Effects Of Alkaloid Evodiamine And Its Derivatives On Platelets Damage Caused By Reactive Oxygen Species

Objective:Evodia rutaecarpa is a Chinese versatile medicinal herb which is commonly used in clinical medicine.Many Pharmacological studies illustrate that Evodamine and rutaecarpine as the most abundant bioactive alkaloids of Evodia rutaecarpa have broad Pharmacological actions in terms of treating tumor,cardiovascular,cerebrovascular and infectious diseases.Whether they can regulate platelet function through apotoposis and autophagy is still unknown while their ability of inhibit platelet activation is well estabilished.This study focus on the investigation of whether Alkaloid Evodiamine and its derivatives have protective effects on platelet damage caused by reactive oxygen species.Methods:Washed platelets were pre-incubated with different concentrations of Rut and Evo,and then treated with H₂O₂.The ROS level was detected by microplate reader;The exposure of Phosphatidylserine（PS）on platelet membrane andΔΨm depolarization was detected by flow cytometry;The expression of bcl-2 m RNA was detected by RT-PCR;Western Blot was used to detect the expression of apoptosis-related proteins of platelets.Results:1.Rut and Evo reduced the level of ROS in platelets;2.Rut inhibited platelets membrane phosphatidylserine（PS）exposure;3.Rutaecarpine inhibitd the expression level of gelsolin;4.Rut inhibitedΔΨm depolarization;5.Rutaecarpine inhibit the expression level of cytochrome C in platelets;6.Rutaecarpine did not inhibit the P53 expression,but reduced the Phosphorylation level of p53 in high concenteation;Conclusions:Alkaloid Evodiamine and its derivatives can ruduce platelet damage that caused by reactive oxygen species.