OBJECTIVE:To investigate the effect of quercetin,oleanolic acid,icariin and their compatibility on the apoptosis of hippocampal neurons of Sprague-Dawley (SD) rats cultured with high glu-cose medium and the possible mechanism.METHODS:The extracts were purchased from Chi-na Food and Drug Control Institute and Sellect.Hip-pocampus was obtained from newborn 24 h SD rats.After culturing the hippocampus in different medium for 72 h,flow cytometry was used to de-tect the apoptosis of hippocampal neurons,and Western blot was utilized to test the expressions of p-p38,p38,p-c-Jun N-terminal kinase (JNK) and JNK.RESULTS:Compared with the control group (CG),the neuronal apoptosis rate and the ratios of p-p38/p38 and p-JNK/JNK were significantly increased in the high glucose group (GG) (P ＜ 0.01);Compared with the GG,the apoptosis rate and the ratios of p-p38/p38 and p-JNK/JNK were significantly de-creased in other drug groups (P ＜ 0.01);Compared with the monomer groups respectively,the apopto-sis rate and the ratios of p-p38/p38 and p-JNK/JNK in the two-drug groups and the three-drug group all decreased (P ＜ 0.01);Compared with the two-drug groups,the neuronal apoptosis rate and the ratio of p-JNK/JNK of the three-drug group de-creased (P ＜ 0.05).CONCLUSION:Under the condition of high glu-cose,the quercetin,oleanolic acid and icariin can al-leviate the apoptosis of hippocampus neurons,re-duce the phosphorylation of p38 and JNK in p38 mitogen-activated protein kinases and JNK signal-ing pathway.And the efficacy of the three drugs in combination with each other can be strengthened.