Dissection of anti-inflammatory and immunomodulatory activity of
Mangifera indica L. reveals the modulation of mPGES-1/PPARγ axis and
Th17/Treg ratio.
Abstract
Background and Purpose: 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. We, therefore, aimed to evaluate the potential
beneficial effects of this plant extract (MIE, 90% in mangiferin) in a
mouse model of gouty arthritis, dissecting the cellular immune
phenotypes and the biochemical mechanism/s beyond its activity.
Experimental Approach: Gouty arthritis was induced by the
intra-articular administration of MSU crystals (200 μg 20 μl-1). MIE
(0.1-10 mg kg-1) or corresponding vehicle (DMSO/saline 1:3) were orally
administrated concomitantly to 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 several components of
mPGES-1/PPARγ pathway. Moreover, the analysis of pro/anti-inflammatory
cyto-chemokines coupled to the assessment of the cellular infiltrate’s
phenotype was investigated. Key Results: 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 infiltrating inflammatory monocytes
(CD11b+ve/CD115+ve/LY6Chi), and (both infiltrated and circulating) Treg
cells (CD4+ve/CD25+ve/FOXP3+ve) after MIE treatment. Conclusion and
Implications: 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.