Preparation of Low-Molecular-Weight Fucoidan by Irradiation-Induced Degradation and Its Protective Effect Against H2O2-Induced Oxidative Stress in RAW 264.7 Cells

The biological activities of fucoidan from brown algae have attracted considerable attention. Degradation to low-molecular-weight fucoidan reduces viscosity and improves bioavailability, enhancing antioxidant and anti-inflammatory effects. Fucoidan was degraded using acetic acid combined with ⁶⁰Co γ-ray irradiation and fractionated by Bio-Gel P10 chromatography to obtain four fractions (AIF1-AIF4). The fractions were structurally characterized and assessed for in vitro radical-scavenging activity and modulation of oxidative stress markers in H₂O₂-induced RAW264.7 macrophages. Compared with the model group, all fractions significantly increased catalase (CAT) and superoxide dismutase (SOD) activities, with the highest increase of approximately 1.33 U/mgprot for CAT and 20.32 U/mgprot for SOD, while decreasing malondialdehyde (MDA) and intracellular reactive oxygen species (ROS) levels. Among the four fractions, AIF4, with the lowest molecular weight, exhibited the highest antioxidant activity. LMWF treatment also upregulated the <i>mRNA</i> expression of antioxidant-related genes (<i>HO-1</i>, <i>SOD1</i>, <i>SOD2</i>) and signaling molecules (<i>PI3K</i> and <i>Akt</i>), accompanied by increased protein levels of nuclear factor erythroid 2-related factor 2 (<i>Nrf2</i>) and PI3K/Akt pathway components. These findings indicate that LMWF is closely associated with the regulation of the <i>PI3K</i>/<i>Akt</i>-<i>Nrf2</i> signaling axis under oxidative conditions and support its potential application as a dietary antioxidant ingredient.