title: Haemanthus coccineus extract and its main bioactive component narciclasine display profound anti-inflammatory activities in vitro and in vivo.
abstract: Haemanthus coccineus extracts (HCE) have traditionally been used to treat a variety of diseases, like febrile colds or asthma. Since new therapeutic options against inflammatory processes are still urgently needed, we aimed to pharmacologically characterise the anti-inflammatory potential of HCEin vitro and in vivo and to identify the underlying bioactive component(s). The action of HCE on oedema formation and leucocyte infiltration were analysed in two murine models of inflammation (dermal oedema induced by arachidonic acid and croton oil; kidney injury caused by unilateral ureteral obstruction). The interaction of leucocytes with endothelial cells (ECs) as well as the activation parameters of these two cell types were analysed. Moreover, the nuclear factor κB (NFκB) pathway was investigated in detail in ECs. Using different fractions of HCE, the bioactive principle was identified. In vivo, HCE (450 mg/kg orally or 2 mg/kg intraperitoneally) inhibited oedema formation, leucocyte infiltration and cytokine synthesis. In vitro, HCE (100-300 ng/ml) blocked leucocyte-EC interaction as well as the activation of isolated leucocytes (cytokine synthesis and proliferation) and of primary ECs (adhesion molecule expression). HCE suppressed NFκB-dependent gene transcription in the endothelium, but did not interfere with the NFκB activation cascade (IκB degradation, p65 nuclear translocation and NFκB DNA-binding activity). The alkaloid narciclasine was elucidated as the bioactive compound responsible for the anti-inflammatory action of HCE. Our study highlights HCE and its main alkaloid narciclasine as novel interesting approach for the treatment of inflammation-related disorders.
authors.affiliation: Institute of Pharmaceutical Biology, Biocenter, Goethe-University, Frankfurt/Main, Germany; Department of Pharmacy, Pharmaceutical Biology, University of Munich, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Fuchs
authors.forename: Louise T
authors.initials: LT
authors.lastname: Hsieh
authors.forename: Werner
authors.initials: W
authors.lastname: Saarberg
authors.forename: Clemens A J
authors.initials: CA
authors.lastname: Erdelmeier
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wichelhaus
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
authors.forename: Egon
authors.initials: E
authors.lastname: Koch
authors.forename: Robert
authors.initials: R
authors.lastname: Fürst
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003436:Croton Oil; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019668:Liliaceae / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D010617:Phenanthridines / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D047151:Amaryllidaceae Alkaloids; D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016328:NF-kappa B; D010617:Phenanthridines; D010936:Plant Extracts; D016718:Arachidonic Acid; C010753:narciclasine; D003436:Croton Oil
keywords: Haemanthus coccineus extract; NFκB; adhesion molecules; endothelium; inflammation; isocarbostyril alkaloid; leucocyte-endothelial cell interactions; narciclasine