Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives: Relationship to antioxidant activity and to iron ion-reducing ability

doi:10.1016/0006-2952(91)90501-U

Biochemical Pharmacology

Volume 42, Issue 9, 9 October 1991, Pages 1673-1681

https://doi.org/10.1016/0006-2952(91)90501-U Get rights and content

Abstract

We investigated the ability of various plant flavonoids (a) to inhibit 5-lipoxygenase and cyclo-oxygenase activities in rat peritoneal leukocytes, (b) to inhibit lipid peroxidation in rat liver microsomes, and (c) to stimulate DNA degradation caused by the antibiotic bleomycin in the presence of ferric ions. These compounds were compared with a range of synthetic phenolic substances including carnosol, vanillin, vitamin E and its analogue trolox c. The flavonoids were potent inhibitors of non-enzymatic peroxidation in membranes but this was not significantly correlated with their ability to inhibit either pathway of eicosanoid synthesis, suggesting that their mode of inhibition of 5-lipoxygenase/cyclo-oxygenase is not simply due to interception of peroxyl radicals generated at the active site of the enzymes. Many of the flavonoids and other compounds (including carnosol, vitamin E and trolox c) stimulated Fe³⁺/bleomycin-dependent DNA degradation. Those flavonoids which stimulated DNA degradation at low concentrations but which inhibited it at higher concentrations (“biphasic” effect, possibly caused by changing relative contributions of ability to reduce ferric-bleomycin or to chelate iron ions from the bleomycin) were selective inhibitors of 5-lipoxygenase compared to cyclo-oxygenase. In contrast, those flavonoids that did not stimulate DNA degradation at all proved to be cyclo-oxygenase selective inhibitors. Compounds that increased Fe³⁺/bleomycin-dependent DNA damage up to a maintained plateau were non-selective inhibitors of both 5-lipoxygenase and cyclo-oxygenase. Thus, a combination of iron-chelating and iron ion-reducing properties appears to be required for selective 5-lipoxygenase inhibition by phenolic compounds. Carnosol, vitamin E and trolox c were also found to be 5-lipoxygenase inhibitors of varying potency, and all were less active as cyclo-oxygenase inhibitors.

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^§: Present address: Pulmonary Medicine Division, UC Davis Medical Center, 4301 X St, Sacramento, CA 95817, U.S.A.

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Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives: Relationship to antioxidant activity and to iron ion-reducing ability

Abstract

Phytochemistry

Biochem Biophys Res Commun

Prostaglandins

Biochem Pharmacol

Biochem Pharmacol

Biochem Med

Biochem Pharmacol

FEBS Lett

J Biol Chem

J Inorg Biochem

Biochim Biophys Acta

J Biol Chem

Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human disease

N Engl J Med

Leukotriene biosynthesis inhibitors

Pharm Res

Selectivity of neutrophil 5-lipoxygenase and cyclo-oxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids

J Pharm Pharmacol