Comparison of the Antioxidant Activities and Neuroprotective Effects from Different Parts of Citrus Unshiu against H₂O₂-induced Oxidative Stress in HT22 Cells

This study evaluates the antioxidant and neuroprotective effects of extracts derived from different parts of Citrus unshiu (the flavedo, albedo, and pulp) by using an oxidative-stress-induced neuronal cell model. Total phenolic content and total flavonoid content were analyzed, with antioxidant activities assessed through DPPH, ABTS radical scavenging, and FRAP assays. The flavedo extract showed the highest levels of TPC and TFC, followed by the albedo and pulp. Consistently, the flavedo extract exhibited the lowest IC50 values in all antioxidant assays, indicating the strongest antioxidant capacity. To evaluate neuroprotective effects, HT22 hippocampal neuronal cells were treated with H2O2 and rotenone to induce oxidative stress. Treatment with Citrus unshiu extracts improved cell viability, with the flavedo extract demonstrating the most potent protective effect. Additionally, the flavedo extract significantly reduced intracellular ROS levels and upregulated the expression of key antioxidant proteins (SOD1) and anti-apoptotic (BCl-2) proteins, suggesting a dual ROS suppression and apoptosis inhibition mechanism. These findings indicate that the flavedo from Citrus unshiu, which is often discarded as waste, is rich in bioactive compounds with potent antioxidant and neuroprotective potential. Thus, it holds promise as a valuable functional ingredient for developing health-promoting food or pharmaceutical applications.