Oilseed Cakes  : A Promising Source of Antioxidant, and Anti-Inflammatory Agents-Insights from Lactuca sativa

This study evaluated the antioxidant and antibacterial properties of methanolic extracts derived from oilseed cakes of Lactuca sativa (lettuce), Nigella sativa (black seed), Eruca sativa (rocket), and Linum usitatissimum (linseed). Lettuce methanolic extract showed the highest potential, so it was selected for further investigation. High-performance liquid chromatography (HPLC-DAD) analysis and bioassay-guided fractionation of lettuce seed cake extract led to the isolation of five compounds: 1,3-propanediol-2-amino-1-(3',4'-methylenedioxyphenyl) (1), luteolin (2), luteolin-7-O-β-D-glucoside (3), apigenin-7-O-β-D-glucoside (4), and β-sitosterol 3-O-β-D-glucoside (5). Compound (1) was identified from Lactuca species for the first time, with high yield. The cytotoxic effects of the isolated compounds were tested on liver (HepG2) and breast (MCF-7) cancer cell lines, compared to normal cells (WI-38). Compounds (2), (3), and (4) exhibited strong activity in all assays, while compound (1) showed weak antioxidant, antimicrobial, and cytotoxic effects. The anti-inflammatory activity of lettuce seed cake extract and compound (1) was evaluated in vivo using a carrageenan-induced paw oedema model. Compound (1) and its combination with ibuprofen significantly reduced paw oedema, lowered inflammatory mediators (IL-1β, TNF-α, PGE2), and restored antioxidant enzyme activity. Additionally, compound (1) showed promising COX-1 and COX-2 inhibition in an in vitro enzymatic anti-inflammatory assay, with IC₅₀ values of 17.31 ± 0.65 and 4.814 ± 0.24, respectively. Molecular docking revealed unique interactions of compound (1) with COX-1 and COX-2, suggesting the potential for targeted inhibition. These findings underscore the value of oilseed cakes as a source of bioactive compounds that merit further investigation.