RESUMEN
Type II arabinogalactan (AG) is a polysaccharide found in Maytenus ilicifolia (Celastraceae), a plant reputed as gastroprotective. Oral and intraperitoneal administration of the AG protected rats from gastric ulcers induced by ethanol. No alteration of mechanisms related to acid gastric secretion and gastrointestinal motility were observed. In vitro, the AG showed a potent scavenging activity against the radical of DPPH (2,2-diphenyl-1-picrylhydrazyl) with an IC50 value of 9.3 microM. However, the mechanism of the gastroprotective action remains to be identified.
Asunto(s)
Galactanos/farmacología , Tracto Gastrointestinal/efectos de los fármacos , Maytenus/química , Animales , Femenino , Galactanos/aislamiento & purificación , Técnicas In Vitro , Ratas , Ratas WistarRESUMEN
The present study examined the antinociceptive effects of a hydroalcoholic extract of Polygala paniculata in chemical and thermal behavioural models of pain in mice. The antinociceptive effects of hydroalcoholic extract was evaluated in chemical (acetic-acid, formalin, capsaicin, cinnamaldehyde and glutamate tests) and thermal (tail-flick and hot-plate test) models of pain or by biting behaviour following intratecal administration of both ionotropic and metabotropic agonists of excitatory amino acids receptors glutamate and cytokines such as interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) in mice. When given orally, hydroalcoholic extract (0.001-10 mg/kg), produced potent and dose-dependent inhibition of acetic acid-induced visceral pain. In the formalin test, the hydroalcoholic extract (0.0001-0.1 mg/kg orally) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking. However, it was more potent and efficacious in relation to the late phase of the formalin test. The capsaicin-induced nociception was also reduced at a dose of only 1.0 mg/kg orally. The hydroalcoholic extract significantly reduced the cinnamaldehyde-induced nociception at doses of 0.01, 0.1 and 1.0 mg/kg orally. Moreover, the hydroalcoholic extract (0.001-1.0 mg/kg orally) caused significant and dose-dependent inhibition of glutamate-induced pain. However, only rutin, but not phebalosin or aurapten, isolated from P. paniculata, administered intraperitoneally to mice, produced dose-related inhibition of glutamate-induced pain. Furthermore, the hydroalcoholic extract (0.1-100 mg/kg orally) had no effect in the tail-flick test. On the other hand, the hydroalcoholic extract caused a significant increase in the latency to response at a dose of 10 mg/kg orally, in the hot-plate test. The hydroalcoholic extract (0.1 mg/kg orally) antinociception, in the glutamate test, was neither affected by intraperitoenal treatment of animals with l-arginine (precursor of nitric oxide, 600 mg/kg) and naloxone (opioid receptor antagonist, 1 mg/kg) nor associated with non-specific effects such as muscle relaxation or sedation. In addition, oral administration of hydroalcoholic extract produced a great inhibition of the pain-related behaviours induced by intrathecal injection of glutamate, N-methyl-D-aspartate (NMDA), IL-1beta and TNF-alpha, but not by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), kainate or trans-1-amino-1.3-cyclopentanediocarboxylic acid (trans-ACPD). Together, our results suggest that inhibition of glutamatergic ionotropic receptors, may account for the antinociceptive action reported for the hydroalcoholic extract from P. paniculata in models of chemical pain used in this study.
Asunto(s)
Analgésicos/farmacología , Dolor/tratamiento farmacológico , Extractos Vegetales/farmacología , Polygala/química , Administración Oral , Analgésicos/administración & dosificación , Analgésicos/aislamiento & purificación , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inyecciones Intraperitoneales , Masculino , Ratones , Dimensión del Dolor , Extractos Vegetales/administración & dosificación , Receptores de Glutamato/efectos de los fármacos , Receptores de Glutamato/metabolismo , Rutina/administración & dosificación , Rutina/aislamiento & purificación , Rutina/farmacologíaRESUMEN
Persea major Kopp (Lauraceae) is used in folk medicine to treat skin wounds and gastric disorders. This study evaluates the potential of crude hydroalcoholic extract (EHA) as gastroprotective and its acute toxicity. Swiss mice were treated with EHA by oral (p.o.) and intraperitoneal (i.p.) routes with doses of 0.125 to 10 g/kg and were observed until 14 days after the administration of the extract. The calculated LD50 of EHA after i.p. administration was 480 mg/kg in mice and the LD50 values of EHA by the oral route were calculated to be up to 10 g/kg in mice. Wistar rats were orally pretreated with EHA (30, 100, 300 and 1000 mg/kg) before induction of gastric lesions by 70 percent ethanol (0.5 mL/animal, p.o.), indomethacin (20 mg/kg, s.c.) and hypothermic restraint stress (during 3 h at 4 ºC). The EHA protected the gastric mucosa against lesions induced by ethanol, but did not reduce the stress- and indomethacin-induced gastric lesions. When the EHA was injected into the duodenal lumen (i.d.), the volume, pH and total acidity of the gastric secretion of rats with pylorus ligature was not altered with different doses of the extract. Results therefore suggest that the cytoprotective effect of this extract against the direct necrosing action of ethanol and its effect were not related with reduction of gastric acid secretion.
