{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:28:01Z","timestamp":1785414481071,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["PBsd 2010"],"award-info":[{"award-number":["PBsd 2010"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PBsd 2010"],"award-info":[{"award-number":["PBsd 2010"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Shikonins are natural naphthoquinones that exhibit a range of biological activities. They are typically extracted using nonpolar solvents; however, green extraction approaches remain underexplored. Methods: Phytochemical profiling of E. vulgare root extracts was performed using HPLC-ESI-QTOF-MS\/MS and quantitative analysis using HPLC-PDA. Shikonin extraction was performed using VNADESs based on thymol, camphor, menthol and benzyl alcohol. The feasibility of removing the VNADES from the extracts via freeze-drying was assessed. The cytotoxic, antioxidant, anti-inflammatory and antimicrobial activities of the hexane extract and the selected VNADES-based extract (TBa 2:8) were compared. Results: Eight shikonin derivatives were identified in the extracts. VNADES extracts contained comparable amounts of shikonin to hexane extracts; however, freeze-drying resulted in significant shikonin content loss. TBa 2:8 extract exhibited noticeably lower cytotoxicity than the hexane extract while its antioxidant potential depended on the assay applied. In contrast to the hexane extract, TBa 2:8 demonstrated the ability to reduce intracellular ROS and NO levels. However, the hexane extract exhibited stronger antimicrobial activity. Conclusions: VNADES systems enable efficient extraction of shikonin derivatives with performance comparable to hexane. Although the resulting extracts exhibit multidirectional biological activity, it remains challenging to remove the VNADESs effectively without losing the shikonins.<\/jats:p>","DOI":"10.3390\/molecules31091434","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:49:36Z","timestamp":1777362576000},"page":"1434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Volatile Natural Deep Eutectic Solvents (VNADESs) for Extraction of Shikonin Derivatives from Echium vulgare Roots and Evaluation of Biological Activity"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-7413","authenticated-orcid":false,"given":"Magdalena","family":"Kulinowska","sequence":"first","affiliation":[{"name":"Doctoral School, Medical University of Lublin, 7 Chodzki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-3748","authenticated-orcid":false,"given":"S\u0142awomir","family":"Dresler","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Lublin, 4A Chodzki Str., 20-093 Lublin, Poland"},{"name":"Department of Plant Physiology and Biophysics, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Sk\u0142odowska University, 19 Akademicka St., 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Grzegorczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology, Medical University of Lublin, 1 Chodzki Str., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-1332","authenticated-orcid":false,"given":"Martyna","family":"Zag\u00f3rska-Dziok","sequence":"additional","affiliation":[{"name":"Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, 2 Sucharskiego St., 35-225 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8871-8911","authenticated-orcid":false,"given":"Aleksandra","family":"Ziemlewska","sequence":"additional","affiliation":[{"name":"Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, 2 Sucharskiego St., 35-225 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-600X","authenticated-orcid":false,"given":"Wirginia","family":"Kukula-Koch","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Sawa-Wejksza","sequence":"additional","affiliation":[{"name":"Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sk\u0142odowska University, 19 Akademicka St., 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0039-4455","authenticated-orcid":false,"given":"Maciej","family":"Strzemski","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Lublin, 4A Chodzki Str., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gautam, S., Lap\u010d\u00edk, L., and Lap\u010d\u00edkov\u00e1, B. (2024). Pharmacological Significance of Boraginaceae with Special Insights into Shikonin and Its Potential in the Food Industry. Foods, 13.","DOI":"10.3390\/foods13091350"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1080\/13880209.2016.1265986","article-title":"Comparison of some secondary metabolite content in the seventeen species of the boraginaceae family","volume":"55","author":"Dresler","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/(SICI)1521-3773(19990201)38:3<270::AID-ANIE270>3.0.CO;2-0","article-title":"The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products","volume":"38","author":"Papageorgiou","year":"1999","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s12967-017-1223-7","article-title":"Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells","volume":"15","author":"Kim","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"583","DOI":"10.2174\/138527206776055277","article-title":"Analytical Methods for the Determination of Alkannins and Shikonins","volume":"10","author":"Papageorgiou","year":"2006","journal-title":"Curr. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114314","DOI":"10.1016\/j.ejmech.2022.114314","article-title":"Recent advances of antitumor shikonin\/alkannin derivatives: A comprehensive overview focusing on structural classification, synthetic approaches, and mechanisms of action","volume":"235","author":"Valipour","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15619","DOI":"10.1007\/s13399-024-06211-y","article-title":"Enhancing extraction of shikonin and phenolic antioxidants from Echium italicum L. using ultrasound and response surface methodology: Optimizing temperature, time, and liquid\u2013solid ratio","volume":"15","author":"Gheisary","year":"2025","journal-title":"Biomass Convers. Biorefinery"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116249","DOI":"10.1016\/j.ejmech.2024.116249","article-title":"Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties","volume":"268","author":"Plano","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/j.1349-7006.2002.tb01341.x","article-title":"\u03b2-Hydroxyisovaleryshikonin is a novel and potent inhibitor of protein tyrosine kinases","volume":"93","author":"Hashimoto","year":"2002","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"520578","DOI":"10.1155\/2015\/520578","article-title":"The mechanism underlying the antibacterial activity of shikonin against methicillin-resistant staphylococcus aureus","volume":"2015","author":"Lee","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wnorowska, S., Grzegorczyk, A., Kurzepa, J., Maggi, F., and Strzemski, M. (2024). Fractionation of Carlina acaulis L. Root Methanolic Extract as a Promising Path towards New Formulations against Bacillus cereus and Methicillin-Resistant Staphylococcus aureus. Molecules, 29.","DOI":"10.3390\/molecules29091939"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e01588-17","DOI":"10.1128\/JCM.01588-17","article-title":"Candida auris: An emerging fungal pathogen","volume":"56","author":"Spivak","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S1473-3099(13)70190-7","article-title":"Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases","volume":"13","author":"Poirel","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1128\/AAC.01015-06","article-title":"Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients","volume":"51","author":"Hachem","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1086\/518170","article-title":"An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex infection in the US military health care system associated with military operations in Iraq","volume":"44","author":"Scott","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1248\/cpb.44.249","article-title":"Kinetic studies of the photochemical decomposition of alkannin\/shikonin enantiomers","volume":"44","author":"Chen","year":"1996","journal-title":"Chem. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"138898","DOI":"10.1016\/j.molstruc.2024.138898","article-title":"Unveiling the photostability of the molecule of colour shikonin: From solution to the solid state","volume":"1316","author":"Pinto","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1080\/10826076.2014.951767","article-title":"Determination of shikonin and rosmarinic acid in Echium vulgare L. and Echium russicum J.F. Gmel. by capillary electrophoresis","volume":"38","author":"Dresler","year":"2015","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_19","first-page":"271","article-title":"Hexane","volume":"Volume 5","author":"Bolt","year":"2023","journal-title":"Encyclopedia of Toxicology, Fourth Edition: Volume 1\u20139"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3109\/10408444.2015.1016216","article-title":"Characterization of the toxicological hazards of hydrocarbon solvents","volume":"45","author":"McKee","year":"2015","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kulinowska, M., Dresler, S., Skalska-Kami\u0144ska, A., Hanaka, A., and Strzemski, M. (2023). Methodological Aspects of Green Extraction of Usnic Acid Using Natural Deep Eutectic Solvents. Molecules, 28.","DOI":"10.3390\/molecules28145321"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1021\/acs.jnatprod.7b00945","article-title":"Natural Deep Eutectic Solvents: Properties, Applications, and Perspectives","volume":"81","author":"Liu","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kulinowska, M., Grzegorczyk, A., Dresler, S., Skalska-Kami\u0144ska, A., Dubaj, K., and Strzemski, M. (2025). Evaluation of the Antioxidant and Antimicrobial Activity of Natural Deep Eutectic Solvents (NADESs) Based on Primary and Specialized Plant Metabolites. Molecules, 30.","DOI":"10.3390\/molecules30214219"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bossard, E., Cartabia, A., Lalaymia, I., Tsafantakis, N., Aligiannis, N., Chinou, I., Declerck, S., and Fokialakis, N. (2025). Innovative Hydroponic Culture of Alkanna tinctoria (L.) Tausch: An Approach Towards Sustainable Extraction Process from Plant Roots. Plants, 