Moleculer Design And Mechanism Of Small Peptide PSN In Skin Rejuvenation

Skin aging is the most direct external manifestation of body aging and is a natural process caused by both intrinsic changes and extrinsic damage.The physiological functions of aging skin fibroblasts have the various changes that eventually lead to sagging and wrinkles deepen,such as mitochondrial dysfunction,reactive oxygen content accumulation,increased inflammatory response and less synthesis of collagen I(COL-1).Skin aging seriously affects the body aesthetic and health,thus to explore how to postpone skin aging has become a hot research topic in the field of anti-aging.In recent years,biopeptide anti-aging agents have attracted extensive attention due to their advantages such as less adverse reactions and better stability,but their high molecular weight and low bioavailability limit their wide application.In addition,it has been found that inhibiting the AKT/mTOR pathway can extend the life span in a variety of model organisms,but whether it regulates skin aging remains to be explored.The purpose of this study is to design a safe and stable small anti-aging peptide with small molecular weight,based on the concept of scavenging the accumulation of reactive oxygen species(ROS)and the molecular design of reducing the molecular weight of anti-aging short peptide and improving the synthesis of collagen.Firstly,four original template peptides were selected from the natural active peptide library,and nine modified peptides were obtained by optimizing the design of common molecular modification methods,such as amino acid sequence deletion and point mutation.After a series of activity detection experiments,it has been consistently demonstrated that PSN is the best modified body that combines strong antioxidant and anti-inflammatory capacity,low toxicity as well as promotes collagen transcription.Then,the protective effect of PSN on aging skin was verified from many aspects.The experimental data of macroscopic morphology,elasticity and thickness of mice prove that PSN has the dual protective function of prevention and repair of aging skin.On the basis of the cell model,the mechanism of PSN in skin aging was further explored.Experiments have proved that PSN can slow down oxidative stress and inhibit skin fibroblast senescence by protecting mitochondrial function and reducing the expression of pro-inflammatory factors related to aging.Western blotting results showed that PSN inhibited the abnormal activation of AKT/mTOR pathway and NF-κB pathway,thereby reducing the expression of collagenolytic enzyme(MMP-1)and promoting the transcriptional synthesis of collagen I(COL-1).Meanwhile,PSN can alleviate oxidative stress and enhance autophagy activity of cells by regulating AKT/mTOR pathway,thus delaying skin aging.Finally,the stability and safety of PSN were verified by experiments.When the concentration of PSN was 160 μg/mL,its cytotoxicity and hemolytic activity were only 2.91 % and 0.62 %,respectively.By testing the stability of PSN,the experiment proves that PSN has a strong resistance to salt solution and serum protease,which has a broad application prospect in the field of cosmetics and pharmaceuticals in the future.