The human skin barrier is organized as stacked bilayers of fully extended ceramides with cholesterol molecules associated with the ceramide sphingoid moiety.

The skin barrier is fundamental to terrestrial life and its evolution; it upholds homeostasis and protects against the environment. Skin barrier capacity is controlled by lipids that fill the extracellular space of the skin's surface layer--the stratum corneum. Here we report on the determination of the molecular organization of the skin's lipid matrix in situ, in its near-native state, using a methodological approach combining very high magnification cryo-electron microscopy (EM) of vitreous skin section defocus series, molecular modeling, and EM simulation. The lipids are organized in an arrangement not previously described in a biological system-stacked bilayers of fully extended ceramides (CERs) with cholesterol molecules associated with the CER sphingoid moiety. This arrangement rationalizes the skin's low permeability toward water and toward hydrophilic and lipophilic substances, as well as the skin barrier's robustness toward hydration and dehydration, environmental temperature and pressure changes, stretching, compression, bending, and shearing.

Effect of cosmetic ingredients as anticellulite agents: synergistic action of actives with in vitro and in vivo efficacy.

BACKGROUND: The pathophysiology of cellulite involves changes in the subcutaneous adipose layer and the extracellular matrix (ECM) that supports it together with overlying dermal layer. Cellular mechanisms governing cellulite are not fully understood. However, it is accepted that changes include enhanced lipogenesis, decreased lipolysis, and increased lipid storage within the adipocytes as well as changes in the dermal architecture. AIM: In our studies the ability of cosmetic agents Furcellaria lumbricalis, Fucus vesiculosus, retinoid, conjugated linoleic acid (CLA), and a glaucine mixture to stimulate in vitro 1) lipolysis in human adipocytes and 2) production of pro-collagen I by fibroblasts was investigated in vitro. The ability of these ingredients to improve cellulite condition in vivo was also determined. PATIENTS/METHODS: Mature adipocytes and 'aged' fibroblasts were used for in vitro studies. The assessment of cellulite in vivo was performed by dermatological grading and ultrasound measurements. RESULTS: Mature adipocytes treated with combined actives resulted in a significant synergistic increase in free glycerol release. On "aged" fibroblasts, combined treatment of F. vesiculosus and F. lumbricalis stimulated pro-collagen I production. CLA increased pro-collagen I production, but the glaucine mixture had no effect. The clinical study demonstrated a significant improvement in cellulite grading by a dermatologist after 8 and 12 weeks vs. vehicle, and ultrasound imaging showed a significant decrease in fat thickness compared with placebo after 12 weeks. CONCLUSIONS: Our studies revealed a potent cocktail of ingredients that when combined together can act in vitro to markedly improve lipolysis mechanisms and by way of stimulating pro-collagen I can also have an effect on the surrounding extracellular matrix. The in vitro actions of the ingredients were translated in vivo, where a clinical improvement of cellulite condition was observed.

Three clinical studies showing the anti-aging benefits of sodium salicylate in human skin.

BACKGROUND: Anti-aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin. AIMS: To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti-aging benefits. METHODS: The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen-1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double-blind, placebo-controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double-blind, placebo-controlled study. RESULTS: In the first study SS produced significant increases of the fibrillin and collagen-1 anti-aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: -8.2 ± 1.40% and -11.4 ± 1.07%; Ra: -7.8 ± 1.33% and -11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS-containing formulation compared to its placebo (P < 0.05). Equally, non-expert graders recorded the SS formulation superior to its placebo. CONCLUSION: Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti-aging effects of SS that are especially suitable for subjects with sensitive skin.

Synergistic action of a triple peptide complex on an essential extra-cellular matrix protein exhibits significant anti-aging benefits.

Basement membranes are thin structures present in the extracellular matrix that provide a supporting framework on which epithelial and endothelial cells reside. Type IV collagen is present ubiquitously in all basement membranes and plays an important role in cell adhesion, migration differentiation, and growth. These are especially important at the dermoepidermal junction (DEJ) in skin. A reduction in the levels of DEJ proteins occurs in photodamaged skin and especially Type IV collagen at the base of a wrinkle. In these studies, the ability of a triple peptide complex (TPC) to stimulate the production of collagen IV in human skin fibroblasts and its effects on photoaged skin was investigated. Fibroblasts, matured to represent "aged" cells, were stimulated for 72 h with the TPC as well as the three individual peptides constituting the complex, and collagen IV production by the fibroblasts was determined immunochemically. The results show that stimulation with the individual peptides at doses found in 1% (v/v) of the TPC did not result in soluble collagen IV production above levels detected by the non-stimulated cells. However, after stimulation with 1% (v/v) of the TPC, collagen IV was produced by the cells (1.4 ng/ng total protein +/- 0.4 SD, n = 5) when compared to control un-stimulated cells (0.32 ng/ng total protein +/- 0.1 SD, n = 5). This indicates that the combination of the individual peptides is necessary to synergistically stimulate collagen IV production. These findings suggest that the TPC could play a role in the strengthening of the DEJ through its ability to produce collagen IV. In order to determine whether these results translated into significant effects in vivo, we performed two studies. In the first four-week study, a double blind, placebo-controlled and fully randomized clinical study on 22 healthy Caucasian volunteers displaying moderate periorbital wrinkles, a significant reduction in wrinkle parameters determined by profilometry was observed over the 4-week period in comparison to the placebo. This result was reproduced in a 12-week monadic study which also showed improvements in expertly graded wrinkle scores. Collectively, these results effectively demonstrate the anti-aging applications of the TPC.