Studies on the Anti-Inflammatory Activity of Phytopharmaceuticals Prepared from Arnica Flowers1

Phytopharmaceuticals prepared from flowerheads of Arnica montana of Spanish origin and of the new type ”Arbo”, which can be easily and economically cultivated, were studied for their capability to impair activation of the transcription factors NF-κB and NF-AT. Both proteins are responsible for the transcription of genes encoding various inflammatory mediators. Additionally, their influence on the release of the cytokines IL-1 and TNF-α were examined. The inhibitory activities correlate with their quantitative and qualitative content of sesquiterpene lactones (Sls). Moreover, it was shown that the inhibitory potency of 11α,13-dihydrohelenalin derivatives being the main Sls in the Spanish flowers depend on their esterfication. Compounds with unsaturated acyl moieties, such as methacrylate and tiglinate, exhibited a stronger activity in the NF-κB EMSA as well as in the croton oil ear test in mice than the acetate derivative. Abbreviations Arbo tincture:tincture prepared from Arnica flowerheads type Arbo AP-1:activator protein 1 BSA:bovine serum albumen c.p.m.:counts per minute DTT:dithiothreitol EDTA:ethylenediaminetetraacetic acid EGTA:ethylene glycol-bis(β-aminoethyl ether)- N,N,N′,N′ -tetraacetic acid EMSA:electrophoretic mobility shift assay FCS:fetal calf serum HEPES: N -[2-hydroxyethyl]-piperazine- N ′- [2-ethanesulfonic acid] IL:interleukin NP-40:nonylphenoxypolyethoxyethanol NF-AT:nuclear factor of activated T cells BPS:phosphate buffered saline PMA:phorbol myristate acetate PMSF:phenylmethylsulfonyl fluoride Poly (dI-dC):polydeoxyinosinicdeoxycytidylic acid, double-stranded alternating copolymer Spanish tincture:tincture prepared from Spanish Arnica flowerheads Sl:sesquiterpene lactone TNF-α:tumor necrosis factor alpha