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J Ethnopharmacol. 2019 Apr 6;233:73-79. doi: 10.1016/j.jep.2018.12.043. Epub 2018 Dec 31.

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

Author information

1
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea. Electronic address: qkrgpwls0523@naver.com.
2
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul, Republic of Korea. Electronic address: inhojung@dhpharm.co.kr.
3
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea. Electronic address: kwonhuiyoung@naver.com.
4
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea. Electronic address: wlals2463@naver.com.
5
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea. Electronic address: bee2634@naver.com.
6
Daehwa Pharmaceutical Co., Ltd., Seongnam 13488, Republic of Korea.
7
School of Natural Resources and Environmental Science, Kangwon National University, ChoonCheon, Republic of Korea. Electronic address: sejinpark@kangwon.ac.kr.
8
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea. Electronic address: yclee@dau.ac.kr.
9
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: mose79@dau.ac.kr.
10
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

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.

AIMS OF STUDY:

The present study aimed to provide evidence showing that the ethanol extract of Zizyphus jujuba var. spinosa seeds (EEZS), which may regulate plasmin activity, has the potential to serve as a therapeutic agent for AD.

MATERIALS AND METHODS:

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.

RESULTS:

Our in vitro 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 (P < 0.05). Additionally, EEZS significantly elevated the plasmin level and activity in the hippocampal slices from 5XFAD mice (P < 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 in vitro study, the results of our in vivo 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.

CONCLUSIONS:

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.

KEYWORDS:

5XFAD mice; 6-aminocaproic acid; Alzheimer's disease; Donepezil; Ethanol extracts of the seed of Zizyphus jujua var. spinosa; Plasmin

PMID:
30605739
DOI:
10.1016/j.jep.2018.12.043
[Indexed for MEDLINE]

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