Inhibitory effect of glycyrrhetinic acid derivatives on arachidonic acid-induced mouse ear oedema.

The inhibitory effects of glycyrrhetinic acid and its derivatives were examined on arachidonic acid (AA)-induced ear oedema in mice. Of the compounds, dihemiphthalate derivatives of 18 beta-olean-12-ene-3 beta, 30-diol (IId, IId'), 18 beta-olean-9(11)12-diene-3 beta, 30-diol (IIIa, IIIa') and olean-11, 13(18)-diene-3 beta, 30-diol (IVa, IVa') showed a strong inhibition of ear oedema on both tropical (ID50, 1.9, 2.8 and 1.7 mg/ear, respectively) and oral (ID50, 90, 130 and 88 mg kg-1, respectively) administration. Topical ID50 values were approximately the same potency as nordihydroguaiaretic acid (ID50, 2.1 mg/ear). Given topically these compounds were also capable of inhibiting PGE2 and LTC4 formation at an early stage of AA-induced ear oedema. However, glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the fundamental skeletons of the derivatives, showed no detectable inhibition of oedema at a dose of 1 mg/ear (topical) or 200 mg kg-1 (oral). The most effective time for the topical administration of the compound IId against ear oedema was 0-30 min before AA application; this is different from dexamethasone which requires a time lag for reaction. The results suggest that the inhibitory effect of the hemiphthalate compounds (IId, IId', IIIa, IIIa', IVa and IVa') is a direct action, and does not involve the anti-inflammatory action of steroids mediated by the secondary formation of a reactive protein.