Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity

• Published in: PloS one 2017-03, Vol.12 (3), p.e0173628-e0173628
• Main Authors: Okuda-Tanino, Asa, Sugawara, Daiki, Tashiro, Takumi, Iwashita, Masaya, Obara, Yutaro, Moriya, Takahiro, Tsushima, Chisato, Saigusa, Daisuke, Tomioka, Yoshihisa, Ishii, Kuniaki, Nakahata, Norimichi
• Format: Article
• Language: English
• Subjects: Acids; Adenosine diphosphate; Agglomeration; Animals; Anticancer properties; Antitumor agents; Arachidonic acid; Bacteria; Binding sites; Biological properties; Biology and Life Sciences; Blood platelets; Blood Platelets - enzymology; Chalcones - chemistry; Chalcones - isolation & purification; Chalcones - pharmacology; Collagen; Collagen - pharmacology; COX-2 inhibitors; Cyclooxygenase 1 - metabolism; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - isolation & purification; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase-1; Cyclooxygenase-2; Dosage and administration; Glycyrrhiza; Glycyrrhiza - chemistry; Health aspects; Inflammation; Inhibition; Kinases; Kinetics; Licochalcone A; Licorice (Plant); Male; Medicine and Health Sciences; Oncology; Pharmaceutical sciences; Pharmacy; Physiological aspects; Platelet aggregation; Platelet Aggregation - drug effects; Platelets; Prostaglandin E2; Rabbits; Reaction kinetics; Research and Analysis Methods; Scanning electron microscopy; Thrombin; Thromboxane A2
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0173628

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.