# A proteoglycan-based topical treatment for hair greying: in vitro antioxidant and pro-melanogenic effects

**Authors:** David Vega Diez, Eva María Arias, Nuria Floriach, Estela Bravo

PMC · DOI: 10.3389/fmed.2025.1734454 · Frontiers in Medicine · 2026-01-14

## TL;DR

This study explores a topical treatment that may help prevent or treat hair greying by boosting melanocyte function and reducing oxidative stress and inflammation.

## Contribution

The study introduces a proteoglycan-based formulation with combined pro-melanogenic, antioxidant, and anti-inflammatory effects for hair greying.

## Key findings

- PP-PTKL significantly increased MITF expression in human melanocytes under Wnt/β-catenin inhibition.
- The formulation showed synergistic antioxidant activity, four times higher than the sum of its components.
- PP-PTKL reduced histamine release and inflammatory markers, indicating anti-inflammatory effects.

## Abstract

Hair greying (canities) is a common and impactful feature of hair aging, primarily driven by oxidative stress, mitochondrial dysfunction, and progressive impairment of melanocyte function. Reactive oxygen species disrupt key melanogenic pathways, including Wnt/β-catenin signaling and microphthalmia-associated transcription factor (MITF) activity. Given the central role of oxidative and inflammatory processes in pigment loss, antioxidant and melanocyte-stimulating strategies represent promising approaches to delay hair greying.

The present study evaluated the in vitro antioxidant, anti-inflammatory, and pro-melanogenic effects of PP-PTKL (Pilopeptan® Woman Proteokel), a proteoglycan-based topical formulation. Total antioxidant capacity was assessed using a copper reduction assay. Pro-melanogenic activity was evaluated in Normal Human Epidermal Melanocytes (NHEM) under Wnt/β-catenin inhibition induced by FH535. Anti-inflammatory effects were assessed through histamine release in mast cells and by measuring IL-1Ra and S100A8/9 levels using ELISA.

PP-PTKL significantly restored MITF expression in a dose-dependent manner in human melanocytes subjected to Wnt/β-catenin pathway inhibition, with increases of 43.1% at 1% and a 3.7-fold increase at 5%. The formulation exhibited strong synergistic antioxidant activity, with total antioxidant capacity nearly four times higher than the sum of its individual components. In addition, histamine release was significantly reduced in mast cells, while IL-1Ra and S100A8/9 levels were significantly decreased compared with placebo, indicating attenuation of inflammation-associated oxidative stress.

PP-PTKL demonstrates combined pro-melanogenic, antioxidant, and anti-inflammatory activity in vitro, supporting its potential as a preventive or therapeutic strategy for hair greying. Further in vivo and clinical studies are warranted to confirm these findings.

## Linked entities

- **Genes:** MITF (melanocyte inducing transcription factor) [NCBI Gene 4286]
- **Proteins:** IL1R1 (interleukin 1 receptor type 1)
- **Chemicals:** FH535 (PubChem CID 3463933)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, MITF (melanocyte inducing transcription factor) [NCBI Gene 4286] {aka CMM8, COMMAD, MI, MITF-A, WS2, WS2A}
- **Diseases:** inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361)
- **Chemicals:** copper (MESH:D003300), Reactive oxygen species (MESH:D017382), FH535 (MESH:C575430), histamine (MESH:D006632), PP-PTKL (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12846973/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12846973/full.md

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Source: https://tomesphere.com/paper/PMC12846973