title: Leoligin, the Major Lignan from Edelweiss (Leontopodium nivale subsp. alpinum), Promotes Cholesterol Efflux from THP-1 Macrophages.
abstract: Leoligin is a natural lignan found in Edelweiss (Leontopodium nivale ssp. alpinum). The aim of this study was to examine its influence on cholesterol efflux and to address the underlying mechanism of action. Leoligin increases apo A1- as well as 1% human plasma-mediated cholesterol efflux in THP-1 macrophages without affecting cell viability as determined by resazurin conversion. Western blot analysis revealed that the protein levels of the cholesterol efflux transporters ABCA1 and ABCG1 were upregulated, whereas the SR-B1 protein level remained unchanged upon treatment with leoligin (10 μM, 24 h). Quantitative reverse transcription PCR further uncovered that leoligin also increased ABCA1 and ABCG1 mRNA levels without affecting the half-life of the two mRNAs in the presence of actinomycin D, a transcription inhibitor. Proteome analysis revealed the modulation of protein expression fingerprint in the presence of leoligin. Taken together, these results suggest that leoligin induces cholesterol efflux in THP-1-derived macrophages by upregulating ABCA1 and ABCG1 expression. This novel activity suggests leoligin as a promising candidate for further studies addressing a possible preventive or therapeutic application in the context of atherosclerosis.
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Ladurner
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Latkolik
authors.affiliation: Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences, University of Innsbruck , Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.affiliation: Institute of Applied Synthetic Chemistry, Vienna University of Technology , Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Linder
authors.affiliation: Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno , Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hošek
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Palme
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schilcher
authors.affiliation: Veterinary Research Institute , Brno, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Polanský
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Elke H
authors.initials: EH
authors.lastname: Heiss
authors.affiliation: Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna , Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Stangl
authors.affiliation: Institute of Applied Synthetic Chemistry, Vienna University of Technology , Vienna, Austria.
authors.forename: Marko D
authors.initials: MD
authors.lastname: Mihovilovic
authors.affiliation: Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences, University of Innsbruck , Innsbruck, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
authors.affiliation: Department of Pharmacognosy, University of Vienna , Vienna, Austria.|Institute of Genetics and Animal Breeding of the Polish Academy of Sciences , 05-552 Jastrzebiec, Poland.
authors.forename: Atanas G
authors.initials: AG
authors.lastname: Atanasov
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D019659:Asteraceae / Q000737:chemistry*; D050197:Atherosclerosis; D001692:Biological Transport; D015153:Blotting, Western; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014966:Xanthenes / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D017705:Lignans; D057093:Orphan Nuclear Receptors; D010078:Oxazines; D012333:RNA, Messenger; D014966:Xanthenes; C542788:leoligin; D003609:Dactinomycin; C005843:resazurin