Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio

Anella Saviano; Federica Raucci; Gian Marco Casillo; Adel Abo Mansour; Vincenzo Piccolo; Camilla Montesano; Martina Smimmo; Valentina Vellecco; Gennaro Capasso; Amedeo Boscaino; Vincenzo Summa; Nicola Mascolo; Asif Jilani Iqbal; Raffaella Sorrentino; Roberta d'Emmanuele di Villa Bianca; Mariarosaria Bucci; Vincenzo Brancaleone; Francesco Maione

doi:10.1016/j.phrs.2022.106283

Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio

Anella Saviano, Federica Raucci, Gian Marco Casillo, Adel Abo Mansour, Vincenzo Piccolo, Camilla Montesano, Martina Smimmo, Valentina Vellecco, Gennaro Capasso, Amedeo Boscaino, Vincenzo Summa, Nicola Mascolo, Asif Jilani Iqbal, Raffaella Sorrentino, Roberta d'Emmanuele di Villa Bianca, Mariarosaria Bucci, Vincenzo Brancaleone, Francesco Maione

Cardiovascular Sciences

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

39 Downloads (Pure)

Abstract

In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity.

Gouty arthritis was induced by the intra-articular administration of MSU crystals (200 μg 20 µl^-1), whereas MIE (0.1-10 mg kg^-1) or corresponding vehicle (DMSO/saline 1:3) were orally administrated concomitantly with MSU (time 0), 6 and 12 h after the stimulus. Thereafter, knee joint score and oedema were evaluated in addition to western blot analysis for COX-2/mPGES-1 axis. Moreover, the analysis of pro/anti-inflammatory cyto-chemokines coupled with the phenotyping of the cellular infiltrate was performed.

Treatment with MIE revealed a dose-dependent reduction in joint inflammatory scores with maximal inhibition observed at 10 mg kg^-1. MIE significantly reduced leukocyte infiltration and activation and the expression of different pro-inflammatory cyto-chemokines in inflamed tissues. Furthermore, biochemical analysis revealed that MIE modulated COX-2/mPGES-1 and mPGDS-1/PPARγ pathways. Flow cytometry analysis also highlighted a prominent modulation of inflammatory monocytes (CD11b⁺/CD115⁺/LY6C^hi), and Treg cells (CD4⁺/CD25⁺/FOXP3⁺) after MIE treatment.

Collectively, the results of this study demonstrate a novel function of MIE to positively affect the local and systemic inflammatory/immunological perturbance in the onset and progression of gouty arthritis.

Original language	English
Article number	106283
Number of pages	17
Journal	Pharmacological Research
Volume	182
Early online date	1 Jun 2022
DOIs	https://doi.org/10.1016/j.phrs.2022.106283
Publication status	Published - Aug 2022

Bibliographical note

Funding Information:
This work was supported by MIUR (PRIN 2017; 2017,A95NCJ/2017A95NCJ_002 , “Stolen molecules - Stealing natural products from the depot and reselling them as new drug candidates”). A.J.I. is supported by Birmingham Fellowship. A.A.M. is supported by King Khalid University funded scholarship ( 57875 ). F.R. and M.S. are supported by the University of Naples Federico II PhD scholarship in Pharmaceutical Sciences whereas A.S. and V.P. are supported by Dompé Farmaceutici S.p.A fellowship for PhD program in "Nutraceuticals, functional foods and human health" (University of Naples Federico II).

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

Gouty arthritis
Inflammatory monocytes
Mangiferin
MPGES-1
PPARγ
Th17/Treg
sodium chloride (PubChem CID: 5234)
sodium urate (PubChem CID: 23697816)
deuterated dimethyl sulfoxide (PubChem CID: 75151)
ethanol (PubChem CID: 702)
mangiferin (PubChem CID: 5281647)
dimethyl sulfoxide (PubChem CID: 679)
phosphate-buffered saline (PubChem CID: 24978514)
Benzoic acid (PubChem CID: 243)
EDTA (PubChem CID: 6049)

ASJC Scopus subject areas

Pharmacology

Access to Document

10.1016/j.phrs.2022.106283Licence: None: All rights reserved

savianoa2022antiinflammatoryAccepted author manuscript, 10.4 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

Cite this

Saviano, A., Raucci, F., Casillo, G. M., Mansour, A. A., Piccolo, V., Montesano, C., Smimmo, M., Vellecco, V., Capasso, G., Boscaino, A., Summa, V., Mascolo, N., Iqbal, A. J., Sorrentino, R., d'Emmanuele di Villa Bianca, R., Bucci, M., Brancaleone, V., & Maione, F. (2022). Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio. Pharmacological Research, 182, Article 106283. https://doi.org/10.1016/j.phrs.2022.106283

