Utilization of Safflower Oil Byproducts: Phenylpropanoid Amides of 5‐Hydroxytryptamine (PAHA)‐Enriched Extract as a Solution for Antioxidant and Inflammatory Pathway Modulation

Safflower seed oil is one of the eight major oil resources worldwide, generating substantial byproducts after oil extraction each year. Efficient recycling and utilization of these byproducts are critical for sustainability. This study explored the potential use of safflower seed coating by isolating bioactive compounds and evaluating their functionality. Extraction methods to isolate phenylpropanoid amides of 5-hydroxytryptamine (PAHA), specifically coumaroyl-5-hydroxytryptamine (CS) and feruloyl-5-hydroxytryptamine (FS), were first optimized and the results demonstrated that PAHA was highly presented in the safflower seed coating. The bioactivity was systematically evaluated, showing that the extract exhibited substantial antioxidant capacity. In vitro anti-inflammatory assays demonstrated that the PAHA-enriched extract had remarked inhibitive capability on of bovine serum albumin denaturation, erythrocyte membrane lysis, and lipoxygenase (LOX) activity. In an IPEC-J2 cell model, PAHA compounds significantly attenuated E. coli-induced inflammatory responses, resulting in reduced expression of genes of proinflammatory markers IL-1α, IL-6, TNF-α, and COX-2. Further analysis of molecular docking suggesting strong binding affinities between the two independent PAHA components (CS and FS) and the key inflammatory enzymes COX-2 and 5-LOX. The current study revealed the excellent bioactivity of PAHA-enriched extract from safflower seed coating, which could be utilized in the future as a naturally derived dual COX/LOX inhibitor as food preservatives or in functional food.