1 Pure and Naturally Derived Meadowderm : Discover the Secret to Beautiful Skin
2 Imagine walking through a field of blooming white little flowers with a pleasant fresh sensation. This is like wandering through a field of beautiful Meadowfoam Flowers (Limnanthes alba), our source for unique and high value cosmetic ingredients. 2
4 Meadowfoam Seed Oil - A source for unique ingredients Meadowfoam Seed Oil unique molecular structure not found in any other naturally occurring substance high content of long-chain fatty acids offers extraordinary oxidative stability due to combination of lack of conjugated double bonds and its natural antioxidants
5 Meadowderm - The key to beautiful skin Meadowderm, the unique naturally derived active ingredient, provides measurable and meaningful anti-aging benefits (INCI: Meadowfoam Delta-Lactone)
6 Meadowderm Healthy and beautiful skin how? Studies conducted to prove the anti-aging benefits In-vitro studies targeting key genetic markers, demonstrate the bioactivity to improve the level of relevant key proteins inside the skin for youthfulness In-vivo data show significant improvements in skin texture, total wrinkle surface area and appearance in close-up images and silicone replica images
7 In-vitro Gene Expression Analysis of Full-Thickness Skin Cultures
8 Gene Expression - Biological Processes and Skin Appearance Changes in skin appearance caused by complex physiological and biological processes: Phenotype Day 0 Day 90 Wrinkles, pores size, age spots, gray tone, Changes in Processes Extracellular matrix integrity, anti-oxidant production, aging, DNA repair, hydration Genotype Changes in gene expression of Metalloproteinases, collagens, sirtuins, growth factors, enzymes,
9 The Extracellular Matrix (ECM) The Extracellular Matrix (ECM) is the non-cellular component present within all tissues and organs. It provides structure and biochemical support to the surrounding cells. The ECM provides essential physical scaffolding for cells It is composed of water, proteins, polysaccharides and other tissue-specific components Collagen: most abundant protein in the ECM It is required for tissue morphogenesis and differentiation
10 Fold-Change vs. Untreated Control Meadowderm increases expression of relevant ECM markers Extracellular Matrix Function FMOD 7 : Fibromodulin LUM 7 : Lumican DCN: Decorin TGFB1 8 : Transforming growth factor-ß FMOD LUM DCN TGFB1 TIMP2 COL4A2 TIMP2 9 : Tissue inhibitor of metalloprotease 2 COL4A2: Collagen 4A2 Control 2% Meadowderm Meadowderm treated samples demonstrate an increase in the expression of relevant components of the extracellular matrix.
11 ECM markers Family of Proteoglycans Proteoglycans Fibromodulin (FMOD), Decorin (DCN) and Lumican (LUM) Major components of the ECM Large ECM stabilising complexes together with other proteoglycans, hyaluronan and fibrous matrix proteins like collagen Assembly of collagen fibers Positive impact on hydration level due to net negative charge and attraction of Na + ions, which attract water molecules During aging structural differences and lower protein content of proteoglycans are known
12 ECM markers Other main structural proteins Transforming Growth Factor (TGFB1) 8 Known for stimulation of collagen synthesis Aged skin expresses less TGFB1, therefore less collagen synthesis foreseen Tissue Inhibitor of metalloprotease 2 (TIMP2) 9 Natural inhibitors of MMP s, therefore less degradation of extracellular matrix proteins like collagen Maintenance of tissue homeostasis of suspression of proliferation Collagen 4A2 (COL4A2) Major structural component of basement membrane Between dermis and epidermis Network collagen type Structural proteins of ECM are upregulated
13 Meadowderm actively contributes to Anti-Aging processes Interaction of Relevant Markers for ECM Breakdown and Anti-Aging SIRT1 Sirt 1 6 : Sirtuin 1 MMP-9 5 : matrix metallo-proteinase 9 MMP Control 2% Meadowderm Meadowderm treated samples show an increased Sirt 1 expression and a decreased MMP-9 expression.
14 Fold-Change vs. Untreated Control Meadowderm prevents skin cells from oxidative stress Increase in Anti-Oxidant Response (MT2A) 1 : Metallothionein isoform 2A (SOD2) 2,3 : Superoxide dismutase MT2A Control SOD2 2% Meadowderm Meadowderm treated samples show an increase in the expression of relevant proteins protecting the cell structures from oxidative stress.
15 Important markers of cellular Anti-Oxidant Response Meadowderm treated samples show an increase in the expression of relevant proteins protecting the cell structures from oxidative stress Oxidative stress Reactive Oxygen Species (ROS) are natural byproducts of metabolism and can contribute to aging Metallothionein isoform 2A (MT2A) 1 inhibits ROS- (reactive oxygen species) mediated cell death MT2A has a protective role against oxidative stress Superoxide dismutase 2 (SOD2) 2,3 is the main anti-oxidant enzyme that scavenges ROS Acts as a first line of defense against oxidative damage
16 Fold-Change vs. Untreated Control Meadowderm as skin hydrator to prevent aging 2.0 Skin Hydration GBA Control HAS2 2% Meadowderm GBA: Glucosidase, beta acid HAS2: Hyaluronan synthase Meadowderm treated samples lead to increased expression of Hyaluronan synthase 2 and Glucosidase, beta acid.
