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

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.

Occurrence and spatial distribution of dioxin and dioxin-like compounds in topsoil of Taranto (Apulia, Italy) by GC-MS analysis and DR-CALUX® bioassay.

The aim of the present study was to assess the occurrence and spatial distribution of PCDD/Fs and dioxin-like compounds in topsoils of Taranto (Apulia Region), one of the most heavily industrialized and contaminated area of Southern Italy. A combined approach of chemical analysis by GC-MS/MS and AhR reporter gene bioassay was applied in a subset of topsoil samples (n = 20) collected in 2017-18 from ten sites embracing three levels of risk (from high to low) in the framework of a large survey inside Taranto municipality. TCDD-BEQs and GC-MS/MS TEQWHO and TEQTHEORETICAL revealed a decreasing trend with the distance from main industrial settings and landfill areas. A strong correlation between TCDD-BEQs and TEQWHO values (R2 = 0.85) and TEQTHEORETICAL (R2 = 0.88) was also found. In 3 out of 10 topsoil investigated, BEQs and TEQWHO/THEORETICAL resulted above Italian National Regulatory Limits for ∑PCDD/Fs in green, private and recreational used soils (10 ng TEQ/kg d.w. D.Lgs 152/2006) and for ∑PCDD/F/dl-PCBs in agricultural and farming soil (6 ng TEQ/kg d.w. D.M. 46/2019). GC-MS/MS pattern revealed the highest prevalence of dl-PCBs in 6 out of 10 sites, followed by PCDFs and PCDDs. Those sites are all located in proximity of main industrial steel and iron ore sinter plant, steel plant's landfills and illegal dumping sites. An update on occurrence and spatial distribution of PCDD/Fs and dl-PCBs contamination of Taranto urban soils was obtained and the DR-CALUX® bioassay was further recommended as a suitable screening tool for environmental and human risk assessment.