@article{09b1d9ec40a0478699a0c6fff032fd0b,

title = "Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio",

abstract = "In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity. Gouty arthritis was induced by the intra-articular administration of MSU crystals (200 μg 20 µl-1), whereas MIE (0.1-10 mg kg-1) or corresponding vehicle (DMSO/saline 1:3) were orally administrated concomitantly with MSU (time 0), 6 and 12 h after the stimulus. Thereafter, knee joint score and oedema were evaluated in addition to western blot analysis for COX-2/mPGES-1 axis. Moreover, the analysis of pro/anti-inflammatory cyto-chemokines coupled with the phenotyping of the cellular infiltrate was performed. Treatment with MIE revealed a dose-dependent reduction in joint inflammatory scores with maximal inhibition observed at 10 mg kg-1. MIE significantly reduced leukocyte infiltration and activation and the expression of different pro-inflammatory cyto-chemokines in inflamed tissues. Furthermore, biochemical analysis revealed that MIE modulated COX-2/mPGES-1 and mPGDS-1/PPARγ pathways. Flow cytometry analysis also highlighted a prominent modulation of inflammatory monocytes (CD11b+/CD115+/LY6Chi), and Treg cells (CD4+/CD25+/FOXP3+) after MIE treatment. Collectively, the results of this study demonstrate a novel function of MIE to positively affect the local and systemic inflammatory/immunological perturbance in the onset and progression of gouty arthritis. ",

keywords = "Gouty arthritis, Inflammatory monocytes, Mangiferin, MPGES-1, PPARγ, Th17/Treg, sodium chloride (PubChem CID: 5234), sodium urate (PubChem CID: 23697816), deuterated dimethyl sulfoxide (PubChem CID: 75151), ethanol (PubChem CID: 702), mangiferin (PubChem CID: 5281647), dimethyl sulfoxide (PubChem CID: 679), phosphate-buffered saline (PubChem CID: 24978514), Benzoic acid (PubChem CID: 243), EDTA (PubChem CID: 6049)",

author = "Anella Saviano and Federica Raucci and Casillo, {Gian Marco} and Mansour, {Adel Abo} and Vincenzo Piccolo and Camilla Montesano and Martina Smimmo and Valentina Vellecco and Gennaro Capasso and Amedeo Boscaino and Vincenzo Summa and Nicola Mascolo and Iqbal, {Asif Jilani} and Raffaella Sorrentino and {d'Emmanuele di Villa Bianca}, Roberta and Mariarosaria Bucci and Vincenzo Brancaleone and Francesco Maione",

note = "Funding Information: This work was supported by MIUR (PRIN 2017; 2017,A95NCJ/2017A95NCJ_002 , “Stolen molecules - Stealing natural products from the depot and reselling them as new drug candidates”). A.J.I. is supported by Birmingham Fellowship. A.A.M. is supported by King Khalid University funded scholarship ( 57875 ). F.R. and M.S. are supported by the University of Naples Federico II PhD scholarship in Pharmaceutical Sciences whereas A.S. and V.P. are supported by Domp{\'e} Farmaceutici S.p.A fellowship for PhD program in {"}Nutraceuticals, functional foods and human health{"} (University of Naples Federico II). Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = aug,

doi = "10.1016/j.phrs.2022.106283",

language = "English",

volume = "182",

journal = "Pharmacological Research",

issn = "1043-6618",

publisher = "Elsevier",

}

Saviano, A, Raucci, F, Casillo, GM, Mansour, AA, Piccolo, V, Montesano, C, Smimmo, M, Vellecco, V, Capasso, G, Boscaino, A, Summa, V, Mascolo, N, Iqbal, AJ, Sorrentino, R, d'Emmanuele di Villa Bianca, R, Bucci, M, Brancaleone, V & Maione, F 2022, 'Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio', Pharmacological Research, vol. 182, 106283. https://doi.org/10.1016/j.phrs.2022.106283

