrhiza glabra L. Methanolic Extract: An Exploratory Study in the Context of Rosacea"],"prefix":"10.3390","volume":"15","author":[{"given":"Iulia","family":"Semenescu","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy-Phytotherapy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research and Processing Center of Medicinal and Aromatic Plants, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-4770","authenticated-orcid":false,"given":"Larisa","family":"Bora","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy-Phytotherapy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research and Processing Center of Medicinal and Aromatic Plants, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3300-4910","authenticated-orcid":false,"given":"Adina Octavia","family":"Du\u0219e","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Physical Medicine and Rheumatology, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Municipal Clinical Emergency Hospital, 300254 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2498-4732","authenticated-orcid":false,"given":"Claudia Geanina","family":"Watz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Physics, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research Center for Pharmaco-Toxicological Evaluation, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"OncoGen Center for Gene and Cellular Therapies in the Treatment of Cancer, \u201cPius Br\u00eenzeu\u201d County Clinical, Emergency Hospital Timi\u0219oara, Blvd. Liviu Rebreanu, 156, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4824-6769","authenticated-orcid":false,"given":"\u0218tefana","family":"Avram","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy-Phytotherapy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research and Processing Center of Medicinal and Aromatic Plants, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-8876","authenticated-orcid":false,"given":"Szilvia","family":"Berk\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-4634","authenticated-orcid":false,"given":"Gheorghe Emilian","family":"Olteanu","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluation, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Infectious Diseases, Discipline of Pulmonology, Center for Research and Innovation in Personalized Medicine of Respiratory Diseases, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5587-1733","authenticated-orcid":false,"given":"Adina","family":"C\u0103ta","sequence":"additional","affiliation":[{"name":"National Institute of Research and Development for Electrochemistry and Condensed Matter, 144 Dr. A. P. Podeanu, 300569 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5325-3859","authenticated-orcid":false,"given":"Zori\u021ba","family":"Diaconeasa","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, Faculty of Food Science and Technology, University of Agricultural Science and Veterinary Medicine, Calea Manastur, 3-5, 400372 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-4908","authenticated-orcid":false,"given":"Daliana Ionela","family":"Minda","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy-Phytotherapy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research and Processing Center of Medicinal and Aromatic Plants, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Adriana","family":"Dehelean","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluation, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Toxicology and Drug Industry, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9100-4530","authenticated-orcid":false,"given":"Delia","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Multidisciplinary Research Center on Antimicrobial Resistance, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5999-1214","authenticated-orcid":false,"given":"Corina","family":"Danciu","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy-Phytotherapy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research and Processing Center of Medicinal and Aromatic Plants, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1089\/acm.2016.0398","article-title":"The Role of Polyphenols in Rosacea Treatment: A Systematic Review","volume":"23","author":"Saric","year":"2017","journal-title":"J. Altern. Complement. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00403-007-0816-z","article-title":"A Study of the Pathogenesis of Rosacea: How Angiogenesis and Mast Cells May Participate in a Complex Multifactorial Process","volume":"300","author":"Aroni","year":"2008","journal-title":"Arch. Dermatol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s40257-021-00595-7","article-title":"Rosacea: New Concepts in Classification and Treatment","volume":"22","author":"Arents","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/14728214.2021.1887138","article-title":"Emerging Topical Drugs for the Treatment of Rosacea","volume":"26","author":"Nasca","year":"2021","journal-title":"Expert. Opin. Emerg. