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.

Nitric oxide-dependent vasorelaxation induced by extractive solutions and fractions of Maytenus ilicifolia Mart ex Reissek (Celastraceae) leaves.

This study reveals that an ethanolic supernatant obtained from an aqueous extractive solution prepared from residues of methanolic extracts of ground leaves of Maytenus ilicifolia is able to cause a concentration- and endothelium-dependent relaxation in pre-contract rat aorta rings, with EC(50) of 199.7 (190-210) microg/ml. The non-selective nitric oxide synthase inhibitors l-NAME and l-NMMA abolished this effect, while superoxide dismutase and MnTBAP (a non-enzymatic superoxide dismutase mimetic) enhanced it. Further, relaxation induced by this ethanolic supernatant have been strongly inhibited by the guanylate cyclase inhibitors methylene blue and ODQ, as well as by the potassium channel blockers 4-aminopyridine and tetraethylammonium, but was unchanged by the cyclooxygenase inhibitor indomethacin and the membrane receptor antagonists atropine, HOE-140 and pirilamine. Partition of the ethanolic supernatant between H(2)O and EtOAc generated a fraction several times more potent, able to fully relax endothelium-intact aorta rings with an EC(50) of 4.3 (3.9-4.8) microg/ml. (13)C NMR spectrum of this fraction showed signals typical of catechin. This study reveals that the leaves of M. ilicifolia possess one or more potent substances able to relax endothelium-intact rat aorta rings, an event that appears to involve nitric oxide production, guanylate cyclase activation and potassium channel opening.

Effects of alkaloids of Himatanthus lancifolius (Muell. Arg.) Woodson, Apocynaceae, on smooth muscle responsiveness.

Himatanthus lancifolius, popularly known as "agoniada" in Brazil, is largely used in folk medicine against asthma, dysmenorrhea and as an emenagogue and abortive. This study reveals the effects of an alkaloid rich fraction (AlkF) obtained from the bark of Himatanthus lancifolius in vascular and non-vascular smooth muscle responsiveness. Incubation of AlkF (3-30 microg/ml) during 15 min generates a concentration-related and fully reversible reduction in maximal contractile responses evoked by acetylcholine and phenylephrine in rat jejune and aorta preparations, respectively. Exposition of endothelium-denuded pre-contracted rat aorta rings to AlkF results in a complete relaxation, with EC(50) of 22.2 (16.2-28.2 microg/ml). AlkF is also able to induce a concentration-related rightward shift of cumulative concentration curves for calcium in uterus and aorta rings maintained in depolarizing nutritive solution. Moreover, addition of AlkF in calcium-free solution also reduces, in a concentration-dependent manner, the ability of caffeine and phenylephrine to contract aorta rings. This study reveals that the bark of Himatanthus lancifolius possesses one or more indole alkaloids able to alter non-vascular and vascular smooth muscle responsiveness, an event that may involve the blocking of calcium entry or changes on intracellular calcium utilization or mobilization.