In vivo assessment of safety and mechanisms underlying in vitro relaxation induced by Mikania laevigata Schultz Bip. ex Baker in the rat trachea.

Mikania laevigata, popularly known in Brazil as "guaco", is largely used in folk medicine against respiratory diseases. However, neither the assessment of the toxicity of "guaco" syrup (GS, used by humans) nor its efficacy or mechanisms of action has been properly investigated. Using in vitro procedures, we showed that the hydroalcoholic extract (HE) from Mikania laevigata induces a concentration-dependent relaxation of rat trachea which does not depend on epithelium-derived substances but involves changes in the cellular mobilization of calcium, perhaps due to a direct effect on membrane potassium channels. In addition, we assessed both oral and intraperitoneal acute toxicity, as well as the oral subchronic and chronic toxicity of GS containing controlled amounts of coumarin, the main biological marker of Mikania laevigata preparations used in humans. The calculated LD(50) of GS after intraperitoneal administration was 0.904 g/kg in mice (both sexes) and 0.967 and 0.548 g/kg in male and female rats, respectively. However, the LD(50) values of GS by the oral route were calculated to be up to 10 g/kg, in both male and female mice and rats. Repeated dose 28- or 90-day oral treatment with GS (75, 150 and 300 mg/kg) did not produce any disturbances in the hematological or biochemical parameters of either male or female rats, nor did it provide evidence of toxicity in the hepatic, renal or pancreatic systems. Besides the mechanistic findings, our results provide evidence of the safety of Mikania laevigata in rodents, even after subchronic and chronic administration, at least in relation to the evaluated parameters.

Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic treatment in Wistar rats.

Achillea millefolium L. (Asteraceae), popularly known as yarrow, has been used in folk medicine to treat complaints such as inflammation, pain, wounds, hemorrhages and gastrointestinal disturbances. The aim of the present study was to assess the safety and efficacy of the aqueous extract (AE) of the plant after chronic exposure. Indeed, the AE was effective in protecting the gastric mucosa against acute gastric lesions induced by ethanol and indomethacin and in healing chronic gastric lesions induced by acetic acid with (ED(50)=32 mg/kg, p.o.). Safety studies were performed in female and male Wistar rats treated daily with AE (0.3-1.2 g/kg, p.o./day) or vehicle (water, 10 ml/kg/day) for 28 or 90 consecutive days. Satellite groups consisted of animals sacrificed 30 days after the end of these treatments. Clinical observations, body and organ weight measurements, gross autopsy, hematology, clinical biochemical and histopathological examinations were performed. Slight changes in liver weight, cholesterol, HDL-cholesterol and glucose were observed in male and female animals. These changes were not correlated with dose or time of exposure of the animals to the AE. Overall, the results show the antiulcer potential of the aerial parts of the Achillea millefolium which is accompanied by no signs of relevant toxicity even at very long chronic exposure.

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.

Involvement of nitric oxide in the gastroprotective effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats.

The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degrees C), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NOx levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach.

Vasorelaxant and hypotensive effects of the extract and the isolated flavonoid rutin obtained from Polygala paniculata L.

OBJECTIVES: This study aimed to investigate the in-vitro and in-vivo cardiovascular effects of the crude hydroalcoholic extract from Polygala paniculata (HEPP) in rats. METHODS: The procedures were performed on aortic rings and on normotensive anaesthetized rats. KEY FINDINGS: When tested in endothelium-intact aorta rings, HEPP (30-1000 µg/ml) produced a significant non-concentration-dependent relaxing effect (∼40%), which was completely prevented by incubation with L-NAME (nitric oxide synthase inhibitor), ODQ (soluble guanylate cyclase inhibitor) and partially inhibited by tetraethylammonium (TEA; a non-selective potassium channel blocker) and charybdotoxin (a large- and intermediate-conductance calcium-activated potassium channel blocker). In contrast, atropine (a muscarinic receptor antagonist) or pyrilamine(a histamine H1 receptor antagonist) had no effect. Furthermore, oral administration of HEPP (30-300 mg/kg) in anaesthetized rats caused a dose-dependent and sustained hypotensive action. This effect was unchanged by atropine or TEA, but was strongly reduced in rats continuously infused with L-NAME or methylene blue. Moreover, rutin (1-3 mg/kg) administered by an intravenous route also caused a dose-dependent hypotensive effect in rats. CONCLUSIONS: Our results demonstrated that the extract obtained from P. paniculata induces potent hypotensive and vasorelaxant effects that are dependent on the nitric oxide/guanylate cyclase pathway. These effects could be related, at least in part, to the rutin contents in this extract.

Gastroprotective mechanisms of indole alkaloids from Himatanthus lancifolius.

