{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:04:01Z","timestamp":1789542241366,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Izmir Katip Celebi University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Plant Foods Hum Nutr"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>\n            <jats:italic>Heliotropium dolosum<\/jats:italic> (Boraginaceae) is traditionally used for its choleretic, antipyretic, and cicatrizing properties. Despite some reports on its traditional uses, this species\u2019 cytotoxic and nitric oxide (NO) inhibitory potential and its polyphenolic compounds have not been previously investigated. This study aims to evaluate the antioxidant, cytotoxic, and NO inhibitory activities of <jats:italic>H. dolosum<\/jats:italic> extracts and to identify polyphenolic compounds that could be contributing to these effects. The antioxidant activity of <jats:italic>H. dolosum<\/jats:italic> extracts (ethanol, methanol, chloroform, water) was assessed using six in vitro models. Total phenolics, flavonoids, and saponins were quantified via colorimetric assays, while phenolic compounds were identified using HPLC. Cytotoxicity was evaluated through brine shrimp lethality and cancer cell assays, and NO inhibitory activity was measured in LPS-induced cancer cells. The methanol extract displayed the highest antioxidant activity, with major phenolic compounds identified as caffeic acid, 2,5-dihydroxybenzoic acid, and ellagic acid with 12.307, 5.710 and 5.061\u00a0mg\/g, respectively. It showed notable cytotoxicity (LC\u2085\u2080 = 18.1\u00a0\u00b5g\/mL) and concentration-dependent effects on cancer cells. The highest NO inhibition was observed in HCC78 cells (15.56 \u00b5M nitrite). <jats:italic>H. dolosum<\/jats:italic> demonstrates potential as a wild plant source of bioactive compounds with antioxidant, cytotoxic, and NO inhibitory properties, highlighting its promise for functional food development and nutraceutical applications.<\/jats:p>","DOI":"10.1007\/s11130-025-01313-y","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T11:09:09Z","timestamp":1741259349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unveiling the Cytotoxic and NO Inhibitory Potential of Heliotropium dolosum Extracts from T\u00fcrkiye: A First Insight Into Its Phenolic Profile"],"prefix":"10.1007","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-6122","authenticated-orcid":false,"given":"Cennet","family":"\u00d6zay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"1313_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13002-017-0201-8","volume":"14","author":"A Akgul","year":"2018","unstructured":"Akgul A, Akgul A, Senol SG et al (2018) An ethnobotanical study in Midyat (Turkey), a city on the silk road where cultures meet. J Ethnobiol Ethnomed 14:12. https:\/\/doi.org\/10.1186\/s13002-017-0201-8","journal-title":"J Ethnobiol Ethnomed"},{"key":"1313_CR2","doi-asserted-by":"publisher","first-page":"112609","DOI":"10.1016\/j.indcrop.2020.112609","volume":"153","author":"M Selseleh","year":"2020","unstructured":"Selseleh M, Ebrahimi SN, Aliahmadi A et al (2020) Metabolic profiling, antioxidant, and antibacterial activity of some Iranian Verbascum L. species. Ind Crop Prod 153:112609. https:\/\/doi.org\/10.1016\/j.indcrop.2020.112609","journal-title":"Ind Crop Prod"},{"key":"1313_CR3","volume-title":"A checklist of Flora of Turkey (vascular plants)","author":"A Guner","year":"2012","unstructured":"Guner A, Ekim T, Vural M et al (2012) A checklist of Flora of Turkey (vascular plants). Nezahat G\u00f6kyi\u011fit Botanic Garden and Publication of Flora Researches Association, Istanbul"},{"key":"1313_CR4","doi-asserted-by":"publisher","first-page":"259","DOI":"10.5505\/tjps.2016.20591","volume":"13","author":"MK Ghori","year":"2016","unstructured":"Ghori MK, Ghaffari MA, Hussain SN et al (2016) Ethnopharmacological, phytochemical and pharmacognostic potential of genus Heliotropium L. Turk J Pharm Sci 