Benefits of Circulating Human Metabolites from Fish Cartilage Hydrolysate on Primary Human Dermal Fibroblasts, an Ex Vivo Clinical Investigation for Skin Health Applications

Abstract

Due to its significant exposure to stressful environmental factors, the skin undergoes a high remodeling rate over time, which alters not only its appearance but also its functionality. This alteration of the skin, namely photoaging, is characterized by dryness and a loss of elasticity that mainly originates from the dysregulation of dermal fibroblast activities. In order to overcome such tissue outcome, cosmetic products have evolved toward nutricosmetics, thus promoting beauty from within. Among bio-actives of interest, bio-peptides deriving from plant or animal sources may exert various biological activities beyond their nutritional value. However, studies remain mostly descriptive and the mode of action at the cellular level in clinic remains a concern. In a recent clinical trial, it was showed that supplementation with a fish cartilage hydrolysate (FCH) improved signs of chronological and photoaging-induced skin changes in healthy women. Here, using an original ex vivo clinical approach adapted to nutricosmetic purpose, we further demonstrated that this fish cartilage hydrolysate was absorbed and that the circulating metabolites produced in humans following FCH intake stimulate human dermal fibroblast growth, promote specific hyaluronan production, up-regulate elastin synthesis and inhibit MMP-1 and 3 expression along with the enhancement of TGF-β release. Altogether, these data provide clues on the mechanisms likely contributing to the beneficial impact of FCH on human skin functionality by supporting hydration, elasticity and limiting the expression of catabolic factors involved in photoaging onset.

Human Serum Enriched After Absorption of Fish Cartilage Hydrolysate Enhances the Healing of Primary Human Dermal Fibroblasts Through the Expression of Proteins with Anti-Inflammatory and Immunomodulatory Properties

“…Our precedent study demonstrated the beneficial effects of FCH for nutricosmetic applications, by supporting hydration, elasticity and limiting the expression of catabolic factors involved in photoaging [19]. Here, we studied whether FCH could promote the healing process, using a mimicking fibroblast lesion in vitro.…”

“…Indeed, the human serum enriched with circulating metabolites resulting from FCH ingestion (FCH-enriched serum), stimulated the growth of human dermal fibroblasts (HDFs), promoted the specific production of hyaluronan, up-regulated the synthesis of elastin and inhibited the expressions of matrix metalloproteinases (MMP)-1 and 3 along with an increase in TGF-β release. Thus, FCH promotes hydration, elasticity and limits the expression of catabolic factors involved in photoaging [19]. Additionally, it was previously showed that supplementation of middle-aged healthy women with this FCH led to both, a significant reduction in wrinkles and an increase of dermis density [20].…”

“…As previously described [19], according to the circulating hydroxyproline and CS concentration profiles, the collection of human FCH-enriched serum was set at 140 min post-ingestion. Moreover, we previously showed that human serum, enriched or not, had no cytotoxic effect on HDFs cultures.…”

Reduced Production of Pro-Inflammatory and Pro-Catabolic Factors by Human Serum Metabolites Derived from a Patented Saffron Extract Intake

“…Relevance and robustness of such an ex vivo clinical trial were initially validated by Wittrant’s group [ 28 , 29 , 30 , 31 , 32 , 33 ]. A sample size of 10 subjects was hypothesized to detect a minimum effect size of 1, with a two-sided 5% significance level and a power of 90%.…”

“…To address both of these knowledge gaps and to contribute to the understanding of saffron's mechanisms in humans, in particular in chronic inflammation diseases, we designed an ex vivo approach combining human serum compounds derived from the intake of a saffron extract and cell cultures and evaluated in this study whether these human circulating bioactives may influence the response to inflammatory stress in chondrocytes and intestine epithelial cells. Relevance and robustness of such an ex vivo clinical trial were initially validated by Wittrant's group [28][29][30][31][32][33]. A sample size of 10 subjects was hypothesized to detect a minimum effect size of 1, with a two-sided 5% significance level and a power of 90%.…”