Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets

Ye-Ming Lee,Joen-Rong Sheu,Kuan-Hung Lin,Kuo-Hsien Hsieh,Hsiu-Chu Chou,Li-Ming Lien,Duen-Suey Chou,Wan-Jung Lu

doi:10.1155/2012/852362

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 [Ca2+]i mobilization, thromboxane A2 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 A2 formation, thereby leading to inhibition of [Ca2+]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.

Highlights

Dietary factors play key roles in developing and preventing various human diseases, including cardiovascular diseases (CVDs)
Xanthohumol inhibited platelet activation accompanied by relative [Ca2+]i mobilization, thromboxane A2 formation, hydroxyl radical (OH) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Akt phosphorylation
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 A2 formation, thereby leading to inhibition of [Ca2+]i and inhibition of platelet aggregation

Summary

Introduction

Dietary factors play key roles in developing and preventing various human diseases, including cardiovascular diseases (CVDs). In traditional Chinese medicine, hops are used to treat insomnia, restlessness, dyspepsia, and lack of an appetite. Alcoholic extracts of hops are clinicall used in China to treat leprosy, pulmonary tuberculosis, acute bacterial dysentery, silicosis, and asbestosis with positive outcomes [2]. Xanthohumol (1∼50 μM) was shown to suppress tumor growth by inhibiting cell proliferation and inducing apoptosis in various carcinoma cells [4,5,6]. It exhibited antiangiogenic activity through inhibiting nuclear factor (NF)-κB and Akt activation in vascular endothelial cells [7]. Xanthohumol was reported to regulate the function and survival of immune cells by inhibiting the production of two important cytokines, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α, in lipopolysaccharide-stim-

Objectives

Methods

Results

Conclusion