Ziyuglycoside I attenuates coagulopathy induced by Deinagkistrodon acutus venom in human whole blood: a thromboelastography-based study.

INTRODUCTION: Ziyuglycoside I, a hemostatic saponin isolated from Sanguisorba officinalis (Di-Yu), has reported anti-hemorrhagic properties. Deinagkistrodon acutus venom (DAV) is associated with venom-induced consumptive coagulopathy, but its effects on whole-blood coagulation and potential adjunctive interventions remain insufficiently characterized. This study evaluated whether Ziyuglycoside I attenuates DAV-induced coagulation abnormalities using thromboelastography (TEG) and molecular docking. METHODS: Citrated whole blood from healthy donors was exposed to 10, 20, or 30 μg DAV to characterize concentration-related coagulation changes and select a challenge dose. Based on these results, 20 μg DAV was used for subsequent intervention experiments with Ziyuglycoside I, antivenom serum (ASV), or their combination. TEG assessed reaction time (R), clot formation time (K), α-angle, maximum amplitude (MA), and lysis at 30 min (LY30). Molecular docking evaluated the potential interaction between Ziyuglycoside I and a representative snake venom metalloproteinase (SVMP). RESULTS: DAV induced progressively more pronounced TEG abnormalities with increasing concentrations, and 20 μg was selected as a marked but quantifiable challenge dose. At this concentration, DAV prolonged R and K, decreased α-angle and MA, and increased LY30. Ziyuglycoside I significantly improved clot formation kinetics and clot strength, whereas ASV markedly suppressed LY30 elevation. Compared with ASV alone, combination treatment further increased MA, indicating additional improvement in clot strength. Molecular docking predicted a favorable binding pose of Ziyuglycoside I near the active region of the representative SVMP (-8.2 kcal/mol). CONCLUSION: Ziyuglycoside I attenuated DAV-induced coagulation abnormalities mainly by improving clot formation and strength, whereas ASV more strongly inhibited hyperfibrinolysis. Their combination further improved clot strength, supporting Ziyuglycoside I as a potential adjunctive compound for DAV-induced hemostatic disturbances.