Abstract Title:

Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in vivo.

Abstract Source:

Cell Mol Life Sci. 2009 Aug;66(16):2759-71. Epub 2009 Jul 5. PMID: 19579006

Abstract Author(s):

Christian Feisst, Carlo Pergola, Marija Rakonjac, Antonietta Rossi, Andreas Koeberle, Gabriele Dodt, Marika Hoffmann, Christina Hoernig, Lutz Fischer, Dieter Steinhilber, Lutz Franke, Gisbert Schneider, Olof Rådmark, Lidia Sautebin, Oliver Werz

Abstract:

 We previously showed that, in vitro, hyperforin from St. John's wort (Hypericum perforatum) inhibits 5-lipoxygenase (5-LO), the key enzyme in leukotriene biosynthesis. Here, we demonstrate that hyperforin possesses a novel and unique molecular pharmacological profile as a 5-LO inhibitor with remarkable efficacy in vivo. Hyperforin (4 mg/kg, i.p.) significantly suppressed leukotriene B(4) formation in pleural exudates of carrageenan-treated rats associated with potent anti-inflammatory effectiveness. Inhibition of 5-LO by hyperforin, but not by the iron-ligand type 5-LO inhibitor BWA4C or the nonredox-type inhibitor ZM230487, was abolished in the presence of phosphatidylcholine and strongly reduced by mutation (W13A-W75A-W102A) of the 5-LO C2-like domain. Moreover, hyperforin impaired the interaction of 5-LO with coactosin-like protein and abrogated 5-LO nuclear membrane translocation in ionomycin-stimulated neutrophils, processes that are typically mediated via the regulatory 5-LO C2-like domain. Together, hyperforin is a novel type of 5-LO inhibitor apparently acting by interference with the C2-like domain, with high effectiveness in vivo.

Study Type : Animal Study
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