Epigallocatechin gallate (EGCG) inhibits adhesion and migration of neural progenitor cells in vitro

Abstract

Food supplements based on herbal products are widely used during pregnancy as part of a self-care approach. The idea that such supplements are safe and healthy is deeply seated in the general population, although they do not underlie the same strict safety regulations than medical drugs. We aimed to characterize the neurodevelopmental effects of the green tea catechin epigallocatechin gallate (EGCG), which is now commercialized as high-dose food supplement. We used the "Neurosphere Assay" to study the effects and unravel underlying molecular mechanisms of EGCG treatment on human and rat neural progenitor cells (NPCs) development in vitro. EGCG alters human and rat NPC development in vitro. It disturbs migration distance, migration pattern, and nuclear density of NPCs growing as neurospheres. These functional impairments are initiated by EGCG binding to the extracellular matrix glycoprotein laminin, preventing its binding to β1-integrin subunits, thereby prohibiting cell adhesion and resulting in altered glia alignment and decreased number of migrating young neurons. Our data raise a concern on the intake of high-dose EGCG food supplements during pregnancy and highlight the need of an in vivo characterization of the effects of high-dose EGCG exposure during neurodevelopment.

BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action

“…However, in case of e.g. RT-PCR evaluation of cell type-specific markers the desired cell population might only be a fraction of the total cell number like in this study, where we find 6–8% oligodendrocytes after 5 days of differentiation34. With regards to the species comparison, the timing aspect has to be carefully considered as speed of developmental processes observed in neurospheres seem to reflect at least to some extent the pace of the species of cell origin, which is very different between humans and rodents33.…”

In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities

“…Human neural stem cells present an alternative source. These cells can be expanded in vitro, differentiated to various cell types, and used for (developmental) neurotoxicity testing (Gassmann et al 2012;Barenys et al 2016).…”

Comparison of migration disturbance potency of epigallocatechin gallate (EGCG) synthetic analogs and EGCG PEGylated PLGA nanoparticles in rat neurospheres

“…In a previous study, EGCG exposure for 24h disturbed migration of NPCs in both human and rat neurospheres (Barenys et al, 2017a). As there were no significant differences in sensitivity towards adverse EGCG effects between both species, we tested EGCG and five different relatedsubstances in only one model: the rat neurospheres.…”

“…In our study we included the original compound EGCG, EGCG PEGylated-PLGA nanoparticles (Nano-EGCG), the polyphenolic compounds G37 and G56 with two galloyl units and a naphtyl or a biphenyl moiety, respectively, and M1 and M2 with one galloyl group (Figure 1). The inclusion of the latter was motivated by the results in our previous study where we observed that the natural catechin with only one galloyl group epigallocatechin (EGC, CAS: 970-74-1) disturbed the adhesion of NPCs less potently than EGCG (Barenys et al, 2017a). These five compounds: Nano-EGCG, G37, G56, M1, and M2, have already been tested for some beneficial effects related with, for example, their anticancer, anti-seizure, antibacterial and/or analgesic activity (Cano et al, 2018;Crous-Masó et al, 2018;Xifró et al, 2015), yet their potential to interfere with neurodevelopmental processes like migration needs evaluation before they are tested as prenatal therapies or prenatal nutritional supplements.…”