Two Collagen Peptides from Pig Skin Shield Skin Cells from UV Damage

Scientists in China have isolated two small collagen peptides from pig skin that helped laboratory-grown human skin cells survive ultraviolet B radiation, and their detailed analysis suggests the reason the two molecules worked well is that each one engages several damage-related targets at once rather than a single pathway. The study, published in the journal Collagen and Leather, combined peptide purification, molecular docking, cell experiments and network pharmacology to trace how the peptides FGPYGF and GPPSGGFG protect keratinocytes from UVB-induced photoaging. Because all of the work was carried out in cultured HaCaT keratinocytes, the findings are a proof of mechanism at the cellular stage, not yet evidence of a benefit in living skin or in people.

The research team started with porcine skin, a cheap and abundant collagen source whose amino acid composition resembles that of human skin collagen. Collagen was extracted through a multi-step chemical process involving alkaline degreasing, salt washing, acid swelling and pepsin digestion, then broken down with an acid protease at 45 degrees Celsius to produce porcine skin collagen hydrolysates. Enzymatic hydrolysis is the preferred way to make collagen peptides because it is controllable and environmentally benign, but the resulting mixture is a heterogeneous soup of fragments, so rigorous purification is needed before any single active sequence can be studied.

Ultrafiltration split the hydrolysate into four fractions by molecular weight, and the smallest one, containing peptides below one kilodalton, proved the most photoprotective. In UVB-damaged HaCaT cells this fraction raised cell viability in a dose-dependent manner, reaching 68.69 percent at 400 micrograms per milliliter, while the two heavier fractions showed no significant improvement. The low-molecular-weight fraction was then run through a Sephadex G-25 gel column, yielding four subfractions, of which G4 showed the strongest effect, lifting viability to 76.51 percent at 200 micrograms per milliliter. Importantly, the researchers ran a control with free glycine at equivalent concentrations, and glycine did nothing, confirming that the activity came from specific peptide sequences rather than from a bulk amino acid effect.

Mass spectrometry sequencing of the G4 fraction identified 107 peptide sequences with molecular weights between about 249 and 1058 daltons, roughly half of them just four or five residues long. An online neural-network predictor, PeptideRanker, scored each sequence for likely bioactivity, and with the threshold raised to a stringent 0.85, 51 candidate photoprotective peptides advanced to the next stage. Rather than docking candidates against a single enzyme, as most previous screens have done, the team selected four targets spanning the two major signaling axes of photoaging: MMP-1 and MMP-9, matrix-metalloproteinases that degrade collagen and elastin downstream of the MAPK pathway, and NF-κB and IL-1β, core components of the UVB-triggered inflammatory cascade.

The docking results singled out two peptides with the broadest and strongest binding profiles. FGPYGF bound MMP-1 with an energy of minus 9.70 kilocalories per mole, forming three hydrogen bonds and directly coordinating the catalytic zinc ion in the enzyme’s active center, and it also bound MMP-9, NF-κB and IL-1β with energies between minus 8.35 and minus 9.95 kilocalories per mole. GPPSGGFG showed the strongest dual-pathway potential, with the lowest binding energies for MMP-9, minus 10.06 kilocalories per mole, and NF-κB, minus 9.20 kilocalories per mole, its NF-κB interaction combining hydrogen bonding, an ionic contact and π-π stacking right at the DNA-binding domain. Two narrower peptides served as pathway-specific controls: QPPGP bound IL-1β strongly at minus 10.89 kilocalories per mole but barely touched the MMPs, while FGPY bound the two MMPs selectively and interacted only weakly with the inflammatory targets. Across the four peptides and four targets, binding energies ranged from minus 8.34 to minus 18.37 kilocalories per mole.

