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Life Extension Magazine November 2013

Skin care

Efficient topical delivery of chlorogenic acid by an oil-in-water microemulsion to protect skin against UV-induced damage.

We examined the intradermal delivery of a hydrophilic polyphenol chlorogenic acid by in vitro study using excised guinea pig dorsal skin and Yucatan micropig skin. Skin accumulation as well as the solubility of chlorogenic acid in aqueous vehicles was much greater than for other polyphenols such as quercetin and genistein. However, since enhancement of skin delivery seemed to be necessary to exhibit its protective effects against oxidative damage of skin, we examined the effects of microemulsions as vehicles. Using microemulsions consisting of 150 mM NaCl solution, isopropyl myristate, polyoxyethylene sorbitan monooleate (Tween 80) and ethanol, skin accumulation as well as solubility of chlorogenic acid further increased. Enhancement effect of an oil-in-water (o/w-type) microemulsion was greater than that of a water-in-oil (w/o-type) microemulsion possibly due to the greater increase in solubility. This finding was quite different from previous findings on relatively hydrophobic polyphenols such as quercetin and genistein. Pretreatment of guinea pig dorsal skin with chlorogenic acid containing microemulsion gel prevented erythema formation induced by UV irradiation. These findings indicate the potential use of hydrophilic chlorogenic acid with o/w-type microemulsion as a vehicle to protect skin against UV-induced oxidative damage.

Chem Pharm Bull (Tokyo). 2011;59(6):793-6

Protection from photodamage by topical application of caffeine after ultraviolet irradiation.

BACKGROUND: Characterization of mechanisms that can reverse residual damage from prior skin exposure to ultraviolet (UV) would be of considerable biological and therapeutic interest. Topical caffeine application to mouse skin that had previously been treated with UV has been shown to inhibit the subsequent development of squamous cell carcinomas. OBJECTIVES: We used an established mouse photodamage model to investigate other possible effects of topical caffeine application after UV. METHODS: SKH-1 hairless mice were treated with ultraviolet B (UVB) followed immediately by topical application of caffeine or vehicle three times weekly for 11 weeks. RESULTS: Caffeine applied topically after UV treatment resulted in a significant decrease in UV-induced skin roughness/transverse rhytides as assessed by treatment-blinded examiners. Histologically, topical caffeine application after a single dose of UVB more than doubled the number of apoptotic keratinocytes as evaluated by sunburn cell formation, caspase 3 cleavage and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) staining. A trend towards decreased solar elastosis was noted in the caffeine-treated group although this was not statistically significant. Other histological parameters including epidermal hyperplasia, solar elastosis and angiogenesis were increased in mice treated with UV but topical application of caffeine did not alter these particular UV effects. CONCLUSIONS: These findings support the concept that topical application of caffeine to mouse skin after UV irradiation promotes the deletion of DNA-damaged keratinocytes and may partially diminish photodamage as well as photocarcinogenesis.

Br J Dermatol. 2007 May;156(5):957-64

Effect of green Coffea arabica L. seed oil on extracellular matrix components and water-channel expression in in vitro and ex vivo human skin models.

BACKGROUND: Green Coffea arabica L. seed oil is being widely
used in cosmetic formulations, although its effects on human skin cells are not clear and most observations are unpublished. AIMS: In this study, we evaluated the in vitro effects of green coffee (C. arabica L.) oil (GCO) on the synthesis of collagen, elastin, and glycosaminoglycans (GAG) and in the release of transforming growth factor-beta1 (TGF-beta1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by human skin fibroblasts. We also investigated the ability of GCO to increase aquaglycerolporins-3 (AQP-3) mRNA expression in cultured keratinocytes and human skin explants. METHODS: Human fibroblasts were incubated for 48 h with several GCO concentrations (3.12, 6.25, 12.5, 25.0 and 50.0 mg/mL). The levels of growth factors and extracellular matrix compounds in the culture supernatant were measured using commercial kits. To evaluate AQP-3 relative expression, using real-time reverse transcription polymerase chain reaction, keratinocytes were incubated for 3-6 h with the GCO optimal concentration of 25.0 mg/mL. Histological sections of human skin were also incubated with GCO (25.0 mg/mL) and immunostained by antiserum against AQP-3. RESULTS: Our results demonstrated that incubation with GCO produces a dose-dependent stimulation in the synthesis of collagen, elastin, and GAG, in addition to increasing the release of the growth factors TGF-beta1 and GM-CSF. GCO also induced the expression of AQP-3 mRNA, which reached levels up to 6.5-fold higher than those of the control cultures. CONCLUSION: The findings presented herein suggest that GCO might improve physiological balance in the skin, thus allowing the formation of new connective tissue, and preventing epidermis dryness by increasing AQP-3 levels. Taking into account the limitations of in vitro studies, it is encouraging in this context to consider CGO as an adjuvant to be used in dermocosmetic formulations. Clinical studies are in progress in our laboratory aiming to further investigate the protective effects of CGO in the skin.

