Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio. (August 2022)

• Record Type: Journal Article
• Authors: Saviano, Anella; Raucci, Federica; Casillo, Gian Marco; Mansour, Adel Abo; Piccolo, Vincenzo; Montesano, Camilla; Smimmo, Martina; Vellecco, Valentina; Capasso, Gennaro; Boscaino, Amedeo; Summa, Vincenzo; Mascolo, Nicola; Iqbal, Asif Jilani; Sorrentino, Raffaella; d'Emmanuele di Villa Bianca, Roberta; Bucci, Mariarosaria; Brancaleone, Vincenzo; Maione, Francesco
• Is Part Of: Pharmacological research. Volume 182(2022)
• Publication Date: 2022-08
• Subjects: BLC B lymphocyte chemoattractant -- C5a component 5a -- Ctrl control -- 15d-PGJ2 15-deoxy-Delta12, 14PGJ2 -- DMSO-d6 deuterated dimethyl sulfoxide -- G-CSF granulocyte-colony stimulating factor -- GM-CSF granulocyte macrophage-colony stimulating factor -- H&E haematoxylin and eosin -- INF-γ interferon-γ -- IP-10 interferon-γ-induced protein-10 -- IS internal standard -- I-TAC interferon-inducible T cell α chemoattractant -- JE junctional epithelium -- KC keratinocyte chemoattractant -- LN lupus nephritis -- 5-LOX 5-lipoxygenase -- LTs leukotrienes -- MCP-5 monocytes chemoattractant protein-5 -- M-CSF macrophage-colony stimulating factor -- MIE Mangifera indica extract -- MIG monokine induced by interferon-γ -- MIP macrophage inflammatory protein -- mPGDS-1 microsomal prostaglandin D synthase-1 -- mPGES microsomal prostaglandin E synthase -- MPO myeloperoxidase -- MSU monosodium urate -- NLRP3 NOD-like receptor family pyrin domain-containing 3 -- NSAID non-steroidal anti-inflammatory drug -- PGs prostaglandins -- PPAR peroxisome proliferators activated receptor -- RA rheumatoid arthritis -- RANTES regulated upon activation normal T cell expressed and secreted -- SDF-1 IL-1β stromal cell-derived factor-1 -- sICAM-1 soluble intercellular adhesion molecular-1 -- TARC thymus and activation-regulated chemokine -- TGF-β transforming growth factor-β -- Th17 T helper 17 cells -- TIMP-1 metallopeptidase inhibitor-1 -- Treg regulatory T cells -- TREM-1 triggering receptor expressed on myeloid cells-1; Benzoic acid (PubChem CID: 243) -- dimethyl sulfoxide (PubChem CID: 679) -- deuterated dimethyl sulfoxide (PubChem CID: 75151) -- EDTA (PubChem CID: 6049) -- ethanol (PubChem CID: 702) -- mangiferin (PubChem CID: 5281647) -- phosphate-buffered saline (PubChem CID: 24978514) -- sodium chloride (PubChem CID: 5234) -- sodium urate (PubChem CID: 23697816); Gouty arthritis -- Inflammatory monocytes -- Mangiferin -- MPGES-1 -- PPARγ -- Th17/Treg; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106283
• Languages: English
• ISSNs: 1043-6618

Abstract

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. Graphical Abstract: ga1 Highlights: Mangifera indica L. (MIE) modulates the onset and progression of gouty arthritis. MIE coordinates the functional regulation of COX-2/mPGES-1/PPARγ axis. MIE orchestrates, in inflamed joints and bloodstream, Th17/Treg repertoire.