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, 66 (16), 2759-71

Hyperforin Is a Novel Type of 5-lipoxygenase Inhibitor With High Efficacy in Vivo

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Hyperforin Is a Novel Type of 5-lipoxygenase Inhibitor With High Efficacy in Vivo

Christian Feisst et al. Cell Mol Life Sci.

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.

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References

    1. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13150-5 - PubMed
    1. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13164-9 - PubMed
    1. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19881-6 - PubMed
    1. Annu Rev Biochem. 1994;63:383-417 - PubMed
    1. N Engl J Med. 2007 Nov 1;357(18):1841-54 - PubMed

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