14.","DOI":"10.3390\/plants14192987"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1016\/j.chroma.2009.01.098","article-title":"Identification of shikonin and its ester derivatives from the roots of Echium italicum L.","volume":"1216","author":"Albreht","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Skoneczny, D., Weston, P.A., Zhu, X., Gurr, G.M., Callaway, R.M., Barrow, R.A., and Weston, L.A. (2017). Metabolic profiling and identification of shikonins in root periderm of two invasive Echium spp. weeds in Australia. Molecules, 22.","DOI":"10.3390\/molecules22020330"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.chroma.2015.11.028","article-title":"Systematic identification of shikonins and shikonofurans in medicinal Zicao species using ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry combined with a data mining strategy","volume":"1425","author":"Liao","year":"2015","journal-title":"J. Chromatogr. A"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","unstructured":"Strzemski, M., Dresler, S., Podko\u015bcielna, B., Skic, K., Sowa, I., Za\u0142uski, D., Verpoorte, R., Zieli\u0144ska, S., Krawczyk, P., and W\u00f3jciak, M. (2022). Effectiveness of Volatile Natural Deep Eutectic Solvents (VNADESs) for the Green Extraction of Chelidonium majus Isoquinoline Alkaloids. Molecules, 27.","DOI":"10.3390\/molecules27092815"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"22742","DOI":"10.1038\/s41598-025-08069-0","article-title":"Extraction of lichen bioactive compounds using volatile natural deep eutectic solvents and comparative analytical approaches","volume":"15","author":"Dresler","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Szopa, D., Wr\u00f3bel, P., Zwoli\u0144ska, J., Anwar, H., Kaniewski, M., and Witek-Krowiak, A. (2026). Influence of Deep Eutectic Solvents and Polyphenolic Extracts on the Structure and Functional Properties of Sodium Alginate Films. Polymers, 18.","DOI":"10.3390\/polym18020186"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6272","DOI":"10.1021\/ac400432p","article-title":"Natural deep eutectic solvents as a new extraction media for phenolic metabolites in Carthamus tinctorius L.","volume":"85","author":"Dai","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1111\/ijfs.13391","article-title":"Influence of freezing, lyophilisation and air-drying on the total monomeric anthocyanins, vitamin C and antioxidant capacity of selected berries","volume":"52","author":"Sadowska","year":"2017","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_35","first-page":"33","article-title":"Stability of vitamin c and beta-carotene during the tomato paste lyophilization process the tomato paste lyophilization process","volume":"84","author":"Kosmala","year":"2022","journal-title":"Biotechnol. Food Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1021\/jf9902853","article-title":"Physical stability of shikonin derivatives from the roots of Lithospermum erythrorhizon cultivated in Korea","volume":"47","author":"Cho","year":"1999","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"ElGamal, R., Song, C., Rayan, A.M., Liu, C., Al-Rejaie, S., and ElMasry, G. (2023). Thermal Degradation of Bioactive Compounds during Drying Process of Horticultural and Agronomic Products: A Comprehensive Overview. Agronomy, 13.","DOI":"10.3390\/agronomy13061580"},{"key":"ref_38","first-page":"14","article-title":"Echium italicum Plant Extracts Have Wound Healing Potential in Human Dermal Fibroblast (HDF) Cell","volume":"3","author":"Akduman","year":"2024","journal-title":"Eurasian J. Mol. Biochem. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Imai, K., Kato, H., Taguchi, Y., and Umeda, M. (2019). Biological effects of shikonin in human gingival fibroblasts via ERK 1\/2 signaling pathway. Molecules, 24.","DOI":"10.3390\/molecules24193542"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Koz\u0142owska, M., \u015acibisz, I., Przyby\u0142, J.L., Laudy, A.E., Majewska, E., Tarnowska, K., Ma\u0142ajowicz, J., and Ziarno, M. (2022). Antioxidant and Antibacterial Activity of Extracts from Selected Plant Material. Appl. Sci., 12.","DOI":"10.3390\/app12199871"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Walasek-Janusz, M., Papli\u0144ski, R., Mysiak, B., and Nurzy\u0144ska-Wierdak, R. (2025). Phenolic Profile and Antioxidant Activity of Extracts from Aerial Parts of Thymus vulgaris L. and Sideritis scardica Griseb. Appl. Sci., 15.","DOI":"10.3390\/app15073842"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.foodchem.2003.12.017","article-title":"Antioxidant activities of alkannin, shikonin and Alkanna tinctoria root extracts in oil substrates","volume":"87","author":"Assimopoulou","year":"2004","journal-title":"Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1089\/jmf.2013.3088","article-title":"Lithospermum erythrorhizon extract protects keratinocytes and fibroblasts against oxidative stress","volume":"17","author":"Yoo","year":"2014","journal-title":"J. Med. Food"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/1521-4184(200208)335:6<262::AID-ARDP262>3.0.CO;2-Y","article-title":"Alkannin and shikonin: Effect on free radical processes and on inflammation\u2014A preliminary pharmacochemical investigation","volume":"335","author":"Kourounakis","year":"2002","journal-title":"Arch. Pharm. (Weinh.)