Structural Modification of Naringenin via γ-Irradiation, Chiral Separation, and Evaluation of Anti-Inflammatory Activity

Naringenin is a flavanone recognized for its diverse pharmacological properties, including anti-inflammatory and anticancer effects. This study aimed to produce novel structures with enhanced biological activity by subjecting (±)-naringenin (1) to γ-irradiation. Compound 1 in an ethanol solution was irradiated at doses of 30, 50, 70, and 100 kGy, among which the 100 kGy dose yielded the highest concentration of radiolysis products. These radiolysis products were further processed through multi-step semi-preparative HPLC utilizing a chiral column, yielding compounds 2–5. These compounds were identified as apigenin (2) and three stereoisomers of 2-(1-hydroxyethyl)-naringenin (2,3-dihydro-5,7-dihydroxy-2-(1-hydroxyethyl)-2-phenyl-4H-1-benzopyran-4-one; 3–5) via high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The absolute stereochemistry of compounds 3–5 was determined to be (2S,11S)-, (2S,11R)-, and (2R,11S)-configurations, respectively, by comparing experimental electronic circular dichroism data and specific optical rotations. Evaluation of nitric oxide inhibition in lipopolysaccharide-stimulated RAW 264.7 cells revealed that compound 2 exhibited greater activity to the parent compound 1, whereas derivatives 3‒5 were inactive. These findings indicate that γ-irradiation is an effective strategy for structural modification and enhancing the bioactivity in flavonoids.