J Cosmet Dermatol. 2009 Mar;8(1):56-62

Mechanisms of photoaging and chronological skin aging.

Human skin, like all other organs, undergoes chronological aging. In addition, unlike other organs, skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmental damage. The primary environmental factor that causes human skin aging is UV irradiation from the sun. This sun-induced skin aging (photoaging), like chronological aging, is a cumulative process. However, unlike chronological aging, which depends on the passage of time per se, photoaging depends primarily on the degree of sun exposure and skin pigment. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms that bring about chronological aging and photoaging. This emerging information reveals that chronological aging and photoaging share fundamental molecular pathways. These new insights regarding convergence of the molecular basis of chronological aging and photoaging provide exciting new opportunities for the development of new anti-aging therapies. This article reviews our current understanding and presents new data about the molecular pathways that mediate skin damage by UV irradiation and by the passage of time.

Arch Dermatol. 2002 Nov;138(11):1462-70

Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging.

BACKGROUND: The periorbital area is a key wrinkle-prone region, where the first signs of aging usually appear. AIMS: To demonstrate the ability of new anti-aging moisturizing products to improve overall smoothness and wrinkle depth appearance in the periorbital region via the Fast Optical in vivo Topometry of Human Skin (FOITS). METHODS: Two double-blind, randomized, controlled, split-face studies (n = 42, Study 1; n = 35, Study 2) were conducted in women 30-70 years old with moderate to distinct periorbital wrinkles. Subjects applied 0.5 g of individual products to half their face twice daily for 4 weeks. Four test products containing niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine were used and included a daytime SPF 30 lotion also containing antioxidants, a night cream, an eye cream also containing caffeine, and a wrinkle treatment containing retinyl propionate. The wrinkle treatment was only tested in Study 2. The FOITS technique was used to measure changes in periorbital R(a) (mean roughness) and R(z) (average maximum roughness) at 2 and 4 weeks. RESULTS: In Study 1, the daytime SPF 30 lotion, night cream, and eye cream significantly improved crow’s feet smoothness after 4 weeks relative to no treatment. After 4 weeks, the daytime SPF 30 lotion and night cream, but not the eye cream, were significantly better than no treatment at improving R(z). In Study 2, the night cream, eye cream, and wrinkle treatment, but not the daytime SPF 30 lotion, significantly improved both R(a) and R(z) after 4 weeks. To increase power and precision of estimates, a meta-analysis was performed; the pooled data showed all three products were significantly better than no treatment at improving R(a) and R(z) after 4 weeks. CONCLUSIONS: Four weeks of treatment with these products was shown to improve the smoothness of periorbital skin and to reduce the apparent depth of larger wrinkles.

J Cosmet Dermatol. 2009 Sep;8(3):228-33

Effects of caffeine and siloxanetriol alginate caffeine, as anticellulite agents, on fatty tissue: histological evaluation.

