Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway

Redox status and inflammation are related to the pathogenesis of the majority of diseases. Therefore, understanding the role of specific food-derived molecules in the regulation of their specific pathways is a relevant issue. Our previous studies indicated that <b>K-8-K</b> and <b>...

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Main Authors: Federica Tonolo, Alessandra Folda, Valeria Scalcon, Oriano Marin, Alberto Bindoli, Maria Pia Rigobello
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/8/4382
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author Federica Tonolo
Alessandra Folda
Valeria Scalcon
Oriano Marin
Alberto Bindoli
Maria Pia Rigobello
author_facet Federica Tonolo
Alessandra Folda
Valeria Scalcon
Oriano Marin
Alberto Bindoli
Maria Pia Rigobello
author_sort Federica Tonolo
collection DOAJ
description Redox status and inflammation are related to the pathogenesis of the majority of diseases. Therefore, understanding the role of specific food-derived molecules in the regulation of their specific pathways is a relevant issue. Our previous studies indicated that <b>K-8-K</b> and <b>S-10-S</b>, milk and soy-derived bioactive peptides, respectively, exert antioxidant effects through activation of the Keap1/Nrf2 pathway. A crosstalk between Nrf2 and NF-κB, mediated by the action of heme oxygenase (HO-1), is well known. On this basis, we studied if these peptides, in addition to their antioxidant activity, could exert anti-inflammatory effects in human cells. First, we observed an increase of HO-1 expression in Caco-2 cells treated with <b>K-8-K</b> and <b>S-10-S</b>, following the activation of the Keap1/Nrf2 pathway. Moreover, when cells are treated with the two peptides and stimulated by TNF-α, the levels of NF-κB in the nucleus decreased in comparison with TNF-α alone. In the same conditions, we observed the downregulation of the gene expression of proinflammatory cytokines (<i>IL1B</i>, <i>IL6</i>, and <i>TNF</i>), while the anti-inflammatory cytokine gene, <i>IL1RN</i>, was upregulated in Caco-2 cells processed as reported above. Then, when the cells were pretreated with the two peptides and stimulated with LPS, a different proinflammatory factor, (TNF-α) was estimated to have a lower secretion in the supernatant of cells. In conclusion, these observations confirmed that Nrf2-activating bioactive peptides, <b>K-8-K</b> and <b>S-10-S</b>, exerted anti-inflammatory effects by inhibiting the NF-κB pathway.
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spelling doaj.art-06b2d6a88c444fad83be070bfd7ecf382023-12-01T21:04:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238438210.3390/ijms23084382Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB PathwayFederica Tonolo0Alessandra Folda1Valeria Scalcon2Oriano Marin3Alberto Bindoli4Maria Pia Rigobello5Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/b, 35131 Padova, ItalyInstitute of Neuroscience, CNR, Via G Colombo 3, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/b, 35131 Padova, ItalyRedox status and inflammation are related to the pathogenesis of the majority of diseases. Therefore, understanding the role of specific food-derived molecules in the regulation of their specific pathways is a relevant issue. Our previous studies indicated that <b>K-8-K</b> and <b>S-10-S</b>, milk and soy-derived bioactive peptides, respectively, exert antioxidant effects through activation of the Keap1/Nrf2 pathway. A crosstalk between Nrf2 and NF-κB, mediated by the action of heme oxygenase (HO-1), is well known. On this basis, we studied if these peptides, in addition to their antioxidant activity, could exert anti-inflammatory effects in human cells. First, we observed an increase of HO-1 expression in Caco-2 cells treated with <b>K-8-K</b> and <b>S-10-S</b>, following the activation of the Keap1/Nrf2 pathway. Moreover, when cells are treated with the two peptides and stimulated by TNF-α, the levels of NF-κB in the nucleus decreased in comparison with TNF-α alone. In the same conditions, we observed the downregulation of the gene expression of proinflammatory cytokines (<i>IL1B</i>, <i>IL6</i>, and <i>TNF</i>), while the anti-inflammatory cytokine gene, <i>IL1RN</i>, was upregulated in Caco-2 cells processed as reported above. Then, when the cells were pretreated with the two peptides and stimulated with LPS, a different proinflammatory factor, (TNF-α) was estimated to have a lower secretion in the supernatant of cells. In conclusion, these observations confirmed that Nrf2-activating bioactive peptides, <b>K-8-K</b> and <b>S-10-S</b>, exerted anti-inflammatory effects by inhibiting the NF-κB pathway.https://www.mdpi.com/1422-0067/23/8/4382bioactive peptidesantioxidantanti-inflammatoryNrf2NF-κB
spellingShingle Federica Tonolo
Alessandra Folda
Valeria Scalcon
Oriano Marin
Alberto Bindoli
Maria Pia Rigobello
Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
International Journal of Molecular Sciences
bioactive peptides
antioxidant
anti-inflammatory
Nrf2
NF-κB
title Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
title_full Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
title_fullStr Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
title_full_unstemmed Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
title_short Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
title_sort nrf2 activating bioactive peptides exert anti inflammatory activity through inhibition of the nf κb pathway
topic bioactive peptides
antioxidant
anti-inflammatory
Nrf2
NF-κB
url https://www.mdpi.com/1422-0067/23/8/4382
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