Cellular assays combined with metabolomics highlight the dual face of phenolics: From high permeability to morphological cell damage

Gabriele Rocchetti; Luigi Lucini; José Eduardo Gonçalves; Ihosvany Camps; Amanda Dos Santos Lima; Daniel Granato; Lucas Cezar Pinheiro; Luciana Azevedo

doi:10.1016/j.foodchem.2023.137081

Cellular assays combined with metabolomics highlight the dual face of phenolics: From high permeability to morphological cell damage

Food Chem. 2024 Jan 1:430:137081. doi: 10.1016/j.foodchem.2023.137081. Epub 2023 Aug 4.

Authors

Gabriele Rocchetti¹, Luigi Lucini², José Eduardo Gonçalves³, Ihosvany Camps⁴, Amanda Dos Santos Lima⁵, Daniel Granato⁶, Lucas Cezar Pinheiro⁷, Luciana Azevedo⁸

Affiliations

¹ Department of Animal Science, Food and Nutrition, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy. Electronic address: gabriele.rocchetti@unicatt.it.
² Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy. Electronic address: luigi.lucini@unicatt.it.
³ Department of Pharmaceutical Products, College of Pharmacy, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, MG, Brazil.
⁴ Department of Physics, Federal University of Alfenas, Av. Jovino Fernandes Sales, 2600, Santa Clara, Alfenas, 37133-840 Minas Gerais, Brazil. Electronic address: icamps@unifal-mg.edu.br.
⁵ Faculty of Nutrition, LANTIN (Laboratory of Nutritional and Toxicological Analyses in vitro and in vivo), Federal University of Alfenas, R. Gabriel Monteiro da Silva, 700, Alfenas, 37130-001 Minas Gerais, Brazil.
⁶ Department of Biological Sciences, Faculty of Science and Engineering, University of Limerick, Faculty of Science and Engineering, V94 T9PX Limerick, Ireland. Electronic address: daniel.granato@ul.ie.
⁷ Department of Pharmacology, Bioactivity & Applications Lab, Universidade Federal de Santa Catarina, R. Eng. Agronômico Andrei Cristian Ferreira, Florianópolis, Santa Catarina, Brazil.
⁸ Faculty of Nutrition, LANTIN (Laboratory of Nutritional and Toxicological Analyses in vitro and in vivo), Federal University of Alfenas, R. Gabriel Monteiro da Silva, 700, Alfenas, 37130-001 Minas Gerais, Brazil. Electronic address: gabriele.rocchetti@unicatt.it.

PMID: 37557028
DOI: 10.1016/j.foodchem.2023.137081

Abstract

The Caco-2 cellular permeability of phenolic aqueous extracts from blackcurrant press cake (BC), Norway spruce bark (NS), scots pine bark (SP), and sea buckthorn leaves (SB) was evaluated by combining high-resolution mass spectrometry and atomic force microscopy. Besides, Caco-2 and HepG2 cells allowed the study of intracellular oxidative stress assessed in both apical and basolateral domains. Overall, BC and NS showed the highest total phenolic contents, 4.38 and 3.76 µg/mL, respectively. Multivariate statistics discriminated NS and BC from SP and SB extracts because of their phenolic profile. Polyphenols were classified as highly permeable, thus suggesting their potentially high bioavailability through the gastrointestinal tract. All the phenolic subclasses showed efflux ratio values < 1, except for BC flavonols, flavan-3-ols, and stilbenes. Regarding cellular damage, NS and BC extracts, when acting on the basolateral cellular side, caused epithelial leakage and morphological shape cell damage on Caco-2 cells associated with ROS production.

Keywords: Cellular assays; Industrial by-products; Metabolomics; Permeability; Polyphenols.

MeSH terms

Caco-2 Cells
Humans
Metabolomics
Permeability
Phenols* / analysis
Plant Extracts / chemistry
Polyphenols* / analysis

Substances

Phenols
Polyphenols
Plant Extracts