Chrysotoxine Attenuates Key Atherogenic Processes via Antioxidant, Anti-Inflammatory, and COX-Dependent Antiplatelet Mechanisms

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 <i>Dendrobium pulchellum</i>, 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.