{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T15:56:11Z","timestamp":1787932571889,"version":"build-2784847793"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-68\/2020-14\/200114"],"award-info":[{"award-number":["451-03-68\/2020-14\/200114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: The aim of this work was to determine the phenolic composition of sweet wormwood (Artemisia annua L., Asteraceae) from controlled cultivation in Serbia and to assess the potential antioxidant effects and cytotoxicity. Methods: High-performance liquid chromatography was used to determine the phenolic composition of Artemisia annua ethanolic extract. The antioxidant activity was studied using in vitro tests of inhibition of the neutralization of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), and nitroso (NO) radicals, as well as the process of inhibiting lipid peroxidation and the ferric reducing antioxidant power (FRAP). The cytotoxicity was evaluated by the effect on three cell lines (the rat pancreatic insulinoma cell line (Rin-5F), the rat hepatoma cell line (H4IIE), and human hepatocellular carcinoma (Hep G2)) using the MTT test of viability. Results: Ethanol extract showed the highest potency in inhibiting the DPPH radical, and the half maximal inhibitory concentration (IC50) was 5.17 \u03bcg\/mL. Chlorogenic acid was the dominant phenolic compound with an amount of 651 \u03bcg\/g of dry extract. The results of the MTT viability test showed that the extract has the potential to inhibit the growth of the Rin-5F and Hep G2 cell lines, while no growth inhibition was observed on the H4IIE cell line. Conclusions: Undoubtedly, Artemisia annua is a powerful plant and a rich source of phenolic compounds. Inhibitory activity on causes of oxidative stress shows that the plant has a good antioxidant effect. Also, the anticancer activity shown through the inhibition of cell growth is not negligible.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070890","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T15:19:31Z","timestamp":1752247171000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Unlocking the Bioactivity of Sweet Wormwood (Artemisia annua L., Asteraceae) Ethanolic Extract: Phenolics, Antioxidants, and Cytotoxic Effects"],"prefix":"10.3390","volume":"17","author":[{"given":"Neda","family":"Gavari\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5346-1412","authenticated-orcid":false,"given":"Milica","family":"A\u0107imovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Field and Vegetable Crops Novi Sad, National Institute of the Republic of Serbia, Maksima Gorkog 30, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-6412","authenticated-orcid":false,"given":"Neboj\u0161a","family":"Kladar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7612-4785","authenticated-orcid":false,"given":"Maja","family":"Hitl","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Drlja\u010da Lero","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8595-6065","authenticated-orcid":false,"given":"Nata\u0161a","family":"Mili\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-8340","authenticated-orcid":false,"given":"Katarina","family":"Radovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sadiq, A., Hayat, M.Q., and Ashraf, M. (2013). Ethnopharmacology of Artemisia annua L.: A Review. Artemisia Annua\u2014Pharmacology and Biotechnology, Springer.","DOI":"10.1007\/978-3-642-41027-7_2"},{"key":"ref_2","first-page":"107650","article-title":"Traditional application and modern pharmacological research of Artemisia annua L. Pharmacol","volume":"216","author":"Feng","year":"2020","journal-title":"Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4986","DOI":"10.3390\/ijms21144986","article-title":"Artemisia annua, a traditional plant brought to light","volume":"21","author":"Marodon","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","first-page":"4573","article-title":"Artemisia annua (Qinghao): A pharmacological review","volume":"3","author":"Das","year":"2012","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1080\/10412905.2014.949881","article-title":"Effect of method of distillation on the yield and chemical composition of Artemisia annua essential oil","volume":"26","author":"Syamasundar","year":"2014","journal-title":"J. Essent. Oil Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bano\u017ei\u0107, M., Wronska, A.W., Jakovljevi\u0107 Kova\u010d, M., Aladi\u0107, K., Jerkovi\u0107, I., and Joki\u0107, S. (2023). Comparative Evaluation of Different Extraction Techniques for Separation of Artemisinin from Sweet Wormwood (Artemisia annua L.). Horticulturae, 9.","DOI":"10.3390\/horticulturae9060629"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.indcrop.2012.12.022","article-title":"Artemisia annua L.: Essential oil and acetone extract composition and antioxidant capacity","volume":"45","author":"Gouveia","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"159819","DOI":"10.1155\/2014\/159819","article-title":"Essential oil of Artemisia annua L.: An extraordinary component with numerous antimicrobial properties","volume":"2014","author":"Bilia","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_9","first-page":"42","article-title":"Anti-diabetic effect of Artemisia judaica extracts","volume":"4","author":"Nofal","year":"2009","journal-title":"Res. J. Med. Sci."