{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:46:37Z","timestamp":1790178397914,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Natural deep eutectic solvents (NADES) have been extensively used for the extraction of a wide spectrum of plant materials. However, limited data about the in vivo toxicity of NADES extracts restrict their future practical application. In this study, we are aiming to assess the safety of a Sorbitol\u2013lactic acid (3:1 mol.\/mol.; 30% water) NADES extract of Glycyrrhiza roots (GR) in mice. LC-MS\/MS analysis revealed the presence of 17 metabolites, including phenolic acids, flavonoids, their glycosides, chalcones, terpene saponins, and coumarins. Interestingly, most of the identified compounds were found in higher amounts in NADES extract compared to water and EtOH extracts. No skin edema, inflammation, or erythema was observed in mice after topical application of NADES extract of GR and NADES at the doses of 50, 100, and 150 \u00b5L\/mice in comparison with the control group. The calculated primary irritation index was about 0.45 both for NADES and NADES extract of GR only in high doses and falls into mild irritant categories. The individual Draize scores indicate that erythema was evident in the first three days and that all signs had disappeared by day five. No acute toxic signs or mortality of animals was observed in mice following oral administration of single doses of 4, 6, and 20 g\/kg of NADES or NADES extract of GR. The NADES and extract seem to be safe at doses of up to 20 g\/kg, and the LD50 was considered to be &gt;20 g\/kg. Our results open prospects for the use of NADES extract of GR for the development of transdermal and peroral formulations in the cosmetic, food, and pharmaceutical industries.<\/jats:p>","DOI":"10.3390\/molecules30244704","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T09:02:50Z","timestamp":1765270970000},"page":"4704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Safety of NADES Extract of Glycyrrhiza Roots After Topical Application and Peroral Administration to Mice"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3028-4238","authenticated-orcid":false,"given":"Veronika A.","family":"Shikova","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Formulations, St. Petersburg State Chemical Pharmaceutical University, Prof. Popov Str., 14, 197376 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-0665","authenticated-orcid":false,"given":"Olga N.","family":"Pozharitskaya","sequence":"additional","affiliation":[{"name":"Murmansk Marine Biological Institute of the Russian Academy of Sciences (MMBI RAS), Vladimirskaya Str., 17, 183038 Murmansk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Flisyuk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Formulations, St. Petersburg State Chemical Pharmaceutical University, Prof. Popov Str., 14, 197376 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9273-6864","authenticated-orcid":false,"given":"Dmitry Yu.","family":"Ivkin","sequence":"additional","affiliation":[{"name":"Center of Experimental Pharmacology, St. Petersburg State Chemical Pharmaceutical University, Prof. Popov Str., 14, 197376 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8616-3543","authenticated-orcid":false,"given":"Dmitrii N.","family":"Borovikov","sequence":"additional","affiliation":[{"name":"Infochemistry Scientific Center, School of Life Sciences, ITMO University, Lomonosov Str., 9, 191002 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-9858","authenticated-orcid":false,"given":"Olga L.","family":"Balabanova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, St. Petersburg State Chemical Pharmaceutical University, Prof. Popov Str., 14, 197376 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-0695","authenticated-orcid":false,"given":"Alexander N.","family":"Shikov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Formulations, St. Petersburg State Chemical Pharmaceutical University, Prof. Popov Str., 14, 197376 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1104\/pp.111.178426","article-title":"Are natural deep eutectic solvents the missing link in understanding cellular metabolism and physiology?","volume":"156","author":"Choi","year":"2011","journal-title":"Plant Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kaleta, A., Frolova, N., Orlova, A., Soboleva, A., Osmolovskaya, N., Flisyuk, E., Pozharitskaya, O., Frolov, A., and Shikov, A. (2024). The Effects of selected extraction methods and natural deep eutectic solvents on the recovery of active principles from Aralia elata var. mandshurica (Rupr. & Maxim.) J. Wen: A non-targeted metabolomics approach. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030355"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139508","DOI":"10.1016\/j.foodchem.2024.139508","article-title":"Green and efficient extraction of flavonoids from Perilla frutescens (L.) Britt. leaves based on natural deep eutectic solvents: Process optimization, component identification, and biological activity","volume":"452","author":"Wang","year":"2024","journal-title":"Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"118059","DOI":"10.1016\/j.indcrop.2024.118059","article-title":"An eco-friendly approach to extract anthocyanins from rose flowers using natural deep eutectic solvents","volume":"210","author":"Prakash","year":"2024","journal-title":"Ind. Crops Prod."