BACKGROUND: Cellulite is a physiological condition that presents etiologic plurality. Caffeine and its derivatives are used in anticellulite cosmetics due to their lipolytic activity on fatty cells. Siloxanetriol alginate caffeine (SAC) is a silanol derived from organic silicon. Radicals primarily from SAC are caffeine and the mannuronic acid. AIMS: This study aims to analyze the effects of caffeine and siloxanetriol alginate caffeine on fatty tissue by histological evaluation. METHODS: Formulations were developed with caffeine, caffeine + sodium benzoate or SAC and were applied topically for 21 days on Wistar female mice. The study regarded the histological aspects by determination of diameter and number of fatty cells with a light microscope. RESULTS: Emulsion with caffeine caused a reduction of 17% on the diameter of the fatty cells compared with the control. The emulsion with caffeine + sodium benzoate did not cause alterations on cell diameter. Emulsion with SAC provoked reduction on fatty cell diameters of 16%. No significant alterations were observed on the diameter of the fatty cells treated with gels, although it was noticed that gel with SAC promoted a reduction of 26% on the number of fatty cells. CONCLUSIONS: Emulsion with SAC was considered more indicated to promote the lipolytic action on fatty tissue, acting as a complement to treat cellulite. When sodium benzoate was added to the preparations, it inhibited the caffeine efficiency. Gel was not an adequate vehicle to be incorporated with caffeine and SAC.

J Cosmet Dermatol. 2008 Mar;7(1):23-9


Among harmful environmental factors that contribute to extrinsic aging, long-term effects of repeated exposure to ultraviolet light are the most significant and are referred to as photoaging. Photoaging is a multisystem degenerative process that involves the skin and skin support system. It is a cumulative process and depends primarily on the degree of sun exposure and skin pigment. The epidermis and dermis are both affected by UVB, but the dermis is also affected to a significant extent by UVA. It has long been thought that the majority of human photo-lesions due to UVB rays, now it is believed that UVA play a substantial role in photoaging. Photoaging affects the sun-exposed areas and is characterized clinically by fine and coarse wrinkling, roughness, dryness, laxity, teleangiectasia, loss of tensile strength and pigmentary changes. There is also an increase in development of benign and malignant neoplasms on photoaged skin. During the years the progress has been made in understanding the photoaging in human skin. UV irradiation invokes a complex sequence of specific molecular responses that damage skin connective tissue. Restriction of UV irradiation and the use of high-protection, broad-spectrum sunscreens may slow progression of photoaging.

Coll Antropol. 2008 Oct;32 Suppl 2:177-80

A double-blind, randomized, controlled clinical trial evaluating the efficacy and tolerance of a novel phenolic antioxidant skin care system containing Coffea arabica and concentrated fruit and vegetable extracts.

OBJECTIVE: This 12-week, double-blinded, randomized, controlled clinical usage study was conducted to evaluate the efficacy and tolerance of a novel topical, multi-ingredient, polyphenol, high antioxidant skin care system (facial wash, day lotion, night crème and eye serum) to reduce the appearance of photoaging. METHODS: A total of 40 Caucasian female participants were randomly assigned to apply the test regimen or control regimen for 12 weeks. One group washed with the test antioxidant facial wash twice daily, applied the test antioxidant day lotion each morning and the test antioxidant night creme and eye serum each evening. The second group washed with a control facial wash twice daily and applied a control moisturizer each morning and evening. Clinical evaluations for efficacy were made by a board-certified dermatologist at baseline and after six and 12 weeks of product use. Efficacy was also measured by subjects’ self-assessments and via photography and instrumentation. RESULTS AND CONCLUSION: Overall, the results of the study showed that the test regimen produced statistically significant improvements in the appearance of photodamaged skin. Most impressive was the significantly greater improvements produced by the test regimen over the control regimen for nearly every grading parameter. The results from this study demonstrate that this high Total ORACsc scoring antioxidant skin care system was well tolerated, with no adverse events reported by the participants during the course of the study, and improved, significantly greater than a control regimen, the appearance of wrinkles, firmness, hyperpigmentation, blotchy redness, tactile roughness and clarity in photodamaged skin. Post-baseline clinical grading scores, silicone replica parameters, cutometer and corneometer scores were statistically compared to baseline using a paired t test at the P?0.05 significance level.

J Drugs Dermatol. 2010 Dec;9(12):1480-7