title: Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity.
abstract: Licochalcones extracted from Glycyrrhiza inflata are known to have a variety of biological properties such as anti-inflammatory, anti-bacterial, and anti-tumor activities, but their action on platelet aggregation has not yet been reported. Therefore, in this study we investigated the effects of licochalcones on platelet aggregation. Collagen and U46619, a thromboxane A2 receptor agonist, caused rabbit platelet aggregation, which was reversed by pretreatment with licochalcones A, C and D in concentration-dependent manners. Among these compounds, licochalcone A caused the most potent inhibitory effect on collagen-induced platelet aggregation. However, the licochalcones showed marginal inhibitory effects on thrombin or ADP-induced platelet aggregation. In addition to rabbit platelets, licochalcone A attenuated collagen-induced aggregation in human platelets. Because licochalcone A also inhibited arachidonic acid-induced platelet aggregation and production of thromboxane A2 induced by collagen in intact platelets, we further examined the direct interaction of licochalcone A with cyclooxygenase (COX)-1. As expected, licochalcone A caused an inhibitory effect on both COX-1 and COX-2 in vitro. Regarding the effect of licochalcone A on COX-1 enzyme reaction kinetics, although licochalcone A showed a stronger inhibition of prostaglandin E2 synthesis induced by lower concentrations of arachidonic acid, Vmax values in the presence or absence of licochalcone A were comparable, suggesting that it competes with arachidonic acid at the same binding site on COX-1. These results suggest that licochalcones inhibit collagen-induced platelet aggregation accompanied by inhibition of COX-1 activity.
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Asa
authors.initials: A
authors.lastname: Okuda-Tanino
authors.affiliation: Department of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Sugawara
authors.affiliation: Department of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Tashiro
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Iwashita
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.|Department of Pharmacology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Obara
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Moriya
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Tsushima
authors.affiliation: Department of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saigusa
authors.affiliation: Department of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Tomioka
authors.affiliation: Department of Pharmacology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits
chemical_list: D047188:Chalcones; D016861:Cyclooxygenase Inhibitors; D003094:Collagen; D051545:Cyclooxygenase 1; C070840:licochalcone A