Effects Of Marine Indolone Compound FGFC1 On Physiological Characteristics Of Platelets And Vascular Endothelial Cells

The platelets play a physiological role of aggregation,secretion,and adhesion on blood.When the body is damaged or stimulated by other drugs,the platelets will change and abnormal activation will occur.Abnormal activation of platelets directly leads to endogenous coagulation of platelet aggregation.It also leads to presents thrombotic cardiovascular and cerebrovascular diseases such as pulmonary thrombosis,cerebral thrombosis and myocardial infarction.The factors that cause abnormal activation of platelets will also affect the changes of physiological functions of vascular endothelial cells.It is found that fibrinolytic active compounds affected platelet regulation of blood coagulation and correlated the physiological characteristics of vascular endothelial cells,possibly in the establishment of new fibrinolysis theory and thrombolytic drugs.Based on the unique thrombolytic mechanism of marine indolone fibrinolytic active compound FGFC1,the relationship between novel marine indolone fibrinolytic active compounds and blood coagulation was studied.The interaction between fibrinolytic active compounds and vascular endothelial cells was investigated.To lay a theoretical foundation for the indepth study of marine indolone fibrinolytic active compounds.To investigate the effect of novel marine indolone fibrinolytic active compound(FGFC1)on platelet aggregation.The relationship between the FGFC1 and changes in the platelet physiological factors was studied.At the same time,the similarities and differences in the action of the bisindole compound FGFC1 and the indole compound FGFC2 on platelets were compared.FGFC1 inhibited ADP and AA-induced platelet aggregation and the maximum inhibition rates were 42.58%±1.7% and 47.82%±2.18%,respectively.FGFC2 also inhibited ADP,AA and collagen-induced platelet aggregation and the maximum inhibition rate of 50.12%±1.02%,45.28%±1.09% and 50.28%±2.12%,respectively.Both FGFC1 and FGFC2 can increase the cAMP in platelets,and FGFC2 is significantly reduced the content of thromboxane A2 in platelets.Conclusion The marine bisindole fibrinolytic active compound significantly inhibits platelet aggregation.FGFC1 inhibits platelet aggregation by affecting the content of platelet cAMP.FGFC2 may inhibit platelet aggregation through more than one pathway.Therefore,this study clearly depicted that the inhibition of platelet aggregation by guanidine compounds is closely related to their molecular structure.In coagulation experiments,by detecting the markers of endogenous coagulation pathways and exogenous coagulation pathways in mice,explore the way of FGFC1 and FGFC2 act on blood coagulation pathways.FGFC1 significantly prolonged PT and APTT after injection.After 10 mg/kg FGFC1 injection,PT was 15.41±0.68 s,APTT was 39.42±0.92 s,and coagulation factor VIII level was significantly decreased.It is indicated that the marine fibrinolytic active compound FGFC1 prolongs the clotting time by affecting the exogenous coagulation pathway and factor VIII in the endogenous coagulation pathway.Whether it specifically affects the level of other coagulation factors needs further study.There was no significant difference in PT after FGFC2 injection,which significantly prolonged APTT.After 5 mg/kg FGFC2 injection,the PT was 14.12±0.03 s,APTT was 36.82±2.21 s,and the level of coagulation factor VIII was decreased.It is indicated that the marine fibrinolytic active compound FGFC2 mainly achieves the effect of prolonging the clotting time by affecting the endogenous coagulation pathway.And it acts by affecting factor VIII in the endogenous coagulation pathway.Human periodontal ligament fibroblasts and human umbilical vein endothelial cells were induced by LPS as an inflammatory model to explore the anti-inflammatory effects of marine fibrinolytic active compounds FGFC1 and FGFC2.The dexamethasone treatment group was used as a positive control group.The levels of IL-1,IL-6 and TNF-inflammatory factors secreted by HPLFs and HUVECs were measured under LPS induction.FGFC1 and FGFC2 significantly down-regulated the levels of IL-1,IL-6 and TNF-inflammatory factors secreted by HPLFs and HUVECs induced by LPS.And as the concentration increases,the effect is enhanced.Compared with the dexamethasonepositive control group,there was no significant difference in the levels of IL-1,IL-6 and TNF-secreted by HPLFs and HUVECs in the high-concentration FGFC1 and FGFC2 treatment groups.Indolone have a variety of biological activities and are widely used in medicine.The indolone FGFC1 and FGFC2 have fibrinolysis which derived from marine organisms.The results of this study showed that the marine fibrinolytic active compounds FGFC1 and FGFC2 inhibit platelet aggregation,affect the clotting time by affecting the endogenous coagulation pathway and the exogenous coagulation pathway.And they also have the characteristics of inhibiting the secretion of inflammatory factors.