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/12034754241253195","article-title":"Efficacy of Treatments in Reducing Inflammatory Lesion Count in Rosacea: A Systematic Review","volume":"28","author":"Geng","year":"2024","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1177\/12034754241229365","article-title":"Rosacea: Pathogenesis and Therapeutic Correlates","volume":"28","author":"Geng","year":"2024","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.intimp.2018.12.031","article-title":"Tranexamic Acid Ameliorates Rosacea Symptoms Through Regulating Immune Response and Angiogenesis","volume":"67","author":"Li","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/jid.2015.141","article-title":"Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1\/Th17 Pathways","volume":"135","author":"Buhl","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","first-page":"17","article-title":"History and significance of phytotherapy in the human history. The development of phytotherapy from the Middle Ages to modern times","volume":"24","year":"2020","journal-title":"Arch. Physiother. Glob. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101270","DOI":"10.1016\/j.eujim.2020.101270","article-title":"Recent Progess in Phytotherapy: A Brazilian Perspective","volume":"41","author":"Leite","year":"2021","journal-title":"Eur. J. Integr. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1021\/acs.molpharmaceut.3c00324","article-title":"Rosacea Topical Treatment and Care: From Traditional to New Drug Delivery Systems","volume":"20","author":"Peixoto","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_12","first-page":"7","article-title":"Recent Progess in Phytotherapy: A Brazilian Perspective","volume":"10","author":"Colalto","year":"2018","journal-title":"J. Siena Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wahab, S., Annadurai, S., Abullais, S.S., Das, G., Ahmad, W., Ahmad, M.F., Kandasamy, G., Vasudevan, R., Ali, M.S., and Amir, M. (2021). Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology. Plants, 10.","DOI":"10.3390\/plants10122751"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Alobaidi, A.H., Hamad, E.S., Alsamarai, A.M., and Kudair, K.A. (2015). Evaluation of Glycyrrhiza glabra Cream as Treatmentfor Melasma. Evid.-Based Strateg. Herbal. Med. Psychiatr. Disord. Emerg. Med.","DOI":"10.5772\/58918"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113688","DOI":"10.1016\/j.indcrop.2021.113688","article-title":"Specialized Metabolite Profiling of Different Glycyrrhiza glabra Organs by Untargeted UHPLC-HRMS","volume":"170","author":"Celano","year":"2021","journal-title":"Ind. Crops Prod."},{"key":"ref_16","first-page":"2470","article-title":"Glycyrrhiza glabra: A Phytopharmacological Review","volume":"4","author":"Kaur","year":"2013","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.47583\/ijpsrr.2021.v67i01.030","article-title":"Phytochemistry and Pharmacological Studies of Glycyrrhiza glabra: A Medicinal Plant Review","volume":"67","author":"Sharma","year":"2021","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sharma, V., Katiyar, A., and Agrawal, R.C. (2017). Glycyrrhiza glabra: Chemistry and Pharmacological Activity. Sweeteners, Springer.","DOI":"10.1007\/978-3-319-27027-2_21"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Babich, O., Ivanova, S., Ulrikh, E., Popov, A., Larina, V., Frolov, A., and Prosekov, A. (2022). Study of the Chemical Composition and Biologically Active Properties of Glycyrrhiza glabra Extracts. Life, 12.","DOI":"10.3390\/life12111772"},{"key":"ref_20","first-page":"487","article-title":"Evaluation of Phytochemical, Antioxidant and Antimicrobial Properties of Glycyrrhizin Extracted from Roots of Glycyrrhiza glabra","volume":"75","author":"Thakur","year":"2016","journal-title":"J. Sci. Ind. