Effect of Allicin on Learning and Memory Ability of Vascular Dementia Rats and Its Mechanism / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of allicin （ALL） on learning and memory ability of rats with vascular dementia （VD） and the possible mechanism. Method:The VD rats induced by modified bilateral common carotid artery occlusion （BCCAO） were randomly divided into the VD group， low- and high-dose ALL （ALL-L and ALL-H） groups， and the sham operation （S） group， with 15 rats in each group. In the ALL-L and ALL-H groups， ALL was injected into the femoral vein at 5 mg·kg^-1 and 20 mg·kg^-1， respectively， while the same volume of normal saline was injected in the S and VD groups， once a day， for two successive weeks. Morris water maze （MWM） was used to test the learning and memory ability of rats. Hematoxylin and eosin （HE） staining was conducted to observe the pathological changes in hippocampal tissue， followed by the detection of inflammatory factors tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， and IL-1<italic>β</italic> as well as oxidative stress indexes malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in rat hippocampus. The apoptosis of hippocampal cells was detected by TdT-mediated dUTP Nick end Labeling（TUNEL） assay. The expression levels of apoptosis and autophagy-related proteins cysteinyl aspartate-specific protease-3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， LC3Ⅰ， and the mammalian homolog of yeast ATG6 （Beclin 1） in hippocampus were determined by Western blot. Result:The comparison with the VD group revealed that the learning and memory abilities of rats in the ALL-H and ALL-L groups were significantly improved （<italic>P</italic><0.05）. The TNF-<italic>α</italic>， IL-6， IL-1<italic>β</italic>， and MDA levels in hippocampus were lowered （<italic>P</italic><0.05）， whereas the SOD and GSH-Px activities were enhanced （<italic>P</italic><0.05）. The apoptosis rates were declined （<italic>P</italic><0.05）， with an even lower rate noticed in the ALL-H group （<italic>P</italic><0.05）. The expression levels of Caspase-3， Bax， LC3Ⅱ/LC3Ⅰ ratio， and Beclin-1 in the ALL-H and ALL-L groups were significantly down-regulated in contrast to those in the VD group （<italic>P</italic><0.05）， while that of Bcl-2 was up-regulated （<italic>P</italic><0.05）. The ALL-H group exhibited better performances than the ALL-L group （<italic>P</italic><0.05）. Conclusion:ALL could improve the learning and memory ability of VD rats to some extent， which may be attributed to its inhibition against inflammatory reaction， oxidative stress， and neuronal apoptosis and autophagy.