RESUMO
Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since ß-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus ß-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and ß-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of ß-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K+ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with ß-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.
RESUMO
Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle.
Assuntos
Anacardiaceae , Antiulcerosos , Úlcera Gástrica , Ratos , Animais , Prostaglandinas/farmacologia , Óxido Nítrico/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Antiulcerosos/química , Hexanos/farmacologia , Ratos Wistar , Compostos de Sulfidrila/farmacologia , Extratos Vegetais/química , Mucosa GástricaRESUMO
CONTEXT: The gastroprotective effect of Heliotropium indicum L. (Boraginaceae), a plant traditionally used in Mexico to treat gastric ulcers, has been previously reported. However, no active compound was identified. OBJECTIVE: The current contribution aimed to isolate, through a bioassay-guided study, at least one compound from H. indicum with considerable gastroprotective activity, examine its effect on ethanol-induced gastric lesions in mice, and explore possible mechanisms of action. MATERIALS AND METHODS: Three extracts (hexane, dichloromethane, and methanol) were obtained from H. indicum leaves. Their 30 and 100 mg/kg doses were assessed on ethanol-induced gastric lesions in male CD1 mice. Since the dichloromethane extract was the most active, successive chromatographies were carried out leading to the identification of the most active compound. This compound (at 3-100 mg/kg) was compared to carbenoxolone (at 10-100 mg/kg) in biological evaluations in mice. Pre-treatments with indomethacin (10 mg/kg, s.c.), L-NAME (70 mg/kg, i.p.), and NEM (10 mg/kg, s.c.) were performed independently to determine the participation of prostaglandins, nitric oxide, and/or sulfhydryl groups, respectively, in the mechanism of action of the compound. RESULTS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from H. indicum, afforded dose-dependent gastroprotective activity. The maximum effect was observed at 100 mg/kg (90.13 ± 3.08%), with an ED50 of 5.92 ± 2.48 mg/kg. Gastroprotection was not modified by pre-treatment with indomethacin, L-NAME, or NEM. CONCLUSIONS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, isolated from H. indicum, was found to produce a substantial gastroprotective effect. Prostaglandins, nitric oxide, and non-protein sulfhydryl groups are not involved in its mechanism of action.
Assuntos
Antiulcerosos , Heliotropium , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Etanol , Indometacina/farmacologia , Masculino , Cloreto de Metileno , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico , Prostaglandinas , Ratos , Ratos Wistar , Compostos de SulfidrilaRESUMO
Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.
RESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug-drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56-320 mg/kg), antiallodynic (100-562 mg/kg), and antihyperalgesic and anti-inflammatory (10-178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diterpenos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Administração Oral , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Diterpenos/administração & dosagem , Diterpenos/química , Diterpenos/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Ligadura , Naproxeno/farmacologia , Naproxeno/uso terapêutico , Ratos Wistar , Nervos Espinhais/efeitos dos fármacos , Fatores de TempoRESUMO
Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED30) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (Cmax) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED30 values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was Cmax for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.
Assuntos
Analgésicos , Diclofenaco , Eugenol/análogos & derivados , Cetorolaco , Analgésicos/farmacocinética , Analgésicos/farmacologia , Animais , Diclofenaco/agonistas , Diclofenaco/farmacocinética , Diclofenaco/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Eugenol/agonistas , Eugenol/farmacocinética , Eugenol/farmacologia , Cetorolaco/agonistas , Cetorolaco/farmacocinética , Cetorolaco/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Peptic ulcer disease, the most common gastrointestinal disorder, is currently treated with several types of drugs, but all have severe side effects. The aim of the present study was to evaluate the gastroprotective activity of juanislamin, isolated from Calea urticifolia, in a rat model of ethanol-induced gastric lesions. Thirty minutes after orally administering a given dose of juanislamin (from 1 to 30 mg/kg) or carbenoxolone (the reference drug, at 1-100 mg/kg) to rats, 1 mL of ethanol was applied, and the animals were sacrificed 2 h later. The stomachs were removed and opened to measure the total area of lesions in each. To examine the possible participation of prostaglandins, nitric oxide and/or sulfhydryl groups in the mechanism of action of juanislamin, the rats received indomethacin, NG-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or N-ethylmaleimide pretreatment, respectively, before being given juanislamin and undergoing the rest of the methodology. Juanislamin inhibited gastric lesions produced by ethanol in a non-dose-dependent manner, showing the maximum gastroprotective effect (100%) at 10 mg/kg. The activity of juanislamin was not modified by pretreatment with indomethacin, l-NAME or N-ethylmaleimide. In conclusion, juanislamin protected the gastric mucosa from ethanol-induced damage, and its mechanism of action apparently does not involve prostaglandins, nitric oxide or sulfhydryl groups.