The indole alkaloids mixture (AlkF) obtained from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson was evaluated for gastroprotective properties in rodents. The AlkF potently protected rats from experimentally induced gastric lesions by ethanol (ED (50) = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED (50) = 82 mg/kg, i. d.). Protective effects of the AlkF in the ethanol and hypersecretion models included increase of GSH levels of gastric mucosa indicating activation of GSH-dependent cytoprotective mechanisms. Also, an increase of the antioxidant capacity as measured through glutathione S-transferase activity was observed in the hypersecretory but not in the ulcerative model. Furthermore, the amount of nitric oxide derivatives (NO (3) + NO (2)) in the forestomach was increased while the amount released into the gastric juice during pylorus ligature was decreased by the AlkF suggesting an alteration of NO-related mechanisms. Reduction of gastric acid hypersecretion induced by pylorus ligature seems to correlate with the blockade of H (+),K (+)-ATPase activity as determined in vitro by the capacity of the AlkF mix to decrease the hydrolysis of ATP by the ATPase isolated from dog gastric mucosa (EC (50) = 212 microg/mL). Cholinergic mechanisms can be excluded since intestinal transit was not modified with doses up to 100 mg/kg ( p. o.). GC-MS investigation of components of the AlkF resulted in the identification of 3 main indole alkaloids, uleine (53 %), its isomer (13 %), demethoxyaspidormine (23.8 %) and traces of at least other five alkaloids. Collectively, the results show the novel gastroprotective properties of the indole AlkF of H. lancifolius through a variety of mechanisms.

Gastroprotective effects of a crude extract of Baccharis illinita DC in rats.

Baccharis illinita DC (Compositae) is used in folk medicine to treat gastric disorders. The crude hydroalcoholic extract of leaves and stems tested on mice at doses from 1.0 to 6.0 g/kg, PO, did not produce signs of toxicity. Only the aqueous extract of leaves (0.1 g/kg, PO) increased intestinal motility in mice. The crude hydroalcoholic extract of stems and leaves (HESL) protected rats against lesions induced by ethanol or restraint-in-cold. The crude aqueous extract of roots protected against ulcers induced by ethanol, indomethacin or restraint-in-cold, and the crude aqueous extract of flowers only protected against lesions induced by ethanol. When injected into the duodenal lumen, the aqueous root extract inhibited basal acid secretion in pylorus-ligated rats. The results obtained in the present pharmacological assays indicate that this plant has a protective action against gastric lesions of the mucosa involving the maintenance of protective factors such as mucus, bicarbonate and blood flow, besides the reduction of gastric acid secretion.

Actions of crude hydroalcoholic extract of Pfaffia sp on gastrointestinal tract

The plants that compound the Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of a crude hydroalcoholic extract of Pfaffia sp on the gastrointestinal tract. Female Wistar rats were pretreated orally (p.o.) with the hydroalcoholic extract of Pfaffia (0.5, 1 and 2 g.kg-1) before the induction of ulcer with hypothermic restraint stress (HRS), ethanol (ET) or indomethacin (IND). Control animals received water (C) or ranitidine (60mg/kg) p.o. The hydroalcoholic extract of Pfaffia (0.5, 1 and 2 mg.kg-1) protected rats against HRS and ET - induced ulcers, but was not able to protect the gastric mucosa against IND - induced ulcers. When injected into the duodenal lumen, the hydroalcoholic extract of Pfaffia inhibited basal and stimulated acid secretion in pylorus-ligated rats. These results indicate that this plant has a protective action against gastric lesions of the mucosa involving the reduction of gastric acid secretion

Action of crude aqueous extract of leaves of Achillea millefolium L. (Compositae) on gastrointestinal tract

Achillea millefolium L. (Compositeae) is used in folk medicine to treat gastric disturbances. Doses of 125, 1500 and 2000 mg/kg protected rats against ulcers induced by ethanol and restraint-in-cold-stress, but not against indomethacininduced ulcers. Injected into the duodenal lumen the extract inhibited the basal acid secretion. Data from studies indicate that the antiulcer activity of A. millefolium must been related to a inhibition of gastric secretion or to a increase of protective factors in gastric mucosa as mucus, bicarbonate and blood flow. In conclusion, this extract effectively protected the gastric mucosa and inhibited gastric acid secretion. Further studies should also be provided for the stimulation of receptors in the parietal cell to elucidate the route whereby the extract produce this action.

A "mentira" do alcoolico: Um estudo relacionado ao consumo de álcool / The \"lie\" of alcoholic: A study related to alcohol consumptiom

Neste estudo comparou-se os relatos de 104 pacientes dependentes de álcool (DSM-III-R) quanto à última ingesta de bebidas alcoólicas antes da entrevista, com o nìvel de álcool na urina. Os resultados mostraram que apenas 5//dos pacientes apresentavam discordância entre o relato e o exame laboratorial. Possìveis causas para estes resultados (engajamento em projeto de pesquisa, tratamento voluntário, nìvel de gravidade, etc.) säo discutidos