meiyanol Anti-dark circles Anti-eye bags Anti-oxidation Iron chelation

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meiyanol Anti-dark circles Anti-eye bags Anti-inflammation Iron chelation

Eye contour : Dark circles and puffy eyes Applications The area around eyes is extremely sensitive to environmental stress (UV, pollution, fatigue, aging ) as the skin is the thinnest of the body at this location. The most visible symptoms to address for under-eye treatments are eye bags and dark circles, both of which are caused by a three-step inflammation reaction: EPIDERMIS UV POLLUTION AGING... FATIGUE 1 Stress (UV, pollution, aging,...) triggers a signaling cascade with the upstream release of pro-inflammatory cytokines (mostly TNFα) that leads to the activation of NFkB. ROS, and especially iron-mediated ROS formation play a key role in this process. DEJ Fibroblast Pro-inflammatory Cytokines (such as TNF-α) 2 NFκB is also responsible for the expression of cellular adhesion molecules (such as VCAM-1 and ICAM-1) in blood vessels. These proteins will bind the attracted leukocytes (white blood cells) at the inflammation area. 3 Bound leukocytes lead to endothelial barrier disruption that allows leukocytes to undertake the extravasation process: translocation from blood vessels to the dermis. This mechanism also causes a leakage of plasma and of a multitude of red blood cells in the surrounding tissue. The accumulation of plasma is responsible for eye bags (edema), and the red blood cells leak is responsible for the apparition of a dark red coloration : dark circles. DERMIS Blood vessel Lumen 1 2 Proteoglycans TNF receptor Rolling White blood cells Endothelial cells NFkB activation VCAM-1 ICAM-1 Diapedesis Extravasation Red blood cells 3 INCI name: SAMBUCUS nigra flower extract Skin benefits. Decreases inflammation. Reduces anchoring proteins expression at the surface of endothelial cells Improves microcirculation. Iron chelation C H I N A I A N T C O M P L Detailed scientific files are available on demand for each of these benefits. Developed in collaboration with perfumers from Grasse (France), is an ecoresponsible extract of elderberry (Sambucus nigra) flowers which are rich in flavonoids and other polyphenols for strong anti-oxidant and anti-inflammatory properties. Obtained by optimized extraction methods and biorefining techniques, is capable of reducing both edema and dark circles around the eyes. Cosmetic applications. Anti-dark circles. Anti-puffy eyes. Reduces redness. Reduces edema

: ROS scavenging and iron-chelating properties limit inflammation Inflammation TNF α ROS Iron-mediated ROS DPPH Iron chelation Ferrozine test IC 50 (g/l) 0.34 3.8 Free radicals, and especially ROS (reactive oxygen species) have a key role in the inflammation process leading to the apparition of dark circles and puffy eyes. Indeed, ROS have the ability to enhance the inflammatory reaction. is capable of efficiently scavenging and neutralizing ROS as observed using DPPH assay. Iron also plays a role in inflammation as it takes part in the oxidation reaction that results in ROS generation. This is especially true for the undereye area where dark circles are mostly due to an accumulation of red blood cells rich in iron (hemoglobin). has strong iron chelating properties as measured using the ferrozine assay. Because of both its anti-oxidant and iron chelating properties, is able to neutralize ROS and to prevent the formation of new iron-mediated free radicals. inhibits the expression of anchoring proteins Expression of attachment proteins VCAM-1, ICAM-1 Leukocytes attachment to blood vessels wall is an early response to proinflammatory signals, leading to vessels permeabilization and edema. This attachment is mediated by cell adhesion molecules (CAMs) expressed by endothelial cells in the lumen surface of micro-vessels. Vascular CAM 1 (VCAM-1) and Intercellular CAM 1 (ICAM-1) are two key attachment proteins involved in both leukocytes adhesion and diapedesis (permeabilization of endothelial barrier). Treatment with inhibits the expression of anchoring proteins (VCAM-1 in green, nuclei in blue (DAPI)) at the surface of endothelial cells. (g) VCAM-1 expression (% of control) 600 500 400 300 200 100 0 TNFα TNFα reduces the attachment of white blood cells Attachment of white blood cells Disruption of endothelial barrier Because fewer attachment proteins are expressed at the surface of endothelial cells, fewer white blood cells will be bound in the lumen of blood vessels. Treatment with reduces the number of white blood cells (in green) bound to endothelial cells (nuclei in blue, DAPI) hence decreasing the disruption of the endothelial barrier and both plasma and red blood cells leaks. (g) Number of bound white blood cells per 100 HDMEC 75 50 25 0 TNFα TNFα limits red blood cells darkening White blood cells extravasation Plasma leak Red blood cells leak Once outside the vascular system, red blood cells quickly burst and release free hemoglobin (Hb), which is readily oxidized to form colorful (and pro-inflammatory) brownish byproducts. Treatment with reduces the oxidation of hemoglobin hence decreasing the blood darkening in the under-eye area. (g) Blood coloration (a.u.) 14 13 12 11 10 9 8 7 Edema Eye bags Dark circles D0 D0

Clinical trial Realized under dermatological control, a clinical trial was performed on 22 volunteers aged 30 to 50. The volunteers received a treatment with (1,5%) or a placebo applied twice a day on the face for 28 days. for the treatment of puffy eyes C H I N A I A N T C O M P L Using macrophotographs analysis methods, the volume of eye bags was measured. A treatment with efficiently decreased puffy eyes in the greatest majority of subjects. BEFORE ANALYTICAL COMPOSITION Sambucus nigra 5% Propanediol 50% Water (sq) 100% Δ % (on mean) Subjects showing improvement AFTER PHYSICO-CHEMICAL CHARACTERISTICS Limpid to slightly opalescent, orange to burgundy-red liquid ph 5 Density at 20 C 1.06 Miscible with water, alcohol and glycols. Δ (D28-D0) -13% 91% PRESERVATIVES No preservative for the treatment of dark circles Using the TiVi method that allows to observe the accumulation of red blood cells in selected area, the dark circle intensity was measured. TOLERANCE AND TOXICITY STUDIES does not show any toxicity, and tolerance studies show that it is perfectly tolerated. BEFORE AFTER A treatment with efficiently decreased the intensity of dark circles in the greatest majority of subjects. This is due to the double action of for reducing the red blood cells leak, and for preventing the darkening of hemoglobin. Dark circles are fainter and lighter. Macrophotographs FORMULATION Advised doses : 0.5% - 1.5%. No particular formulation restriction. Δ % (on mean) Subjects showing improvement TiVi Availabilities is available in 5kg and 30kg drums Δ (D28-D0) -11% 91%

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