Screening Anti-ischemia Of Cerebra And Myocardium Drugs And Research On Rhodioside Derivative S01 Mechanism Of Anti-ischemia Activity

AIM(1)To find compounds possessing anti-ischemia and anti-anoxia activity from compounds derived from Salidroside and provides the scientific experimental data for newdrug -research.METHODS(1)SH-SY5Y cells and cultured neonatal rat myocardial cells were pretreated with each compound(40,200 and 1000 ug·ml^-1,respectively)and then induced damage by glutamate or hypoxia/reoxygenation,the inhibition rate of Lactate dehydrogenase(LDH) release was detected by colorimetry.(2)S01 which has better acticity and simpler synthesis method was selected as the representative to research the drug action and anti-ischemia/anti-anoxia mechanism.SH-SY5Y cells and cultured neonatal rat myocardial cells were pretreated with S01(2,10 and 50 ug·ml^-1,respectively)and then induced damage by glutamate or hypoxia/reoxygenation,then the content of LDH,AST,CK enzymes and the cell apoptosis degree in cultured neonatal rat myocardia cells,the content of LDH enzyme and cell viability in SH-SY5Y cells,cell the free Ca²⁺concentration([Ca²⁺]_i),intracellular reactive oxygen species(ROS)level,adenosine triphosphate(ATP)level,nitric oxide(NO)level, oxide dismutase(SOD)activity and malondialdehyde(MDA)level were detected.The anti-fatigue and anti-hypoxia ability of mice were also detected.RESULTS(1)4 compounds were found to have better anti-ischemia and anti-anoxia activity than lead compounds.(2)Compared with model groups,in cultured neonatal rat myocardial cells,S01(2,10 and 50 ug·ml^-1)can reduce LDH,AST,CK release induced by hypoxia/reoxygenation,in SH-SY5Y cells,S01 can reduce LDH release and levated the cell survival rate induced by glutamate.Moreover,results indicate that S01 can increase SOD activity and ATP level,and inhibited the increase of MDA,ROS,Ca²⁺overload,apoptosis and NO levels induced by glutamate or hypoxia/reoxygenation.Furthermore,S01 can increase the anti-fatigue and anti-hypoxia ability of mice. CONCLUSION The compounds can protect cells from the damage induced by glutamate and oxygen-glucose deprivation through some mechanism,which indicates that they may have the potential to treat cerebral or myocardium ischemia.