Camelus bactrianus placenta peptides inhibit MMP-1 and reverse skin aging in human fibroblasts and mice

Skin aging is a complex process characterized by extracellular matrix (ECM) degradation, reduced collagen synthesis, and increased oxidative stress, leading to wrinkles and loss of elasticity. Current anti-aging strategies often fall short in comprehensively addressing these multifaceted mechanisms. Traditional medicine, particularly Mongolian medicine, has long utilized Camelus bactrianus placenta (CBP) for its purported anti-aging benefits, known as "Haliyasu." However, the scientific validation of its efficacy and the identification of specific active compounds and their molecular mechanisms have been largely unexplored, representing a significant gap this study aims to fill.

Researchers prepared eleven Camelus bactrianus placenta enzymatic hydrolysates (CBPHs) and screened them for hydrolysis efficiency, antioxidant activity, and ECM-degrading enzyme inhibition. The most promising hydrolysate, CBPH-Flavourzyme, was then evaluated in D-galactose (D-Gal)-induced senescent human skin fibroblasts (HSFs) and aging C57BL/6 mice. Network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict core therapeutic targets and identify active peptides. The identified peptides were subsequently validated for their effects on MMP-1 inhibition and Collagen Type I synthesis in HSFs using ELISA and qPCR.

CBPH-Flavourzyme demonstrated potent antioxidant activity, effectively scavenging ABTS+ and DPPH radicals. It significantly inhibited ECM-degrading enzymes, including collagenase, elastase, and notably, matrix metalloproteinase-1 (MMP-1). In D-Gal-induced senescent HSFs, CBPH-Flavourzyme significantly reduced levels of senescence-associated β-galactosidase (SA-β-gal), IL-6, and IL-18, while concurrently increasing Collagen Type I synthesis. The in vivo mouse model mirrored these benefits:

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 comprehensive anti-skin-aging effects. Network pharmacology identified MMP-1, IL-6, and TNF-α as key targets, with specific peptides showing strong binding affinity and inhibitory effects on MMP-1 in further in vitro validation.