title: Isoliquiritigenin selectively inhibits H(2) 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 H(2) histamine receptor (H(2)R) antagonistic effect and remarkably reduced several H(2)R-mediated physiological responses. Preincubation of U937 and HL60 hematopoietic cells with isoliquiritigenin significantly inhibited H(2)R agonist-induced cAMP response in a concentration-dependent manner without affecting the viability of cells. Isoliquiritigenin also blocked the binding affinity of [(3)H]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 G(s) protein, effector enzyme, adenylyl cyclase, or beta(2)-adrenoceptor. Isoliquiritigenin affected neither H(1)R-nor H(3)R-mediated signaling. In molecular docking studies, isoliquiritigenin exhibited more favorable interactions with H(2)R than histamine. Isoliquiritigenin prominently inhibited H(2)R 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 H(2)R antagonist and provides the basis for designing novel H(2)R antagonist.
authors: Department of Life Science, POSTECH, San 31, Hyoja Dong, Pohang 790-784, Republic of Korea.
authors: Dong-Chan
authors: DC
authors: Kim
authors: Se-Young
authors: SY
authors: Choi
authors: Sun-Hee
authors: SH
authors: Kim
authors: Bong-Sik
authors: BS
authors: Yun
authors: Ick-Dong
authors: ID
authors: Yoo
authors: Nanga Ravi Prakash
authors: NR
authors: Reddy
authors: Ho Sup
authors: HS
authors: Yoon
authors: Kyong-Tai
authors: KT
authors: Kim