Skin Lipids Research Articles

The Role of MicroRNAs in Epidermal Barrier.

MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

The Elovl4 Spinocerebellar Ataxia-34 Mutation 736T>G (p.W246G) Impairs Retinal Function in the Absence of Photoreceptor Degeneration

Elongation of very long chain fatty acids-4 (ELOVL4) is essential for synthesis of very long chain polyunsaturated and saturated fatty acids (VLC-PUFA and VLC-SFA, respectively) of chain length greater than 26 carbons. Mutations in the ELOVL4 gene cause several distinct neurodegenerative diseases including Stargardt-like macular dystrophy (STGD3), spinocerebellar ataxia 34 (SCA34), and a neuro-ichthyotic syndrome with severe seizures and spasticity, as well as erythrokeratitis variabilis (EKV), a skin disorder. However, the relationship between ELOVL4 mutations, its VLC-PUFA and VLC-SFA products, and specific neurological symptoms remains unclear. We generated a knock-in rat line (SCA34-KI) that expresses the 736T>G (p.W246G) form of ELOVL4 that causes human SCA34. Lipids were analyzed by gas chromatography and mass spectrometry. Retinal function was assessed using electroretinography. Retinal integrity was assessed by histology, optical coherence tomography, and immunolabeling. Analysis of retina and skin lipids showed that the W246G mutation selectively impaired synthesis of VLC-SFA, but not VLC-PUFA. Homozygous SCA34-KI rats showed reduced ERG a- and b-wave amplitudes by 90 days of age, particularly for scotopic responses. Anatomical analyses revealed no indication of neurodegeneration in heterozygote or homozygote SCA34-KI rats out to 6–7 months of age. These studies reveal a previously unrecognized role for VLC-SFA in regulating retinal function, particularly transmission from photoreceptors to the inner retina, in the absence of neurodegeneration. Furthermore, these findings suggest that the tissue specificity and symptoms associated with disease-causing ELOVL4 mutations likely arise from selective differences in the ability of the mutant ELOVL4 enzymes to support synthesis of VLC-PUFA and/or VLC-SFA.

The Sphingosine and Acyl Chains of Ceramide [NS] Show Very Different Structure and Dynamics That Challenge Our Understanding of the Skin Barrier.

The lipid phase of the uppermost human skin layer is thought to comprise highly rigid lipids in an orthorhombic phase state to protect the body against the environment. By synthesizing sphingosine‐d28 deuterated N‐lignoceroyl‐d‐erythro‐sphingosine (ceramide [NS]), we compare the structure and dynamics of both chains of that lipid in biologically relevant mixtures using X‐ray diffraction, 2H NMR analysis, and infrared spectroscopy. Our results reveal a substantial fraction of sphingosine chains in a fluid and dynamic phase state at physiological temperature. These findings prompt revision of our current understanding of the skin lipid barrier, where an extended ceramide [NS] conformation is preferred and a possible domain structure is proposed. Mobile lipid chains may be crucial for skin elasticity and the translocation of physiologically important molecules.

An Investigation of the Skin Barrier Restoring Effects of a Cream and Lotion Containing Ceramides in a Multi-vesicular Emulsion in People with Dry, Eczema-Prone, Skin: The RESTORE Study Phase1.

IntroductionThe replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids.MethodsA double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 μl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application).ResultsThe test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h.ConclusionThe sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3–4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis.

Paclitaxel skin delivery by micelles-embedded Carbopol 940 hydrogel for local therapy of melanoma.

