Phytoprostanes and phytofurans modulate COX-2-linked inflammation markers in LPS-stimulated THP-1 monocytes by...

Inflammation is a fundamental pathophysiological process which occurs in the course of several diseases. The present work describes the capacity of phytoprostanes (PhytoPs) and phytofurans (PhytoFs) (plant oxylipins), present in plant-based foods, to modulate inflammatory processes mediated by prostaglandins (PGs, human oxylipins) in lipopolysaccharide (LPS)-stimulated THP-1 monocytic cells, through a panel of 21 PGs and PG's metabolites, analyzed by UHPLC-QqQ-ESI-MS/MS. Also, the assessment of the cytotoxicity of PhytoPs and PhytoFs on THP-1 cells evidenced percentages of cell viability higher than 90% when treated with up to 100 μM. Accordingly, 50 μM of the individual PhytoPs and PhytoFs 9-F_1t-PhytoP, 9-epi-9-F_1t-PhytoP, ent-16-F_1t-PhytoP, ent-16-epi-16-F_1t-PhytoP, ent-9-D_1t-PhytoP, 16-B₁-PhytoP, 9-L₁-PhytoP, ent-16(RS)-9-epi-ST-Δ¹⁴-10-PhytoF, ent-9(RS)-12-epi-ST-Δ¹⁰-13-PhytoF, and ent-16(RS)-13-epi-ST-Δ¹⁴-9-PhytoF were evaluated on their capacity to modulate the expression of inflammatory markers. The results obtained demonstrated the presence of 7 metabolites (15-keto-PGF_2α, PGF_2α, 11β-PGF_2α, PGE₂, PGD₂, PGDM, and PGF_1α) in THP-1 monocytic cells, which expression was significantly modulated when exposed to LPS. The evaluation of the capacity of the individual PhytoPs and PhytoFs to revert the modification of the quantitative profile of PGs induced by LPS revealed the anti-inflammatory ability of 9-F_1t-PhytoP, ent-9-D_1t-PhytoP, 16-B₁-PhytoP, 9-L₁-PhytoP, and ent-9(RS)-12-epi-ST-Δ¹⁰-13-PhytoF, as evidenced by their capacity to prevent the up-regulation of 15-keto-PGF_2α, PGF_2α, PGE₂, PGF_1α, PGDM, and PGD₂ induced by LPS. These results indicated that specific plant oxylipins can protect against inflammatory events, encouraging further investigations using plant-based foods rich in these oxylipins or enriched extracts, to identify specific bioactivities of the diverse individual molecules, which can be useful for nutrition and health in the frame of well-defined pathophysiological processes.