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Molnar, M., Jakovljevi\u0107 Kova\u010d, M., and Pavi\u0107, V. (2024). A Comprehensive analysis of diversity, structure, biosynthesis and extraction of biologically active tannins from various plant-based materials using deep eutectic solvents. Molecules, 29.","DOI":"10.3390\/molecules29112615"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114886","DOI":"10.1016\/j.indcrop.2022.114886","article-title":"An eco-friendly approach to enhance the extraction and recovery efficiency of isoflavones from kudzu roots and soy molasses wastes using ultrasound-assisted extraction with natural deep eutectic solvents (NADES)","volume":"182","author":"Duru","year":"2022","journal-title":"Ind. Crops Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.aca.2012.12.019","article-title":"Natural deep eutectic solvents as new potential media for green technology","volume":"766","author":"Dai","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ivkovic, D., Cvijetic, I., Radoicic, A., Stojkovic-Filipovic, J., Trifkovic, J., Krstic Ristivojevic, M., and Ristivojevic, P. (2024). NADES-Based extracts of selected medicinal herbs as promising formulations for cosmetic usage. Processes, 12.","DOI":"10.3390\/pr12050992"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101654","DOI":"10.1016\/j.scp.2024.101654","article-title":"Single-step extraction\/pre-formulation process for B-phycoerythrin using glycerol-based eutectic solvents: A step toward more sustainable production of phycobiliproteins","volume":"40","author":"Odou","year":"2024","journal-title":"Sustain. Chem. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37092","DOI":"10.1039\/C8RA08536F","article-title":"A Novel switchable-hydrophilicity, natural deep eutectic solvent (NADES)-based system for bio-safe biorefinery","volume":"8","author":"Sed","year":"2018","journal-title":"RSC Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8360","DOI":"10.1039\/D4GC06386D","article-title":"Natural Deep Eutectic Solvents (NADES): Green solvents for pharmaceutical applications and beyond","volume":"27","author":"Choi","year":"2025","journal-title":"Green Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10649","DOI":"10.1021\/acssuschemeng.9b01306","article-title":"Probing the environmental toxicity of deep eutectic solvents and their components: An in silico modeling approach","volume":"7","author":"Halder","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114878","DOI":"10.1016\/j.molliq.2020.114878","article-title":"Assessment and design of greener deep eutectic solvents\u2014A multicriteria decision analysis","volume":"321","author":"Bystrzanowska","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14188","DOI":"10.1007\/s11356-018-1669-z","article-title":"Antimicrobial, cytotoxic and antioxidative evaluation of natural deep eutectic solvents","volume":"25","author":"Markov","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1021\/acssuschemeng.5b01124","article-title":"Ecotoxicity of cholinium-based deep eutectic solvents","volume":"3","author":"Coutinho","year":"2015","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pozharitskaya, O.N., Obluchinskaya, E.D., Shikova, V.A., Flisyuk, E.V., Vishnyakov, E.V., Makarevich, E.V., and Shikov, A.N. (2024). Physicochemical and antimicrobial properties of lactic acid-based natural deep eutectic solvents as a function of water content. Appl. Sci., 14.","DOI":"10.3390\/app142210409"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1021\/sc500096j","article-title":"Natural deep eutectic solvents\u2014Solvents for the 21st century","volume":"2","author":"Paiva","year":"2014","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1039\/D2RA07488E","article-title":"Cytotoxicity profiling of choline chloride-based natural deep eutectic solvents","volume":"13","author":"Macedo","year":"2023","journal-title":"RSC Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/j.bpj.2015.07.046","article-title":"Osmotic regulation is required for cancer cell survival under solid stress","volume":"109","author":"McGrail","year":"2015","journal-title":"Biophys. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hayyan, M., Looi, C.Y., Hayyan, A., Wong, W.F., and Hashim, M.A. (2015). In vitro and in vivo toxicity profiling of ammonium-based deep eutectic solvents. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117934"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jchromb.2017.08.016","article-title":"The effect of deep eutectic solvent on the pharmacokinetics of salvianolic acid B in rats and its acute toxicity test","volume":"1063","author":"Chen","year":"2017","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6205","DOI":"10.1021\/acs.jafc.8b01746","article-title":"Toxicity of natural deep eutectic solvent betaine:glycerol in rats","volume":"66","author":"Benlebna","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109718","DOI":"10.1016\/j.foodres.2020.109718","article-title":"Natural deep eutectic solvent (NADES)-based blueberry extracts protect against ethanol-induced gastric ulcer in rats","volume":"138","author":"Rodrigues","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.procbio.2020.11.023","article-title":"Green extraction of glycyrrhizic acid from Glycyrrhiza glabra using choline chloride based natural deep eutectic solvents (NADESs)","volume":"102","author":"Lanjekar","year":"2021","journal-title":"Process Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9532","DOI":"10.1021\/acs.iecr.1c00862","article-title":"Application of ultrasound and natural deep eutectic solvent for the extraction of glycyrrhizic acid from Glycyrrhiza glabra: Optimization and kinetic evaluation","volume":"60","author":"Lanjekar","year":"2021","journal-title":"Ind. Eng. Chem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37649","DOI":"10.1039\/D1RA06338C","article-title":"Natural deep eutectic solvents as tailored and sustainable media for the extraction of five compounds from compound liquorice tablets and their comparison with conventional organic Solvents","volume":"11","author":"Dong","year":"2021","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/pca.2664","article-title":"RP-HPLC-DAD-ESI-QTOF-MS based metabolic profiling of the potential Olea europaea by-product \u201cwood\u201d and its comparison with leaf counterpart","volume":"28","author":"Ammar","year":"2017","journal-title":"Phytochem. Anal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1248\/cpb.c19-00423","article-title":"Comparative metabolite profiling of wild and cultivated licorice based on ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry","volume":"67","author":"Wang","year":"2019","journal-title":"Chem. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.phytochem.2011.12.010","article-title":"Comparative metabolite profiling and fingerprinting of medicinal licorice roots using a multiplex approach of GC\u2013MS, LC\u2013MS and 1D NMR techniques","volume":"76","author":"Farag","year":"2012","journal-title":"Phytochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jpba.2010.10.004","article-title":"Metabolic profiling of roots of liquorice (Glycyrrhiza glabra) from different geographical areas by ESI\/MS\/MS and determination of major metabolites by LC-ESI\/MS and LC-ESI\/MS\/MS","volume":"54","author":"Paola","year":"2011","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.chroma.2008.08.038","article-title":"Rapid analysis of a chinese herbal prescription by liquid chromatography-time-of-flight tandem mass spectrometry","volume":"1206","author":"Zheng","year":"2008","journal-title":"J. Chromatogr. A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.fitote.2011.01.009","article-title":"Phytocomplexes from liquorice (Glycyrrhiza glabra L.) leaves\u2014Chemical characterization and evaluation of their antioxidant, anti-genotoxic and anti-inflammatory activity","volume":"82","author":"Siracusa","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jiang, L., Akram, W., Luo, B., Hu, S., Faruque, M.O., Ahmad, S., Yasin, N.A., Khan, W.U., Ahmad, A., and Shikov, A.N. (2021). Metabolomic and pharmacologic insights of aerial and underground parts of Glycyrrhiza uralensis Fisch. ex DC. for maximum utilization of medicinal resources. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.658670"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acs.jnatprod.5b00877","article-title":"Bioactive constituents of Glycyrrhiza uralensis (licorice): Discovery of the effective components of a traditional herbal medicine","volume":"79","author":"Ji","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1093\/chromsci\/bms086","article-title":"Simultaneous determination of oleanolic acid, p-coumaric acid, ferulic acid, kaemperol and quercetin in rat plasma by LC\u2013MS-MS and application to a pharmacokinetic study of Oldenlandia diffusa extract in rats","volume":"50","author":"Li","year":"2012","journal-title":"J. Chromatogr. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13020-021-00459-6","article-title":"The combination of UHPLC-HRMS and molecular networking improving discovery efficiency of chemical components in chinese classical formula","volume":"16","author":"Xue","year":"2021","journal-title":"Chin. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/jsfa.1873","article-title":"Ferulic acid: Pharmaceutical functions, preparation and applications in foods","volume":"84","author":"Ou","year":"2004","journal-title":"J. Sci. Food Agric."},{"key":"ref_38","first-page":"132","article-title":"A recent overview on the biological and pharmacological activities of ferulic acid","volume":"18","author":"Kim","year":"2019","journal-title":"EXCLI J."