Planta Med 2013; 79 - PN35
DOI: 10.1055/s-0033-1352378

Haemanthus coccineus extract and its main alkaloid narciclasine exert potent anti-inflammatory effects in vitro and in vivo

S Fuchs 1, W Müsch 2, AM Vollmar 3, CA Erdelmeier 2, E Koch 2, R Fürst 4
  • 1Goethe-University Frankfurt, Biocenter, Institute of Pharmaceutical Biology, Frankfurt/Main (60438), Germany University of Munich, Department of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Munich (81377), Germany
  • 2Dr. Willmar Schwabe Pharmaceuticals, Preclinical Research, Karlsruhe (76227), Germany
  • 3University of Munich, Department of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Munich (81377), Germany
  • 4Goethe-University Frankfurt, Biocenter, Institute of Pharmaceutical Biology, Frankfurt/Main (60438), Germany

Haemanthus coccineus (Amaryllidaceae) extracts have been used in traditional African medicine against febrile colds and asthma. Interestingly, the extracts' main alkaloid, narciclasine, was recently reported to induce apoptosis in different tumor cell lines. Beyond this anti-cancer action, we hypothesized that HCE and narciclasine could exhibit an anti-inflammatory potential.

Dried bulbs of H. coccineus were extracted using 60% (w/w) ethanol. The ethanol was largely removed and the remaining solution was partitioned with ethyl acetate. The organic phase was separated and dried (DER 50:1). The resulting H. coccineus extract (HCE) contained 2.2% narciclasine. In a croton oil-induced ear edema model in mice, HCE was found to clearly reduce edema formation upon oral application (450 mg/kg). In vitro, HCE (3 ng/ml – 10 µg/ml) concentration-dependently inhibited the proliferation of lymphocytes and the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) in macrophages. Moreover, HCE decreased the TNFα-induced adhesion of neutrophils to human endothelial cells (ECs) and the surface expression of EC adhesion molecules (ICAM-1, VCAM-1, E-selectin) without affecting EC viability. Also the main alkaloid narciclasine (1 nM – 10µM) clearly reduced adhesion molecule expression without inducing cytotoxicity. Interested in the underlying mechanisms of action, we could reveal that HCE as well as narciclasine attenuated the TNFα-triggered NF-κB-dependent gene expression in a reporter gene assay. HCE treatment also reduced the DNA-binding activity of NF-κB (gel shift assay). However, surprisingly, HCE and narciclasine did not affect the phosphorylation and translocation of the NF-κB p65 subunit (Western blot and microscopical analysis). This interesting phenomenon is currently under further investigation.

In conclusion, our study highlights H. coccineus extract and narciclasine as novel promising anti-inflammatory approaches.