Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isol ated from the aerial flowering parts of Helichrysum picordii Boiss. & Reute r (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-l ipoxygenase pathways of arachidonate metabolism in stimulated rat peritonea l leukocytes, and for its effects on leukocyte granular enzyme release, cel l viability and interactions with reactive oxyen species. Gnaphalin dose-de pendently inhibited generation of the cyclooxygenase metabolite thromboxane B-2 (IC50 = 39.9 +/- 3.91 mu M), and of the 5-lipoxygenase metabolite leuk otriene B-4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 m u M). At concentrations of 6 to 320 mu M, gnaphalin did not affect secretio n of the pro-inflammatory enzymes lysozyme, myeloperoxidase and P-glucuroni dase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged sup eroxide radicals generated in the hypoxanthine/xanthine oxidase system (IC5 0 approximate to 40 mu M) and by PMA-stimulated leukocytes (>60% at 500 mu M), directly inhibited xanthine oxidase (85 % at 395 mu M) and inhibited Fe 3+-ascorbate-induced liposomal peroxidation (IC50 approximate to 215 mu M). Thus, like some other flavonoids found in medicinal herbs, gnaphalin posse sses an array of potentially beneficial anti-eicosanoid and free-radical sc avenging properties which may alongside other constituents contribute to th e claimed medicinal properties of the plant from which it is derived.