Characterization, Identification, and Antioxidant Mechanism of Antioxidant Peptides From Schisandra chinensis Based on Peptidome and Molecular Docking/Dynamics

Schisandra chinensis , a traditional Chinese medicine‐food homologous plant, is widely used for alleviating oxidative stress induced damage in hepatocytes and neurons due to its antioxidant activity. However, significant gaps remain in the research regarding the sequence, structure, and antioxidant mechanism of its bioactive peptides. Herein, we aimed to evaluate the antioxidant capacity of S. chinensis peptides (SCP), screen the optimal bioactive peptide sequences, and elucidate underlying antioxidant mechanisms. The results demonstrated that SCP exhibited potent free radical scavenging activity, with scavenging rates of over 90% and 50% against DPPH and ABTS radicals at 10 mg/mL, respectively. At 100 μg/mL, SCP restored the levels of ROS and MDA in UVB‐induced HaCaT to those of the undamaged control group. Meanwhile, SCP maintained over 65% DPPH radical scavenging activity under various physicochemical conditions and exhibited excellent biosafety with a hemolysis rate below 0.8% at a high concentration of 8 mg/mL. In total, 63 bioactive peptides were identified through peptidome and bioinformatics analyses, and 8 high affinity peptides for DPPH and ABTS were further screened out. FF4, FW4, and IL6 were capable of forming stable complexes with Keap1, primarily driven by hydrogen bonds and hydrophobic interactions, as revealed by molecular docking and molecular dynamics simulations. Specifically, the Keap1‐IL6 complex showed the most stable conformation, with DPPH and ABTS radical scavenging rates above 50% at 10 mg/mL and hemolytic activity below 10%. Collectively, these findings provide a scientific basis for clarifying the molecular mechanism of SCP in regulating antioxidant pathway and facilitating its subsequent industrialization.