Assuntos
Antiulcerosos/administração & dosagem , Asteraceae/química , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Óxido Nítrico/farmacologia , Prostaglandinas/farmacologia , Úlcera Gástrica/prevenção & controle , Compostos de Sulfidrila/farmacologia , Animais , Carbenoxolona/administração & dosagem , Etilmaleimida/farmacologia , Mucosa Gástrica/patologia , Indometacina/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológicoRESUMO
Peptic ulcers are currently treated with various drugs, all having serious side effects. The aim of this study was to evaluate the gastroprotective activity of calein D (from Calea urticifolia), a sesquiterpene lactone with a germacrane skeleton. Gastric lesions were induced in mice by administering ethanol (0.2 mL) after oral treatment with calein D at 3, 10 and 30 mg/kg, resulting in 13.15 ± 3.44%, 77.65 ± 7.38% and 95.76 ± 2.18% gastroprotection, respectively, to be compared with that of the control group. The effect found for 30 mg/kg of calein D was not reversed by pretreatment with NG-nitro-l-arginine methyl ester (l-NAME, 70 mg/kg, ip), indomethacin (10 mg/kg, sc) or N-ethylmaleimide (NEM, 10 mg/kg, sc). Hence, the mechanism of action of calein D does not involve NO, prostaglandins or sulfhydryl compounds. Calein D was more potent than carbenoxolone, the reference drug. The findings for the latter are in agreement with previous reports.
Assuntos
Asteraceae/química , Etanol/efeitos adversos , Lactonas/administração & dosagem , Sesquiterpenos de Germacrano/administração & dosagem , Úlcera Gástrica/prevenção & controle , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etilmaleimida/administração & dosagem , Etilmaleimida/farmacologia , Indometacina/administração & dosagem , Indometacina/farmacologia , Lactonas/química , Lactonas/farmacologia , Camundongos , Estrutura Molecular , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prostaglandinas/metabolismo , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Compostos de Sulfidrila/metabolismoRESUMO
Peperomia hispidula (Sw.) A. Dietr. is used in Mexican traditional medicine for treating respiratory illnesses such as asthma. The latter disorder results from an excessive and inappropriate constriction of airway smooth muscle. The aim of the present study was to evaluate the relaxant activity of P. hispidula on isolated rat tracheal rings contracted with carbachol. The methyleugenol was identified as the main active constituent in the dichloromethane extract. To explore the possible mechanism of action, concentration-response curves were constructed in the presence and absence of propranolol (3 µM), indomethacin (10 µM), glibenclamide (1 µM), and L-NAME (300 µM), finding that neither reduced methyleugenol-induced smooth muscle relaxation. In conclusion, P. hispidula herein displayed relaxant activity on rat tracheal rings. The effect of methyleugenol, was probably not related to the activation of ß2-adrenoceptors, prostaglandins, K+ATP channels or nitric oxide.
Peperomia hispidula (Sw.) A. Dietr. es utilizada en la medicina tradicional mexicana para tratar enfermedades respiratorias como el asma. Este uÌltimo trastorno es el resultado de una contraccioÌn excesiva e inapropiada del muÌsculo liso de las viÌas respiratorias. El objetivo del presente estudio fue evaluar la actividad relajante de P. hispidula sobre anillos aislados de traÌquea de rata contraiÌdos con carbacol. El metileugenol fue identificado como el principal constituyente activo en el extracto de diclorometano. Para explorar el posible mecanismo de accioÌn, se construyeron curvas concentracioÌn-respuesta en presencia y ausencia de propranolol (3 µM), indometacina (10 µM), glibenclamida (1 µM), y L-NAME (300 µM), encontrando que ninguno redujo la relajacioÌn del muÌsculo liso inducida por metileugenol. En conclusioÌn, P. hispidula muestra actividad relajante en anillos de traÌquea de rata. El efecto de metileugenol, al parecer no estaÌ implicado con la activacioÌn de los receptores ß2-adreneÌrgicos, prostaglandinas, canales de K+ATP u oÌxido niÌtrico.
Assuntos
Animais , Masculino , Ratos , Traqueia/efeitos dos fármacos , Eugenol/análogos & derivados , Eugenol/farmacologia , Extratos Vegetais/farmacologia , Peperomia , Asma/metabolismo , Estenose Traqueal/induzido quimicamente , Eugenol/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Cloreto de Metileno/química , Relaxamento Muscular/efeitos dos fármacosRESUMO
(â)-Encecanescin (1) has been isolated from the leaves of Eupatorium aschembornianum. Two conformers are present in the crystal structure as a result of molecular disorder. The structure of 1 was established by 1H- and 13C-NMR spectroscopy in CDCl3 solution using 2D NMR techniques (gHSQC, gHMBC and NOESY). A Monte Carlo random search using molecular mechanics followed by the geometry optimization of each minimum energy structure using density functional theory (DFT) calculations at the B3LYP/6-31G* level and a Boltzmann analysis of the total energies generated accurate molecular models describing the conformational behavior of 1. The three most stable conformers 2-4 of compound 1 were reoptimized at the B3LYP/6-311++G(d,p) level of theory using CHCl3 as a solvent. Correlations between the experimental 1H- and 13C-NMR chemical shifts (δexp) have been found, and the GIAO/B3LYP/6-311++G(d,p) calculated magnetic isotropic shielding tensors (σcalc) for conformers 2 and 3, δexp=a+b σcalc, are reported. A good linear relationship between the experimental and calculated NMR data has been obtained for protons and carbon atoms.
