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.
Keywords: Haemanthus coccineus extract; NFκB; adhesion molecules; endothelium; inflammation; isocarbostyril alkaloid; leucocyte-endothelial cell interactions; narciclasine.
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.