},{"key":"ref_10","unstructured":"Dewick, P.M. (2009). The mevalonate and methylerythritol phosphate pathways: Terpenoids and steroid. Medicinal Natural Products: A Biosynthetic Approach, John Wiley & Sons. [3rd ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"126070","DOI":"10.1016\/j.foodchem.2019.126070","article-title":"Phytochemical analysis and geographic assessment of flavonoids, coumarins and sesquiterpenes in Artemisia annua L. based on HPLC-DAD quantification and LC-ESI-QTOF-MS\/MS confirmation","volume":"312","author":"Fu","year":"2020","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.phymed.2010.02.008","article-title":"Inhibition of tumor cell proliferation and induction of apoptosis in human lung carcinoma 95-D cells by a new sesquiterpene from hairy root cultures of Artemisia annua","volume":"17","author":"Zhai","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Acquaviva, A., Bouyahya, A., Zengin, G., Di Simone, S.C., Recinella, L., Leone, S., Brunetti, L., Uba, A.I., and Cakilcio\u011flu, U. (2023). Chemical Characterization of Different Extracts from Artemisia annua and Their Antioxidant, Enzyme Inhibitory and Anti-Inflammatory Properties. Chem. Biodivers., 20.","DOI":"10.1002\/cbdv.202300547"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Abate, G., Yhang, L., Pucci, M., Morbini, G., Mac Sweeney, G., Ribaudo, G., Gianoncelli, A., Uberti, D., Memo, M., and Lucini, L. (2021). Phytochemical Analysis and Anti-Inflammatory Activity of Different Ethanolic Phyto-Extracts of Artemisia annua L. . Biomolecules, 11.","DOI":"10.3390\/biom11070975"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.indcrop.2010.11.005","article-title":"Phenolic composition and antioxidant capacity of six Artemisia species","volume":"33","author":"Carvalho","year":"2011","journal-title":"Ind. Crops Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.3390\/molecules15053135","article-title":"Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer","volume":"15","author":"Ferreira","year":"2010","journal-title":"Molecules"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jpba.2008.02.013","article-title":"Characterization of phenolic compounds in the Chinese herbal drug Artemisia annua by liquid chromatography coupled to electrospray ionization mass spectrometry","volume":"47","author":"Han","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jchromb.2006.10.028","article-title":"Identification and characterization of major flavonoids and caffeoylquinic acids in three Compositae plants by LC\/DAD-APCI\/MS","volume":"848","author":"Lai","year":"2007","journal-title":"J. Chromatogr. B"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nath, A., Sharma, A., Singh, S.K., and Sundaram, S. (2024). Bio Prospecting of Endophytes and PGPRs in Artemisinin Production for the Socio-economic Advancement. Curr. Microbiol., 81.","DOI":"10.1007\/s00284-023-03516-5"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11733","DOI":"10.3390\/molecules181011733","article-title":"Impact of origin and biological source on chemical composition, anticholinesterase and antioxidant properties of some St. John\u2019s wort species (Hypericum spp., Hypericaceae) from the Central Balkans","volume":"18","author":"Kladar","year":"2013","journal-title":"Molecules"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.indcrop.2015.05.070","article-title":"Postdistillation waste material of thyme (Thymus vulgaris L., Lamiaceae) as a potential source of biologically active compounds","volume":"74","author":"Kladar","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103347","DOI":"10.1016\/j.arabjc.2021.103347","article-title":"Traditional multi-herbal formula in diabetes therapy\u2013Antihyperglycemic and antioxidant potential","volume":"14","author":"Salaj","year":"2021","journal-title":"Arab. J. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bjeli\u0107, K., Sr\u0111enovi\u0107 \u010coni\u0107, B., Prpa, B., Pilija, V., Vukmirovi\u0107, S., and Kladar, N. (2024). The Potential of Hemp Extracts to Modify the Course of Oxidative-Stress Related Conditions. Plants, 13.","DOI":"10.3390\/plants13121630"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s40415-015-0177-3","article-title":"Ecologically and ontogenetically induced variations in phenolic compounds and biological activities of Hypericum maculatum subsp. maculatum, Hypericaceae","volume":"38","author":"Kladar","year":"2015","journal-title":"Braz. J. Bot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2865610","DOI":"10.1155\/2017\/2865610","article-title":"Hypericum perforatum: Synthesis of active principles during flowering and fruitification\u2014Novel aspects of biological potential","volume":"2017","author":"Kladar","year":"2017","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1111\/cns.13889","article-title":"Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line","volume":"28","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"012119","DOI":"10.1088\/1755-1315\/974\/1\/012119","article-title":"Antioxidant activity of Artemisia (Artemisia annua) extract on several concentrations and solvents","volume":"974","author":"Sembiring","year":"2022","journal-title":"IOP Conf. Ser. Earth Environ. