The ethanol extract of <i>Zizyphus jujuba var. spinosa</i> seeds ameliorates the memory deficits in Alzheimer's disease model mice

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>The seeds of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) have long been treated as hypnotic agent for sleep disturbances in traditional Chinese and Korean medicine and many previous studies have focused on its effect in central nervous system.</P> <P><B>Aims of study</B></P> <P>The present study aimed to provide evidence showing that the ethanol extract of <I>Zizyphus jujuba</I> var. <I>spinosa</I> seeds (EEZS), which may regulate plasmin activity, has the potential to serve as a therapeutic agent for AD.</P> <P><B>Materials and methods</B></P> <P>Synaptic function was determined by measuring long-term potentiation (LTP) in Shaffer-collateral pathway of the hippocampus. Protein levels of plasmin or plasminogen were examined using western blotting. Plasmin activity was measured using ELISA. Cognitive functions were measured using passive avoidance and object recognition tests in the 5XFAD mice.</P> <P><B>Results</B></P> <P>Our <I>in vitro</I> analysis revealed that EEZS-treated hippocampal slices from 5XFAD mice, a mouse model of AD, showed significantly higher long-term potentiation levels than did vehicle-treated hippocampal slices from 5XFAD mice (<I>P</I> < 0.05). Additionally, EEZS significantly elevated the plasmin level and activity in the hippocampal slices from 5XFAD mice (<I>P</I> < 0.05). Co-treating the slices with EEZS and 6-aminocaproic acid, a plasmin inhibitor, blocked the ameliorating effects of EEZS on the synaptic deficits that were present in 5XFAD mice. Compatible with the <I>in vitro</I> study, the results of our <I>in vivo</I> investigation showed that administering EEZS orally to 5XFAD mice ameliorated their memory impairments. Orally administered EEZS also elevated the plasmin level and activity in the hippocampus of 5XFAD mice.</P> <P><B>Conclusions</B></P> <P>Collectively, our findings suggest that EEZS alleviates the AD-like symptoms in 5XFAD mice by regulating of plasmin activity and EEZS may be a suitable treatment for AD.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>