PT  - JOURNAL ARTICLE
AU  - Dong-Chan Kim
AU  - Se-Young Choi
AU  - Sun-Hee Kim
AU  - Bong-Sik Yun
AU  - Ick-Dong Yoo
AU  - Nanga. Ravi Prakash Reddy
AU  - Ho Sup Yoon
AU  - Kyong-Tai Kim
TI  - Isoliquiritigenin Selectively Inhibits H<sub>2</sub> Histamine Receptor Signaling
AID  - 10.1124/mol.106.023226
DP  - 2006 Aug 01
TA  - Molecular Pharmacology
PG  - 493--500
VI  - 70
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/70/2/493.short
4100  - http://molpharm.aspetjournals.org/content/70/2/493.full
SO  - Mol Pharmacol2006 Aug 01; 70
AB  - 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 β2-adrenoceptor. Isoliquiritigenin affected neither 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 pylorus-ligated rat model. Taken together, the results demonstrate that isoliquiritigenin is an effective H2R antagonist and provides the basis for designing novel H2R antagonist.