},{"key":"ref_39","first-page":"1061","article-title":"A comprehensive review of the classification, sources, biosynthesis, and biological properties of hydroxybenzoic and hydroxycinnamic acids","volume":"24","author":"Sganzerla","year":"2023","journal-title":"Phytochem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"298","DOI":"10.2174\/138955711795305335","article-title":"A review on the dietary flavonoid kaempferol","volume":"11","year":"2011","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1080\/19390211.2022.2050875","article-title":"Assessment of herb-drug interaction potential of five common species of licorice and their phytochemical constituents","volume":"20","author":"Haron","year":"2023","journal-title":"J. Diet. Suppl."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.2174\/0113862073298262240705045345","article-title":"Jiawei Duhuo Jisheng mixture mitigates osteoarthritis progression in rabbits by inhibiting inflammation: A network pharmacology and experimental approach","volume":"28","author":"Kaiyun","year":"2025","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1631\/jzus.B1300138","article-title":"Neuroprotective effects of flavonoids extracted from licorice on kainate-induced seizure in mice through their antioxidant properties","volume":"14","author":"Zeng","year":"2013","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Eltahir, A.O.E., Omoruyi, S.I., Augustine, T.N., Luckay, R.C., and Hussein, A.A. (2024). Neuroprotective effects of Glycyrrhiza glabra total extract and isolated compounds. Pharmaceuticals, 17.","DOI":"10.3390\/ph17070852"},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1021\/acs.jnatprod.9b00262","article-title":"Prenylated Phenolic compounds from the aerial parts of Glycyrrhiza uralensis as PTP1B and \u03b1-glucosidase inhibitors","volume":"83","author":"Fan","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"199","DOI":"10.15789\/2220-7619-2016-3-199-206","article-title":"Anti-viral activity of glycirrhetinic and glycirrhizic acids","volume":"6","author":"Zarubaev","year":"2016","journal-title":"Russ. J. Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s11418-019-01329-0","article-title":"Isolation, structural elucidation and in vitro hepatoprotective activity of flavonoids from Glycyrrhiza uralensis","volume":"73","author":"Cheng","year":"2019","journal-title":"J. Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Leite, C.d.S., Bonaf\u00e9, G.A., Carvalho Santos, J., Martinez, C.A.R., Ortega, M.M., and Ribeiro, M.L. (2022). The anti-inflammatory properties of licorice (Glycyrrhiza glabra)-derived compounds in intestinal disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084121"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"119948","DOI":"10.1016\/j.jep.2025.119948","article-title":"Glycyrrhiza glabra extract as a skin-whitening agent: Identification of active components and CRTC1\/MITF pathway-inhibition mechanism","volume":"349","author":"Liu","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jphotobiol.2015.05.003","article-title":"Glycyrrhizic acid (GA) inhibits reactive oxygen species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts","volume":"148","author":"Farrukh","year":"2015","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/10915810701351228","article-title":"Final report on the safety assessment of glycyrrhetinic acid, potassium glycyrrhetinate, disodium succinoyl glycyrrhetinate, glyceryl glycyrrhetinate, glycyrrhetinyl stearate, stearyl glycyrrhetinate, glycyrrhizic acid, ammonium glycyrrhizate, dipotassium glycyrrhizate, disodium glycyrrhizate, trisodium glycyrrhizate, methyl glycyrrhizate, and potassium glycyrrhizinate","volume":"26","author":"Andersen","year":"2007","journal-title":"Int. J. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7090","DOI":"10.1111\/jocd.15383","article-title":"Glycyrrhizic acid suppresses atopic dermatitis-like symptoms by regulating the immune balance","volume":"21","author":"Hou","year":"2022","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jep.2012.11.005","article-title":"Antispasmodic effect of shakuyakukanzoto extract on experimental muscle cramps in vivo: Role of the active constituents of Glycyrrhizae radix","volume":"145","author":"Lee","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.5897\/AJMR12.1182","article-title":"Antimicrobial potential of licorice: Leaves versus roots","volume":"6","author":"Bassyouni","year":"2012","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e36119","DOI":"10.1097\/MD.0000000000036119","article-title":"Research on the resistance of isoviolanthin to hydrogen peroxide-triggered injury of skin keratinocytes based on Transcriptome sequencing and molecular docking","volume":"102","author":"Wang","year":"2023","journal-title":"Medicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115257","DOI":"10.1016\/j.jep.2022.115257","article-title":"Pharmacological activities and pharmacokinetics of liquiritin: A Review","volume":"293","author":"Qin","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mce.2007.11.020","article-title":"Liquiritigenin is a plant-derived highly selective estrogen receptor agonist","volume":"283","author":"Mersereau","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_59","first-page":"165","article-title":"Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-\u03baB-dependent iNOS and proinflammatory cytokines production","volume":"154","author":"Kim","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ramalingam, M., Kim, H., Lee, Y., and Lee, Y.I. (2018). Phytochemical and Pharmacological role of liquiritigenin and isoliquiritigenin from radix Glycyrrhizae in human health and disease models. