Ellagic Acid Identified through Metabolomic Analysis Is an Active Metabolite in Strawberry ('Seolhyang') Regulating Lipopolysaccharide-Induced Inflammation

This study employed the metabolomic approach to identify the key constituent exerting anti-inflammatory activity in murine macrophage RAW 264.7 cells. Among the six different fractions (SF1-SF6) of the strawberry 'Seolhyang', SF4 showed more significant inhibition on iNOS expression than SF3, and ellagic acid was determined as the most significant different component between SF4 and SF3 using orthogonal partial least-squares discriminant analysis. Ellagic acid (0.3 and 1.0 mu M) and SF4 (100 mu g/mL) were found to regulate the same inflammatory mediators, inhibitory kappa B (I kappa B) and mitogen-activated protein kinases (MAPKs), which led to the reduction of tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and iNOS expressions. These results demonstrate that ellagic acid from strawberry 'Seolhyang' is the major component playing a crucial role in inflammation, suggesting the possible application of metabolomic analysis to determining the key ingredients having biological functions in the complicated food matrix.