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

@article{Feisst2009HyperforinIA,
  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},
  year={2009},
  volume={66},
  pages={2759-2771}
}
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.
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