Inhibition of Leukocyte Eicosanoid Generation and Radical Scavenging Activity by Gnaphalin, a Lipophilic Flavonol Isolated from Helichrysum picardii

Abstract

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxyen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B₂ (IC₅₀ = 39.9 ± 3.9 µM), and of the 5-lipoxygenase metabolite leukotriene B₄, although the potency was two-fold less (IC₅₀ = 81.8 ± 12.9 µM). At concentrations of 6 to 320 µM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and β-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC₅₀ ≍ 40 µM) and by PMA-stimulated leukocytes (> 60% at 500 µ;M), directly inhibited xanthine oxidase (85% at 395 µM) and inhibited Fe³⁺-ascorbate-induced liposomal peroxidation (IC₅₀ ≍ 215 µM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.

Key words

Helichrysum picardii - Asteraceae - anti-inflammatory drugs - 5-lipoxygenase - cyclo-oxygenase - reactive oxygen species - radical scavenger