A Cistus incanus Extract Blocks Psychological Stress Signaling and Reduces Neurogenic Inflammation and Signs of Aging in Skin, as Shown in In-Vitro Models and a Randomized Clinical Trial

Psychological stress exerts its effects mainly through the release of corticotropin releasing hormone (CRH), which activates inflammatory pathways in skin (inter alia), resulting in redness, extracellular matrix degradation, loss of skin elasticity and firmness, and the appearance of wrinkles—namely, accelerated skin aging. In order to propose a solution to this neurogenic aging phenomenon, we report here on studies using a myricitrin-rich extract of Cistus incanus, a Mediterranean shrub used in traditional medicine for the treatment of inflammatory and other diseases. These studies include a CRH receptor (CRH-R1) blocking assay; in vitro inflammatory cytokine reduction under CRH stimulation, and ex vivo NF-kB inhibition; and a double-blind clinical trial performed on highly stressed panelists, evaluating skin inflammation and wrinkling (active formulation vs. placebo control, applied split-face following a computer-generated randomization scheme; 36 subjects recruited and randomized, 30 analyzed; no adverse effects recorded; EMA/INFARMED registration #118505, internally funded). The results show that this extract can effectively block the CRH-R1 receptor, preventing NF-κB activation and the production of related pro-inflammatory cytokines. In a clinical setting, this same extract delivered significant anti-inflammatory and anti-aging effects. Taken together, these results demonstrate the value of this extract as a cosmetic active to counter neurogenic inflammation and skin aging

A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

International audienceOlfactory receptors (ORs) are expressed and active in various human tissues, including the skin. Although the sense of smell plays an important physiological role in the regulation of mood and stress, a link between olfactive compounds, ORs, and skin stress has yet to be established. This study aims to investigate the role of newly identified skin ORs and agonists in the modulation of skin stress. Screening for odorant molecules was done with cAMP functional assay to identify OR agonists. RT-qPCR and immunofluorescence microscopy were conducted to identify and quantify ORs in epidermal keratinocytes (NHEKs) and human skin explants, as well as to evaluate specific markers (G6PDH, loricrin, and γH2AX) of stress-induced skin alterations. A randomized double-blinded, split-face clinical study was performed on a panel of stressed women to measure the benefits of OR agonist treatment for skin. Three new ORs (OR10A6, OR2AG2, and OR11H4) were identified in skin. A specific Rose extract and its major constituent (phenylethyl alcohol) were found to activate these ORs. The extract composition was revealed by both GC/FID and GC/MS analyses simultaneously and showed the presence of 34 volatiles molecules. Moreover, epinephrine induces a skin stress response characterized by increased expression of G6PD, loricrin, and γH2AX biomarkers, and a decrease of OR expression. These effects were prevented in the presence of rose extract and its benefits were confirmed clinically by a decrease in the appearance of under-eye dark circles. Altogether, our findings suggest that ORs may represent a new, promising way to treat stress-associated skin disorders

A <i>Cistus incanus</i> Extract Blocks Psychological Stress Signaling and Reduces Neurogenic Inflammation and Signs of Aging in Skin, as Shown in In-Vitro Models and a Randomized Clinical Trial

Psychological stress exerts its effects mainly through the release of corticotropin releasing hormone (CRH), which activates inflammatory pathways in skin (inter alia), resulting in redness, extracellular matrix degradation, loss of skin elasticity and firmness, and the appearance of wrinkles—namely, accelerated skin aging. In order to propose a solution to this neurogenic aging phenomenon, we report here on studies using a myricitrin-rich extract of Cistus incanus, a Mediterranean shrub used in traditional medicine for the treatment of inflammatory and other diseases. These studies include a CRH receptor (CRH-R1) blocking assay; in vitro inflammatory cytokine reduction under CRH stimulation, and ex vivo NF-kB inhibition; and a double-blind clinical trial performed on highly stressed panelists, evaluating skin inflammation and wrinkling (active formulation vs. placebo control, applied split-face following a computer-generated randomization scheme; 36 subjects recruited and randomized, 30 analyzed; no adverse effects recorded; EMA/INFARMED registration #118505, internally funded). The results show that this extract can effectively block the CRH-R1 receptor, preventing NF-κB activation and the production of related pro-inflammatory cytokines. In a clinical setting, this same extract delivered significant anti-inflammatory and anti-aging effects. Taken together, these results demonstrate the value of this extract as a cosmetic active to counter neurogenic inflammation and skin aging

A novel dominant-negative mutant form of Epstein–Barr virus latent membrane protein-1 (LMP1) selectively and differentially impairs LMP1 and TNF signaling pathways

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A Dunaliella salina Extract Counteracts Skin Aging under Intense Solar Irradiation Thanks to Its Antiglycation and Anti-Inflammatory Properties

Glycation, and the resulting buildup of advanced glycation end products (AGEs), is recognized as a key driver of cumulative skin damage and skin aging. Dunaliella salina is a halophile microalga adapted to intense solar radiation through the production of carotenoids. We present a natural supercritical CO2 extract of Dunaliella salina rich in the colorless carotenoids phytoene and phytofluene. The extract exhibited antiglycation and anti-inflammatory activities in ex vivo testing, showing strongly reduced formation of N-&epsilon;-carboxy-methyl-lysine with exposure to methylglyoxal, reduced AGE receptor levels, and significantly reduced interleukins 6 and 8. In a placebo-controlled clinical study under intense solar exposure, the extract significantly reduced the skin&rsquo;s glycation scores and its sensitivity to histamine; key skin aging parameters were also significantly improved vs. placebo, including wrinkle counts and spots. These results demonstrate the value of this Dunaliella salina extract, rich in colorless carotenoids, as an antiglycative, anti-inflammatory, and antiaging active ingredient, including in high-irradiation contexts

Two Human Immunodeficiency Virus Vaccinal Lipopeptides Follow Different Cross-Presentation Pathways in Human Dendritic Cells

An efficient vaccine against human immunodeficiency virus (HIV) must induce good cellular immune responses. To do this, it must be processed and presented by dendritic cells, which are required for primary T-lymphocyte stimulation. We have previously shown that a model lipopeptide containing a short epitopic peptide from HIV-1 was endocytosed and presented in association with major histocompatibility complex class I molecules by human dendritic cells to specific CD8(+) T lymphocytes, but the cross-presentation pathway needed to be precisely determined. We have studied a longer lipopeptide (Pol(461-484)) and another lipopeptide (Nef(66-97)) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol(461-484) lipopeptide was internalized by endocytosis, as assessed by confocal microscopy. The lipopeptides were processed by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201-restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope, respectively. Presentation of both lipopeptides was inhibited by brefeldin A. Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome-specific inhibitor, but not by monensin. This shows that it gained access to the cytosol to be digested by the proteasome. In contrast, presentation of the Nef lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a classical inhibitor of acid-dependent endosomal enzyme activity, indicating an endocytic processing pathway yielding to major histocompatibility complex class I-restricted presentation. Therefore, the two lipopeptides followed different cross-presentation pathways, both resulting in efficient presentation to CD8(+) T lymphocytes

Grafting of synthetic mannose receptor-ligands onto onion vectors for human dendritic cells targetingElectronic supplementary information (ESI) available: full experimental details. See http://www.rsc.org/suppdata/cc/b2/b206980f/

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