Pharmacological assay of Cordia verbenacea. III: Oral and topical antiinflammatory activity and gastrotoxicity of a crude leaf extract.

The antiinflammatory effects and gastrotoxicity of a lyophilized 70% ethanol extract of the leaves of Cordia verbenacea were investigated through experimental models in rats and mice. The oral administration of 1.24 mg/kg of the extract significantly inhibited nystatin-induced oedema. Topical application of the extract at a dose of 0.09 mg/ear in mice was clearly more effective than 1.0 mg/ear of naproxen in the reduction of the ear oedema induced by corton oil. At antiinflammatory doses, the extract showed an important protective effect on the gastric mucosa, reducing significantly the number of gastric lesions.

Pharmacological assay of Casearia sylvestris. I: Preventive anti-ulcer activity and toxicity of the leaf crude extract.

An ethanol extract of the leaves of Brazilian Casearia sylvestris, given orally, inhibited gastric secretion in pylorus-ligated rats. At a prophylactic dose of 57.5 mg/kg, the extract showed a reduction of gastric juice more effective than misoprostol (500 micrograms/kg). In reducing hydrochloric acid output, the extract was less effective than misoprostol, cimetidine (32.0 mg/kg) and atropine (5.3 mg/kg). With the extract, the pH of the stomach contents was not significantly different from that of controls. Stress-induced lesions produced by restraint and water immersion were significantly prevented by the extract for all levels of severity when compared with the controls. The extract appeared more effective than misoprostol in suppressing light lesions, was equivalent to cimetidine and misoprostol for moderate lesions, and less effective than cimetidine and misoprostol for severe lesions. Toxicological experiments indicated a low acute toxicity, confirmed by subchronic daily testing. The oral LD50 value of greater than 1840 mg/kg was over 32 times higher than the antiulcerogenic ED50 (57.5 mg/kg).

Anti-inflammatory activity and sub-acute toxicity of artemetin.

The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.

Anti-inflammatory activity of oleoresin from Brazilian Copaifera.

The oleoresin from Brazilian Copaifera species yielded copalic acid and sesquiterpenes and showed marked anti-inflammatory activity using various experimental models in rats. The oleoresin significantly inhibited carrageenin-induced pedal edema following oral doses from 0.70 to 2.69 ml/kg, but was somewhat less effective than 50 mg/kg calcium phenylbutazone. Repeated administration of the oleoresin at a dose of 1.26 ml/kg for a 6-day period reduced granuloma formation with a response comparable to that of 20 mg/kg of calcium phenylbutazone. This same dose of oleoresin also reduced the vascular permeability to intracutaneous histamine. The LD50 value of the oleoresin in rats was estimated to be 3.79 (3.21-4.47) ml/kg.

Anti-inflammatory effects of praseodymium, gadolinium and ytterbium chlorides.

Anti-inflammatory effects of chloride salts of praseodymium, gadolinium and ytterbium were investigated, using various experimental inflammatory models in rats. The lanthanide salts administered by oral route showed no significant effect, but when injected intraperitoneally they significantly inhibited the carrageenin-induced oedema, proportional to their doses ranging from 15 to 75 mg/kg. They also reduced nystatin-induced oedema and vascular permeability response to histamine and serotonin. Pronounced inhibitory effect of lanthanide salts at the dose of 50 mg/kg, i.p., was observed in histamine- and serotonin-induced changes in vascular permeability. Repeated administration of lanthanide salts in the dose of 20 mg/kg for 13 d significantly inhibited arthritis development. The same dose of these salts for a 6-d period similarly reduced granuloma formation. However, praseodymium, gadolinium and ytterbium chlorides showed no significant difference among themselves and their anti-inflammatory effects were smaller than those from phenylbutazone.

Effects of ethanol on experimental inflammation.

The carrageenin and nystatin-induced paw edemas were dose-dependently antagonized by oral administration of ethanol. The combination of ethanol and dexamethasone increased this inhibition. Carrageenin-induced edema was also inhibited by furosemide and pentobarbital. The vascular permeability effects of histamine and serotonin were markedly suppressed by ethanol pretreatment. However, ethanol was unable to suppress the granuloma formation caused by cotton pellet implantation. These results suggest that central depression, cardiovascular alteration and decreased vascular permeability may play an important role for ethanol antiinflammatory activity.

Estudo toxicologico de sudoxicam, potente agente antiinflamatorio nao-esteroide. / Toxicological study of sudoxicam, a potent nonsteroidal anti-inflamatory agent

Os efeitos toxicos de sudoxicam, N-(2-tiazolil)-4-hidroxi-2-metil-2H-1,2-benzotiazina-3-carboxamida 1,1-dioxido, foram estudados em ratos Wistar, determinando suas toxicidades aguda e subaguda. A DL50, baseada na mortalidade ocorrida no periodo de 6 dias apos administracao oral de dose unica de sudoxicam,foi de 144,0 mg/kg. Doses diarias, por via oral, de 1 mg/kg e 5 mg/kg durante 30 dias foram bem toleradas pelos animais. Quanto ao ganho de peso corporal e consumo de racao, nao houve diferenca significante entre os animais tratados e os do grupo controle, nesse periodo experimental. O exame macroscopico do figado, baco e rins nao revelou nenhuma lesao nos orgaos. A atividade teratogenica de sudoxicam foi testada em embrioes de galinha, injetando-o no saco vitelino de ovos embrionados de galinhas Garrinson, no 8o. dia de incubacao. Observou-se maior letalidade com a utilizacao de doses elevadas. Entretanto, nao foi constatada nenhuma malformacao nas doses de 5 micrograma/ovo e 500 micrograma/ovo