Study on the Improvement Effect of Ginsenoside Rb 3 Combined with β-asarone on Vascular Dementia Model Mice and Its Mechanism / 中国药房

ABSTRACT

OBJECTIVE：To study the improvement effects of ginsenoside Rb 3 combined with β-asarone on vascular dementia （VD）model mice and its mechanism. METHODS ：ICR mice were randomly divided into model group ，ginsenoside Rb 3 group（10 mg/kg），β-asarone group （10 mg/kg），drug combination group （ginsenoside Rb 3 10 mg/kg+β-asarone 10 mg/kg），positive control group（donepezil hydrochloride 1 mg/kg）and Akt inhibitor group （LY294002，1 mg/kg），and sham operation group was set up ， with 10 mice in each group. Except for sham operation group ，VD model was induced by four vessel occlusion method in other groups. After modeling ，sham operation group and model group were given constant volume of normal saline ，Akt inhibitor group was given relevant medicine intraperitoneally ，and other groups were given relevant medicine intragastrically ，twice a day ，for consecutive 30 d. After last administration ，the learning and memory ability of mice was detected by avoiding darkness test. The contents of 4-hydroxydecenoic acid （4-HNE），8-hydroxydeoxyguanosine （8-OHdG） and reactive oxygen species （ROS） in hippocampus was detected by ELISA. RT-PCR assay was used ， to detect the mRNA expression of Bcl- 2 and Bax inhippocampus. The protein expression of Bcl- 2 in cortex wadetected by immunofluorescence method. Western blotting deng- assay was used to detect the protein expression of Bcl- 2 and mz1@126.com Bax in hippocampus. RESULTS ： Compared with sham operation group ，the incubation period of avoiding darkness xiaoyinlanlp@126.com test in model group was shortened significantly ； and the number of errors was increased significa ntly；4-HNE，8-OHdG and ROS contents ，mRNA and protein expression of Bax were increased significantly ，and mRNA and protein expression of Bcl- 2 was decreased significantly （P＜0.01）. Compared with model group，the incubation period of avoiding darkness test was prolonged significantly in ginsenoside Rb 3 group，β-asarone group ，drug combination group and positive control group ，the number of errors was decreased significantly ；4-HNE，8-OHdG，ROS contents ， mRNA and protein expression of Bax were decreased significantly ，and mRNA and protein expression of Bcl- 2 were increased significantly，especially in drug combination group （P＜0.05 or P＜0.01）. But the incubation period of avoiding darkness test was shortened significantly in Akt inhibitor group ，and the number of errors was increased significantly ；4-HNE，8-OHdG，ROS contents，mRNA and protein expression of Bax were increased significantly ，and mRNA and protein expression of Bcl- 2 were decreased significantly （P＜0.05）. CONCLUSIONS ：Ginsenoside Rb 3 combined with β-asarone has a protective effect on VD model mice ，and the effect was better than that of each compound alone. The mechanism of which may be associated with anti-oxidative stress and anti-apoptosis of hippocampus.