Preparation, identification, and multi-target anti-photoaging mechanisms of bioactive collagen peptides

Abstract

This study aimed to identify anti-photoaging peptides in porcine skin and to elucidate their bioactive mechanisms using physicochemical property prediction, molecular docking, cell experiments, and network pharmacology. Four collagen peptides were identified from porcine skin hydrolysates via ultrafiltration, gel chromatography, and multi-pathway molecular docking. Among them, FGPYGF and GPPSGGFG exhibited superior photoprotective efficacy which increased the viability of UVB-damaged HaCaT cells to 72.15% and 66.36% at 400 µM, respectively, while effectively suppressing cellular senescence at 200 µM. Molecular docking revealed that synergetic and stronger binding was mediated by hydrogen bonding, ionic interactions, and π-π stacking in forming complexes between both bioactive peptides and four target enzymes (MMP-1, MMP-9, NF-κB, and IL-1β), with binding energies ranging from − 8.34 to -18.37 kcal/mol. FGPYGF inhibited MMP-1 expression and promoted type I collagen synthesis, while GPPSGGFG significantly reduced ROS levels. FGPYGF blocked inflammation and matrix degradation by targeting the TNF signaling pathway and collagen catabolic processes (IL1B/MMP9/2), while GPPSGGFG delayed cell cycle progression and enhanced antioxidant capacity via the FoxO/PI3K-Akt pathway (CCND1/SIRT1). This study confirms that multi-target intervention through cross-pathway modulation significantly enhances photoprotection, providing a theoretical basis for the rational design and precision application of anti-photoaging peptides.

Graphical Abstract

Keywords

Collagen peptides / Isolation and characterization / Photoprotective activity / Multi-target docking / Network pharmacology

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Funding

National Natural Science Foundation of China(22378274)

RIGHTS & PERMISSIONS

The Author(s)