Inhibition of rat acute inflammatory paw oedema by dihemiphthalate of glycyrrhetinic acid derivatives: comparison with glycyrrhetinic acid.

The anti-inflammatory profile of dihemiphthalate compounds of glycyrrhetinic acid derivatives in acute rat paw oedema induced by various vasoactive agents was compared with the parent compound. Three dihemiphthalate compounds (the di-sodium salt of 18 beta-olean-12-ene- 3 beta,30-diol di-O-hemiphthalate, 18 beta-olean-9(11),12-dione-3 beta,30-diol di-O-hemiphthalate and olean-11,13(18)-diene-3 beta,30-diol di-O-hemiphthalate), significantly inhibited development of carrageenan-induced rat paw oedema during the first 3 h (ED50 70, 90, and 108 mg kg-1 respectively, p.o.), while glycyrrhetinic acid (ED50, 200 mg kg-1) showed a significant inhibition of paw oedema 3 h after carrageenan treatment. The dihemiphthalate compounds also suppressed mouse paw oedema induced by histamine, bradykinin, and PAF acether at doses of less than 100 mg kg-1. However, these compounds failed to inhibit 5-HT-induced mouse paw oedema. Glycyrrhetinic acid had little effect on mouse paw inflammation induced by the above irritants. The three compounds at 10(-7)-10(-4) M, inhibited histamine-induced contraction of guinea-pig isolated ileum. However, concentration-response curves to 5-HT and bradykinin were not affected by the same compounds. These results suggest that the dihemiphthalate compounds modulate vascular permeability caused by endogenous vasoactive agents as one of the anti-inflammatory mechanisms. This action is quite different from that of glycyrrhetinic acid.