In the study, TRPV1 receptor modulation in response to neuroinflammation induced by a pro-inflammatory stimulus performed on normal human astrocytes (NHA), and the neuro-soothing activity of Rhodosorus marinus was investigated.

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 revealed that the crude Rhodosorus marinus extract could 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% inhibited the release of IL-1α and NGF. 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 neuroinflammation.

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. Alongside, 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.

Active molecules, namely, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization related to the TRPV1 receptors under PMA-induced inflammatory conditions, providing an interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis.

In conclusion,it was demonstrated that the red microalgae Rhodosorus marinus contain several polar metabolites that were able to control the release of pro-inflammatory cytokine and neuro-inflammation mediators, and to positively regulate skin sensitization mechanisms related to the TRPV1 receptors.

The NMR chemical profiling and bioactivity-guided fractionation of the extract revealed the presence of two active molecules, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, with the capacity to significantly decrease TRPV1 over-expression in normal human astrocytes under PMA-induced inflammatory conditions.