Inhibitory Effect of Glycyrrhetinic Acid Derivatives on Capsaicin-Induced Ear Edema in Mice

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We examined the effect of glycyrrhetinic acid (Ia) and its derivatives on ear edema induced by topical application of capsaicin in mice. Three dihemiphthalate compounds: di-sodium salt of 18β-olean12-ene-3β, 30-diol (deoxoglycyrrhetol, IIa) di-<I>O</I>-hemiphthalate (IIb); 18β-olean-9(11), 12-diene-3β, 30-diol di-<I>O</I>-hemiphthalate (IIIa); and olean-11, 13(18)-diene-3β, 30-diol di-<I>O</I>-hemiphthalate (IVa) inhibited capsaicin-induced edema with ED<SUB>50</SUB> values of 52.6, 41.0 and 51.8 mg/kg (p.o.), respectively. However, glycyrrhetinic acid and deoxoglycyrrhetol at a dose of 200 mg/kg (p.o.) had no effect. Compound IIIa (100 mg/kg, p.o.) also inhibited the edema response to capsaicin in mast cell-deficient mice. Furthermore, compounds IIb, IIIa and IVa (25—100 mg/kg, p.o.) prevented ear edema in response to intradermal injection of substance P (SP) and compound 48/80. In addition, these compounds at a high dose of 100 mg/kg (p.o.) produced a significant inhibition of the plasma extravasation in ear skin induced by i.v. administration of SP. The above results suggest that the effect of these compounds on capsaicin-induced ear edema is due at least in part to an inhibition of the increase of vascular permeability induced by vasoactive agents released from mast cells. Moreover, it seems likely that these compounds at a high dose can suppress vasodilatation and plasma extravasation induced by SP involved in capsaicin-induced edema.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 71(4), 281-289, 1996-08-01

    The Japanese Pharmacological Society

References:  33

Cited by:  3


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