Skin aging has attracted much attention among the current aging population of society. The seeds of Cucurbita moschata possess a variety of potential biological activities as a healthy diet. However, limited information is available on the skin-antiaging properties of C. moschata seed protein and its hydrolysate. Herein, we developed a novel strategy for protecting human skin cells against oxidative stress-induced aging by C. moschata seed polypeptides. C. moschata seed polypeptides (CSPs) with different molecular weight distributions were successfully prepared by controlling the protease hydrolysis time. The proportions of < 1,000 Da polypeptides of P-1, P-2, and P-3 were 0.11, 20.26, and 92.72%, respectively. P-3 contained the highest proportion of polypeptides of size < 1,000 Da, which was observed to promote human skin fibroblast (HSF) growth by MTT assay, cell cycle, and morphology. P-3 has an efficient repair effect on the H2O2-induced aging of HSF cells. To explain this phenomenon, cell lifespan, intracellular ROS level, superoxide dismutase (SOD) activity, and glutathione (GSH) content were investigated to reveal the interactions between P-3 and antiaging. With the increase in P-3 concentration, the ROS level significantly decreased, and the SOD activity and GSH content significantly increased in H2O2-induced HSF cells. These findings indicated that CSPs have the potential to inhibit skin aging, which could be advantageous in the health industry for providing personal care.
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