Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts

Suzanne Edgar,Janis Shute,Licia Genovese,Blake Hopley,David Laight,Sara Sibilla

doi:10.1038/s41598-018-28492-w

Suzanne Edgar, Janis Shute + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-28492-w

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Abstract

Nutraceuticals containing collagen peptides, vitamins, minerals and antioxidants are innovative functional food supplements that have been clinically shown to have positive effects on skin hydration and elasticity in vivo. In this study, we investigated the interactions between collagen peptides (0.3–8 kDa) and other constituents present in liquid collagen-based nutraceuticals on normal primary dermal fibroblast function in a novel, physiologically relevant, cell culture model crowded with macromolecular dextran sulphate. Collagen peptides significantly increased fibroblast elastin synthesis, while significantly inhibiting release of MMP-1 and MMP-3 and elastin degradation. The positive effects of the collagen peptides on these responses and on fibroblast proliferation were enhanced in the presence of the antioxidant constituents of the products. These data provide a scientific, cell-based, rationale for the positive effects of these collagen-based nutraceutical supplements on skin properties, suggesting that enhanced formation of stable dermal fibroblast-derived extracellular matrices may follow their oral consumption.

Highlights

The biophysical properties of the skin are determined by the interactions between cells, cytokines and growth factors within a network of extracellular matrix (ECM) proteins[1]
Because transforming growth factor-β (TGF-β) controls expression, deposition and turnover of collagens and other extracellular matrix proteins in the skin[1], and primary dermal fibroblast responses to TGF-β as a positive control in cultures crowded with high molecular weight dextran sulphate have not previously been reported, we initially tested the effect of TGF-β (5 ng/ml) on Normal adult human dermal fibroblasts (NHDF) protein synthesis and proliferation after 48 hour incubation under crowded conditions, compared to media alone (Fig. 1)
TGF-β is a well-recognised pro-fibrotic growth factor that promotes the deposition of ECM proteins, whilst limiting their degradation

Summary

Introduction

The biophysical properties of the skin are determined by the interactions between cells, cytokines and growth factors within a network of extracellular matrix (ECM) proteins[1]. Production of collagen and of the other components of the extracellular matrix is high when there is a sufficient level of mechanical tension on fibroblasts When this tension is reduced, for example with age, the production of the matrix proteins falls and there is an increase of matrix-degrading enzymes[3]. A major cause of ageing-related skin damage is thought to be a consequence of decreased antioxidant defences leading to increased levels of intracellular reactive oxygen species (ROS). These form through aerobic metabolism and stimulate signal transduction resulting in the increased expression of MMPs and decreased collagen I synthesis[14]. Clinical studies have shown that the oral administration of antioxidants can help improve skin condition in photo-aged skin[22,23] and UV-induced erythema[24]

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