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

  title={Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in vivo},
  author={Christian Feisst and Carlo Pergola and Marija Rakonjac and Antonietta Rossi and Andreas Koeberle and Gabriele Dodt and Marika Hoffmann and Christina Hoernig and Lutz Fischer and Dieter Steinhilber and Lutz Franke and Gisbert Schneider and Olof R{\aa}dmark and Lidia Sautebin and Oliver Werz},
  journal={Cellular and Molecular Life Sciences},
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 B4 formation in pleural exudates of carrageenan-treated rats associated with potent anti-inflammatory… 

Hyperforin, an Anti-Inflammatory Constituent from St. John's Wort, Inhibits Microsomal Prostaglandin E2 Synthase-1 and Suppresses Prostaglandin E2 Formation in vivo

It is concluded that the suppression of PGE2 biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp.

Improved bioactivity of the natural product 5-lipoxygenase inhibitor hyperforin by encapsulation into polymeric nanoparticles.

Encapsulation of the highly hydrophobic hyperforin as a representative of lipophilic 5-LO inhibitors into AcDex-based NPs allows for efficient inhibition of 5- LO activity in neutrophils in the presence of albumin due to effective uptake and circumvention of plasma protein binding.

Sulindac sulfide suppresses 5-lipoxygenase at clinically relevant concentrations

Mechanistic analysis demonstrated that SSi directly suppresses 5-LO with an IC50 of 20 μM, which may provide a novel molecular basis to explain the COX-independent pharmacological effects of sulindac under therapy.

Mechanistic insights into the antileukemic activity of hyperforin.

In summary, hyperforin targets molecules involved in signaling pathways that control leukemic cell proliferation, survival, apoptosis, migration and angiogenesis, and shows interesting in vivo properties in animal models.



Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase.

Suppression of receptor-mediated Ca2+ mobilization and functional leukocyte responses by hyperforin.

Nonredox 5-lipoxygenase inhibitors require glutathione peroxidase for efficient inhibition of 5-lipoxygenase activity.

The kinetic analysis revealed a noncompetitive inhibition of 5-LO by ZM 230487 at low hydroperoxide levels, whereas it acted as a competitive inhibitor with low affinity under nonreducing conditions in granulocyte homogenates, suggesting that physiological conditions associated with oxidative stress and increased peroxide levels lead to impaired efficacy of nonredox type 5- LO inhibitors.

5-lipoxygenase: cellular biology and molecular pharmacology.

  • O. Werz
  • Biology
    Current drug targets. Inflammation and allergy
  • 2002
The determinants of cellular 5-LO activity are highlighted, the molecular pharmacology of 5- LO is summarized and the cellular redox tone regulates 5-lo product formation are summarized.

Pharmacological intervention with 5-lipoxygenase: new insights and novel compounds

5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes (LTs) that exert a large number of different biological activities mediated by specific G-protein-coupled receptors. LTB4

5-lipoxygenase inhibitory activity of zileuton.

The effectiveness of this compound for preventing LT formation in vitro, ex vivo and in vivo suggests its utility for preventing the pathophysiological effects of the LTs and other 5-lipoxygenase products in animals and in humans.

Selective inhibition of arachidonate 5‐lipoxygenase by novel acetohydroxamic acids: biochemical assessment in vitro and ex vivo

Three chemically novel acetohydroxamic acids are potent inhibitors of the synthesis of leukotriene B4 from arachidonic acid by human leucocyte homogenates and were also potent, selective inhibitors of LTB4 synthesis induced by A23187 in whole rat blood.

Molecular pharmacological profile of the nonredox‐type 5‐lipoxygenase inhibitor CJ‐13,610

CJ‐13,610 may possess considerable potential as a potent orally active nonredox‐type 5‐ LO inhibitor that lacks certain disadvantages of former representatives of this class of 5‐LO inhibitors.

1-Oleoyl-2-acetylglycerol Stimulates 5-Lipoxygenase Activity via a Putative (Phospho)lipid Binding Site within the N-terminal C2-like Domain*

It is demonstrated that 1-oleoyl-2-acetylglycerol directly stimulates 5-LO by acting at a phospholipid binding site located within the C2-like domain.