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.

Atherosclerosis is a complex vascular disorder driven by oxidative stress, inflammation, and platelet activation. Agents capable of targeting multiple atherogenic pathways may provide improved therapeutic benefits. In this study, we evaluated the anti-atherogenic effects of chrysotoxine, a bibenzyl compound isolated from Dendrobium pulchellum, using in vitro models relevant to atherogenesis. Chrysotoxine significantly suppressed hemin-induced LDL oxidation by reducing lipid peroxidation and apolipoprotein modification. In an endothelial–monocyte co-culture model, chrysotoxine markedly attenuated lipopolysaccharide-induced monocyte adhesion, indicating inhibition of endothelial inflammatory activation. Chrysotoxine also inhibited platelet aggregation induced by arachidonic acid, ADP, and collagen in a concentration-dependent manner, with the strongest effects observed against arachidonic acid–mediated responses, suggesting modulation of the thromboxane pathway. Molecular docking analyses and cyclooxygenase activity assays further indicated that chrysotoxine may interact with both COX-1 and COX-2, exhibiting inhibitory activity in the low micromolar range. Collectively, these findings demonstrate that chrysotoxine modulates multiple key processes involved in atherogenesis, including oxidative LDL modification, vascular inflammation, and platelet activation. Although further in vivo studies are required, chrysotoxine represents a promising plant-derived candidate for the development of multi-target strategies against atherosclerotic disease.