Inhibition of prostaglandin E-4 and leukotriene C-4 in mouse peritoneal macrophages and thromboxane B-2 production in human platelets by flavonoids from Stachys chrysantha and Stachys candida

Seven flavonoids of Stachys chrysantha and Stachys candida have been isolat ed. The structures of the compounds were elucidated by spectroscopic method s, particularly highfield NMR spectroscopy, The effects of the methanol ext racts of these two endemic Greek Stachys sp, and their main flavonoids were examined on arachidonic acid (AA) metabolism in the cellular system (mouse peritoneal macrophages and human platelets). Their cytotoxicity on cells w as also investigated, Most samples assayed did not exhibit any significant effect on prostaglandin E-2 (PGE(2))-release from calcium ionophore-stimula ted mouse peritoneal macrophages. Only chrysoeriol-7-O-beta-D-(3"-E-p-couma royl)-glucopyranoside, at the highest non-cytotoxic dose (50 mu M), inhibit ed the release of PGE(2), but this effect is not statistically significant. The release of leukotriene C-4 (LTC4) by mouse peritoneal macrophages stim ulated with calcium ionophore was inhibited by a crude extract of S, chrysa ntha, with an IC,, value of 34.3 mu g/ml. Xanthomicrol (IC50 = 29.2 mu M) a nd chrysoeriol-7-O-beta-D-(3"-E-p-coumaroyl)-glucopyranoside (IC50 = 11.1 m u M) also inhibited the release of LTC4, although it showed less potency th an the reference compound nordihydroguaiaretic acid (NDGA) (IC50 = 2 mu M). However, most samples assayed showed a significant effect on thromboxane B -2 (TXB2)-release from calcium ionophore-stimulated human platelets, with i nhibition percentages slightly lower than the reference drug ibuprofen (IC5 0 = 7 mu M). The IC50 values are: crude extract of S, candida 23.3 mu g/ml; crude extract of S, chrysantha 23.1 mu g/ml; xanthomicrol 28.8 mu M; calcy copterin 2.66 mu M and chrysoeriol-7-O-beta-D-(3"-E-p-coumaroyl)-glucopyran oside 8.8 mu M. Our results indicate that the selective inhibition of TX-sy nthase enzyme may be the primary target of action of most of these samples, and one of the mechanisms through which thus exert their antiinflammatory effects.