Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells

Tocmo, R. ORCID: https://orcid.org/0009-0007-4850-977X, Le, B. ORCID: https://orcid.org/0000-0002-5908-0215, Heun, A., van Pijkeren, J. P., Parkin, K. and Johnson, J. J. ORCID: https://orcid.org/0000-0001-5489-2372 (2021) Prenylated xanthones from mangosteen (Garcinia mangostana) activate the AhR and Nrf2 pathways and protect intestinal barrier integrity in HT-29 cells. Free Radical Biology and Medicine, 163. pp. 102-115. ISSN 1873-4596 doi: 10.1016/j.freeradbiomed.2020.11.018

Abstract/Summary

Xanthones from the tropical fruit mangosteen (Garcinia mangostana) display anti-inflammatory and anti-oxidative activities. Here, we isolate and identify potential inducers of the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways from mangosteen using a bioassay-guided strategy. Mangosteen fruit pericarp extracts were subjected to sequential solvent extractions, followed by chromatography coupled with NMR spectroscopy and mass spectrometric analyses for identification and isolation of pure compounds. Isolation of active fractions led to seven prenylated xanthones that were identified and subsequently evaluated for bioactivity. In vitro luciferase reporter cellular assays using H1L6.1c3 (AhR induction) and HepG2-ARE (Nrf2 induction) were used to identify AhR and Nrf2 activators. All seven prenylated xanthones displayed AhR inducing activity, whereas only five xanthones activated Nrf2. Garcinone D (GarD) significantly upregulated AhR/Cyp1a1 and Nrf2/HO-1 protein expression and enhanced zonula occludens-1 and occludin protein levels in HT-29 cells. In addition, GarD inhibited oxidative stress-induced intestinal epithelial barrier dysfunction by enhancing tight junction (TJ) proteins and inhibition of reactive oxygen species production. Inhibition of AhR by pretreating cells with an AhR antagonist revealed that the AhR pathway is required for the improved epithelial barrier functions of GarD. These results highlight a dual mechanism by GarD that confers protection against intestinal epithelial barrier dysfunction.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/117214
Identification Number/DOI	10.1016/j.freeradbiomed.2020.11.018
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
Publisher	Elsevier
Download/View statistics	View download statistics for this item