Modulation by glycyrrhetinic acid derivatives of TPA‐induced mouse ear oedema

Abstract

1 The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-0-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2 The formation of ear oedema reached a maximum 5 h after TPA application (2 pg per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3 TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4 Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (Ile, Ile', Ila, Ila', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6mg per ear for Ile, 2.0mg per ear for Ila and 1.6mg per ear for IVa) and oral (ID50, 88mgkg-1 for Ile', 130mgkg-1 for IIIa' and 92 mg kg 1 for IVa') administration. 5 Glycyrrhetinic acid (Ia) and its derivatives applied 30min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment.6 Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (Ila), the parent compounds, produced little inhibition by oral administration at less than 200mg kg-1 7 These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application.

Suppression of inflammatory responses to 12‐O‐tetradecanoylphorbol‐13‐acetate and carrageenin by YM‐26734, a selective inhibitor of extracellular group II phospholipase A2

“…Two animal models were used to investigate extracellular group II PLA2 in inflammatory responses, the TPA-induced mouse ear oedema model and the carrageenin-induced rat pleurisy model. The former is widely used to evaluate the anti-inflammatory activity of PLA2 inhibitors, TPA induces AA release and eicosanoids synthesis in cultured macrophages in vitro (Humes et al, 1982), and TPA challenge to the mouse ear causes PGE2 to accumulate in parallel with the swelling of the ear (Inoue et al, 1989). However, it is not clear if this inflammation is regulated primarily by PLA2 activity, or more specifically by extracellular group II enzymes.…”

Anti-inflammatory and antispasmodic activity of Ipomoea imperati (Vahl) Griseb (Convolvulaceae)

“…It has been firmly established that arachidonic acid metabolites act as mediators of the inflammatory response via COX and lipoxygenase activity, and have therefore been a target for the development of therapeutic agents (21).…”

Synthesis and Inhibitory Effect of Novel Glycyrrhetinic Acid Derivatives on IL-1.BETA.-Induced Prostaglandin E2 Production in Normal Human Dermal Fibroblasts

“…1), in order to enhance the anti-inflammatory activity and suppress the pseudoaldosteronism due to the inhibition of mineralcorticoid metabolism. During the course of this work, 3 was reported to show various anti-inflammatory activities such as the inhibition of increasing vascular permeability, 15) 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, 16) arachidonic acid-induced or capsaicin-induced mouse ear edema, 17,18) and carrageenin-induced rat paw edema. 19) It was suggested that one of the mechanisms by which 3 induces anti-inflammatory effects is the inhibition of cyclooxygenase or lipoxygenase activities at the inflammatory site.…”