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00348"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sajeev, A., Aswani, B.S., Alqahtani, M.S., Abbas, M., Sethi, G., and Kunnumakkara, A.B. (2025). Harnessing liquiritigenin: A Flavonoid-based approach for the prevention and treatment of cancer. Cancers, 17.","DOI":"10.3390\/cancers17142328"},{"key":"ref_62","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. Alternat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ptr.7352","article-title":"O-Glycoside quercetin derivatives: Biological activities, mechanisms of action, and structure-activity relationship for drug design, a review","volume":"36","author":"Alizadeh","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1002\/ptr.5893","article-title":"Toxicological effects of Glycyrrhiza glabra (licorice): A review","volume":"31","author":"Nazari","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"El-Saber Batiha, G., Magdy Beshbishy, A., El-Mleeh, A., Abdel-Daim, M.M., and Prasad Devkota, H. (2020). Traditional uses, bioactive chemical constituents, and pharmacological and toxicological activities of Glycyrrhiza glabra L. (Fabaceae). Biomolecules, 10.","DOI":"10.3390\/biom10030352"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"OECD (2017). Acute Dermal Toxicity. OECD Draft Guidelines for Testing of Chemicals, No. 402, Fixed Procedures, Organization for Economic Cooperation and Development. Available online: https:\/\/www.oecd.org\/en\/publications\/test-no-402-acute-dermal-toxicity_9789264070585-en.html.","DOI":"10.1787\/9789264070585-en"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Grozdanova, T., Trusheva, B., Alipieva, K., Popova, M., Dimitrova, L., Najdenski, H., Zaharieva, M.M., Ilieva, Y., Vasileva, B., and Miloshev, G. (2020). Extracts of medicinal plants with natural deep eutectic solvents: Enhanced antimicrobial activity and low genotoxicity. BMC Chem., 14.","DOI":"10.1186\/s13065-020-00726-x"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"143148","DOI":"10.1016\/j.foodchem.2025.143148","article-title":"Cytotoxic potential of sunflower meal NADES and liquid-liquid extracts","volume":"474","author":"Ramos","year":"2025","journal-title":"Food Chem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Shikov, A.N., Shikova, V.A., Whaley, A.O., Burakova, M.A., Flisyuk, E.V., Whaley, A.K., Terninko, I.I., Generalova, Y.E., Gravel, I.V., and Pozharitskaya, O.N. (2022). The Ability of acid-based natural deep eutectic solvents to co-extract elements from the roots of Glycyrrhiza glabra L. and associated health risks. Molecules, 27.","DOI":"10.3390\/molecules27227690"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"153","DOI":"10.30802\/AALAS-JAALAS-22-000065","article-title":"Effects of depilatory cream formulation and contact time on mouse skin","volume":"62","author":"Reichert","year":"2023","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_71","unstructured":"European Council (2025, October 20). Directive 2010\/63\/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. Available online: http:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=celex%3A32010L0063."},{"key":"ref_72","unstructured":"Karkishenko, N.N., and Grachev, C.V. (2010). Manual for Laboratory Animals and Alternative Models in Biomedical Research, Profile-2C."},{"key":"ref_73","unstructured":"OECD (2002). Irritation\/Corrosion. OECD Guidelines for Testing of Chemicals, No. 404, Organization for Economic Cooperation and Development. Available online: https:\/\/www.oecd.org\/en\/publications\/2002\/04\/test-no-404-acute-dermal-irritation-corrosion_g1gh2929.html."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0022-3565(25)08751-8","article-title":"Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes","volume":"82","author":"Draize","year":"1944","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20763","DOI":"10.9734\/EJMP\/2015\/20763","article-title":"Assessment of dermal irritation and acute toxicity potential of extracts from Synadenium glaucescens on healthy rabbits, wistar albino rats and albino mice","volume":"10","author":"Nyigo","year":"2015","journal-title":"Eur. J. Med. Plants"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/24\/4704\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:33:07Z","timestamp":1765380787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/24\/4704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":75,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["molecules30244704"],"URL":"https:\/\/doi.org\/10.3390\/molecules30244704","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]}}}