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Oxidative damage has been implicated in the pathogenesis of numerous disorders by affecting the normal functions of several tissues. Further, oxidative stress acts within cells to influence cell morphology and the behavior of cell migration. The movement and migration of cells are crucial during the development of organisms as they transition from embryo to adult, and for the homeostasis of adult tissues. Epicatechin (EC) is a natural flavonoid derived mostly from tea, chocolate, and red wine. We investigated the protective impact of EC on D‐galactose(D‐gal)/rotenone‐injured NIH3T3 cells and found alterations in cell dynamics throughout the procedure. The results reveal that D‐gal/rotenone stimulation can cause the cell area to expand and the number of cellular protrusions to increase. EC intervention can considerably minimize the oxidative damage of rotenone on NIH3T3 cells (p < 0.05) but showed little influence on cell damage induced by D‐gal. Furthermore, the corrective ability of EC as an antioxidant is reflected in a dose‐dependent effect on cell movement, including variations in movement speed and distance. Overall, from the perspective of cell morphology and cell motility, EC has a good protective impact on cells harmed by rotenone induced oxidative damage, as well as corrective properties as an antioxidant to balance intracellular oxidative stress, which allowing for a more comprehensive evaluation of antioxidant performance of EC.

Exploring potential food‐derived bioactive substances that relieve oxidative stress is considered an important goal for antioxidant research. We first used the long‐pair electron index and orbital fingerprint to predict the molecular interactions in a range of polyphenols and polypeptides. We found Rutin and peptide PW5 had the highest LPE index values. Subsequently, by D‐galactose (D‐gal)‐induced oxidative NIH3T3 cell model, we proved both Rutin and PW5 could effectively protect cells against D‐gal‐induced damage, through enhancement in cell proliferation and reduction in β‐galactosidase activity. Although Rutin displayed better performance than PW5 in the oxidative stress model, we confirmed Rutin stimulated obvious changes in the morphology and motility of normal NIH3T3 cells based on the real‐time dynamic images. Taken together, combined computational and typical model experiment methods, proved useful in efficiently screening food‐derived antioxidants. Moreover, the analytical results of cell morphology and movement may provide novel insights for the safety evaluation of antioxidants.

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