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Semenescu, I., Avram, S., Similie, D., Minda, D., Diaconeasa, Z., Muntean, D., Lazar, A.E., Gurgus, D., and Danciu, C. (2024). Phytochemical, Antioxidant, Antimicrobial and Safety Profile of Glycyrrhiza glabra L. Extract Obtained from Romania. Plants, 13.","DOI":"10.3390\/plants13233265"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1002\/ptr.5432","article-title":"Phytochemical and Botanical Therapies for Rosacea: A Systematic Review","volume":"29","author":"Fisk","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1468-3083.2005.01248.x","article-title":"Randomized Placebo-Controlled Trial of a Flavonoid-Rich Plant Extract-Based Cream in the Treatment of Rosacea","volume":"19","author":"Rigopoulos","year":"2005","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100206","DOI":"10.1016\/j.phyplu.2021.100206","article-title":"Revisiting Liquorice (Glycyrrhiza glabra L.) as Anti-Inflammatory, Antivirals and Immunomodulators: Potential Pharmacological Applications with Mechanistic Insight","volume":"2","author":"Bisht","year":"2022","journal-title":"Phytomedicine Plus"},{"key":"ref_25","unstructured":"(2025, December 17). Quality and Equivalence of Locally Applied, Locally Acting Cutaneous Products-Scientific Guideline|European Medicines Agency (EMA). Available online: https:\/\/www.ema.europa.eu\/en\/quality-equivalence-locally-applied-locally-acting-cutaneous-products-scientific-guideline."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1001\/archderm.1963.01590240026005","article-title":"Preparation of isolated sheets of human stratum corneum","volume":"88","author":"Kligman","year":"1963","journal-title":"Arch. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","article-title":"Use of a Free Radical Method to Evaluate Antioxidant Activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The Ferric Reducing Ability of Plasma (FRAP) as a Measure of \u201cAntioxidant Power\u201d: The FRAP Assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1021\/jf051960d","article-title":"Modified 2,2-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid (Abts) Method to Measure Antioxidant Capacity of Selected Small Fruits and Comparison to Ferric Reducing Antioxidant Power (FRAP) and 2,2\u2032-Diphenyl-1-Picrylhydrazyl (DPPH) Methods","volume":"54","author":"Ozgen","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","unstructured":"European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2025, September 09). Media Preparation for EUCAST Disk Diffusion Testing and for Determination of MIC Values by the Broth Microdilution Method. Available online: http:\/\/www.eucast.org."},{"key":"ref_31","unstructured":"Patel, J.B. (2016). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moac\u0103, E.A., Watz, C.G., Socoliuc, V., Racoviceanu, R., P\u0103curariu, C., Iano\u015f, R., C\u00eent\u0103-P\u00eenzaru, S., Tudoran, L.B., Nekvapil, F., and Iurciuc, S. (2021). Biocompatible Magnetic Colloidal Suspension Used as a Tool for Localized Hyperthermia in Human Breast Adenocarcinoma Cells: Physicochemical Analysis and Complex In Vitro Biological Profile. Nanomaterials, 11.","DOI":"10.3390\/nano11051189"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ghi\u021bu, A., Schwiebs, A., Radeke, H.H., Avram, S., Zupko, I., Bor, A., Pavel, I.Z., Dehelean, C.A., Oprean, C., and Bojin, F. (2019). A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound. Nutrients, 11.","DOI":"10.3390\/nu11040858"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Corina, D., Delia, M., Ersilia, A., Claudia, F., Camelia, O., Istvan, Z., Andrea, B., Daliana, M., Maria, P., and Valentina, B. (2018). Phytochemical Characterization and Evaluation of the Antimicrobial, Antiproliferative and Pro-Apoptotic Potential of Ephedra Alata Decne. Hydroalcoholic Extract against the MCF-7 Breast Cancer Cell Line. Molecules, 24.","DOI":"10.3390\/molecules24010013"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Avram, \u0218., Bora, L., Vlaia, L.L., Mu\u021b, A.M., Olteanu, G.E., Olariu, I., Magyari-Pavel, I.Z., Minda, D., Diaconeasa, Z., and Sfirloaga, P. (2023). Cutaneous Polymeric-Micelles-Based Hydrogel Containing Origanum vulgare L. Essential Oil: In Vitro Release and Permeation, Angiogenesis, and Safety Profile In Ovo. Pharmaceuticals, 16.","DOI":"10.3390\/ph16070940"},{"key":"ref_36","unstructured":"(2025, November 15). ICCVAM Test Method Validation Report: Current Validation Status of In Vitro Test Methods Proposed for Identifying Eye Injury Hazard Potential of Chemicals and Products-Vol 1|EURL ECVAM-TSAR. Available online: https:\/\/tsar.jrc.ec.europa.eu\/content\/iccvam-test-method-validation-report-current-validation-status-vitro-test-methods-proposed-1."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0278-6915(85)90030-4","article-title":"Hen\u2019s Egg Chorioallantoic Membrane Test for Irritation Potential","volume":"23","author":"Luepke","year":"1985","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.jaad.2023.12.038","article-title":"Epidemiology of Acne and Rosacea: A Worldwide Global Study","volume":"90","author":"Saurat","year":"2024","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jad.2021.12.008","article-title":"Association of Rosacea with Depression and Anxiety: A Systematic Review and Meta-Analysis","volume":"299","author":"Chang","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_40","first-page":"1345","article-title":"Laser Treatment of Rosacea: A Pathoetiological Study","volume":"140","author":"Nordlind","year":"2004","journal-title":"Arch. