Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids

A group of flavonoids isolated from medicinal plants and which are selective inhibitors of lipoxygenase activityin vitro: sideritoflavone, cirsiliol, hypolaetin-8-O--d-glucoside, hypolaetin, oroxindin, quercetagetin-7-O--d-glucoside, gossypin, hibifolin and gossypetin, besides leucocyanidol, have been studied for their effects on acute responses induced by carrageenin in mice. The oral administration of flavonoids to mice inhibited dose-dependently the development of paw oedema at 1, 3 and 5 h after carrageenin injection. A similar administration of flavonoids induced a dose-dependent inhibition of leukocyte accumulation in inflammatory exudates following intraperitoneal injection of carrageenin into mice. Some of the flavonoids exhibited a potency against leukocyte infiltration similar to that seen for inhibition of carrageenin oedema at 3 h of induction. In agreement with data reported in rats, indomethacin was much more effective on inhibition of prostaglandin E₂ (PGE₂) formation than on leukocyte infiltration in mice. The selectivity of flavonoids towards lipoxygenase is not retainedin vivo since they behave as dual inhibitors of PGE₂ and leukotriene B₄ (LTB₄) formation in peritoneal exudates. Our data support the inhibition of arachidonic acid metabolism as one of the mechanisms by which flavonoids exert their anti-inflammatory effects.