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3390\/antiox3010116","article-title":"Antioxidant Properties of Artemisia annua Extracts in Model Food Emulsions","volume":"3","author":"Skowyra","year":"2014","journal-title":"Antioxidants"},{"key":"ref_30","first-page":"119","article-title":"HPLC analysis of phenolic compounds from Artemisia species","volume":"5","author":"Ivanescu","year":"2016","journal-title":"Eur. Chem. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bernatoniene, J., Nemickaite, E., Majiene, D., Marksa, M., and Kopustinskiene, D.M. (2024). In Vitro and In Silico Anti-Glioblastoma Activity of Hydroalcoholic Extracts of Artemisia annua L. and Artemisia vulgaris L.. Molecules, 29.","DOI":"10.3390\/molecules29112460"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"460785","DOI":"10.1016\/j.chroma.2019.460785","article-title":"Combination of molecular network and centrifugal partition chromatography fractionation for targeting and identifying Artemisia annua L. antioxidant compounds","volume":"1615","author":"Messaili","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1186\/s40064-016-3199-9","article-title":"Anti-inflammatory and acetylcholinesterase activity of extract, fractions and five compounds isolated from the leaves and twigs of Artemisia annua growing in Cameroon","volume":"5","author":"Chougouo","year":"2016","journal-title":"Springerplus"},{"key":"ref_34","first-page":"1062","article-title":"Study the cytotoxic and pro-apoptotic activity of Artemisia annua extracts","volume":"3","author":"Emami","year":"2009","journal-title":"Pharmacologyonline"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.3390\/ijms21114090","article-title":"Chrysosplenol d, a flavonol from Artemisia annua, induces ERK1\/2-mediated apoptosis in triple negative human breast cancer cells","volume":"21","author":"Lang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15525","DOI":"10.3390\/ijms242115525","article-title":"Artemisia annua Extract Attenuate Doxorubicin-Induced Hepatic Injury via PI-3K\/Akt\/Nrf-2-Mediated Signaling Pathway in Rats","volume":"24","author":"Haidyrah","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"60","DOI":"10.15407\/biotech14.06.060","article-title":"Simultaneous identification, quantification, and main components analysis of Artemisia annua and Artemisia tilesii \u201chairy\u201d root extracts","volume":"14","author":"Kobylinska","year":"2021","journal-title":"Biotechnol. Acta"},{"key":"ref_38","first-page":"529","article-title":"Contribution to flower colors of flavonoids including anthocyanins: A review","volume":"10","author":"Iwashina","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6020","DOI":"10.3390\/molecules17056020","article-title":"Chemical composition of Artemisia annua L. leaves and antioxidant potential of extracts as a function of extraction solvents","volume":"17","author":"Iqbal","year":"2012","journal-title":"Molecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1007\/s12010-016-2077-9","article-title":"Effect of rol genes on polyphenols biosynthesis in Artemisia annua and their effect on antioxidant and cytotoxic potential of the plant","volume":"179","author":"Dilshad","year":"2016","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_41","first-page":"059","article-title":"Efficient protocol for mass micropropagation of Artemisia annua L. GSC Biol","volume":"5","author":"Zayova","year":"2018","journal-title":"Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.trstmh.2012.07.008","article-title":"First-time comparison of the in vitro antimalarial activity of Artemisia annua herbal tea and artemisinin","volume":"106","author":"Grassi","year":"2012","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/jnci\/djt007","article-title":"The clinical relevance of cancer cell lines","volume":"105","author":"Gillet","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/spmg.19885","article-title":"Cell lines: Valuable tools or useless artifacts","volume":"2","author":"Kaur","year":"2012","journal-title":"Spermatogenesis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.phymed.2015.11.001","article-title":"Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma","volume":"22","author":"Michaelsen","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1615758","DOI":"10.1155\/2019\/1615758","article-title":"Cytotoxic Effects of Artemisia annua L. and Pure Artemisinin on the D-17 Canine Osteosarcoma Cell Line","volume":"2019","author":"Isani","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"152962","DOI":"10.1016\/j.phymed.2019.152962","article-title":"Antitumor activity of an Artemisia annua herbal preparation and identification of active ingredients","volume":"62","author":"Lang","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.tiv.2012.01.004","article-title":"Cytotoxic effects of 109 reference compounds on rat H4IIE and human HepG2 hepatocytes. III: Mechanistic assays on oxygen consumption with MitoXpress and NAD(P)H production with Alamar Blue\u2122","volume":"26","author":"Willem","year":"2012","journal-title":"Toxicol. In Vitro"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:06:58Z","timestamp":1760033218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["pharmaceutics17070890"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17070890","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]}}}