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

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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.

Original languageEnglish
Article number106283
Number of pages17
JournalPharmacological Research
Volume182
Early online date1 Jun 2022
DOIs
Publication statusPublished - 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

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