Local application of anticancer drugs provides a potential mode of chemotherapy for cutaneous melanoma with high compliance. However, the efficiency of drug delivery is highly limited by the physiological barrier from the skin to the tumor, which can not achieve the desired therapeutic effect. In the study, we designed ibuprofen-modified methoxy poly (ethylene glycol)-poly (ethylene imine) polymer to prepare paclitaxel-loaded micelles (PTX-M) and Carbopol 940 hydrogel containing PTX-M (PTX-Gel) to improve skin paclitaxel delivery for the local melanoma treatment. The PTX-M performed well both in the skin penetration and retention study. FT-IR analysis showed that PTX-M or PTX-Gel mainly changed the spatial structure of skin lipid and keratin, thus increasing the fluidity of lipid molecules in the stratum corneum, and the polymer was positively charged to enhance the skin permeation and deposition. Moreover, the positive charge also promoted the cellular uptake of PTX-M in B16 melanoma, resulting in better in vitro cytotoxicity of PTX-M to B16 cells Taxol®. As for in vivo against B16 cells solid tumor test, the Taxol® plus PTX-M/Gel group showed preferable anticancer activity than Taxol® alone.

Development and application of coarse-grained MARTINI model of skin lipid ceramide [AP

Stratum corneum (SC), the outermost layer of the skin, contains large variety of lipids, endowing them with the amphiphilic properties, needed to fulfil their key role in skin's barrier function. The individual role of lipid types in the barrier function is difficult to understand due to the immense heterogeneity and complexity of the lipid's organization within the SC. The lipid organization is being explored using both computational (molecular dynamics simulations) and experimental (neutron diffraction) techniques. Even though atomistic simulations provide unprecedented atomic level details, the major limitation is time and length scale that can be achieved with decent computational facility. Alternatively, coarse-grain (CG) models are currently being used to capture physics at bigger time and length scale without losing essential underlined structural information. In this study, a CG model of α-hydroxy phytosphingosines (CER[AP]) is developed based on philosophy of MARTINI force field. At first, the model is validated with various atomistic simulations and available experimental data. Later on, the model's compatibility with other major skin lipids, cholesterol, and free fatty acid (palmitic acid) is checked by simulating a mixture of lipid multilayer in presence and absence of water. The developed model of CER[AP] is able to predict key structural properties within the acceptable error limits. The phenomena of ceramide conformation transformation, cholesterol flip-flop, and specificity of lipid arrangement within the multilayered systems is observed during the simulation. This signifies the importance of model in capturing higher order structural transformations.

Selective and sensitive spectral signals on confocal Raman spectroscopy for detection of ex vivo skin lipid properties

AbstractSpectral signals of stratum corneum (SC) acquired from confocal Raman spectroscopy (CRS) are employed to track lipid variations and the most sensitive and efficient signals are of high interest. Herein, 1% of sodium lauryl sulfate treated SC was compared to water‐treated one to evaluate statistical difference of spectral signals concerning lipid content, SC thickness and lipid molecular structures. Results showed that peak ratio of 1425 to 1490 cm−1 and 1630 to 1710 cm−1 in fingerprint region and Gaussian‐function deconvoluted lipid‐keratin peak ratio in high wavenumber (HWN) region were both responsive for analyzing lipid content. SC thickness measurement using the full width of half‐maximum (FWHM) of 2920 to 2960 cm−1 signal presented good sensitivity. Nevertheless, the shift of peak 2850 cm−1 indicated less sensitivity compared to trans‐gauche peak signals and 1300 cm−1 peak position for lipid conformation analysis. Meanwhile, the ratio of peak 2880 and 2850 cm−1 indicating lipid lateral packing structure presented to be less responsive. More strikingly, FWHM of peak 2850 cm−1 appeared to be unable for lipid lateral packing order analysis in our study. In summary, this research can serve as a pilot study for further investigation of direct drug delivery and interaction between topical applied compounds and skin components.

