Targeted discovery of anti-skin aging peptides from Camelus bactrianus placenta: Multi-activity screening, network pharmacology, and in vitro validation focusing on MMP-1 inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Placenta has historically been utilized as a therapeutic agent in traditional medicine, notably as "Ziheche" in traditional Chinese medicine. Similarly, Camelus bactrianus placenta (CBP), known as "Haliyasu" in Mongolian medicine, has been traditionally used to promote health, reduce wrinkles, and alleviate signs of aging. However, its anti-skin aging efficacy and underlying molecular mechanisms lack scientific validation, which this study aims to address.

AIM OF THE STUDY: This study aimed to evaluate the anti-skin-aging potential of Camelus bactrianus placenta enzymatic hydrolysates (CBPHs), identify their active peptides, and clarify the related molecular-target mechanisms.

MATERIALS AND METHODS: Eleven CBPHs were prepared and screened based on hydrolysis efficiency, antioxidant activity, and extracellular matrix (ECM) degrading enzyme inhibition. The appropriate hydrolysate was confirmed in D-galactose (D-Gal)-induced senescent human skin fibroblasts (HSFs) and aging C57BL/6 mice. Network pharmacology analysis, molecular docking, combined with molecular dynamics simulations identified core therapeutic targets and active peptides, which were further validated in HSFs.

RESULTS: CBPH-Flavourzyme exhibited potent antioxidant activity, effectively scavenging ABTS+ and DPPH radicals; inhibited ECM-degrading enzymes, including collagenase, elastase, and matrix metalloproteinase-1 (MMP-1); alleviated HSF senescence by significantly reducing the levels of senescence-associated β-galactosidase (SA-β-gal), IL-6, and IL-18, while increasing Collagen Type I synthesis. Meanwhile, in the D-Gal-induced aging mouse model, CBPH-Flavourzyme significantly elevated superoxide dismutase (SOD) and hyaluronic acid (HA) levels, reduced malondialdehyde (MDA) content, promoted Collagen Type I production in dorsal skin tissue, improved disordered collagen fiber arrangement, and increased skin thickness, thereby exerting anti-skin-aging effects. Network pharmacology analysis suggested that CBPH-Flavourzyme can regulate collagen degradation and suppress the expression of key enzymes involved in collagen degradation in the skin tissue of D-Gal-induced aging mice. In vitro enzymatic inhibition assays, combined with molecular docking and molecular dynamics simulations, identified seven peptides (FRCQ, AADW, PGSPP, PSSPF, PGFGAG, PAF, and QGVGF) from CBPH-Flavourzyme as potent MMP-1 inhibitors. Among these, FRCQ demonstrated the strongest MMP-1 inhibitory activity. Subsequent cellular validation demonstrated that FRCQ significantly reduced SA-β-gal activity and increased type I collagen content. These effects were accompanied by decreased levels of AP-1-related proteins (p-c-Fos and p-c-Jun), suggesting that modulation of AP-1 signaling may contribute to the observed anti-senescence effects.

CONCLUSIONS: These findings suggest that Camelus bactrianus placenta-derived peptides may serve as candidates for further development in functional foods, nutricosmetics, or pharmaceutical products, pending additional studies on skin penetration, safety, and formulation stability.