Research Paper Volume 12, Issue 9 pp 8622—8639

Lemon essential oil ameliorates age-associated cognitive dysfunction via modulating hippocampal synaptic density and inhibiting acetylcholinesterase

Bonan Liu1, *, , Jiayuan Kou1, *, , Fuyan Li1, , Da Huo1, , Jiaran Xu1, , Xiaoxi Zhou1, , Dehao Meng1, , Murtaza Ghulam1, , Bobkov Artyom1, , Xu Gao1,2,3,4,5, , Ning Ma1,2,3, , Dong Han1,2,3, ,

  • 1 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China
  • 2 Basic Medical Institute of Heilongjiang Medical Science Academy, Harbin 150081, China
  • 3 Translational Medicine Center of Northern China, Harbin 150081, China
  • 4 Heilongjiang Provincial key Laboratory of Genetically Modified Model Animal, Harbin Medical University, Ministry of Education, Harbin 150081, China
  • 5 China Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin 150081, China
* Equal contribution

Received: October 18, 2019       Accepted: March 24, 2020       Published: May 11, 2020
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The lemon essential oil (LEO), extracted from the fruit of lemon, has been used to treat multiple pathological diseases, such as diabetes, inflammation, cardiovascular diseases, depression and hepatobiliary dysfunction. The study was designed to study the effects of LEO on cognitive dysfunction induced by Alzheimer’s disease (AD). We used APP/PS1 double transgene (APP/PS1) AD mice in the experiment; these mice exhibit significant deficits in synaptic density and hippocampal-dependent spatial related memory. The effects of LEO on learning and memory were examined using the Morris Water Maze (MWM) test, Novel object recognition test, and correlative indicators, including a neurotransmitter (acetylcholinesterase, AChE), a nerve growth factor (brain-derived neurotrophic factor, BDNF), a postsynaptic marker (PSD95), and presynaptic markers (synapsin-1, and synaptophysin), in APP/PS1 mice. Histopathology was performed to estimate the effects of LEO on AD mice. A significantly lowered brain AChE depression in APP/PS1 and wild-type C57BL/6L (WT) mice. PSD95/ Synaptophysin, the index of synaptic density, was noticeably improved in histopathologic changes. Hence, it can be summarized that memory-enhancing activity might be associated with a reduction in the AChE levels and is elevated by BDNF, PSD95, and synaptophysin through enhancing synaptic plasticity.


AD: Alzheimer’s disease; LEO: lemon essential oil; ACh: acetylcholine; AChE: choline acetyltransferase; AKT: protein kinase B; ERK: extracellular signal-regulated kinase; BDNF: brain-derived neurotrophic factor; TrkB: receptor tyrosine kinase; LTP: long-term potentiation; CNS: central nervous system.