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Inhibitory Effects of Glycyrrhizin on Scratching Behavior in Response to Substance P,PAR—2 Agonist, and LTB4 in Mice
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JPY
Abstract
Objective The intravenous preparation of glycyrrhizin(GL)has been used for chronic and antihistamine-resistant pruritus, for example, in hemodialysis(HD) patients. To understand how GL shows anti-pruritic effects, we examined the effects of GL on scratching behavior elicited by histamine, substance P(SP), protease-activated receptor-2(PAR-2)agonistic peptide, or leukotriene B4(LTB4)in mice. Methods Thirty minutes after intravenous administration of GL, each pruritogen; histamine (100 nmol╱site), SP(100 nmol╱site), PAR-2 agonistic peptide(50 nmol╱site), or LTB4(0.03 nmol╱site), was intradermally injected into the back of ICR mice, and the number of scratching was counted. Further, using MiaPaca-2 human pancreatic cancer cells, the effect of GL on LTB4-induced extracellular signal regulated kinase(ERK)1╱2 phosphorylation via BLT1 was also investigated by western blot analysis. Results Intravenously injected GL significantly and dose-dependently reduced scratching induced by SP, PAR-2 agonistic peptide, or LTB4, though GL did not significantly inhibit histamine-induced scratching. Furthermore, GL reduced LTB4-induced ERK 1╱2 phosphorylation in MiaPaca-2 cells. Conclusions We demonstrate for the first time that GL has anti-pruritic effects in animal studies as reported in the clinic. Our data suggest that GL exhibits anti-pruritic effects through a different pathway than existing drugs, such as antihistamines.
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