Lignan phytocomplexes extracted from legumes act as anti-inflammatory agents in a model of adipocyte metaflammation: antioxidant properties and nutriepigenomic effects

Background: Metaflammation, a state of metabolically driven inflammation also referred to as ‘low-grade’ inflammation, is a key contributor to the development of obesity complications such as type 2 diabetes and cardiovascular diseases. Among numerous phytochemicals, lignans are secondary metabolites whose biological properties have not been properly characterized yet. This study aims to investigate the effect on metaflammation of natural mix of lignans isolated from legumes and their synthetic equivalents and to evaluate the possible intermediating role of epigenetic on this process. Methods: An in vitro model of inflamed adipocytes was used. Cytotoxicity of phytocomplexes was evaluated through MTT assay. Antioxidant properties were assessed by chemiluminescence assay. Gene expression of genes involved in inflammation (MCP1, IL6, IL1b, NFkB) or epigenetic regulation (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, HDAC3) were analyzed and global DNA methylation and H3 histone acetylation were measured. Results: A protective effect of the selected mix of lignans against metaflammation in this model was measured. In particular, reduced level of inflammatory genes and altered expression of genes that regulate epigenetic pathways suggest a potential involvement of epigenetic mechanism as responsible for the measured antinflammatory effect. This was observed for both natural and synthetic mixtures, despite a limited antioxidant activity was measured in the second ones. Conclusions: This study suggest that not only antioxidant activity but also nutriepigenomic effects could be responsible for the measured antinflammatory properties of the selected mixtures of lignans extracted from legumes. Further studies are needed to elucidate the underlying epigenetic molecular mechanisms.