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.
Inoue
H
H
Research Laboratory, Minophagen Pharmaceutical Co., Kanagawa, Japan.
Inoue
K
K
Takeuchi
T
T
Nagata
N
N
Shibata
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012701:Serotonin; D006632:Histamine; D002351:Carrageenan; D006034:Glycyrrhetinic Acid; D001920:Bradykinin