A comparative study of metabolites profiles, anti-inflammatory and antioxidant activity of methanolic extracts from three Arthrospira strains in RAW 264.7 macrophages

Arthrospira (spirulina), is a cyanobacterium endowed with antioxidant and anti-inflammatory activity, but strain-dependent production of bioactive compounds may impact these properties. In LPS-stimulated RAW 264.7 macrophages, we compared the antioxidant and anti-inflammatory activity of methanolic extracts from two A. platensis (F&M-C256 and F&M-C260), and an A. maxima (F&M-C258) strains. F&M-C260 (5–25 μg/mL) concentration dependently inhibited LPS-induced NO release (p < 0.01) while F&M-C256 was effective only at the highest concentration (p < 0.01) and F&M-C258 had no activity. Both A. platensis strains significantly suppressed iNOS and COX-2 expression and PGE2 production, while A. maxima lacked effects. Only F&M-C260 up-regulated miR-223 expression (p < 0.001). A. maxima showed the highest inhibition of NLRP3 and IL1-β expression (p < 0.001) and IL1-β secretion (p < 0.01). All extracts displayed direct antioxidant activity and counteracted LPS-induced SOD2 overexpression without affecting HO-1 expression. Metabolites profiles, explored by HPLC-UV and HPLC-HRMS, revealed that F&M-C260 and F&M-C256 were the richest in β-cryptoxanthin and monogalactosyl monoglycerides respectively, with minor differences in zeaxanthin and β-carotene content. These results suggest that the antioxidant activity of the extracts was due to a direct reducing effect rather than to the transcriptional activation of SOD2 and HO-1 and that their differential and multitarget anti-inflammatory effects were correlated to differences in metabolites profiles.