Abstract
Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC50 of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC50 value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.
Highlights
Cardiovascular diseases (CVD) are the leading global cause of morbidity and mortality
We were interested in lusianthridin, a phenanthrene derivative isolated from Dendrobium venustum
Lusianthridin inhibited platelet aggregation induced by arachidonic acid, collagen, and adenosine diphosphate (ADP) with different sensitivities as determined by the IC50 of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively (Figure 2)
Summary
Cardiovascular diseases (CVD) are the leading global cause of morbidity and mortality. The development of CVD is associated with the formation and rupture of atherothrombotic plaques, which are mediated by many factors including lipid peroxidation, foam cell formation, dysfunction of vascular endothelial cell, platelet activation, and depletion or deposition of chemical mediators [2]. Platelet activation is an essential factor for thrombus formation. Platelets maintain hemostasis by preventing blood loss and supporting vascular integrity. When the endothelial layer from a blood vessel is broken, fibers are exposed after an injury or plaque rupture. Collagen attracts platelets like a magnet and induces platelet adhesion, activation, and aggregation to provide hemostatic plugs or thrombus formation [3]. Hypersensitive platelets may lead to CVD, such as thrombosis, atherosclerosis, ischemic stroke, and myocardial infarction
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