Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory eff...

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Main Authors: Francesca Truzzi, Anne Whittaker, Eros D’Amen, Camilla Tibaldi, Antonella Abate, Maria Chiara Valerii, Enzo Spisni, Giovanni Dinelli
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/11/3425
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author Francesca Truzzi
Anne Whittaker
Eros D’Amen
Camilla Tibaldi
Antonella Abate
Maria Chiara Valerii
Enzo Spisni
Giovanni Dinelli
author_facet Francesca Truzzi
Anne Whittaker
Eros D’Amen
Camilla Tibaldi
Antonella Abate
Maria Chiara Valerii
Enzo Spisni
Giovanni Dinelli
author_sort Francesca Truzzi
collection DOAJ
description Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.
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spelling doaj.art-710d880ae52140a2bd32f749591cb4c92023-11-23T14:28:32ZengMDPI AGMolecules1420-30492022-05-012711342510.3390/molecules27113425Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral InfectionsFrancesca Truzzi0Anne Whittaker1Eros D’Amen2Camilla Tibaldi3Antonella Abate4Maria Chiara Valerii5Enzo Spisni6Giovanni Dinelli7Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyDepartment of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, 40127 Bologna, ItalyImpaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.https://www.mdpi.com/1420-3049/27/11/3425SARS-CoV-2spermidineeugenolautophagyinflammationhuman cell lines
spellingShingle Francesca Truzzi
Anne Whittaker
Eros D’Amen
Camilla Tibaldi
Antonella Abate
Maria Chiara Valerii
Enzo Spisni
Giovanni Dinelli
Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections
Molecules
SARS-CoV-2
spermidine
eugenol
autophagy
inflammation
human cell lines
title Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections
title_full Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections
title_fullStr Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections
title_full_unstemmed Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections
title_short Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections
title_sort wheat germ spermidine and clove eugenol in combination stimulate autophagy in vitro showing potential in supporting the immune system against viral infections
topic SARS-CoV-2
spermidine
eugenol
autophagy
inflammation
human cell lines
url https://www.mdpi.com/1420-3049/27/11/3425
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