A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
62
Journal Issue
27
Pages
6326-6336
Date Issued
2014
Author(s)
Hsieh W.-T.
Abstract
Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), £]-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation. ? 2014 American Chemical Society.
Subjects
ginsenosides
human embryonic stem cells
neurogenesis
Parkinson's disease
SDGs
Other Subjects
Amines; Amino acids; Neurodegenerative diseases; Neurons; Amines; Amino acids; Cell growth; Cells; Cytology; Diagnosis; Neurons; Neurophysiology; Pharmacodynamics; Differentiation process; Dopamine transporters; Dopaminergic neurons; Ginsenosides; Human embryonic stem cells; Neurogenesis; Parkinson's disease; Voltage gated ion channels; Parkinsons disease; Cell growth; Stem cells; dopamine; plant medicinal product; cell differentiation; cytology; drug effects; embryonic stem cell; genetics; human; in vitro study; mesencephalon; metabolism; nerve cell; Parkinson disease; Cell Differentiation; Dopamine; Embryonic Stem Cells; Humans; In Vitro Techniques; Mesencephalon; Neurons; Parkinson Disease; Phytochemicals
Type
journal article