TY - JOUR

T1 - Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio

AU - Saviano, Anella

AU - Raucci, Federica

AU - Casillo, Gian Marco

AU - Mansour, Adel Abo

AU - Piccolo, Vincenzo

AU - Montesano, Camilla

AU - Smimmo, Martina

AU - Vellecco, Valentina

AU - Capasso, Gennaro

AU - Boscaino, Amedeo

AU - Summa, Vincenzo

AU - Mascolo, Nicola

AU - Iqbal, Asif Jilani

AU - Sorrentino, Raffaella

AU - d'Emmanuele di Villa Bianca, Roberta

AU - Bucci, Mariarosaria

AU - Brancaleone, Vincenzo

AU - Maione, Francesco

N1 - Funding Information: This work was supported by MIUR (PRIN 2017; 2017,A95NCJ/2017A95NCJ_002 , “Stolen molecules - Stealing natural products from the depot and reselling them as new drug candidates”). A.J.I. is supported by Birmingham Fellowship. A.A.M. is supported by King Khalid University funded scholarship ( 57875 ). F.R. and M.S. are supported by the University of Naples Federico II PhD scholarship in Pharmaceutical Sciences whereas A.S. and V.P. are supported by Dompé Farmaceutici S.p.A fellowship for PhD program in "Nutraceuticals, functional foods and human health" (University of Naples Federico II). Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/8

Y1 - 2022/8

N2 - In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity. Gouty arthritis was induced by the intra-articular administration of MSU crystals (200 μg 20 µl-1), whereas MIE (0.1-10 mg kg-1) or corresponding vehicle (DMSO/saline 1:3) were orally administrated concomitantly with MSU (time 0), 6 and 12 h after the stimulus. Thereafter, knee joint score and oedema were evaluated in addition to western blot analysis for COX-2/mPGES-1 axis. Moreover, the analysis of pro/anti-inflammatory cyto-chemokines coupled with the phenotyping of the cellular infiltrate was performed. Treatment with MIE revealed a dose-dependent reduction in joint inflammatory scores with maximal inhibition observed at 10 mg kg-1. MIE significantly reduced leukocyte infiltration and activation and the expression of different pro-inflammatory cyto-chemokines in inflamed tissues. Furthermore, biochemical analysis revealed that MIE modulated COX-2/mPGES-1 and mPGDS-1/PPARγ pathways. Flow cytometry analysis also highlighted a prominent modulation of inflammatory monocytes (CD11b+/CD115+/LY6Chi), and Treg cells (CD4+/CD25+/FOXP3+) after MIE treatment. Collectively, the results of this study demonstrate a novel function of MIE to positively affect the local and systemic inflammatory/immunological perturbance in the onset and progression of gouty arthritis.

AB - In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity. Gouty arthritis was induced by the intra-articular administration of MSU crystals (200 μg 20 µl-1), whereas MIE (0.1-10 mg kg-1) or corresponding vehicle (DMSO/saline 1:3) were orally administrated concomitantly with MSU (time 0), 6 and 12 h after the stimulus. Thereafter, knee joint score and oedema were evaluated in addition to western blot analysis for COX-2/mPGES-1 axis. Moreover, the analysis of pro/anti-inflammatory cyto-chemokines coupled with the phenotyping of the cellular infiltrate was performed. Treatment with MIE revealed a dose-dependent reduction in joint inflammatory scores with maximal inhibition observed at 10 mg kg-1. MIE significantly reduced leukocyte infiltration and activation and the expression of different pro-inflammatory cyto-chemokines in inflamed tissues. Furthermore, biochemical analysis revealed that MIE modulated COX-2/mPGES-1 and mPGDS-1/PPARγ pathways. Flow cytometry analysis also highlighted a prominent modulation of inflammatory monocytes (CD11b+/CD115+/LY6Chi), and Treg cells (CD4+/CD25+/FOXP3+) after MIE treatment. Collectively, the results of this study demonstrate a novel function of MIE to positively affect the local and systemic inflammatory/immunological perturbance in the onset and progression of gouty arthritis.

KW - Gouty arthritis

KW - Inflammatory monocytes

KW - Mangiferin

KW - MPGES-1

KW - PPARγ

KW - Th17/Treg

KW - sodium chloride (PubChem CID: 5234)

KW - sodium urate (PubChem CID: 23697816)

KW - deuterated dimethyl sulfoxide (PubChem CID: 75151)

KW - ethanol (PubChem CID: 702)

KW - mangiferin (PubChem CID: 5281647)

KW - dimethyl sulfoxide (PubChem CID: 679)

KW - phosphate-buffered saline (PubChem CID: 24978514)

KW - Benzoic acid (PubChem CID: 243)

KW - EDTA (PubChem CID: 6049)

UR - http://www.scopus.com/inward/record.url?scp=85133282166&partnerID=8YFLogxK

U2 - 10.1016/j.phrs.2022.106283

DO - 10.1016/j.phrs.2022.106283

M3 - Article

C2 - 35662629

SN - 1043-6618

VL - 182

JO - Pharmacological Research

JF - Pharmacological Research

M1 - 106283

ER -

Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this