The penetration of reactive oxygen and nitrogen species across the stratum corneum

AbstractThe penetration of reactive oxygen and nitrogen species (RONS) across the stratum corneum (SC) is a necessary and crucial process in many skin‐related plasma medical applications. To gain more insights into this penetration behavior, we combined experimental measurements of the permeability of dry and moist SC layers with computer simulations of model lipid membranes. We measured the permeation of relatively stable molecules, which are typically generated by plasma, namely H2O2, NO3−, and NO2−. Furthermore, we calculated the permeation free energy profiles of the major plasma‐generated RONS and their derivatives (i.e., H2O2, OH, HO2, O2, O3, NO, NO2, N2O4, HNO2, HNO3, NO2−, and NO3−) across native and oxidized SC lipid bilayers, to understand the mechanisms of RONS permeation across the SC. Our results indicate that hydrophobic RONS (i.e., NO, NO2, O2, O3, and N2O4) can translocate more easily across the SC lipid bilayer than hydrophilic RONS (i.e., H2O2, OH, HO2, HNO2, and HNO3) and ions (i.e., NO2− and NO3−) that experience much higher permeation barriers. The permeability of RONS through the SC skin lipids is enhanced when the skin is moist and the lipids are oxidized. These findings may help to understand the underlying mechanisms of plasma interaction with a biomaterial and to optimize the environmental parameters in practice in plasma medical applications.

The Enigma of Bioactivity and Toxicity of Botanical Oils for Skin Care.

Botanical oils have a long history of traditional use and are routinely applied to skin care. The focus of this review is to contrast the functionality of skin oils versus the differential biological and toxicological effects of major plant oils, and to correlate them to their compositional changes. In total, over 70 vegetable oils were clustered according to their lipid composition to promote awareness of health practitioners and botanical product manufacturers for the safety and efficacy of oil-based interventions based on their fatty acid profiles. Since multiple skin disorders result in depletion or disturbance of skin lipids, a tailored mixture of multiple botanical oils to simultaneously maintain natural skin-barrier function, promote repair and regeneration of wounded tissues, and achieve corrective modulation of immune disorders may be required. As bioactive constituents of botanical oils enter the human body by oral or topical application and often accumulate in measurable blood concentrations, there is also a critical need for monitoring their hazardous effects to reduce the possible over-added toxicity and promote maximal normal tissue sparing. The review also provides a useful tool to improve efficacy and functionality of fatty acid profiles in cosmetic applications.

Saturated and aromatic aldehydes originating from skin and cutaneous bacteria activate the Nrf2-keap1 pathway in human keratinocytes.

Skin homeostasis is constantly challenged by environmental factors, affecting its delicate redox balance. The skin is also home to a wide variety of bacterial species, including Staphylococci. The cutaneous redox state is governed by the Nrf2-keap1 pathway, which is responsible for the induction of phase II cytoprotective enzymes, thus sustaining a healthy oxidative state. As part of normal metabolism, both bacteria and cutaneous tissue emit copious amounts of volatile organic compounds (VOCs), one subgroup of which are aldehydes. α,β-unsaturated aldehydes are known activators of Nrf2-keap1 pathway by direct oxidation of the keap1 protein. However, we did not encounter reports of Nrf2 activation by saturated or aromatic aldehydes, neither bacteria nor skin-derived. We hypothesized that non-α,β-unsaturated aldehydes derived from skin or cutaneous bacteria may act as Nrf2-keap1 pathway activators and therefore afford protection against environmental insults. The saturated aldehydes nonanal and decanal (known skin metabolites) and the aromatic aldehyde benzaldehyde (known skin and Staphylococcus epidermidis metabolite) were shown to induce the Nrf2-keap1 pathway in human keratinocytes. We also identified a newly described aromatic aldehyde, 3-furaldehyde (3-FA), emitted from S. aureus and S. epidermidis cultures, which also activated the pathway. Moreover, Nrf2-keap1 induction led to a significant protection against UVB-induced apoptosis. The mechanism involved in this activation has been partially elucidated. This work emphasizes the importance of cutaneous bacteria, as well as healthy skin lipid peroxidation processes in the maintenance and regulation of the cellular antioxidant response, namely with regard to coping with environmental stressors.