The cell experiments then tested whether multi-target binding translated into better protection. UVB irradiation at 40 millijoules per square centimeter dropped HaCaT viability to 53.77 percent, and at 400 micromolar the two multi-target peptides rescued it most effectively: FGPYGF to 72.15 percent and GPPSGGFG to 66.36 percent, compared with 63.99 percent for QPPGP and a non-significant 58.69 percent for FGPY. Cytotoxicity screening showed the peptides were harmless up to 400 micromolar, with only FGPY and FGPYGF becoming toxic at 1000 micromolar. The authors suggest the edge of FGPYGF over GPPSGGFG may partly reflect its higher hydrophobicity, measured by a GRAVY value of 0.12 versus minus 0.35, since hydrophobic peptides penetrate cell membranes more readily.

Deeper markers of photoaging told a consistent story. UVB pushed the fraction of senescence-associated β-galactosidase-positive cells, a standard marker of cellular aging, from 15.73 percent in untreated controls to 47.81 percent; at 200 micromolar, FGPYGF cut that back to 21.77 percent and GPPSGGFG to 25.88 percent, approaching the healthy baseline. Reactive oxygen species, which UVB elevated to 166.03 percent of control levels, were quenched most strongly by GPPSGGFG, down to 104.96 percent, with FGPYGF close behind at 114.78 percent. On the matrix side, UVB nearly doubled MMP-1 to 230.22 percent of baseline while collapsing type I collagen to 57.51 percent; FGPYGF suppressed MMP-1 to 165.80 percent and restored collagen to 70.43 percent, with GPPSGGFG partially restoring collagen as well, whereas the two single-pathway control peptides had negligible effect on collagen levels.

Network pharmacology explained why the two lead peptides, though both multi-target, behaved differently. Cross-referencing computationally predicted peptide targets against 396 known skin-photoaging targets yielded 45 overlapping targets for FGPYGF and 39 for GPPSGGFG. FGPYGF’s network centered on IL1B, STAT3, PTGS2 and MMP9/2, and enrichment analysis pointed to the TNF signaling pathway and collagen catabolic processes, consistent with acute anti-inflammatory and anti-degradation repair. GPPSGGFG instead engaged STAT3, PTGS2, SRC, ACE, SIRT1 and CCND1, with enrichment in cellular senescence and FoxO/PI3K-Akt signaling, G1/S cell-cycle regulation and antioxidant activity, suggesting longer-term protection through metabolic homeostasis and cell-cycle control. The shared nodes STAT3, PTGS2 and SRC indicate overlapping anti-inflammatory mechanisms, forming what the authors describe as a paired paradigm of anti-inflammatory repair and anti-aging metabolic regulation.

The study’s authors frame the work as validation that multi-target intervention through cross-pathway modulation enhances photoprotection, and as a template for rationally designing anti-photoaging peptides using a separation-docking-validation pipeline. The authors suggest applications in functional foods and pharmaceutical products, though such translation would require animal and human studies that this paper does not include.

For now, the results stand as an unusually complete cellular case study: two short sequences from an inexpensive food-industry byproduct, each mapped residue by residue onto four photoaging targets, each validated across viability, senescence, oxidative stress and collagen markers in the same cell system. Whether FGPYGF’s zinc-coordinating grip on MMP-1 or GPPSGGFG’s blockade of the NF-κB DNA-binding domain survives the jump from dish to dermis remains an open question, but the multi-target logic the study demonstrates gives peptide designers a concrete framework to test next.

Subject of Research: Multi-target anti-photoaging collagen peptides identified from porcine skin and tested in UVB-irradiated human keratinocytes

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

Article References: Liu, Z., Yang, Y., Chi, Y., & Xu, Z. (2026). Preparation, identification, and multi-target anti-photoaging mechanisms of bioactive collagen peptides. Collagen and Leather, 8(1), Article 27. https://doi.org/10.1186/s42825-026-00249-6

Image Credits: AI Generated

DOI: 10.1186/s42825-026-00249-6

Keywords: collagen peptides, photoaging, UVB, porcine skin, molecular docking, HaCaT keratinocytes, MMP-1, network pharmacology, reactive oxygen species, cell senescence, NF-κB, type I collagen