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fisher, G.W., Travers, J.B., and Rohan, C.A. (2023). Rosacea Pathogenesis and Therapeutics: Current Treatments and a Look at Future Targets. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1292722"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"56142","DOI":"10.12775\/JEHS.2024.71.56142","article-title":"Role of Inflammatory Pathways in the Development of Rosacea","volume":"71","author":"Sieradocha","year":"2024","journal-title":"J. Educ. Health Sport"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/ics.12771","article-title":"Improved Stability and Skin Penetration through Glycethosomes Loaded with Glycyrrhetinic Acid","volume":"44","author":"Zhang","year":"2022","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1080\/13880209.2024.2385456","article-title":"Bioactive Substance Contents and Therapeutic Potential for Skin Inflammation of an Herbal Gel Containing Derris Reticulata and Glycyrrhiza glabra","volume":"62","author":"Sangkaew","year":"2024","journal-title":"Pharm. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/13880209.2016.1225775","article-title":"The Anti-Inflammatory Activity of Licorice, a Widely Used Chinese Herb","volume":"55","author":"Yang","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.2147\/OTT.S366630","article-title":"Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects","volume":"15","author":"Tuli","year":"2022","journal-title":"Onco Targets Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"68","DOI":"10.11648\/j.plant.20170504.12","article-title":"Antioxidant and Antibacterial Activity of Organic Extracts of Roots of Glycyrrhiza glabra Linn","volume":"5","author":"Iqbal","year":"2017","journal-title":"Plant"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bhusal, S., and Sharma, K.R. (2020). Evaluation of Antioxidant and Antibacterial Activity of Glycyrrhiza glabra Root Extracts. Asian J. Pharm. Clin. Res., 166\u2013170.","DOI":"10.22159\/ajpcr.2020.v13i10.38950"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fatoki, T.H., Ajiboye, B.O., and Aremu, A.O. (2023). In Silico Evaluation of the Antioxidant, Anti-Inflammatory, and Dermatocosmetic Activities of Phytoconstituents in Licorice (Glycyrrhiza glabra L.). Cosmetics, 10.","DOI":"10.3390\/cosmetics10030069"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Graebin, C.S. (2018). The Pharmacological Activities of Glycyrrhizinic Acid (\u201cGlycyrrhizin\u201d) and Glycyrrhetinic Acid. Sweeteners, Springer.","DOI":"10.1007\/978-3-319-27027-2_15"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Semenescu, I., Avram, \u0218., Bora, L., Berk\u00f3, S., Minda, D., and Danciu, C. (2025). Antioxidant Activity of 2% G. glabra L. Hydrogels for Potential Use in Oxidative Stress-Related Skin Conditions. Proceedings, 127.","DOI":"10.3390\/proceedings2025127024"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11309","DOI":"10.1021\/acsami.6b16120","article-title":"Hydrogel-Based Materials for Delivery of Herbal Medicines","volume":"9","author":"Lai","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Nawaz, A., Ullah, S., Alnuwaiser, M.A., Rehman, F.U., Selim, S., Al Jaouni, S.K., and Farid, A. (2022). Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery. Gels, 8.","DOI":"10.3390\/gels8090537"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Singhvi, G., Hans, N., Shiva, N., and Kumar Dubey, S. (2019). Xanthan Gum in Drug Delivery Applications. Nat. Polysacch. Drug Deliv. Biomed. Appl., 121\u2013144.","DOI":"10.1016\/B978-0-12-817055-7.00005-4"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.5530\/pj.2021.13.185","article-title":"Preparation of Euyrycoma Longifolia Jack (E.L) Tongkat Ali (Ta) Root Extract Hydrogel for Wound Application","volume":"13","author":"Yaseen","year":"2021","journal-title":"Pharmacogn. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mees, M.A., Boone, F., Bouwen, T., Vanaerschot, F., Titeca, C., Vikkula, H.K., Catrysse, L., Vananroye, A., Koos, E., and Alexandris, S. (2023). Glycyrrhizin-Based Hydrogels Accelerate Wound Healing of Normoglycemic and Diabetic Mouse Skin. