Haemanthus coccineus extract and its main bioactive component narciclasine display profound anti‐inflammatory activities in vitro and in vivo

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 v...

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Bibliographic Details
Published in:	Journal of cellular and molecular medicine Vol. 19; no. 5; pp. 1021 - 1032
Main Authors:	Fuchs, Simone, Hsieh, Louise T., Saarberg, Werner, Erdelmeier, Clemens A. J., Wichelhaus, Thomas A., Schaefer, Liliana, Koch, Egon, Fürst, Robert
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-05-2015 BlackWell Publishing Ltd
Subjects:	adhesion molecules Amaryllidaceae Alkaloids - pharmacology Animal models Animals Anti-Inflammatory Agents - pharmacology Apoptosis Arachidonic Acid Arthritis Asthma Bioactive compounds Blotting, Western Cancer Cell adhesion & migration Cell Adhesion - drug effects Cell Adhesion Molecules - metabolism Cell Line, Tumor Cells, Cultured Chemokine CCL2 - biosynthesis Croton Oil Cytokines Deoxyribonucleic acid DNA Edema Edema - chemically induced Edema - prevention & control Endothelial cells Endothelial Cells - cytology Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelium Gene expression Haemanthus coccineus extract Humans Humidity Inflammation isocarbostyril alkaloid Kidneys Laboratory animals leucocyte‐endothelial cell interactions Leukocytes Leukocytes - cytology Leukocytes - drug effects Leukocytes - metabolism Ligands Liliaceae - chemistry Lymphocytes Macrophages - drug effects Macrophages - metabolism Male Mice, Inbred C57BL Mice, Inbred Strains Microscopy, Fluorescence narciclasine Neutrophil Infiltration - drug effects NF-kappa B - metabolism NF-κB protein NFκB Nuclear transport Original Penicillin Permeability Phenanthridines - pharmacology Plant Extracts - pharmacology Protein synthesis Signal Transduction - genetics Skin Transcription Translocation Tumor necrosis factor-TNF Germany Haemanthus coccineus extract endothelium NFκB isocarbostyril alkaloid narciclasine adhesion molecules inflammation leucocyte-endothelial cell interactions
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1582-1838 1582-4934
DOI:	10.1111/jcmm.12493