The saponin D39 blocks dissociation of non‐muscular myosin heavy chain IIA from TNF receptor 2, suppressing tissue factor expression and venous thrombosis

• DOI: 10.1111/bph.13885
• Publication Date: 2017-05-26T09:02:44Z
• Authors: Ke‐feng Zhai; Jin‐rong Zheng; You‐mei Tang; Fang Li; Yan‐ni Lv; Yuan‐yuan Zhang; Zhen Gao; Jin Qi; Bo‐yang Yu; Jun‐ping Kou
• Keywords: Male; Venous Thrombosis; 0301 basic medicine; Glycogen Synthase Kinase 3 beta; Myosin Heavy Chains; Tumor Necrosis Factor-alpha; Transcription Factor RelA; Saponins; Thromboplastin; Mice, Inbred C57BL; Molecular Docking Simulation; 03 medical and health sciences; HEK293 Cells; Fibrinolytic Agents; Human Umbilical Vein Endothelial Cells; Animals; Humans; Receptors, Tumor Necrosis Factor, Type II; Proto-Oncogene Proteins c-akt; Cells, Cultured

Background and Purpose Non‐muscular myosin heavy chain IIA (NMMHC IIA) plays a key role in tissue factor expression venous thrombosis. Natural products might inhibit thrombosis through effects on NMMHC IIA. Here, we have shown that natural saponin, D39, from Liriope muscari exerted anti‐thrombotic activity vivo , by targeting Experimental Approach Expression of endothelial cells were analysed vitro Western blot simplified chromogenic assays. Interactions between D39 assessed serial affinity chromatography molecular docking analysis. D39‐dependent interactions TNF receptor 2 (TNFR2) measured immunofluorescence, co‐immunoprecipitation proximity ligation Anti‐thrombotic was evaluated with model inferior vena cava injury mice. Key Results inhibited procoagulant activities HUVECs decreased thrombus weight cava‐ligated mice dose‐dependently. Serial analysis suggested bound to In HEK293T cells, evoked overexpression. This effect blocked knockdown HUVECs. dissociation TNFR2, which subsequently modulated the Akt/GSK3β–NF‐κB signalling pathways. Conclusions Implications formation modulating Akt/GSK3β NF‐κB pathways We identified new product targeted IIA, as potential treatment for thrombotic disorders other vasculopathies.