{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:58:15Z","timestamp":1793746695003,"version":"4.6.1"},"reference-count":25,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,7,2]],"date-time":"2016-07-02T00:00:00Z","timestamp":1467417600000},"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>Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting A\u03b2 toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography\/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (A\u03b2) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract A\u03b2 toxicity. Other mechanisms and possibly other active compounds are involved in this effect.<\/jats:p>","DOI":"10.3390\/molecules21070871","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T10:04:21Z","timestamp":1467626661000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Carlina acaulis Exhibits Antioxidant Activity and Counteracts A\u03b2 Toxicity in Caenorhabditis elegans"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-7273","authenticated-orcid":false,"given":"Pille","family":"Link","sequence":"first","affiliation":[{"name":"Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Roth","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany"},{"name":"Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Sporer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-4510","authenticated-orcid":false,"given":"Michael","family":"Wink","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meusel, H., and K\u00e4stner, A. (1990). Lebensgeschichte der Gold- und Silberdisteln: Monographie der Mediterran-Mitteleurop\u00e4ischen Compositen-Gattung Carlina, Band 1, Springer-Verlag.","DOI":"10.1007\/978-3-7091-6934-6"},{"key":"ref_2","first-page":"409","article-title":"\u00dcber die antibakterielle Wirkung der Silberdistelwurzel","volume":"5b","year":"1950","journal-title":"Z. Naturforsch"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/10412905.1996.9700696","article-title":"Composition of the essential oil from the root of Carlina acaulis L. Asteraceae","volume":"8","author":"Chalchat","year":"1996","journal-title":"J. Essent. Oil Res."},{"key":"ref_4","first-page":"61","article-title":"Influence of solvent on antimicrobial activity of carlinae radix essential oil and decoct","volume":"3","year":"2012","journal-title":"Biol. Nyssana"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1055\/s-0031-1279984","article-title":"Carlina oxide\u2014A natural polyacetylene from Carlina acaulis (Asteraceae) with potent antitrypanosomal and antimicrobial properties","volume":"77","author":"Herrmann","year":"2011","journal-title":"Planta Med."},{"key":"ref_6","first-page":"1213","article-title":"Bioactivity assays on Carlina acaulis and C. acanthifolia root and herb extracts","volume":"7","year":"2012","journal-title":"Dig. J. Nanomater. Biostruct."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jep.2006.08.021","article-title":"Antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities of Carlina acanthifolia root essential oil","volume":"109","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13065-015-0143-y","article-title":"Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases","volume":"9","author":"Chen","year":"2015","journal-title":"Chem. Cent. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1055\/s-0035-1545724","article-title":"Extracts of Glycyrrhiza uralensis and isoliquiritigenin counteract amyloid-beta toxicity in Caenorhabditis elegans","volume":"81","author":"Link","year":"2015","journal-title":"Planta Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.phymed.2013.10.027","article-title":"Eps7630\u00ae from Pelargonium sidoides increases stress resistance in Caenorhabditis elegans probably via the daf-16\/foxo pathway","volume":"21","author":"Rezaizadehnajafi","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cha, M.Y., Han, S.H., Son, S.M., Hong, H.S., Choi, Y.J., Byun, J., and Mook-Jung, I. (2012). Mitochondria-specific accumulation of amyloid \u03b2 induces mitochondrial dysfunction leading to apoptotic cell death. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034929"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37111","DOI":"10.1074\/jbc.274.52.37111","article-title":"Cu(II) potentiation of alzheimer A\u03b2 neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction","volume":"274","author":"Huang","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40302","DOI":"10.1074\/jbc.M206428200","article-title":"Metalloenzyme-like activity of alzheimer\u2019s disease \u03b2-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2","volume":"277","author":"Opazo","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1055\/s-0028-1088378","article-title":"Epigallocatechin gallate from green tea (Camellia sinensis) increases lifespan and stress resistance in caenorhabditis elegans","volume":"75","author":"Abbas","year":"2009","journal-title":"Planta Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/S0960-9822(01)00594-2","article-title":"Daf-16 integrates developmental and environmental inputs to mediate aging in the nematode caenorhabditis elegans","volume":"11","author":"Henderson","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1046\/j.1474-9728.2003.00043.x","article-title":"Transcriptional outputs of the Caenorhabditis elegans forkhead protein daf-16","volume":"2","author":"McElwee","year":"2003","journal-title":"Aging Cell"},{"key":"ref_17","first-page":"171","article-title":"Presence of carlina oxide in plants of hungary. Stabilization and antimicrobial effect","volume":"57","year":"1987","journal-title":"Acta Pharm. Hung."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0197-4580(02)00225-7","article-title":"Oxidative stress precedes fibrillar deposition of alzheimer\u2019s disease amyloid \u03b2-peptide (1\u201342) in a transgenic Caenorhabditis elegans model","volume":"24","author":"Drake","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1126\/science.1124646","article-title":"Opposing activities protect against age-onset proteotoxicity","volume":"313","author":"Cohen","year":"2006","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s10600-005-0163-2","article-title":"Composition of Carlina acanthifolia root essential oil","volume":"41","year":"2005","journal-title":"Chem. Nat. Compd."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.jpba.2006.07.034","article-title":"Quantitative determination of eight components in rhizome (Jianghuang) and tuberous root (Yujin) of Curcuma longa using pressurized liquid extraction and gas chromatography-mass spectrometry","volume":"43","author":"Qin","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant determinations by the use of a stable free radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_23","unstructured":"Wood, W.B. (1988). The Nematode Caenorhabditis elegans, Cold Spring Harbor Laboratory Press."},{"key":"ref_24","first-page":"2252","article-title":"Assaying \u03b2-amyloid toxicity using a transgenic C. elegans model","volume":"44","author":"Dostal","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/pst.426","article-title":"Guidelines for accurate EC50\/IC50 estimation","volume":"10","author":"Sebaugh","year":"2011","journal-title":"Pharm. Stat."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/7\/871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:25:21Z","timestamp":1760210721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/7\/871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,2]]},"references-count":25,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7]]}},"alternative-id":["molecules21070871"],"URL":"https:\/\/doi.org\/10.3390\/molecules21070871","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,2]]}}}