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.canlet.2019.04.033","article-title":"Shikonin derivatives for cancer prevention and therapy","volume":"459","author":"Boulos","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1055\/s-0031-1280430","article-title":"Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones","volume":"78","author":"Landa","year":"2012","journal-title":"Planta Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1055\/s-0033-1350934","article-title":"Pharmacological properties of shikonin\u2014A review of literature since 2002","volume":"79","author":"Giner","year":"2013","journal-title":"Planta Med."},{"key":"ref_48","first-page":"641","article-title":"Biological screening of various medicinal plant extracts for antibacterial and antitumor activities","volume":"36","author":"Yildirim","year":"2012","journal-title":"Turk. J. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"665","DOI":"10.31925\/farmacia.2022.4.12","article-title":"Influence of Solvent Type on the Phenolic Content and Antimicrobial and Antioxidant Properties of Echium vulgare L. Extracts","volume":"70","year":"2022","journal-title":"Farmacia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkae380","article-title":"Bactericidal versus bacteriostatic antibacterials: Clinical significance, differences and synergistic potential in clinical practice","volume":"80","author":"Ishak","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rat, A., Koletti, A.E., Rodi\u0107, N., Papageorgiou, V.P., Willems, A., and Assimopoulou, A.N. (2023). Bacterial responses to plant antimicrobials: The case of alkannin and shikonin derivatives. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1244270"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1248\/bpb.25.669","article-title":"In vitro antifungal activity of naphthoquinone derivatives","volume":"25","author":"Sasaki","year":"2002","journal-title":"Biol. Pharm. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1248\/bpb.b12-00338","article-title":"Inhibitory effect of Shikonin on Candida albicans growth","volume":"35","author":"Miao","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, Q.Q., Chae, H.S., Kang, O.H., and Kwon, D.Y. (2022). Synergistic Antibacterial Activity with Conventional Antibiotics and Mechanism of Action of Shikonin against Methicillin-Resistant Staphylococcus aureus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147551"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1208617","DOI":"10.1155\/2020\/1208617","article-title":"Optimization Extraction of Shikonin Using Ultrasound-Assisted Response Surface Methodology and Antibacterial Studies","volume":"2020","author":"Huang","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1021\/np010599w","article-title":"Antimicrobial activities of naphthazarins from Arnebia euchroma","volume":"65","author":"Shen","year":"2002","journal-title":"J. Nat. Prod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1038\/s41598-021-82207-2","article-title":"Assessment of cytotoxicity and antioxidant properties of berry leaves as by-products with potential application in cosmetic and pharmaceutical products","volume":"11","author":"Ziemlewska","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"G\u0119balski, J., Ma\u0142kowska, M., Kie\u0142kowska, E., Graczyk, F., Wnorowska, S., Ho\u0142y\u0144ska-Iwan, I., Strzemski, M., W\u00f3jciak, M., and Za\u0142uski, D. (2025). Chemical Composition and In Vitro Biological Activity of the Polar and Non-Polar Fractions Obtained from the Roots of Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125619"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"401","DOI":"10.31545\/intagr\/171927","article-title":"Effect of apple pomace (Malus domestica \u2018Gala\u2019) addition on the processing conditions and antioxidant potential of extruded snacks","volume":"37","author":"Soja","year":"2023","journal-title":"Int. Agrophys."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Stasi\u0144ska-Jakubas, M., Hawrylak-Nowak, B., W\u00f3jciak, M., and Dresler, S. (2023). Comparative Effects of Two Forms of Chitosan on Selected Phytochemical Properties of Plectranthus amboinicus (Lour.). Molecules, 28.","DOI":"10.3390\/molecules28010376"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jpha.2015.11.005","article-title":"Methods for in vitro evaluating antimicrobial activity: A review","volume":"6","author":"Balouiri","year":"2016","journal-title":"J. Pharm. Anal."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/9\/1434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:53:11Z","timestamp":1777362791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/9\/1434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,26]]},"references-count":61,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["molecules31091434"],"URL":"https:\/\/doi.org\/10.3390\/molecules31091434","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,26]]}}}