A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease

Anella Saviano; Anna Schettino; Nunzia Iaccarino; Adel Abo Mansour; Jenefa Begum; Noemi Marigliano; Federica Raucci; Francesca Romano; Gelsomina Riccardi; Emma Mitidieri; Roberta d'Emmanuele di Villa Bianca; Ivana Bello; Elisabetta Panza; Martina Smimmo; Valentina Vellecco; Peter Rimmer; Jonathan Cheesbrough; Zhaogong Zhi; Tariq H Iqbal; Stefano Pieretti; Vincenzo Maria D'Amore; Luciana Marinelli; Valeria La Pietra; Raffaella Sorrentino; Luisa Costa; Francesco Caso; Raffaele Scarpa; Giuseppe Cirino; Antonio Randazzo; Mariarosaria Bucci; Helen Michelle McGettrick; Asif Jilani Iqbal; Francesco Maione

doi:10.1016/j.jaut.2024.103181

A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease

Anella Saviano, Anna Schettino, Nunzia Iaccarino, Adel Abo Mansour, Jenefa Begum, Noemi Marigliano, Federica Raucci, Francesca Romano, Gelsomina Riccardi, Emma Mitidieri, Roberta d'Emmanuele di Villa Bianca, Ivana Bello, Elisabetta Panza, Martina Smimmo, Valentina Vellecco, Peter Rimmer, Jonathan Cheesbrough, Zhaogong Zhi, Tariq H Iqbal, Stefano PierettiVincenzo Maria D'Amore, Luciana Marinelli, Valeria La Pietra, Raffaella Sorrentino, Luisa Costa, Francesco Caso, Raffaele Scarpa, Giuseppe Cirino, Antonio Randazzo, Mariarosaria Bucci, Helen Michelle McGettrick, Asif Jilani Iqbal^*, Francesco Maione^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.

Original language	English
Article number	103181
Number of pages	20
Journal	Journal of Autoimmunity
Volume	144
Early online date	23 Mar 2024
DOIs	https://doi.org/10.1016/j.jaut.2024.103181
Publication status	Published - Apr 2024

Bibliographical note

Funding and acknowledgements:
This research has been in part supported by The National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (NIHR203326). This work was also supported by a Medical Research Council project grant MR/T028025/1. A.Sa. is supported by Dompé farmaceutici S.p.A fellowship for PhD program in "Nutraceuticals, functional foods and human health” (University of Naples Federico II), whereas A.Sc. is supported by University of Naples Federico II PhD scholarship in “Nutraceuticals, functional foods and human health” (PNRR DM 118 M4C1– INV 4.1 ricerca PNRR generici). I.B is supported by University of Naples Federico II PhD scholarship in “Nutraceuticals, functional foods and human health”, whereas M.S. is supported by the University of Naples Federico II PhD scholarship in Pharmaceutical Sciences. A.J.I. was supported by Birmingham Fellowship. A.A.M. was supported by a King Khalid University funded PhD Scholarship (57875). The opinions expressed in this paper are those of the authors and do not represent any of the listed organisations. The authors would like to thank L.C.M. Trading S.p.A. (Italy) for excellent technical assistance and scientific discussions on the manuscript. The views expressed in this publication are those of the author(s) and not necessarily those of the L.C.M. Trading S.p.A. and Dompé farmaceutici S.p.A.

Copyright:
© 2024 Elsevier Ltd. All rights reserved.

Keywords

CD4+CD45RBhigh colitis
Functional food
IBD
Mangifera indica L.
Nutraceuticals
Th17
Treg

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Saviano, A., Schettino, A., Iaccarino, N., Abo Mansour, A., Begum, J., Marigliano, N., Raucci, F., Romano, F., Riccardi, G., Mitidieri, E., d'Emmanuele di Villa Bianca, R., Bello, I., Panza, E., Smimmo, M., Vellecco, V., Rimmer, P., Cheesbrough, J., Zhi, Z., Iqbal, T. H., ... Maione, F. (2024). A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease. Journal of Autoimmunity, 144, Article 103181. https://doi.org/10.1016/j.jaut.2024.103181

@article{0a48e1cf7b1a4e588269459cd70d1e31,

title = "A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease",

abstract = "Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.",

keywords = "CD4+CD45RBhigh colitis, Functional food, IBD, Mangifera indica L., Nutraceuticals, Th17, Treg",

author = "Anella Saviano and Anna Schettino and Nunzia Iaccarino and {Abo Mansour}, Adel and Jenefa Begum and Noemi Marigliano and Federica Raucci and Francesca Romano and Gelsomina Riccardi and Emma Mitidieri and {d'Emmanuele di Villa Bianca}, Roberta and Ivana Bello and Elisabetta Panza and Martina Smimmo and Valentina Vellecco and Peter Rimmer and Jonathan Cheesbrough and Zhaogong Zhi and Iqbal, {Tariq H} and Stefano Pieretti and D'Amore, {Vincenzo Maria} and Luciana Marinelli and {La Pietra}, Valeria and Raffaella Sorrentino and Luisa Costa and Francesco Caso and Raffaele Scarpa and Giuseppe Cirino and Antonio Randazzo and Mariarosaria Bucci and McGettrick, {Helen Michelle} and Iqbal, {Asif Jilani} and Francesco Maione",