Persea major Kopp (Lauraceae) é utilizada na medicina tradicional para o tratamento de lesões cutâneas e distúrbios gástricos. O objetivo deste estudo é avaliar o potencial gastroprotetor e a toxicidade aguda do extrato bruto hidroalcóolico da Persea major Kopp (EHA). Camundongos Swiss foram tratados com EHA pelas vias oral (v.o.) e intraperitoneal (i.p.) com as doses de 0,125 a 10 g/kg e foram observados por 14 dias. A DL50 calculada após administração i.p. de EHA foi de 480 mg/kg e superior a 10 g/kg pela via oral, em camundongos. Ratos Wistar foram pré-tratados oralmente com EHA (30, 100,300 e 1000 mg/kg) antes da indução de lesões gástricas por etanol 70 por cento (0,5 mL/animal, v.o.), indometacina (20 mg/kg, s.c.) e estresse por contenção e hipotermia (durante 3 h a 4 ºC). O EHA protegeu a mucosa gástrica contra lesões induzidas por etanol, porém não protegeu contra as lesões induzidas por indometacina e estresse. Quando o EHA foi administrado pela via intraduodenal (i.d.), o volume, o pH e a acidez total da secreção gástrica de ratos com ligadura de piloro não foram alterados com diferentes doses do extrato. Os resultados obtidos sugerem um efeito citoprotetor contra ação necrosante direta do etanol pelo extrato bruto hidroalcoólico da Persea major e este efeito não está relacionado com a redução da secreção ácida gástrica.
Asunto(s)
Animales , Ratones , Ratas , Pruebas de Toxicidad Aguda , Lauraceae , PerseaRESUMEN
The possible gastroprotective effects of the hydroalcoholic extract of Polygala paniculata in rats have been evaluated. We have investigated the effects of this hydroalcoholic extract on acute lesions induced by ethanol (70%, p.o.) and indomethacin (20 mg kg(-1), s.c.). Its influence on mucus secretion was investigated, measured as the amount of Alcian blue dye estimated by colorimetry, and antisecretory effects were assessed in the pylorus ligature model. The treatment of rats with a crude hydroalcoholic extract of P. paniculata (HEPP; 30, 100, 300 mg kg(-1), p.o., or 3, 10 and 30 mg kg(-1), i.p.) decreased the ulcer index, and maintained the gastric mucus production in acute gastric lesions caused by ethanol 70%. In addition, the extract partially protected the mucosa against indomethacin-induced lesions. The extract did not change the volume and acidity of gastric secretion in the pylorus-ligated rat. An additional antioxidant activity of the extract and its isolated flavonoid compound rutin, in the DPPH free radical scavenging assay, was observed. In conclusion, HEPP exhibited marked gastroprotection; these effects may have involved prostaglandins and be related to cytoprotective factors, such as antioxidant activity and maintenance of mucus production.
Asunto(s)
Antiulcerosos/farmacología , Extractos Vegetales/química , Polygala/química , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/administración & dosificación , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Brasil , Colorimetría , Relación Dosis-Respuesta a Droga , Etanol , Femenino , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Jugo Gástrico/efectos de los fármacos , Jugo Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Indometacina , Ligadura , Medicina Tradicional , Píloro , Ratas , Ratas Wistar , Rutina/aislamiento & purificación , Rutina/farmacología , Úlcera Gástrica/inducido químicamenteRESUMEN
The present study examined the antinociceptive effects of the ethanolic extract (EE) and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in chemical and thermal behavioural models of pain in mice. The EE (10-1000 mg/kg) given orally (p.o.), 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with mean ID50 value of 131.9 mg/kg. In the formalin test, the EE (10-300 mg/kg, p.o.) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, however, it was more potent and efficacious in relation to the late phase of the formalin test, with mean ID50 values for the neurogenic and the inflammatory phases of approximately 300 and 88.8 mg/kg, respectively. The EE (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of capsaicin- and glutamate-induced pain, with mean ID50 values of 160.5 and 38.3 mg/kg, respectively. Furthermore, the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene (1-30 mg/kg), given p.o., 1 h prior to testing, also produced dose-related inhibition of glutamate-induced pain, with a mean ID50 value of 5.6 mg/kg. When assessed in a thermal model of pain, the EE (10-300 mg/kg, p.o.) and fentanyl (100 microg/kg, s.c.) caused a significant and marked increase in the latency response on the hot-plate test (50 degrees C). The antinociception caused by EE (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with naloxone (opioid receptor antagonist, 1 mg/kg), pindolol (a 5-HT 1A/1B receptor/beta adrenoceptor antagonist, 1 mg/kg), WAY100635 (a 5-HT 1A receptor antagonist, 0.7 mg/kg) or ketanserin (a 5-HT 2A receptor antagonist, 0.3 mg/kg). In contrast, EE (100 mg/kg, p.o.) antinociception was affected neither by L-arginine (precursor of nitric oxide, 600 mg/kg) nor by ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg) i.p. treatment. It was not associated with non-specific effects such as muscle relaxation or sedation. Together, these results indicate that EE produces dose-related antinociception in several models of chemical and thermal pain through mechanisms that involve an interaction with opioid and serotonergic (i.e., through 5-HT 1A/1B and 5-HT 2A receptors) systems.