13:259\u2013280. https:\/\/doi.org\/10.5505\/tjps.2016.20591","journal-title":"Turk J Pharm Sci"},{"key":"1313_CR5","doi-asserted-by":"publisher","first-page":"757","DOI":"10.2147\/cia.S158513","volume":"13","author":"I Liguori","year":"2018","unstructured":"Liguori I, Russo G, Curcio F et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757\u2013772. https:\/\/doi.org\/10.2147\/cia.S158513","journal-title":"Clin Interv Aging"},{"key":"1313_CR6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/1477-7819-11-118","volume":"11","author":"SK Choudhari","year":"2013","unstructured":"Choudhari SK, Chaudhary M, Bagde S et al (2013) Nitric oxide and cancer: a review. World J Surg Oncol 11:118. https:\/\/doi.org\/10.1186\/1477-7819-11-118","journal-title":"World J Surg Oncol"},{"key":"1313_CR7","doi-asserted-by":"publisher","first-page":"7631","DOI":"10.3390\/ijms25147631","volume":"25","author":"N Cortez","year":"2024","unstructured":"Cortez N, Villegas C, Burgos V et al (2024) Adjuvant properties of Caffeic Acid in Cancer Treatment. Int J Mol Sci 25:7631. https:\/\/doi.org\/10.3390\/ijms25147631","journal-title":"Int J Mol Sci"},{"key":"1313_CR8","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.3390\/biom13111653","volume":"13","author":"M \u010ci\u017em\u00e1rikov\u00e1","year":"2023","unstructured":"\u010ci\u017em\u00e1rikov\u00e1 M, Michalkov\u00e1 R, Mirossay L et al (2023) Ellagic Acid and Cancer Hallmarks: insights from experimental evidence. Biomolecules 13:1653. https:\/\/doi.org\/10.3390\/biom13111653","journal-title":"Biomolecules"},{"key":"1313_CR9","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s43450-022-00235-z","volume":"32","author":"DB Singh","year":"2022","unstructured":"Singh DB, Pathak RK, Rai D et al (2022) From traditional Herbal Medicine to Rational Drug Discovery: strategies, challenges, and future perspectives. Rev Bras Farmacogn 32:147\u2013159. https:\/\/doi.org\/10.1007\/s43450-022-00235-z","journal-title":"Rev Bras Farmacogn"},{"key":"1313_CR10","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/biom11010053","volume":"11","author":"A Arshad","year":"2021","unstructured":"Arshad A, Ahemad S, Saleem H et al (2021) RP-UHPLC-MS chemical profiling, biological and in silico docking studies to unravel the therapeutic potential of Heliotropium Crispum Desf. As a novel source of neuroprotective bioactive compounds. Biomolecules 11:53. https:\/\/doi.org\/10.3390\/biom11010053","journal-title":"Biomolecules"},{"key":"1313_CR11","doi-asserted-by":"publisher","unstructured":"Fayed MA, Abouelela ME, Refaey MS (2022) Heliotropium ramosissimum metabolic profiling, in silico and in vitro evaluation with potent selective cytotoxicity against colorectal carcinoma. Sci Rep 12:12539. https:\/\/doi.org\/10.1038\/s41598-022-16552-1","DOI":"10.1038\/s41598-022-16552-1"},{"key":"1313_CR12","doi-asserted-by":"publisher","unstructured":"Sarkar C, Mondal M, Khanom B et al (2021) Heliotropium indicum L.: from farm to a source of Bioactive compounds with therapeutic activity. Evid Based Complement Altern Med 9965481. https:\/\/doi.org\/10.1155\/2021\/9965481","DOI":"10.1155\/2021\/9965481"},{"key":"1313_CR13","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.18185\/erzifbed.530721","volume":"12","author":"S Karakaya","year":"2019","unstructured":"Karakaya S, Mehmet K, K\u0131l\u0131\u00e7 CS (2019) Antioxidant and anticholinesterase activities of Heliotropium Dolosum, H. Lasiocarpum and H. Hirsutissimum growing in Turkey. Erzincan Uni J Sci Technol 12:1381\u20131391. https:\/\/doi.org\/10.18185\/erzifbed.530721","journal-title":"Erzincan Uni J Sci Technol"},{"key":"1313_CR14","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.33483\/jfpau.1488042","volume":"48","author":"C \u00d6zay","year":"2024","unstructured":"\u00d6zay C, Pehlivan E (2024) Factors affecting the biosynthesis and accumulation of plant secondary metabolites. J Fac Pharm Ankara 48:1248\u20131263. https:\/\/doi.org\/10.33483\/jfpau.1488042","journal-title":"J