How Licorice Root Compounds Affect Human Gut Cells in 3D Models

Jim Crocker
7th September, 2024

How Licorice Root Compounds Affect Human Gut Cells in 3D Models

Schematic overview of the three in vitro intestinal models compared in this study (a), illustrating that the cellular complexity and externally-facing mucus layer of apical-out enteroids (b) provide a more physiologically relevant system than Caco-2 cells or apical-in enteroids.

Image adapted from: Dinteren et al. / CC BY (Source)

Key Findings

  • The study from Wageningen University used a 3D model called apical-out enteroids to mimic the gastrointestinal tract environment
  • Prenylated phenolics from licorice roots, like licochalcone A and glycycoumarin, were found to be non-toxic to the enteroids at concentrations up to 500 μg/mL
  • Glabridin showed significant cytotoxicity and reduced cell viability at the same concentration, highlighting the importance of the mucus layer in these interactions
Recent research from Wageningen University has advanced our understanding of how bioactive compounds in food interact with the mucosal epithelium of the gastrointestinal tract[1]. This study utilized apical-out enteroids, a 3D model that mimics the in vivo environment closely, to investigate the effects of antibacterial prenylated phenolics derived from licorice roots. These compounds include glabridin, licochalcone A, and glycycoumarin. The gastrointestinal tract is lined with a mucus layer that plays a crucial role in protecting the underlying epithelial cells from pathogens and mechanical stress[2]. Mucins, the major component of mucus, are large glycoproteins that facilitate this protective function. The small intestine, in particular, has a single, unattached mucus layer that can become problematic in conditions like cystic fibrosis, where it becomes attached and leads to disease manifestations[2]. The mucus not only serves as a barrier but also houses commensal bacteria that are essential for gut health[3]. The apical-out enteroids developed in this study feature an accessible apical surface and a fucose-containing mucus layer, making them a physiologically relevant model for studying the impact of food compounds. These enteroids were used to evaluate the cytotoxicity, cell viability, barrier integrity, and biotransformation of the prenylated phenolics. The results showed that at concentrations up to 500 μg/mL, licochalcone A and glycycoumarin did not significantly affect the enteroids, with cytotoxicities of -6 ± 2% and -2 ± 2%, and cell viabilities of 77 ± 22% and 77 ± 13%, respectively. However, glabridin exhibited significant cytotoxicity (31 ± 25%) and reduced cell viability (21 ± 14%) at the same concentration. These findings are particularly interesting when compared to previous models like apical-in enteroids and Caco-2 cells, which did not show the same differential sensitivities to the phenolics. This discrepancy underscores the importance of the mucus layer in the apical-out enteroids, which may influence interactions through mechanisms like electrostatic repulsion. The mucus layer's role in maintaining gut health and its dynamic response to mechanical stress has been well-documented[4]. In the small intestine, mucus acts as both a lubricant and a barrier, adapting to varying levels of luminal shear and gut wall contractility. This study adds to our understanding by demonstrating how the mucus layer can affect the interaction of bioactive compounds with the epithelial cells. Moreover, the study also highlights the phase II biotransformation capabilities of the enteroid models, although they differed in the extent of glucuronide conversion. This aspect is crucial for understanding how compounds are metabolized and how their bioavailability and efficacy might be affected in a real-world scenario. In summary, this research from Wageningen University demonstrates the utility of apical-out enteroids in studying the interactions between bioactive food compounds and the mucosal epithelium. The findings suggest that the mucus layer plays a significant role in these interactions, influencing both the cytotoxicity and cell viability of the compounds tested. This study not only advances our understanding of gut health but also opens new avenues for the development of targeted antimicrobial therapies using prenylated phenolics.

MedicineHealthBiochem

References

Main Study

1) Biotransformation and Epithelial Toxicity of Prenylated Phenolics from Licorice Roots (Glycyrrhiza spp.) in 3D Apical-Out Mucus-Producing Human Enteroids.

Published 6th September, 2024

https://doi.org/10.1021/acs.jafc.4c03120

Related Studies

2) The gastrointestinal mucus system in health and disease.

https://doi.org/10.1038/nrgastro.2013.35

3) Mucins in the mucosal barrier to infection.

https://doi.org/10.1038/mi.2008.5

4) Dynamic responses in small intestinal mucus: Relevance for the maintenance of an intact barrier.

https://doi.org/10.1016/j.ejpb.2015.01.024


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