P8123Microegrowth factors for skin rejuvenation

Michael H. Gold, MD, Gold Skin Care Center, Nashville, TN, United States; JulieBiron, Tennessee Clinical Research Center, Nashville, TN, United States

Background: Microegrowth factors are unique peptides with growth factorelikeactivities. They stimulate the formation of extracellular matrix componentsincluding collagens, elastin, and hyaluronic acid. Similarly as for protein growthfactors, microegrowth factors activity results after binding specific cell surfacereceptors. Although their receptor binding affinity is lower than protein growthfactors, their low molecular weight makes them valuable alternatives for topical usein skin rejuvenation.

Objective: To evaluate the safety and efficacy of a specific combination ofmicroegrowth factors for skin rejuvenation in humans. The combination ofmicroegrowth factors has been selected based on their properties to stimulatecollagen I, collagen III, collagen VII, elastin, and hyaluronic acid in human dermalfibroblasts.

Methods: Forty-two females of skin types I to III with at least moderate signs of facialwrinkles were enrolled in this IRB approved, randomized, vehicle controlled,parallel group, double blind study. Subjects used an oil-in-water emulsion creamwith microegrowth factors for 6 months twice daily after a wash-out period of 2weeks. Investigator evaluations included the assessment of periorbital and perioralwrinkles with a 5-point photonumeric visual analogue score before and after 1, 2, 3,and 6 months of treatment. Tactile roughness, skin pores, and skin tone were alsodetermined visually. Skin tolerability and subject’s self-evaluations by questionnaireswere further assessed. Primos analysis and Visia images were captured.

Results: The test product was well tolerated and significantly reduced periorbitaland perioral wrinkles starting after 2 months. Periorbital wrinkles improved (by atleast 1 unit) in 35% of the subjects after 1 month (from 2.96 0.5 before treatment to2.6 6 0.6; mean 6 SD, n ¼ 20), 71% after 3 months (2.1 6 0.6; n ¼ 17), and 88%after 6 months (1.86 0.4; n¼ 17). Perioral wrinkles improved (by at least 1 unit) in30% of the subjects after 1 month (from 2.7 6 0.6 before treatment to 2.4 6 0.6;mean6 SD, n¼ 20), 47% after 3 months (2.26 0.5; n¼ 17), and 71% after 6 months(1.7 6 0.5; n ¼ 17).

Conclusion: This study indicated that a cream with microegrowth factors can beused for skin rejuvenation. Additional studies are warranted in order to compare theefficacy of microegrowth factor with standard, protein growth factor products.

AB26

d 100% by Neocutis, Inc.

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P8158Mitigation of dysfunctional cellular bioenergetics in dermal fibroblasts byniacinamide under oxidative stress conditions

John Oblong, PhD, The Procter & Gamble Company, Mason, OH, United States

Daily exposure of human skin to environmental insults, such as solar radiation,pollution, and smoke, triggers numerous biologic processes that include oxidativestress and inflammation, which can lead to dysfunction of cellular processes,ultimately impacting tissue integrity and appearance. One of the main effects fromoxidative stress on cells is a diminished capacity of cellular bioenergetics. To betterunderstand changes in cellular metabolism caused by oxidative stress, glycolysis andoxidative phosphorylation rates in human dermal fibroblasts were monitored in realtime under controlled nonlethal oxidative stress conditions. Hydrogen peroxidewasused as a surrogate stressor because numerous environmental stressors and intrinsicaging trigger its production. H202 ranging between 0.5-3 mM caused a significantdecrease in glycolytic and oxidative phosphorylation rates along with cellular ATPand NAD+ levels. Niacinamide (Nam) was found to protect and restore glycolyticrates concurrent with restoring ATP to control levels. NAD+ levels were significantlyrestored as well. Nam had an effective dose response range between 0.1-1.0 mM,with maximal effects attained at 0.5 mM. Relative to oxidative phosphorylation,niacinamide was able to provide a diminished but significant level of protection. Aglycolytic stress assessment of niacinamide’s effects on glycolysis under normal andperoxide stress conditions showed a significant ability to mitigate the stress-induceddecrease in glycolytic rates but niacinamide was not able to restore spare glycolyticcapacity. Nam had no effect on restoring spare respiratory capacity. Testing withFK866, a known NAMPT inhibitor, was found to significantly inhibit niacinamideprotective effects, supporting that niacinamide mechanism of action involves NAD+synthesis. These results support ongoing in vitro research showing that niacinamidehas a protective effect on cellular metabolism, particularly glycolysis, underoxidative stress conditions induced by H202 and that part of its mechanism ofaction involves maintenance of NAD+ cellular pools.

d 100% by The Procter & Gamble Company.

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J AM ACAD DERMATOL

P7817Neohesperidin DHC combined with vetegal extracts modulate someantiaging markers in an ex vivo model

Dominique Fagot, L’Oreal Research & Innovation, Aulnay sous Bois, France; AliceLaurent-Lesaffre, L’Oreal Research & Innovation, Chevilly Larue, France; BeatriceRenault, L’Oreal Research & Innovation, Chevilly Larue, France; Isabelle Bossant,L’Oreal Research &Innovation, Chevilly Larue, France; Marie Helene Gaudinat,L’Oreal Paris, Clichy la Varenne, France

Objective: The study aimed at evaluating the modulation of epidermal and dermalskin markers on an artificially aged skin samples following topical applications of acombination of neohesperidin DHC with Cicer arietum and Vigna aconitifoliaextracts.

