How to take care of the window of our soul? Gentiopicroside-rich Gentiana lutea extract: an integrative solution for the eye contour
Podium 15
Presented by: Lauriane Roux-Imbert
Introduction: The eyes are considered to be the window of the soul and the focal point of social interaction (Canigueral and Hamilton, 2019). Take care of this area is thus very important, all the more so after the pandemic we are going through, screen time due to work from home and binge watching having led to dark circles and wrinkles. Because of this, the under-eye area looks worn out and old. Even if the physiopathology of skin ageing is multifactorial, cell degeneration involving the accumulation of advanced glycosylation end products (i.e., Advanced Glycation End-products -AGE) (Ly et al., 2000) is a key factor. Production of AGEs on collagen leads to cross-linking inducing abnormalities in the extracellular matrix, impairing cell-matrix interaction and leading to skin sagging. AGEs also bind to specific receptors on immune cells which triggers the release of inflammatory mediators and generation of ROS leads to increase in the production of AGEs damage. Other factor altering the eye appearance concern the microcirculation, inducing fluid accumulation, and forming puffy eyebags. Besides medical treatment such as plastic surgery for the eye area, topical solutions including caffeine or retinol can be proposed. It has also been shown that Gentiopicroside, the important active component of total secoiridoid glycosides has anti-inflammatory and antibacterial activities (Zhao et al., 2015). In this study, Gentiana lutea Extract (GlE) containing gentiopicroside (65% per dry matter) was evaluated in in vitro, ex vivo and in vivo studies for its activity to create a multi-functional effect on the eye contour.
Methods: The effect of GlE on antioxidant, inflammation and angiogenesis responses was evaluated in vitro by RT-qPCR after treatment of Normal Human Dermal Fibroblasts (NHDF). The effect of GlE on angiogenesis was also investigated by evaluating VEGF-induced pseudotube formation in a co-culture system composed of NHDF and Human Dermal Microvascular Endothelial Cells (HMVEC-dAd). The formation of AGEs (Nε-(carboxymethyl)lysine; CML) and Glyoxalase-1 (GLO-1) expression were quantified on skin explants topically treated with 0.5% (v/v) of GlE or vehicule, in basal and UVA-irradiated conditions. An in vivo study was conducted with two different volunteer panels to ascertain the efficacy of GIE in improving the eye contour. Twice applications per day on eye contour (cream containing 0.5% of GIE on one eye and a placebo cream on the other) were realized by 22 volunteers (43-64 years) with saggy upper eyelids/dark circles, and 22 volunteers (47-64 years) with eye bags/visible tear trough during 28 days. 3D image acquisition using DermaTop and skin color measurement (Spectrocolorimeter) were performed at D0, D14 and D28.
Results: GlE upregulated the gene expression of NFE2L2 and SIRT4 and downregulated the expression of CXCL-8 and Heme Oxygenase-1 (HMOX-1) gene coding for heme-oxygenase involved in the formation of bilirubin. It decreased the vascular permeability and the angiogenesis through the reduction of the VEGF-A gene (Vascular Endothelial Growth Factor) and the formation of pseudotubes in a NHDF-HMVEC-Ad co-culture system when stimulated with VEGF. Significant reduction of CML concentrations in both epidermis (p<0.01) and dermis (p<0.05) following UVA irradiation were noted compared to vehicule. In contrast, GLO-1 was significantly increased (p<0.01), the glyoxalase system being critical for the detoxification of AGEs. At clinical level, compared to placebo, GlE cream significantly reduced skin rugosity (-12% vs D0 (p<0.05); p<0.05 vs placebo) and the fold height of the upper eyelids after 28 days (-15% vs D0 (p<0.01); p<0.05 vs placebo). Of to note, this first clinical benefit was visible as soon as 14 days. Significant decrease in the redness of dark circles, eye bags and tear trough severity were also noted on the GlE-treated area of the face compared to placebo (p<0.05).
Discussion and Conclusion: GIE targeted different cellular pathways and effectively reduced the upper eyelid sagging and the under-eye contour issues (dark circles, eye bags, tear trough), providing a complete care for the eye contour. By targeting glycation pathways which stimulate cell inflammation pathways, inducing alteration of type 1 collagen structure, and through the upregulation of the Nrf2 antioxidant pathway, which can alleviate oxidative damage and oxidized lipid accumulation, and upregulation of glyoxalase system, a primary mechanism that limits AGEs formation, GIE is a systemic anti-ageing strategy for skin care in the eye contour area (Aragonès et al., 2021).