Fac Pharm Ankara"},{"key":"1313_CR15","doi-asserted-by":"publisher","first-page":"112404","DOI":"10.1016\/j.fct.2021.112404","volume":"155","author":"H Saleem","year":"2021","unstructured":"Saleem H, Khurshid U, Sarfraz M et al (2021) Investigation into the biological properties, secondary metabolites composition, and toxicity of aerial and root parts of Capparis spinosa L.: an important medicinal food plant. Food Chem Toxicol 155:112404. https:\/\/doi.org\/10.1016\/j.fct.2021.112404","journal-title":"Food Chem Toxicol"},{"key":"1313_CR16","first-page":"177","volume":"100","author":"C Ozay","year":"2023","unstructured":"Ozay C (2023) Phenolic constituents, antioxidant and anti-inflammatory effects of Heliotropium europaeum (Boraginaceae). Riv Ital Sostanze Grasse 100:177\u2013185. https:\/\/www.innovhub-ssi.it\/kdocs\/2108136\/2023_risg_100_3_4_ozay.pdf","journal-title":"Riv Ital Sostanze Grasse"},{"key":"1313_CR17","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1055\/s-2007-971236","volume":"45","author":"BN Meyer","year":"1982","unstructured":"Meyer BN, Ferrigni NR, Putnam JE et al (1982) Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med 45:31\u201334. https:\/\/doi.org\/10.1055\/s-2007-971236","journal-title":"Planta Med"},{"key":"1313_CR18","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1177\/009286159803200223","volume":"32","author":"JL McLaughlin","year":"1998","unstructured":"McLaughlin JL, Rogers LL, Anderson JE (1998) The use of biological assays to evaluate botanicals. Ther Innov Regul Sci 32:513\u2013524. https:\/\/doi.org\/10.1177\/009286159803200223","journal-title":"Ther Innov Regul Sci"},{"key":"1313_CR19","doi-asserted-by":"publisher","first-page":"111381","DOI":"10.1016\/j.biopha.2021.111381","volume":"137","author":"Z Li","year":"2021","unstructured":"Li Z, Feiyue Z, Gaofeng L (2021) Traditional Chinese medicine and lung cancer\u2013from theory to practice. Biomed Pharmacother 137:111381. https:\/\/doi.org\/10.1016\/j.biopha.2021.111381","journal-title":"Biomed Pharmacother"},{"key":"1313_CR20","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1080\/10408398.2020.1829541","volume":"62","author":"AK Farha","year":"2022","unstructured":"Farha AK, Gan RY, Li HB et al (2022) The anticancer potential of the dietary polyphenol rutin: current status, challenges, and perspectives. Crit Rev Food Sci Nutr 62:832\u2013859. https:\/\/doi.org\/10.1080\/10408398.2020.1829541","journal-title":"Crit Rev Food Sci Nutr"},{"key":"1313_CR21","doi-asserted-by":"publisher","first-page":"619","DOI":"10.32598\/bcn.9.10.1159.2","volume":"10","author":"M Shokrzadeh","year":"2019","unstructured":"Shokrzadeh M, Javanmard H, Golmohammad Zadeh G et al (2019) Evaluation of the anti-apoptotic and anti-cytotoxic effect of Epicatechin Gallate and Edaravone on SH-SY5Y Neuroblastoma cells. Basic Clin Neurosci 10:619\u2013630. https:\/\/doi.org\/10.32598\/bcn.9.10.1159.2","journal-title":"Basic Clin Neurosci"},{"key":"1313_CR22","doi-asserted-by":"publisher","first-page":"e68808","DOI":"10.1371\/journal.pone.0068808","volume":"8","author":"Y Al Dhaheri","year":"2013","unstructured":"Al Dhaheri Y, Attoub S, Arafat K et al (2013) Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NF\u03baB signaling and reduction of nitric oxide production. PLoS ONE 8:e68808. https:\/\/doi.org\/10.1371\/journal.pone.0068808","journal-title":"PLoS ONE"},{"key":"1313_CR23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S1470-2045(00)00256-4","volume":"2","author":"PK Lala","year":"2001","unstructured":"Lala PK, Chakraborty C (2001) Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2:149. https:\/\/doi.org\/10.1016\/S1470-2045(00)00256-4","journal-title":"Lancet Oncol"},{"key":"1313_CR24","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1164\/rccm.200411-1523OC","volume":"172","author":"FA Masri","year":"2005","unstructured":"Masri FA, Comhair SA, Koeck T et al (2005) Abnormalities in nitric oxide and