title: Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans.
abstract: 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 Aβ 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 (Aβ) 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 Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect.
authors.affiliation: Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany. pille.link@gmail.com.
authors.forename: Pille
authors.initials: P
authors.lastname: Link
authors.affiliation: Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany. k.roth@dundee.ac.uk.|Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland DD1 9SY, UK. k.roth@dundee.ac.uk.
authors.forename: Kevin
authors.initials: K
authors.lastname: Roth
authors.affiliation: Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany. frank.sporer@gmx.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Sporer
authors.affiliation: Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany. wink@uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005663:Furans; D010936:Plant Extracts; C054087:carlina oxide
keywords: Caenorhabditis elegans; Carlina acaulis; Carlina oxide; antioxidant; beta-amyloid