title: Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets.
abstract: Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulus L.). Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca(2+)](i) mobilization, thromboxane A(2) formation, hydroxyl radical (OH(●)) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A(2) formation, thereby leading to inhibition of [Ca(2+)](i) and finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.
authors.affiliation: Department of Surgery, Hsinchu Mackay Memorial Hospital, Hsinchu and Mackay Medicine, Nursing and Management College, 92 Zhong-Shan N. Road, Taipei 104, Taiwan.
authors.forename: Ye-Ming
authors.initials: YM
authors.lastname: Lee
authors.forename: Kuo-Hsien
authors.initials: KH
authors.lastname: Hsieh
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Lu
authors.forename: Hsiu-Chu
authors.initials: HC
authors.lastname: Chou
authors.forename: Duen-Suey
authors.initials: DS
authors.lastname: Chou
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lien
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lin