Gamma-irradiation-induced dehydrogenation of hesperetin to diosmetin enhances anti-inflammatory and immunomodulatory activities in bone-marrow-derived dendritic cells

초록

Diosmetin (Dio), an O-methylated flavone with anti-inflammatory activity, is a valuable bioactive compound. However, its low natural abundance and limited production methods restrict its practical use. In this study, gamma irradiation was investigated as a simple and reagent-free strategy for converting hesperetin (Hes) into Dio. Dio was identified as a major irradiation-generated product under selected solvent conditions. Irradiation in ethanol at 100 kGy afforded purified Dio at an isolated yield of approximately 10%. In a cell-free enzymatic assay, Dio showed stronger direct cyclooxygenase-2 (COX-2) inhibitory activity than Hes, while molecular docking provided a possible structural rationale for this difference. In lipopolysaccharide-stimulated bone marrow-derived dendritic cells (BMDCs), Dio exhibited mediator-specific anti-inflammatory and immunomodulatory effects, including suppression of selected pro-inflammatory cytokines and inflammatory mediators, increased IL-10 production, and modulation of activation-associated surface markers. These findings suggest that gamma irradiation can be used to generate Dio from Hes and may provide a useful approach for producing bioactive flavonoid derivatives. © 2026 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

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