Nitrogen fertilization modulates phytochemical profile and enhances anti-inflammatory activity of Cichorium spinosum L. in a carrageenan-induced acute paw edema model in mice

This study investigates how different ratios of nitrogen (N), phosphorus (P), and potassium (K) fertilization affect the phytochemical composition and anti-inflammatory effect of Cichorium spinosum L. The plants were grown under one of six N:P:K conditions: 100:100:100 (C111), 200:100:100 (C211), 200:200:200 ( C 222), 300:100:100 (C311), 300:200:200 (C322), 300:300:300 (C333), or without fertilization (C0). Hydroethanolic extracts were then prepared, and Fourier Transform Infrared Spectroscopy (FTIR-ATR) analysis was performed. Edema inhibition (%) was measured over 1–6 h after carrageenan intraperitoneal injection (0.1 mL of 1% carrageenan in 0.9% NaCl). One hour before carrageenan injection, mice received oral doses of C. spinosum extracts at 50, 150, or 250 mg/kg. The inflammation group (Ci) received distilled water, and the standard (STD) group received diclofenac at 50 mg/kg. After 7 h, paw tissue was collected for histological evaluation. Notably, our results showed that extracts from nitrogen-enriched plants have pronounced spectral signatures of key bioactive functional groups, including O-H (hydroxyl), C=O (carbonyl), and C=C (alkene) bonds. Consistently, all treated groups demonstrated dose-dependent inhibition of inflammation. However, extracts from nitrogen-enriched plants, especially C211 and C311, produced the strongest anti-edematous activity. This was further supported by qualitative histological evaluation, which showed that nitrogen fertilization markedly attenuated inflammation and preserved tissue structure compared with the Ci group. Therefore, the main finding suggests that nitrogen fertilization modulates the phytochemical composition and enhances the anti-inflammatory efficacy of C. spinosum , suggesting agricultural biofortification is a promising strategy.