17 Key markers for water retention in the skin Meadowderm treated samples lead to increased expression of Hyaluronan synthase 2 (HAS2) HAS2 is responsible for hyaluronic acid (HA) synthesis in the skin 10 HA is a key component for water retention in the human skin 11 Meadowderm showed an increase in Glucosidase, beta acid (GBA) GBA is an enzyme responsible for the formation of epidermal ceramides, the main lipid components in cell membranes exhibiting good water binding capacities 12 With aging a decline of ceramides is known
18 In-vivo Three months efficacy testing on facial skin Half-face design
19 Project description skin study (1/2) Volunteers 12 participants Age 35-68, mean age 45 5 participants between years 5 male, 7 female participants Cream A right side of the face Half face design one face side treated with active, the other without active Cream B left side of the face Single-blind experimental set-up participants do not know which face side is treated with the active information was revealed after study was closed
20 Project description skin study (2/2) Application Twice a day with a specified volume of the creams For 3 months Discontinuation No other anti-aging treatments were allowed to be used during the study anti-aging actives in cosmetic formulations forbidden Normal skin regime was allowed decorative cosmetics, sun care without claiming anti-aging, shaving and after-shave products, skin cleaning products Measurement room All measurements and tests were conducted in a temperature controlled room (21 C +/- 1 C)
21 Experimental set-up Skin evaluation with different scientific devices: Valuable data by. VisioFace RD high resolution standardized full face photography Visioline VL 650/Quantirides Skin macro relief by silicone replica and oblique lighting Parameters analyzed: Total Wrinkle surface Wrinkle length Form Factor Wrinkle Depth Total Number of Wrinkles R side with 2% Meadowderm L side without active
22 Total Wrinkle Surface Area reduction Average of Total Wrinkle Surface Area over time Total Wrinkle Surface Area in % based on initial value Days. side treated without active side treated with 2% Meadowderm Initial Total Wrinkle Surface Area reading is taken as base Differences are given in percentage
23 Visible reduction of crow s feet for side with active Meadowderm VisioFace RD photography Day 0 Day 90 Participant stated a recognizable difference for side with active, not for side without
24 Silicon replicas show reduced wrinkle depth with Meadowderm Day 0 Day 90 Visible changes in the silicone replicas
25 No visible improvement for side without active VisioFace RD photography Day 0 Day 90 The side without active did not show any positive change
26 No changes on silicone replicas for side without active Day 0 Day 90 No visible changes on skin replicas for the side without active
27 3D image of selected wrinkle areas Side with active! The marked crow feet wrinkle area was selected for a zoom in. The sections are given in the silicone replica image as red coloured square.
28 3D image of selected wrinkle areas T1 Initial reading on side before applying any active Side with active! T2 After 1 month of using active T3 After 6 weeks of using active T4 After 2 months of using active Visible reduction of wrinkle depth (shown in dark blue) with Meadowderm
29 3D image of selected wrinkle areas Side without active! One section of one crow feet wrinkle was selected for the side treated with the placebo cream without Meadowderm. The sections are given in the silicone replica image as blue coloured square.
30 3D image of selected wrinkle areas T1 Initial reading on side before applying any active Side without active! T2 After 1 month of using active T3 After 6 weeks of using active T5 After 3 months of using active No improvement of wrinkle depth (shown in dark blue) without active
31 Meadowderm - Summary Unique functionally active ingredient for the effective treatment of skin In Vitro skin biomarker analysis led to distinct changes in expression of relevant genes upon treatment with Meadowderm In Vivo skin data confirm the anti-aging effect in reduction of total wrinkle surface area, which can also be seen by eye and in silicone replicas Data suggest that Meadowderm exhibits powerful antiaging characteristics and actively contributes to the health and beauty of our skin
32 List of literature references on gene expression results All our results are in line with published data 1 Reinecke et al (2006): Metallothionein isoform 2A is inducible and protects against ROS-mediated cell death in rotenone-treated HeLa cells. F.H. Biochem. J. 2 Velarde et al (2012): Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and aging phenotypes in the skin. AGING, Vol. 4. No. 1 3 Osborne et al (2013): Practical application of cellular bioenergetics to the care of aged skin. British Journal of Dermatology, 169, Suppl. 2: Rodier et al (2007): Two faces of p53: aging and tumor suppression. Nucleic Acids Research, Vol. 35, No. 22: Lee et al (2010): Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue. Experimental Dermatology, 19: Michan et al (2007): Sirtuins in mammals: insights into their biological function. Biochem J May 15; 404(1) 7 Velez-delValle et al (2008): Fibromodulin gene is expressed in human epidermal keratinocytes in culture and in human epidermis in vivo. Biochemical and Biophysical Research Communications, 371: El-Domyati et al (2014): Expression of transforming growth factor-b after different non-invasive facial rejuvenation modalities. International Journal of Dermatology, doi: /ijd Strongin et al (1995): Mechanism of cell surface activation of 72-kDa type IV collagenase. The Journal of Biological Chemistry, Vol. 270, No.10: Röck et al (2011): Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB). The Journal of Biological Chemistry, Vol. 286, No. 20: Pavicic et al (2011): Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol, 10(9): Uchida et al (2000): Epidermal sphingomyelins are precursors for selected stratum corneum ceramides, Journal of Lipid Research, Vol. 41:
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