Research Paper Volume 13, Issue 20 pp 23739—23756

Loganin substantially ameliorates molecular deficits, pathologies and cognitive impairment in a mouse model of Alzheimer’s disease

Lulin Nie1, *, , Kaiwu He1,2, *, , Fengzhu Xie3, , Shifeng Xiao4, , Shupeng Li2, , Jia Xu1,5, , Kaiqin Zhang1,6, , Chen Yang1, , Li Zhou1, , Jianjun Liu1, , Liangyu Zou7, , Xifei Yang1, ,

  • 1 Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
  • 2 School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China
  • 3 Shenzhen Center for Chronic Disease Control and Prevention, Shenzhen 518020, China
  • 4 Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
  • 5 Department of Pathophysiology, Guangzhou Medical University, Guangzhou 510182, China
  • 6 College of Public Health, University of South China, Hengyang 421001, China
  • 7 Department of Neurology, Shenzhen People’s Hospital, Second Clinical College, Jinan University, Shenzhen 518020, China
* Equal contribution

Received: April 5, 2021       Accepted: June 14, 2021       Published: October 23, 2021
How to Cite

Copyright: © 2021 Nie 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.


Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease threatening the health of the elderly, but the available therapeutic and preventive drugs remain suboptimal. Loganin, an iridoid glycoside extracted from Cornus officinalis, is reported to have anti-inflammatory and memory-enhancing properties. This study is aimed to explore the influence of loganin on cognitive function in 3xTg-AD mice and the underlying mechanism associated with its neuroprotection. According to the results of behavioral tests, we found that administration of loganin could significantly alleviate anxiety behavior and improve memory deficits of 3xTg-AD mice. Furthermore, immunohistochemical analysis displayed that there were decreased Aβ deposition in the hippocampus and cortex of 3xTg-AD mice treated with loganin compared with the control mice. Importantly, the Aβ-related pathological change was mainly involved in altering APP expression and processing. And loganin was also found to reduce the levels of phosphorylated tau (i.e. pTauS396 and pTauS262) in 3xTg-AD mice. By performing 2D-DIGE combined with MALDI-TOF-MS/MS, we revealed 28 differentially expressed proteins in the 3xTg-AD mice treated with loganin compared with the control mice. Notably, 10 proteins largely involved in energy metabolism, synaptic proteins, inflammatory response, and ATP binding were simultaneously detected in 3xTg-AD mice compared to WT mice. The abnormal changes of energy metabolism (PAGM1 and ENO1), synaptic proteins (SYN2 and Cplx2), inflammatory response (1433Z) were verified by western blot. Overall, our study suggested that loganin could be used as a feasible candidate drug to ameliorate molecular deficits, pathologies and cognitive impairment for prevention and treatment of AD.


AD: Alzheimer’s disease; LTP: long-term potentiation; 2D-DIGE: two-dimensional fluorescence differential gel electrophoresis; Aβ: β-Amyloid; BACE1: β-secretase; TCA: glycolysis and tricarboxylic acid cyclic; PGAM1: Phosphoglycerate mutase 1; 3PG: 3-phosphoglycerate; 2PG: 2-phosphoglycerate; ENO1: Alpha-enolase; SYN2: synapsin-2; Cplx2: complexin-2; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; DTT: DL-dithiothreitol; IAA: 3-indoleacrylic acid; SDS: sodium dodecyl sulfate; ACN: acetonitrile; TFA: trifluoroacetic acid; CHCA: α-Cyano-4-hydroxycinnamic acid; OPT: open field test; EPM: elevated plus maze; MWM: Morris water maze; DAB: diaminobenzidine; IEF: isoelectric focusing; DIA: Differential In-gel Analysis; GO: gene ontology; PPI: protein-protein interaction.