Abstract
The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract. Two active molecules, namely, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization mechanisms related to the TRPV1 receptors under PMA-induced inflammatory conditions, therefore providing interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis.
Highlights
Skin is the first defensive barrier to protect the body against external aggressions including, for instance, temperature variation, bacterial/viral infections, or exposure to chemicals
Sensitive skins are generally predisposed to hyperalgesia promoted by the secretion of neuro-active molecules such as the nerve growth factor (NGF), substance P, or calcitonin gene-related peptide (CGRP) [8]
Transcriptomic analyses of the polar Rhodosorus marinus extract were performed on normal human epidermal keratinocytes using the TaqMan card which targets epidermis functions, to determine if the whole extract at 3% could have potential activity against neuro-inflammation
Summary
Skin is the first defensive barrier to protect the body against external aggressions including, for instance, temperature variation, bacterial/viral infections, or exposure to chemicals. Some types of skin are subjected to barrier function impairments that promote cutaneous permeability [5] In this case, the skin responds with an inflammatory reaction led by keratinocytes, skin immune cells, and recruitment of macrophages and neutrophils for the release of pro-inflammatory cytokines such as IL-1α, IL-1B, IL-6, IL-8, and CCL5 [6]. The skin responds with an inflammatory reaction led by keratinocytes, skin immune cells, and recruitment of macrophages and neutrophils for the release of pro-inflammatory cytokines such as IL-1α, IL-1B, IL-6, IL-8, and CCL5 [6] This chronic inflammation process results in roughness, dryness, burning, and redness that represent the physical features of sensitive and atopic skins [7].
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