Received for publication February 6, 2006.
Revised May 2, 2006.
Accepted for publication May 3, 2006.

Isoliquiritigenin selectively inhibits H₂ histamine receptor signaling

Abstract

Isoliquiritigenin, one of the major constituents of Glycyrrhiza uralensis (licorice), is a natural pigment with a simple chalcone structure 4,2',4'-trihydroxychalcone. In this study, isoliquiritigenin showed selective H₂ histamine receptor (H₂R) antagonistic effect and remarkably reduced several H₂R-mediated physiological responses. Preincubation of U937 and HL60 hematopoietic cells with isoliquiritigenin significantly inhibited H₂R agonist-induced cAMP response in a concentration-dependent manner without affecting the viability of cells. Isoliquiritigenin also blocked the binding affinity of [³H]-tiotidine to membrane receptors in HL-60 cells. Isoliquiritigenin did not affect the elevation of cAMP levels induced by cholera toxin, forskolin or isoproterenol, indicating that the action site of isoliquiritigenin is not Gs protein, effector enzyme, adenylyl cyclase, or ₂-adrenoceptor. Isoliquiritigenin neither affect H₁R- nor H₃R-mediated signaling. In molecular docking studies, isoliquiritigenin exhibited more favorable interactions with H₂R than histamine. Isoliquiritigenin prominently inhibited H₂R selective agonist dimaprit-induced cAMP generation in MKN-45 gastric cancer cell. Moreover, isoliquiritigenin reduced gastric acid secretion and protected gastric mucosal lesion formation in pylori ligated rat model. Taken together, the results demonstrate that isoliquiritigenin is an effective H₂R antagonist and provides the basis for designing novel H₂R antagonist

Key words: Histamine, cAMP, Receptor binding studies, Receptor-mediated