Macrostachyols A-D, oligostilbenes from Gnetum macrostachyum inhibited in vitro human platelet aggregation

Introduction: Gnetum macrostachyum is a known Thai medicinal plant as a source of bioactive oligostilbenes, which possess platelet inhibitory activities. The study aimed to evaluate the in vitro human platelet aggregation inhibitory activities of macrostachyols A-D (compounds ۱-۴) isolated from the roots of G. macrostachyum. Methods: The in vitro human platelet aggregation assay was assayed with a ۹۶-well microtiter plate format. The well-known aggregating agents were used to investigate the possible mechanism of inhibition, including adenosine diphosphate (ADP), arachidonic acid (AA), thromboxane A۲ analog (U-۴۶۶۱۹), collagen, thrombin, and thrombin receptor-activating peptide-۶ (TRAP-۶). Results: Compound ۱ was more potent than ibuprofen (positive control) on the adenosine diphosphate- induced platelet aggregation assay (P < ۰.۰۵). Compound ۳ was more potent than ۱, ۲, and ۴ (P < ۰.۰۵), but all active oligostilbenes were less potent than the positive control (P < ۰.۰۵) on the arachidonic acid-induced platelet aggregation assay. The oligostilbenes ۱, ۲, ۳, and ۴ also displayed the inhibitory effects on the U-۴۶۶۱۹-induced platelet aggregation. The tetrameric stilbenes ۱ was the only compound that exhibited inhibitory effects on thrombin-induced platelet aggregation without TRAP-۶ mediated platelet aggregation. Conclusion: The findings revealed the inhibitory effects of oligostilbenes on human platelet aggregation through a target-specific experimental design. It suggests that oligostilbenes from this plant might be applied as antiplatelet aggregation agents in platelet hyperreactivity- related diseases.