GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization

Autor: Romain Reynaud, Amandine Scandolera, Audrey De Bizemont, Jean-Hugues Renault, Jane Hubert, Carole Lambert, Jean-Marc Nuzillard, Abdelmajid Kaouas, Anne Humeau, Chris Winkel
Přispěvatelé: Givaudan ACI, Soliance, Chimie des Substances Naturelles (ICMRCSN), Institut de Chimie Moléculaire de Reims - UMR 7312 (ICMR), SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Givaudan
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Keratinocytes
0301 basic medicine
pain sensing
TRPV1
TRPV Cation Channels
Pharmaceutical Science
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Pharmacology
TRPV1 receptor
pro-inflammatory cytokines
Receptor
Nerve Growth Factor
Article
Proinflammatory cytokine
Rhodosorus marinus
03 medical and health sciences
neuro-inflammation
0302 clinical medicine
Interleukin-1alpha
Nerve Growth Factor
Drug Discovery
medicine
Humans
Secretion
microalgae
NMR-based dereplication
Receptor
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
lcsh:QH301-705.5
Cells
Cultured
gamma-Aminobutyric Acid
Skin
Inflammation
Neurons
Alanine
Chemistry
Biological activity
In vitro
Epithelium
030104 developmental biology
medicine.anatomical_structure
Nerve growth factor
lcsh:Biology (General)
Tetradecanoylphorbol Acetate
Inflammation Mediators
030217 neurology & neurosurgery
Zdroj: Marine Drugs, Vol 16, Iss 3, p 96 (2018)
Marine Drugs
Marine drugs
Marine drugs, MDPI, 2018, 16 (3), pp.96. ⟨10.3390/md16030096⟩
Marine Drugs; Volume 16; Issue 3; Pages: 96
ISSN: 1660-3397
DOI: 10.3390/md16030096⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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