Revealing Serotonin Derivatives in Safflower Seed Meal as Potential Anti-Ulcerative Colitis Drugs: In Vitro and Computational Evidence

TL;DR

This study identifies serotonin derivatives in safflower seeds that may help treat ulcerative colitis by reducing inflammation and targeting key disease-related pathways.

Contribution

Two novel serotonin derivatives were isolated from safflower seed meal, and one showed strong anti-inflammatory potential through multi-target mechanisms.

Findings

Eleven serotonin derivatives were isolated, including two novel compounds.

N-feruloyl serotonin (FS) showed the strongest anti-inflammatory activity in macrophages.

FS targets key molecules like STAT3 and EGFR, modulating pathways linked to inflammation and cancer.

Abstract

This study evaluated the in vitro anti-inflammatory activity of serotonin derivatives from safflower seed powder and elucidated their mechanism against ulcerative colitis using network pharmacology. Compounds were extracted and purified via silica gel column chromatography, Sephadex LH-20 and semi-preparative HPLC. Structural characterization employed NMR and UPLC-Q-TOF-MS/MS with literature comparisons. Anti-inflammatory efficacy was assessed in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Network pharmacology predicted targets, molecular docking analyzed binding interactions and molecular dynamics simulations assessed complex stability. Eleven serotonin derivatives were isolated; N-trans-Feruloyl-3,5-dihydroxyindolin-2-one (1) and Bufoserotonin A (2) were identified in safflower seed meal for the first time. Compounds 1, 3–7 and 10 significantly reduced inflammatory factors, with N-feruloyl serotonin (4, FS) showing the strongest activity. Mechanistic studies revealed FS targets key molecules (STAT3, EGFR, ESR1, PTGS2, NF-κB1, and JUN), modulating PI3K-Akt, MAPK and cancer-related pathways. Molecular dynamics simulations confirmed FS-EGFR complex stability. Thus, two novel derivatives were isolated and FS demonstrated significant anti-inflammatory and potential anti-ulcerative colitis effects through multi-target, multi-pathway synergy, providing a foundation for developing safflower seed meal therapeutics.

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