Radiolysis Derivatives from p-Coumaric Acid via Gamma Irradiation and Their Anti-Inflammatory Activities

Gamma irradiation serves as a robust platform for the structural diversification of natural compounds, utilizing high-energy reactions with free radicals to generate novel scaffolds with improved biological properties. In present study, p-coumaric acid was exposed to ionizing radiation at various doses to induce molecular transformations. Significant degradation of the precursor was confirmed at a dose of 60 kGy, which provided the optimal range for the generation of radiolysis products. The chromatographic fraction of the resulting mixture afforded two novel derivatives, 1 and 2, along with a known analog 3. Comprehensive spectroscopic characterization assigned their structures as (3R,4R)-3-hydroxymethyl-4-(4-hydroxyphenyl)-dihydrofuran-2(3H)one (1), (3R*,4S*)-3-hydroxymethyl-4-(4-hydroxyphenyl)-dihydrofuran-2(3H)-one (2), and (4S)-4-(4-hydroxyphenyl)-dihydrofuran-2(3H)-one (3). The anti-inflammatory effects of the isolates were evaluated using lipopolysaccharide-stimulated RAW264.7 macrophages. While neither the parent compound p-coumaric acid nor its derivatives exhibited significant cytotoxicity at concentrations up to 40 μM, their anti-inflammatory potencies varied significantly. Notably, compound 1 exhibited potent inhibitory effects on pro-inflammatory signaling, significantly inhibiting the production of TNF-α, IL-6, and IL-12p70, surpassing the bioactivity of the parent compound. Compound 2 displayed a similar, attenuated inhibitory trend, suppressing the secretion of TNF-α and IL-12p70. Compound 3 modulated the immune response by promoting anti-inflammatory cytokine IL-10 production, despite an inconsistent suppressive effect on pro-inflammatory cytokines. These results suggest that gamma-induced radiolysis is a useful strategy for enhancing the therapeutic potential of dietary phenolic compounds.