The relaxation of isolated rabbit corpus cavernosum by the herbal medicine Catuama and its constituents

The effects of the Brazilian herbal medicine Catuama and each of its plant constituents (Paullinia cupana, Trichilia catigua, Zingiber officinalis and Ptychopetalum olacoides) were investigated on rabbit corpus cavernosum (RbCC) using a bioassay cascade. Catuama caused short-lived and dose-dependent relaxations (11% +/- 7%, 26% +/- 5% and 82% +/- 9%, at doses of 1, 3 and 10 mg, respectively). Neither the nitric oxide synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 10 microM) nor the soluble guanylate cyclase inhibitor ODQ (10 microM) significantly affected the Catuama-induced relaxations. Similarly, the selective ATP-dependent K(+) channel (K(ATP)) blocker glibenclamide (10 microM), the muscarinic receptor antagonist atropine (1 microM) and the voltage-dependent Na(+) channel blocker tetrodotoxin (1 microM) all failed to affect significantly the Catuama-induced relaxations. These results indicate that the relaxations induced by Catuama involve neither nitric oxide release nor K(ATP) channel activation. The extracts of P. cupana, Z. officinalis and P. olacoides caused short-lived and dose-dependent RbCC relaxations, whereas T. catigua evoked long-lasting relaxations which were occasionally preceded by a brief contractile effect. The extract of P. cupana was the most active in relaxing RbCC strips. The relaxations induced by all extracts were not significantly affected by L-NAME (10 microM). The infusion of ODQ (10 microM) had no significant effect on the P. cupana- and Z. officinalis-induced relaxations but reduced by >50% (p < 0.05) those evoked by P. olacoides and T. catigua. Incubations of RbCC with Catuama(10 mg/mL for 0.25 to 5 min) caused increases of cAMP levels (143% increase at 5 min of incubation). Incubations of RbCC with P. cupana extract (1 mg/mL) increased the cAMP levels by 200% whereas higher doses (10 and 100 mg/mL) caused smaller increases in the nucleotide levels (150% and 89%, respectively). The extracts of Z. officinalis and P. olacoides (same doses) caused smaller increases of the cAMP levels compared with the P. cupana extract, whereas T. catigua (1-100 mg) did not increase the levels of this nucleotide above the basal values. Our results show that of the four extracts assayed, P. cupana was the most effective, indicating that it is the main extract responsible for the relaxing effect of Catuama on rabbit cavernosal tissue.     

Analgesic Effect of the Herbal Medicine Catuama in Thermal and Chemical Models of Nociception in Mice

The antinociceptive effect of the herbal medicine Catuama and the hydroalcoholic extract (HE) of each plant present in this extract were investigated in chemical and thermal models of nociception in mice. The extract of Catuama (200 mg/kg, p.o.) caused time-dependent and long-lasting antinociception against acetic acid-induced writhing, formalin and capsaicin-induced licking and also in the tail-flick and hot-plate assays. Its maximal analgesic effect was reached 6 h after its oral administration and this effect lasted for at least 12 h. When given 6 h prior to testing (100 and 200 mg/kg, p.o.), the extract elicited dose-related antinociception, but at 400 mg/kg, its analgesic effect was greatly reduced. The antinociception caused by the extract of Catauma, like those produced by morphine, was largely antagonized by naloxone. The daily administration of the extract (200 mg/kg, p.o. for 4 days) or morphine (5 mg/kg, s.c. for 4 days) produced progressive tolerance, an effect which was reverted by naloxone (5 mg/kg, i.p.). In addition, the Catuama extract showed cross-tolerance with morphine. The Catuama antinociception was not due to its non-specific effects such as muscle relaxation or sedation of animals, nor was it secondary to its antiinflammatory property. When analysed separately the hydroalcoholic extract (HE) obtained from Trichilia catigua, Paullinia cupana, Ptychopelatum olacoids, Zinziber officinalis (200 mg/kg, p.o., 6 h prior) all inhibited acetic acid-induced pain (82%±2%; 66%±2%; 42%±2% and 30%±4% of inhibition, respectively ( p <0.01). In the formalin test the HE of P. olacoids; P. cupana; T. catigua and to a lesser extent, Z. officinalis (200 mg/kg, p.o., 6 h prior) also inhibited both phases of formalin-induced pain ( p <0.01). Thus, antinociception caused by the Catuama extract seems to be dependent on the interaction of the several active principles present in these plants. The mechanisms underlying the antinociception caused by extract of herbal medicine Catuama is still not completely understood, but a significant number of these effects are related to its interaction with the naloxone sensitive opioid system. Together, the results indicate that the herbal medicine Catuama may constitute a useful therapeutic agent for the treatment of clinical pain. © 1997 by John Wiley & Sons, Ltd.     

Vascular action of the crude hydroalcoholic extract from Hymenaea martiana on the isolated rat and rabbit aorta

The present study investigates the effect of the hydroalcoholic extract (HE) from Hymenaea martiana (Leguminosae) on endothelium-dependent and independent relaxation responses induced by acetylcholine (ACh), histamine (His), calcium ionophore (A23187) and sodium nitroprusside in precontracted aortic rings from rat and rabbit. In addition, we have also evaluated the action of the HE on noradrenaline- (NA), angiotensin I-(AI) and AII-induced contractions in the rabbit aorta. The HE (0.25–0.5 mg/mL) inhibited in a concentration-dependent manner the relaxant response induced by ACh in rings of rabbit aorta and by His in rat aorta. Relaxation in response to A23187 was inhibited in rat but not in rabbit aortic rings. In contrast, the HE was completely ineffective against endothelium-independent relaxations caused/by sodium nitroprusside in rabbit aorta rings. The HE (0.5–1.0 mg/mL) significantly enhanced the maximal contractile responses induced by NA in rabbit aorta set up with the endothelium, but caused no effect in endothelium rubbed preparations. In addition, the HE (0.5 mg/mL) markedly antagonized the contractile responses elicited by AI, but caused only a slight effect on AII-induced contractile responses in rabbit aorta. These findings indicate that the active principle(s) present in the HE from the bark of Hymenaea martiana selectively inhibit the endothelium-dependent vasorelaxant responses caused by several substances in aortic rings from rat and rabbit, presumably by a mechanism related with endothelium-derived relaxation factor synthesis and/or inactivation. The HE also antagonized AI but not AII-induced contractions in rabbit aorta, suggesting some interference with the angiotensin converting enzyme.