EXTRACT AND COMPOUNDS OBTAINED FROM MANDEVILLA-VELUTINA INHIBIT ARACHIDONIC ACID-INDUCED EAR EDEMA IN MICE, BUT NOT RAT STOMACH CONTRACTION

This study was designed to analyse the effect of crude extract (CE) and some pure compounds isolated from M. velutina on arachidonic acid (AA)-induced ear oedema in mice. The effect of these compounds on contractions in the rat stomach induced by AA and prostaglandin E2 (PGE2) was also investigated. The CE given orally to mice (50-400 mg/kg) 1h before inhibited the ear oedema in a dose-dependent manner, with a maximal inhibition (MI) of 56%. Given topically, compound MV8612 (200-600 mg/ear) isolated from this plant inhibited the oedema in a concentration-dependent manner with a MI of 66%, while compounds MV8608 and MV8610 (100-600 mg/ear) caused less inhibition, MI 29% and 39% respectively. Compound MV8612, given i.p. (3-30 mg/kg) 30 min before, also caused a dose-dependent inhibition of AA-induced ear oedema (MI of 60.5% compared with 28% and 49% for MV8608 and MV8610). Indomethacin (0.25-1.0 mg/ear) applied topically had no effect, but orally (1-10 mg/kg) gave MI of 66%. Phenidone given orally (10-100 mg/kg) gave a MI of 30% but it was very potent topically (0.5-2 mg/ear) (MI 66%). Nordihydroguaiaretic acid applied either topically (0.5-2.0 mg/ear) or orally (10-100 mg/kg) caused MI of 63% and 47%, respectively. BW 755C, orally (10-100 mg/kg), inhibited the AA-induced oedema in a dose-dependent manner (MI 48%), but was less effective when applied topically (0.25-1 mg/ear) (MI 32%). In the rat stomach preparation, compounds MV8608 and MV8612 (0.1-20-mu-g/ml) had no significant effect on contractions to AA or PGE2, while indomethacin (0.01-3-mu-g/ml) potently inhibited AA contraction, but had no effect on the PGE2 response. These results indicate that MV8608 and MV8612 exhibit both a topical and a systemic anti-inflammatory profile, presumably by a mechanism not related to inhibition of cyclooxygenase.