Involvement of the nitric oxide/soluble guanylate cyclase pathway in the anti-oedematogenic action of Pfaffia glomerata (Spreng) Pedersen in mice

Pfaffia glomerata is used in southern American countries against inflammatory diseases. We have explored the ability of a crude hydroalcoholic extract of P. glomerata root (HEPG) to prevent the oedematogenic action of several inflammatory agents in mice. We have examined also the duration of its effects and the mechanisms involved. The oral or intraperitoneal treatment of mice with HEPG (1, 10, 30, 100 or 300 mg kg(-1)) reduced, in a dose-dependent manner, carrageenan-induced paw oedema in the early (1-4 h) and late (48 h) periods. In the early period, the ID50 value (the median dose that caused 50% inhibition) of HEPG was 60.5 (28.5-128.71) and 20.4 (14.8-28.3) mg kg(-1) after oral and intraperitoneal administration, respectively. This effect was still evident when HEPG was administered up to 6 h before carrageenan. HEPG inhibited also paw oedema induced by histamine, serotonin, bradykinin, substance P and bacterial lipopolysaccharide. In addition, oral administration of HEPG increased the levels of nitrate and nitrite in the blood of mice. Further, its anti-oedematogenic action against carrageenan was prevented fully by N(G) nitro-L-arginine-methyl-ester (10 mg kg(-1), s.c.), as well as by methylene blue (20 mg kg(-1), s.c.) or 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (2 mg kg(-1), s.c.). The results indicated that stimulation of endogenous production of nitric oxide, followed by soluble guanylate cyclase activation, was implicated in the anti-oedematogenic action of HEPG.