Effect of preventive administration of icariin on learning and memory abilities and brain mitochondrial oxidative stress in SAMP8 / 中国药理学通报

ABSTRACT

Aim To investigate the effect of preventive administration of icariin on learning and memory abili-ties and brain mitochondrial oxidative stress in senes-cence-accelerated mouse prone8 ( SAMP8 ) . Methods The 6-month-old SAMP8 mice were randomly divid-ed into the SAMP8 model group, ICA groups (75, 150 mg · kg-1 ) , the positive Diethylstilbestrol ( DES ) group and estrogen receptor inhibitor ICI182780 com-bined with ICA (150 mg·kg-1 ) group, with 8 mice in each group. 8 same month old SAMR1 mice were selected as the normal control group. After oral admin-istration for 8 weeks, Morris water maze test and step-down passive test were used to investigate the effects of preventive administration of ICA on learning and mem-ory abilities in SAMP8 mice. Cerebral cortex mitochon-dria were isolated to determine the effect of preventive administration of ICA on the oxidative stress by detec-ting reactive oxygen species ( ROS) level, lipid perox-ides ( MDA ) content, glutathione GSH content and catalase ( CAT ) activity. Results Preventive treat-ment of ICA could significantly improve the abilities of place navigation and space exploration of SAMP8 mice, enhance their reflex ability in step-down passive test. ICA could also reduce the level of ROS and MDA content, increase GSH content in brain mitochondria of SAMP8 mice. CAT activity was not obviously changed. Compared with ICA high dose group, the learning and memory abilities of mice in ICA and estrogen receptor inhibitor ICI182780 co-administrated group were signif-icantly decreased. However,brain mitochondria oxida-tive stress was not changed obviously. Conclusion Preventive administration of icariin can significantly improve learning and memory abilities and brain mito-chondrial oxidative stress in SAMP8 mice. The mecha-nism of ICA improving learning and memory abilities may be related to its estrogen-like effect;while the ac-tion on brain mitochondrial oxidative stress may be in-dependent of estrogen receptor.