Research Paper Volume 12, Issue 6 pp 5516—5538

Microarray analysis of verbenalin-treated human amniotic epithelial cells reveals therapeutic potential for Alzheimer’s Disease

Farhana Ferdousi1, , Shinji Kondo2, , Kazunori Sasaki1,3, , Yoshiaki Uchida4, , Nobuhiro Ohkohchi5, , Yun-Wen Zheng5, , Hiroko Isoda1,2,3,6, ,

  • 1 Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8577, Ibaraki, Japan
  • 2 R&D Center for Tailor-Made QOL, University of Tsukuba, Tsukuba 305-8550, Ibaraki, Japan
  • 3 National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Ibaraki, Japan
  • 4 School of Integrative and Global Majors, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
  • 5 Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
  • 6 Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan

Received: September 10, 2019       Accepted: March 24, 2020       Published: March 29, 2020
How to Cite

Copyright © 2020 Ferdousi 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) has become a major world health problem as the population ages. There is still no available treatment that can stop or reverse the progression of AD. Human amnion epithelial cells (hAECs), an alternative source for stem cells, have shown neuroprotective and neurorestorative potentials when transplanted in vivo. Besides, studies have suggested that stem cell priming with plant-derived bioactive compounds can enhance stem cell proliferation and differentiation and improve the disease-treating capability of stem cells. Verbenalin is an iridoid glucoside found in medicinal herbs of Verbenaceae family. In the present study, we have conducted microarray gene expression profiling of verbenalin-treated hAECs to explore its therapeutic potential for AD. Gene set enrichment analysis revealed verbenalin treatment significantly enriched AD-associated gene sets. Genes associated with lysosomal dysfunction, pathologic angiogenesis, pathologic protein aggregation, circadian rhythm, age-related neurometabolism, and neurogenesis were differentially expressed in the verbenalin-treated hAECs compared to control cells. Additionally, the neuroprotective effect of verbenalin was confirmed against amyloid beta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Our present study is the first to report the therapeutic potential of verbenalin for AD; however, further in-depth research in the in vitro and in vivo models are required to confirm our preliminary findings.


AD: Alzheimer’s disease; Aβ: amyloid-beta; DEGs: differentially expressed genes; EGFR: epidermal growth factor; GO: Gene Ontology; GSEA: gene set enrichment analysis; hAECs: human amnion epithelial cells; NRG: neuregulin; VEGF: vascular endothelial growth factor.