ANTI-AGEING
associated with a decline during skin ageing. Secondly, molecular docking was used to
evaluate the affinity of the rosewood extract with retinoic acid receptors. Retinoids are natural and biologically active compounds of vitamin A (retinol, retinal and retinoic acid) as well as synthetic analogues of retinol. Activation of the retinoic acid signaling pathway is a well- known skin anti-ageing strategy.5
Retinoids are
active molecules influencing the structure of the skin, but they have irritating side effects. The molecular docking technique is used
to predict how a ligand (a small molecule) interacts with a protein (an enzyme or a receptor) of known three-dimensional structure. The goal is to find the preferred orientation, affinity, and interaction of the ligand in the protein’s binding site. Molecular docking involves searching high-dimensional spaces effectively and using a scoring function that ranks candidate dockings. Therefore, the first step was to identify
the binding site of some retinoid receptors through known crystal structures, then to place a molecule in random orientations within the binding site and calculate a binding energy or score. The cotoïn, a molecule identified in the rosewood extract, obtained a high score for the binding with retinoic acid receptor gamma (RAR-γ) and with the Cell Retinoic Acid Binding Protein-II (CRABP2). Molecular docking did predict that the rosewood extract could be associated with retinoid-like benefits.
Validation of the biological activity of rosewood extract on seven key influential markers in Asian and Caucasian skin, in vitro The experimental validation of the efficacy of the rosewood extract on the seven face- sculpting markers including fibulin 7, collagen 17, collagen 5A3 was carried out in ex vivo Caucasian and Asian skin. Fibulin-7, in addition to its involvement in the shape and contours of the face, interacts with the extracellular matrix and plays a crucial role in the maintenance of epidermal stem cells during skin ageing.6 Collagen 17 is a transmembrane structural
component of the hemidesmosome that mediate adhesion of keratinocytes to the underlying membrane. In addition to its
FIBULIN 7
47
Figure 1: Exploring and mapping all genes associated with face sculpting using in silico research The topical application of 1% rosewood
involvement in the shape and contours of the face, collagen 17 mediates stem cell interactions with surrounding cells and the matrix, allowing the maintenance of stem cells and their niche.7 Collagen 17 is significantly reduced in
naturally aged, photoaged, and acute UV- irradiated human skin in vivo.8
Collagen
17 deficiency also leads to phenotypes of premature hair ageing and junctional epidermolysis bullosa.9 Collagen 5 is a fibrillar collagen present in the skin dermis and described to co-assemble with collagen 1 into heterotypic fibrils, acting as a dominant regulator of collagen fibrillogenesis. Recent research showed that genetic variations in the alpha 3 subunit of Collagen 5 (collagen 5A3) were associated with genetic predispositions related to sagging skin and wrinkles in the corner of the eye in an Asian study panel.10
In addition, a deficiency
in Collagen 5A3 induced by the action of MMP9 metalloprotease could be significantly associated with eczema.11
COLLAGEN 5A3 COLLAGEN 17
extract on normal human skin biopsies obtained from plastic surgery was associated with an observed increase in fibulin 7, collagen 5A3 and collagen 17 content after 48 hours (+39%, 24% and +94%, respectively), see Figure 2.
Cell retinol binding protein-II (CRABP2) Retinoids play an important role in epidermal cell growth and differentiation and are beneficial to counteract skin ageing. Cellular retinoic acid binding protein-II (CRABP2) selectively binds all transretinoic acid, the most active retinoid metabolite, contributing to regulate intracytoplasmic retinoid trafficking and keratinocyte differentiation. A deficiency in the expression of CRABP2 accelerates and promotes skin ageing.12
The
topical application of 1% rosewood extract on human skin biopsies showed an increase in CRABP2 in both Asian and Caucasian skin and confirmed in silico predictions with molecular docking technique (Figure 3). Additional tests showed that the topical
application of 1% rosewood extract on ex vivo Asia skin did not increase the IL-1 receptor (IL1R1) associated with inflammation, compared to retinoic acid where IL1-R1 was significantly increased.
34 year-old 54 year-old 39 year-old
Figure 2: Immunodetection of fibulin 7, collagen 5A3, collagen 17 in Asian skin biopsies treated with 1% rosewood extract for 48 hours
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Clinical trials show less visible, smoother wrinkles and lifted facial contours Two double blind clinical studies were carried out on Asian and Caucasian study participants applying a cream with 1% rosewood or the placebo formulation, twice a day, for 28 and 56 days respectively. Results on Asian study participants showed less visible crow’s feet wrinkles after seven days, compared to placebo formulation (Figure 4).
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