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010027"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1055\/s-2002-34587","article-title":"History of the Endocrine Effects of Licorice","volume":"110","author":"Armanini","year":"2002","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00281-013-0375-7","article-title":"Low Density Granulocytes: A Distinct Class of Neutrophils in Systemic Autoimmunity","volume":"35","author":"Kaplan","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_59","first-page":"e1-4","article-title":"Systemic Antioxidants and Skin Health","volume":"11","author":"Nguyen","year":"2012","journal-title":"J. Drugs Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ghica, A., Drumea, V., Moro\u0219an, A., Mihaiescu, D.E., Costea, L., Lu\u021b\u0103, E.A., Mihai, D.P., Balaci, D.T., Fi\u021ba, A.C., and Olaru, O.T. (2023). Phytochemical Screening and Antioxidant Potential of Selected Extracts from Betula Alba Var. Pendula Roth., Glycyrrhiza glabra L., and Avena sativa L.. Plants, 12.","DOI":"10.3390\/plants12132510"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11034","DOI":"10.1038\/s41598-024-61711-1","article-title":"Introducing the Glycyrrhizic Acid and Glabridin Rich Genotypes from the Cultivated Iranian Licorice (Glycyrrhiza glabra L.) Populations to Exploit in Production Systems","volume":"14","author":"Esmaeili","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"707","DOI":"10.12691\/jfnr-8-12-3","article-title":"Chemical Composition, Antioxidant, Antimicrobial and Anticancer Activities of Licorice (Glycyrrhiza glabra L.) Root and Its Application in Functional Yoghurt","volume":"8","author":"Hamad","year":"2020","journal-title":"J. Food Nutr. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2147\/DDDT.S385981","article-title":"Review on the Diverse Biological Effects of Glabridin","volume":"17","author":"Zhang","year":"2023","journal-title":"Drug Des. Devel Ther."},{"key":"ref_64","first-page":"1","article-title":"Glycyrrhiza glabra: A Phytochemical and Pharmacological Review","volume":"8","year":"2018","journal-title":"IOSR J. Pharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jaad.2014.08.028","article-title":"Rosacea: Part I. Introduction, Categorization, Histology, Pathogenesis, and Risk Factors","volume":"72","author":"Two","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chen, C., Wang, P., Zhang, L., Liu, X., Zhang, H., Cao, Y., Wang, X., and Zeng, Q. (2023). Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates. Biomedicines, 11.","DOI":"10.20944\/preprints202307.0397.v1"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.freeradbiomed.2015.06.016","article-title":"A Polyphenolic Flavonoid Glabridin: Oxidative Stress Response in Multidrug-Resistant Staphylococcus Aureus","volume":"87","author":"Singh","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12105","DOI":"10.1039\/D2FO02197H","article-title":"Valorisation of Liquorice (Glycyrrhiza) Roots: Antimicrobial Activity and Cytotoxicity of Prenylated (Iso)Flavonoids and Chalcones from Liquorice Spent (G. Glabra, G. Inflata, and G. Uralensis)","volume":"13","author":"Meijerink","year":"2022","journal-title":"Food Funct."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/jid.2010.351","article-title":"TLR2 Expression Is Increased in Rosacea and Stimulates Enhanced Serine Protease Production by Keratinocytes","volume":"131","author":"Yamasaki","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Peng, L., Jiang, J., Chen, T., Xu, D., Hou, F., Huang, Q., Peng, Y., Ye, C., Hu, D.L., and Fang, R. (2021). Toxic Shock Syndrome Toxin 1 Induces Immune Response via the Activation of NLRP3 Inflammasome. Toxins, 13.","DOI":"10.3390\/toxins13010068"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1111\/exd.14098","article-title":"Comparison of the Skin Microbiota in Acne and Rosacea","volume":"30","author":"Thompson","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_72","first-page":"83","article-title":"Acne and Diet: A Review of Pathogenic Mechanisms","volume":"79","year":"2022","journal-title":"Bol. Med. Hosp. Infant. Mex."},{"key":"ref_73","first-page":"20","article-title":"Kallikrein 5-Mediated Inflammation in Rosacea: Clinically Relevant Correlations with Acute and Chronic Manifestations in Rosacea and How Individual Treatments May Provide Therapeutic Benefit","volume":"7","author":"Two","year":"2014","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Roh, K.B., Jang, Y., Cho, E., Park, D., Kweon, D.H., and Jung, E. (2022). Chlorogenic Acid Isomers Isolated from Artemisia Lavandulaefolia Exhibit Anti-Rosacea Effects In Vitro. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020463"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Matsubara, Y., Matsumoto, T., Koseki, J., Kaneko, A., Aiba, S., and Yamasaki, K. (2017). Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources. Molecules, 22.","DOI":"10.3390\/molecules22111829"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8438101","DOI":"10.1155\/2018\/8438101","article-title":"Inhibitory Effects of Glycyrrhiza glabra and Its Major Constituent Glycyrrhizin on Inflammation-Associated Corneal Neovascularization","volume":"2018","author":"Shah","year":"2018","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1248\/bpb.b20-00038","article-title":"Glabridin Alleviates Inflammation and Nociception in Rodents by Activating BKCa Channels and Reducing NO Levels","volume":"43","author":"Parlar","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s13555-016-0168-8","article-title":"Acne and Rosacea","volume":"7","author":"Picardo","year":"2017","journal-title":"Dermatol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"105754","DOI":"10.1016\/j.jddst.2024.105754","article-title":"Application of Glycyrrhizic Acid and Glycyrrhetinic Acid in the Drug Delivery System","volume":"97","author":"Zhao","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Yang, F., Wang, L., Song, D., Zhang, L., Wang, X., Du, D., and Jiang, X. (2024). Signaling Pathways and Targeted Therapy for Rosacea. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1367994"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lee, H.J., Hong, Y.J., and Kim, M. (2021). Angiogenesis in Chronic Inflammatory Skin Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222112035"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/jidsymp.2011.6","article-title":"Neurovascular and Neuroimmune Aspects in the Pathophysiology of Rosacea","volume":"15","author":"Schwab","year":"2011","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/jidsymp.2011.5","article-title":"The Cutaneous Vascular System in Chronic Skin Inflammation","volume":"15","author":"Huggenberger","year":"2011","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Pun, C.K., Huang, H.C., Chang, C.C., Chuang, C.L., Yen, C.H., Hsu, S.J., Lee, F.Y., Hou, M.C., and Huang, Y.H. (2021). Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147662"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1136\/bjophthalmol-2011-300110","article-title":"Isoliquiritigenin from Licorice Root Suppressed Neovascularisation in Experimental Ocular Angiogenesis Models","volume":"95","author":"Jhanji","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.intimp.2005.07.002","article-title":"Angiogenic and Proliferative Effects of the Cytokine VEGF in Ehrlich Ascites Tumor Cells Is Inhibited by Glycyrrhiza glabra","volume":"6","author":"Sheela","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4103\/ejdv.ejdv_39_23","article-title":"Regulation of Angiogenesis and Inflammatory Pathways by Glycyrrhizic Acid","volume":"44","author":"Mohamed","year":"2024","journal-title":"Egypt. J. Dermatol. Venereol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s10238-025-01859-w","article-title":"The Role of Skin Barrier and Immune Abnormalities in the Pathogenesis of Rosacea","volume":"25","author":"Chen","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"109181","DOI":"10.1016\/j.biopha.2019.109181","article-title":"Artemisinin, a Potential Option to Inhibit Inflammation and Angiogenesis in Rosacea","volume":"117","author":"Yuan","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Semenescu, I., Similie, D., Diaconeasa, Z., and Danciu, C. (2024). Recent Advances in the Management of Rosacea through Natural Compounds. Pharmaceuticals, 17.","DOI":"10.3390\/ph17020212"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Andrusiewicz, A., Khimuk, S., Mijas, D., Shmorhun, B., Nowicka, D., Andrusiewicz, A., Khimuk, S., Mijas, D., Shmorhun, B., and Nowicka, D. (2025). Molecular Mechanisms in the Etiopathology of Rosacea\u2014Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311292"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1021\/acs.jafc.9b00185","article-title":"Liquiritin from Glycyrrhiza Uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway","volume":"67","author":"Zhai","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_93","first-page":"9523071.","article-title":"Pharmacological Effects and Underlying Mechanisms of Licorice-Derived Flavonoids","volume":"2022","author":"Wu","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9988167","DOI":"10.1155\/2024\/9988167","article-title":"Exploring the Role of Licorice and Its Derivatives in Cell Signaling Pathway NF-\u039aB and MAPK","volume":"2024","author":"Fatima","year":"2024","journal-title":"J. Nutr. Metab."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/2\/158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T14:10:06Z","timestamp":1769177406000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/2\/158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":94,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["antiox15020158"],"URL":"https:\/\/doi.org\/10.3390\/antiox15020158","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}