note = "Funding and acknowledgements: This research has been in part supported by The National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (NIHR203326). This work was also supported by a Medical Research Council project grant MR/T028025/1. A.Sa. is supported by Domp{\'e} farmaceutici S.p.A fellowship for PhD program in {"}Nutraceuticals, functional foods and human health” (University of Naples Federico II), whereas A.Sc. is supported by University of Naples Federico II PhD scholarship in “Nutraceuticals, functional foods and human health” (PNRR DM 118 M4C1– INV 4.1 ricerca PNRR generici). I.B is supported by University of Naples Federico II PhD scholarship in “Nutraceuticals, functional foods and human health”, whereas M.S. is supported by the University of Naples Federico II PhD scholarship in Pharmaceutical Sciences. A.J.I. was supported by Birmingham Fellowship. A.A.M. was supported by a King Khalid University funded PhD Scholarship (57875). The opinions expressed in this paper are those of the authors and do not represent any of the listed organisations. The authors would like to thank L.C.M. Trading S.p.A. (Italy) for excellent technical assistance and scientific discussions on the manuscript. The views expressed in this publication are those of the author(s) and not necessarily those of the L.C.M. Trading S.p.A. and Domp{\'e} farmaceutici S.p.A. Copyright: {\textcopyright} 2024 Elsevier Ltd. All rights reserved.",

year = "2024",

month = apr,

doi = "10.1016/j.jaut.2024.103181",

language = "English",

volume = "144",

journal = "Journal of Autoimmunity",

issn = "0896-8411",

publisher = "Elsevier",

}

Saviano, A, Schettino, A, Iaccarino, N, Abo Mansour, A, Begum, J, Marigliano, N, Raucci, F, Romano, F, Riccardi, G, Mitidieri, E, d'Emmanuele di Villa Bianca, R, Bello, I, Panza, E, Smimmo, M, Vellecco, V, Rimmer, P, Cheesbrough, J, Zhi, Z, Iqbal, TH, Pieretti, S, D'Amore, VM, Marinelli, L, La Pietra, V, Sorrentino, R, Costa, L, Caso, F, Scarpa, R, Cirino, G, Randazzo, A, Bucci, M, McGettrick, HM , Iqbal, AJ & Maione, F 2024, 'A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease', Journal of Autoimmunity, vol. 144, 103181. https://doi.org/10.1016/j.jaut.2024.103181

TY - JOUR

T1 - A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease

AU - Saviano, Anella

AU - Schettino, Anna

AU - Iaccarino, Nunzia

AU - Abo Mansour, Adel

AU - Begum, Jenefa

AU - Marigliano, Noemi

AU - Raucci, Federica

AU - Romano, Francesca

AU - Riccardi, Gelsomina

AU - Mitidieri, Emma

AU - d'Emmanuele di Villa Bianca, Roberta

AU - Bello, Ivana

AU - Panza, Elisabetta

AU - Smimmo, Martina

AU - Vellecco, Valentina

AU - Rimmer, Peter

AU - Cheesbrough, Jonathan

AU - Zhi, Zhaogong

AU - Iqbal, Tariq H

AU - Pieretti, Stefano

AU - D'Amore, Vincenzo Maria

AU - Marinelli, Luciana

AU - La Pietra, Valeria

AU - Sorrentino, Raffaella

AU - Costa, Luisa

AU - Caso, Francesco

AU - Scarpa, Raffaele

AU - Cirino, Giuseppe

AU - Randazzo, Antonio

AU - Bucci, Mariarosaria

AU - McGettrick, Helen Michelle

AU - Iqbal, Asif Jilani

AU - Maione, Francesco

N1 - Funding and acknowledgements: This research has been in part supported by The National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (NIHR203326). This work was also supported by a Medical Research Council project grant MR/T028025/1. A.Sa. is supported by Dompé farmaceutici S.p.A fellowship for PhD program in "Nutraceuticals, functional foods and human health” (University of Naples Federico II), whereas A.Sc. is supported by University of Naples Federico II PhD scholarship in “Nutraceuticals, functional foods and human health” (PNRR DM 118 M4C1– INV 4.1 ricerca PNRR generici). I.B is supported by University of Naples Federico II PhD scholarship in “Nutraceuticals, functional foods and human health”, whereas M.S. is supported by the University of Naples Federico II PhD scholarship in Pharmaceutical Sciences. A.J.I. was supported by Birmingham Fellowship. A.A.M. was supported by a King Khalid University funded PhD Scholarship (57875). The opinions expressed in this paper are those of the authors and do not represent any of the listed organisations. The authors would like to thank L.C.M. Trading S.p.A. (Italy) for excellent technical assistance and scientific discussions on the manuscript. The views expressed in this publication are those of the author(s) and not necessarily those of the L.C.M. Trading S.p.A. and Dompé farmaceutici S.p.A. Copyright: © 2024 Elsevier Ltd. All rights reserved.

PY - 2024/4

Y1 - 2024/4

N2 - Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.

AB - Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.

KW - CD4+CD45RBhigh colitis

KW - Functional food

KW - IBD

KW - Mangifera indica L.

KW - Nutraceuticals

KW - Th17

KW - Treg

U2 - 10.1016/j.jaut.2024.103181

DO - 10.1016/j.jaut.2024.103181

M3 - Article

C2 - 38522129

SN - 0896-8411

VL - 144

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

M1 - 103181

ER -

A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease

Abstract

Bibliographical note

Keywords

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New therapeutic avenues in arthritis: exploring the role of PEPITEM in RA

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