its derivatives in lung cancer. Am J Respir Crit Care Med 172:597\u2013605. https:\/\/doi.org\/10.1164\/rccm.200411-1523OC","journal-title":"Am J Respir Crit Care Med"},{"key":"1313_CR25","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/ncponc0140","volume":"2","author":"JR Mann","year":"2005","unstructured":"Mann JR, Backlund MG, DuBois RN (2005) Mechanisms of disease: inflammatory mediators and cancer prevention. Nat Clin Pract Oncol 2:202\u2013210. https:\/\/doi.org\/10.1038\/ncponc0140","journal-title":"Nat Clin Pract Oncol"},{"key":"1313_CR26","doi-asserted-by":"publisher","first-page":"482","DOI":"10.3390\/plants8110482","volume":"8","author":"AM Abd-ElGawad","year":"2019","unstructured":"Abd-ElGawad AM, Elshamy AI, Al-Rowaily SL et al (2019) Habitat affects the chemical profile, allelopathy, and antioxidant properties of essential oils and phenolic enriched extracts of the invasive plant Heliotropium curassavicum. Plants 8:482\u2013494. https:\/\/doi.org\/10.3390\/plants8110482","journal-title":"Plants"},{"key":"1313_CR27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.12688\/f1000research.22966.1","volume":"9","author":"P Ghosh","year":"2020","unstructured":"Ghosh P, Das C, Biswas S et al (2020) Phytochemical composition analysis and evaluation of in vitro medicinal properties and cytotoxicity of five wild weeds: a comparative study. F1000Res 9:493. https:\/\/doi.org\/10.12688\/f1000research.22966.1","journal-title":"F1000Res"},{"key":"1313_CR28","doi-asserted-by":"publisher","first-page":"4973","DOI":"10.26538\/tjnpr\/v7i10.38","volume":"7","author":"OO Joel","year":"2023","unstructured":"Joel OO, Maryann UC, Idowu OJ et al (2023) Prostaglandin synthesis inhibitory activity of Heliotropium indicum L. (Boraginaceae) and HPLC-DAD analysis. Trop J Nat Prod Res 7:4973\u20134979. https:\/\/doi.org\/10.26538\/tjnpr\/v7i10.38","journal-title":"Trop J Nat Prod Res"},{"key":"1313_CR29","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.3390\/molecules28031008","volume":"28","author":"K-M Ozntamar-Pouloglou","year":"2023","unstructured":"Ozntamar-Pouloglou K-M, Cheilari A, Zengin G et al (2023) Heliotropium procubens taxonomiconomic significance and characterization of phenolic compounds via UHPLC\u2013HRMS- in vitro antioxidant and enzyme inhibitory activities. Molecules 28:1008. https:\/\/doi.org\/10.3390\/molecules28031008","journal-title":"Molecules"},{"key":"1313_CR30","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/cbdv.200490161","volume":"2","author":"K Iqbal","year":"2005","unstructured":"Iqbal K, Nawaz SA, Malik A et al (2005) Isolation and lipoxygenase-inhibition studies of phenolic constituents from Ehretia Obtusifolia. Chem Biodivers 2:104\u2013111. https:\/\/doi.org\/10.1002\/cbdv.200490161","journal-title":"Chem Biodivers"},{"key":"1313_CR31","doi-asserted-by":"publisher","first-page":"19487","DOI":"10.1038\/s41598-020-76620-2","volume":"10","author":"A Mardani-Ghahfarokhi","year":"2020","unstructured":"Mardani-Ghahfarokhi A, Farhoosh R (2020) Antioxidant activity and mechanism of inhibitory action of gentisic and \u03b1-resorcylic acids. Sci Rep 10:19487. https:\/\/doi.org\/10.1038\/s41598-020-76620-2","journal-title":"Sci Rep"}],"container-title":["Plant Foods for Human Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11130-025-01313-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11130-025-01313-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11130-025-01313-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T23:25:59Z","timestamp":1743377159000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11130-025-01313-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["1313"],"URL":"https:\/\/doi.org\/10.1007\/s11130-025-01313-y","relation":{},"ISSN":["0921-9668","1573-9104"],"issn-type":[{"value":"0921-9668","type":"print"},{"value":"1573-9104","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"4 February 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"86"}}