Assuntos
Benzopiranos/química , Eupatorium/química , Folhas de Planta/química , Prótons , Benzopiranos/isolamento & purificação , Carbono/química , Clorofórmio , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Método de Monte Carlo , Extratos Vegetais/química , Teoria Quântica , Solventes , Estereoisomerismo , TermodinâmicaRESUMO
Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, NG-nitro-l-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups.
Assuntos
Compostos Alílicos/farmacologia , Dioxóis/farmacologia , Peperomia/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Compostos Alílicos/isolamento & purificação , Compostos Alílicos/uso terapêutico , Animais , Dioxóis/isolamento & purificação , Dioxóis/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Etanol , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamenteRESUMO
Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg), and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg) was attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.
Assuntos
Antiulcerosos/farmacologia , Hyptis/química , Óxido Nítrico/fisiologia , Extratos Vegetais/farmacologia , Compostos Policíclicos/farmacologia , Prostaglandinas/fisiologia , Úlcera Gástrica/tratamento farmacológico , Compostos de Sulfidrila/fisiologia , Animais , Antiulcerosos/isolamento & purificação , Antiulcerosos/uso terapêutico , Carbenoxolona/farmacologia , Carbenoxolona/uso terapêutico , Inibidores de Ciclo-Oxigenase/farmacologia , Etanol , Etilmaleimida/farmacologia , Indometacina/farmacologia , Masculino , Estrutura Molecular , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Compostos Policíclicos/isolamento & purificação , Compostos Policíclicos/uso terapêutico , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Compostos de Sulfidrila/antagonistas & inibidores , Reagentes de Sulfidrila/farmacologiaRESUMO
Tithonia diversifolia is a medicinal plant from the Municipality of Suchiapa, Chiapas, Mexico, that according to local folk medicine is considered useful in the treatment of gastric ulcers. The aim of the present study was to investigate the gastroprotective activity of T. diversifolia by using an ethanol-induced gastric ulcer experimental model in male Wistar rats. The results showed that T. diversifolia had gastroprotective activity, and that the dichloromethane extract had the highest protective activity (close to 90% when using doses between 10 to 100 mg/kg), and that further the compound tagitinin C isolated from this extract was the main active gastroprotective agent. Rats treated with tagitinin C suspended in Tween 80 at 1, 3, 10 and 30 mg/kg showed 37.7, 70.1, 100, and 100% gastroprotection, respectively. The effect elicited by tagitinin C (30 mg/kg) was not attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups, or indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, which suggests that the gastroprotective mechanism of action of this sesquiterpene lactone does not involve NO, sulfhydryl groups or prostaglandins.
Assuntos
Antiulcerosos/isolamento & purificação , Asteraceae/química , Bioensaio , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Sesquiterpenos/isolamento & purificação , Compostos de Sulfidrila/fisiologia , Animais , Antiulcerosos/química , Antiulcerosos/farmacologia , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
We investigated the mechanisms of action of Gnaphalium liebmannii which is used as a folk medicine in México for treating various respiratory diseases such as gripe, fever, asthma, cough, cold, bronchitis, expectorating, and bronchial affections. The tension changes of guinea pig tracheal segments were isometrically recorder on a polygraph. Hexane extract of Gnaphalium liebmannii was the most active relaxant extract (IC(30)=54.23+/-19.79 microg/mL with 99.5+/-3.2 % of relaxation), followed by dichloromethane extract (IC(30)=120.22+/-5.27 microg/mL) and methanol extract (IC(30)=190.25+/-30.02 microg/mL). Hexane extract produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner (pA(2)=-2.4), but did not modify the concentration-response curves for histamine. The relaxant effect of hexane extract of Gnaphalium liebmannii was unaffected by the presence of propranolol (3x10(-6)M) or glibenclamide (10 microM). However hexane extract produced a leftward shifts of the concentration-response curve of forskolin (10(-8) to 10(-3)M), nitroprusside (10(-10) to 10(-6)M), isoproterenol (3x10(-10) to 3x10(-5)M) and aminophylline (10(-11) to 10(-2)M). The above results suggest that Gnaphalium liebmannii induce relaxation of the tracheal muscle, probably via phosphodiesterase inhibition. The bronchodilator effect of Gnaphalium liebmannii might explain in part their traditional use as anti-asthmatic remedy.