Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 13, Pages -Publisher
MDPI
DOI: 10.3390/ijms22136846
Keywords
lusianthridin; antiplatelet aggregation; ADP; arachidonic acid; cyclooxygenase enzymes; cAMP
Funding
- Fund of the Faculty of Pharmaceutical Sciences, Chulalongkorn University [Phar2563-RG008]
- Ratchadaphiseksomphot Endowment Fund for the Natural Products for Ageing and Chronic Diseases, Chulalongkorn University [GRU 6404733002-1]
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Lusianthridin inhibited platelet aggregation induced by various stimuli and showed inhibitory effects on both COX-1 and COX-2 enzymatic activities. Its mechanisms of action may involve the arachidonic acid-thromboxane and adenylate cyclase pathways.
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 mu M and 0.17 +/- 1.62 mu M, 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.
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