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

Abstract

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 indepth research in the in vitro and in vivo models are required to confirm our preliminary findings. * GSEA online software (http://software.broadinstitute.org/gsea/index.jsp). 1 Generation of cells within the nervous system. 2 Any process that modulates the frequency, rate or extent of neuron differentiation. 3 Any process that modulates the frequency, rate or extent of nervous system development, the origin and formation of nervous tissue. 4 Any process pertaining to the functions of the nervous and muscular systems of an organism.

Application of human amniotic epithelial cells in regenerative medicine: a systematic review

“…Furthermore, hAECs treated with vitamin C showed increased survival after transplantation and secreted a greater amount of growth factors, which improved the therapeutic potential of hAECs in mice with POF [ 124 ]. The plant-derived bioactive compound verbenalin significantly increased gene expression in hAECs, contributing to the enhanced neural repair potential of hAECs for AD [ 125 ].…”

Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells

“…Natural compounds with proven bioactivities can control cellular behavior and early biological and molecular events to direct the targeted differentiation of stem cells in a lineage-specific manner. Only a handful of studies were conducted to evaluate the effects of naturally occurring compounds on hAECs ( Ferdousi et al, 2019 , 2020 ; Hou et al, 2020 ). Furthermore, while current researches focus on the safety and efficacy of translating hAEC therapy into clinical practices ( Murphy et al, 2010 ; Strom et al, 2013 ; Lim et al, 2017 , 2018 ; Srinivasan et al, 2020 ), priming approaches using natural bioactive compounds to improve its effectiveness has not been explored.…”

“…However, despite the fact that hAECs were discovered decades ago, few researches have been done on using natural compounds to optimize the microenvironment or to regulate the early biological events for controlled differentiation of hAECs. In our previous studies, we have reported that a natural compound rosmarinic acid could induce neuronal differentiation in hAEC (Ferdousi et al, 2019), whereas verbenalin-treated hAECs showed therapeutic potential for Alzheimer's disease (Ferdousi et al, 2020). Another recent study has reported that vitamin C, a natural antioxidant, could promote the proliferation, migration, and self-renewal of hAECs in vitro and elevate the therapeutic potential of hAECs in premature ovarian insufficiency model mice (Hou et al, 2020).…”

Effects of Isorhamnetin in Human Amniotic Epithelial Stem Cells in vitro and Its Cardioprotective Effects in vivo

“…The procedure of cell isolation and cell culture have been explained elsewhere in detail ( Ferdousi et al, 2019 , 2020 ; Furuya et al, 2019 ). Briefly, hAESCs were obtained from the term placenta donated by mothers who underwent cesarean delivery.…”

“…Besides, hAESCs cultured in a 3D microenvironment as spheroids, have highly expressed the stemness-related genes compared to their 2D counterpart as well as compared to iPSCs and MSCs ( Ferdousi et al, 2019 ). We have previously investigated the gene expression profiles of several natural compounds in hAESCs ( Ferdousi et al, 2019 , 2020 ) in an effort to screen eligible natural compounds for further in-depth investigations. Among the compounds that we have screened in hAESCs, isorhamnetin (ISO) exerts cardiac morphogenesis, and antifibrotic potential.…”