Methods: Skin samples were obtained from plastic surgery and were artificially‘‘aged’’ at D0 and D1 by topical applications of a class II dermocorticoid(betamethasone 0.05%: 2 mg/cm2). Four groups were tested: (1) control skin; (2)artificially ‘‘aged’’ skin without any further application, (3) positive control(artificially ‘‘aged’’ skin treated with TGF-beta 5 ng/mL), and (4) artificially ‘‘aged’’skin with a daily topical application at D1, D2, and D3 of a combination ofneohesperidin DHC at 30 �M with C arietum at 0.2% and V aconitifolia at 0.3%extracts. Histologic and immunohistologic analysis were performed: cell prolifera-tion was analyzed by quantifying mitotic cells (KI67 marker); papillary extensionthickness was measured by image analysis of hematoxylineeosin (H&E) stainedsamples. Laminin 5 and a 6 integrin at the DEJ level were quantified byimmunohistologic labeling. Histologic staining with alcian blue allowed glycosami-noglycans to be evaluated.

Results: ‘‘Aged’’ skin samples showed a significant decrease of the mitotic index,epidermal thickness, laminin 5 expression, and a decreasing trend in a6 integrinexpression and in glycosaminoglycans quantity versus control skin. ‘‘Aged’’ skinsamples treated with the 3 ingredient combination showed a significant increase inthe expression of the mitotic index and in the papillary extension thickness versuspositive control. A strengthening of the DEJ was also observed with a significantincrease in laminin 5 expression versus positive control. An increase of theepidermal anchorage was observed with a significant increase in expression of a 6integrin versus positive control. These markers are both involved in adhesion ofepidermal stem cell environment to the basal membrane for optimal epidermalrenewal. An increase in glycosaminoglycans at the dermis level was also found.

Conclusion: This study demonstrated the benefits of the association of neohesper-idin DHC with C arietum and V aconitifolia extracts in the positive modulation ofseveral biologic and histologic markers of skin aging ex vivo.

cial support: None identified.

Commer

P8132Novel antioxidant serum with high antioxidant capacity: An ESR-basedstudy

Frank Dreher, PhD, Neocutis, Inc, San Francisco, CA, United States; Alan Olansky,MD, Olansky Dermatology Associates, Atlanta, GA, United States; Jens Thiele,MD, PhD, Dermatology Specialists, Inc, Oceanside, CA, United States

Background: Apart from using sunscreens, supplementation of the skin withtopically applied antioxidants and thereby strengthening its antioxidative capacity(AC) is an established approach in limiting oxidative stress induced skin damages.The quantification of antioxidant capacity of an antioxidant preparation is, however,a challenging task. For instance, decolorization assays including the Oxygen RadicalAbsorbance Capacity (ORAC) have been recognized as artifact- prone, and also notapplicable for colored or opaque. A novel method based on electron spin resonance(ESR) spectroscopy was described as more accurate and further allowing measuringantioxidant capacity in colored or opaque samples, ex vivo, and in vivo.

Objective: To evaluate the AC of a novel antioxidant serum comprising 15% ascorbicacid and 1% alpha-tocopherol combined with epigallocatechin gallate, dimethylme-thoxy chromanol, and creatine in a silicon-oil based preparation; and to compare itsantioxidant capacity to other marketed antioxidant products using a novel ESR-method.

Methods: AC of a novel antioxidant serum and the other antioxidant products wasdetermined by following the reducing activity against the stable test radicaldiphenyl-picryl-hydrazyl with ESR-spectroscopy using the X-band ESR spectrometerMiniscope MS 300 (Magnettech, Germany). The results were expressed inantioxidative units (AU), where 1 AU corresponds to the activity of a 1 ppm solutionof ascorbic acid as a benchmark; and reaction time (minutes). Three differentbatches of each product were tested.

Results: The AC of the novel antioxidant serum was with 156.866 6 13.497 AUsignificantly higher than a test product comprising 15% ascorbic acid, 1% alpha-tocopherol and 0.5% ferulic acid, which reached 100.271 6 17.197 AU. Anotherproduct comprising 10% ascorbic acid, 5% tetrahexyldecyl ascorbate, and acombination of tocopherol and tocopherol acetate reached 69.237 6 3.799 AU.The novel antioxidant serum further revealed the fastest reaction time of all threeproducts with 0.17 6 0.00 min as compared to 0.23 6 0.01 min for both otherproducts.

Conclusion: Using an ESR-based method to determine AC, a novel antioxidant serumwas shown to be of high antioxidant power and fast reaction time. Since this methodallows measuring the AC more accurately than ORAC, it should be preferentiallyused to describe topical antioxidant preparations.

d 100% by Neocutis, Inc.

Supporte

MAY 2014