Open AccessHonokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin
Author(s) -
HU He,
ZHANG Xiaoxue,
WANG Yinye,
CHEN Shizhong
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00164.x
Subject(s) - prostacyclin , thrombosis , stimulation , medicine , pharmacology , platelet , endothelial stem cell , cardiology , chemistry , in vitro , biochemistry
Aim: To study the effect of honokiol on arterial thrombosis and endothelial cells. Methods: Rabbit platelet aggregation was performed with Born's turbid method. Thrombosis was produced by the endothelial injury stimulated with electric current. Rat aortic endothelial cells (RAEC) were cultured and cell viability was assessed using the MTT assay. Nitric oxide (NO) concentrations in serum‐free media of RAEC were determined using the kinetic cadmium‐reduction method. The stable metabolite prostacyclin was measured in serum‐free media of RAEC by radioimmunoassay. Results: Honokiol (37.6–376 μol/L) decreased rabbit platelet aggregation in vitro in a concentration‐dependent manner, while intravenously injection of honokiol (0.12–12 μg/kg) significantly inhibited rabbit platelet aggregation induced by collagen ex vivo. In the electrical current‐stimulated carotid thrombosis model in rats, honokiol (5–50 μg/kg, iv) prolonged the thrombus occlusion time in a does‐dependent manner. In vitro honokiol (0.376–37.6 μmol/L) effectively protected cultured RAEC against oxidized low density lipoprotein (ox‐LDL) injury, and significantly increased 6‐keto‐PGF 1α (the stable metabolite of prostacyclin) in serum‐free media of RAEC. Honokiol also increased NO level in RAEC serum‐free medium at a lower concentration range (0.0376–0.376 μol/L), but honokiol 3.76 μmol/L decreased NO level. Conclusion: Honokiol is a potent arterial thrombosis inhibitor. Endothelial cell protection and the stimulation of prostacyclin release may be its main anti‐thrombosis mechanism. Stimulation of NO release in endothelial cells may play a role, but it is not a key factor.