Solvent Effects on Skin Penetration and Spatial Distribution of the Hydrophilic Nitroxide Spin Probe PCA Investigated by EPR

Oxidative stress occurs in extrinsic skin aging processes and diseases when the enhanced production of free radicals exceeds the homeostatic antioxidant capacity of the skin. The spin probe, 3-(carboxy)-2,2,5,5-tetramethylpyrrolidin-1-oxyl (PCA), is frequently used to study the cutaneous radical production by electron paramagnetic resonance (EPR) spectroscopy. This approach requires delivering PCA into the skin, yet solvent effects on the skin penetration and spatial distribution of PCA have not been thoroughly investigated. Three solvents of ethanol, phosphate-buffered saline (PBS) and ethanol-PBS (1:1) were studied. For both human and porcine skin ex vivo, the amount of PCA in the stratum corneum (SC) was the lowest when using ethanol and very similar for PBS and ethanol-PBS. The highest amount of PCA in the viable skin layers was detected for ethanol-PBS, yet it only took up less than 5% of the total amount. The majority of PCA was localized in the SC, among which PCA with high mobility was predominantly distributed in the hydrophilic microenvironment of corneocytes and PCA with lower mobility was mainly in the less hydrophilic microenvironment of intercellular skin lipids. A higher ethanol concentration in the solvent could improve the distribution of PCA in the hydrophilic microenvironments of the SC. The results suggest that ethanol-PBS (1:1) is best-suited for delivering most PCA deep into the skin. This work enhances the understanding of solvent effects on the skin penetration and distribution of PCA and supports the utilization of PCA in studying cutaneous radical production.

Impact of intercellular crosstalk between epidermal keratinocytes and dermal fibroblasts on skin homeostasis

Dermal fibroblasts seem critical for epidermal maturation and differentiation and recent work demonstrated that diseased fibroblasts may drive pathophysiological processes. Nevertheless, still very little is known about the actual crosstalk between epidermal keratinocytes and dermal fibroblasts and the impact of dermal fibroblasts on epidermal maturation and differentiation. Aiming for a more fundamental understanding of the impact of the cellular crosstalk between keratinocytes and fibroblasts on the skin homeostasis, we generated full-thickness skin equivalents with and without fibroblasts and subsequently analysed them for the expression of skin differentiation markers, their barrier function, skin lipid content and epidermal cell signalling. Skin equivalents without fibroblasts consistently showed an impaired differentiation and dysregulated expression of skin barrier and tight junction proteins, increased skin permeability, and a decreased skin lipid/protein ratio. Most interestingly, impaired Ras/Raf/ERK/MEK signalling was evident in skin equivalents without fibroblasts.Our data clearly indicate that the epidermal-dermal crosstalk between keratinocytes and fibroblasts is critical for adequate skin differentiation and that fibroblasts orchestrate epidermal differentiation processes.

Lipid depletion enables permeation of Staphylococcus aureus bacteria through human stratum corneum

ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory disease that affects approximately 2-5% of adults worldwide. The pathogenesis of AD continues to be a well-debated point of conjecture, with numerous hypotheses having been proposed. AD conditions are associated with increased populations of Staphylococcus aureus and reduced skin lipids. In this study, we evaluate the ability of S. aureus to permeate across human stratum corneum (SC) exhibiting both normal and depleted lipid conditions consistent with AD. This permeation would enable bacteria to interact with underlying viable epidermal cells, which could serve as a trigger for inflammation and disease onset. Our results indicate that permeation of S. aureus through SC exhibiting normal lipid conditions is not statistically significant. However, bacteria can readily permeate through lipid depleted tissue over a 9-d period. These findings suggest that S. aureus may potentially act as the mechanistic cause, rather than merely the result of AD. Abbreviations AD: Atopic dermatitis; SC: Stratum Corneum; AMP: Antimicrobial peptide; DIW: Deionized water; PDMS: Polydimethylsiloxane; GFP: Green fluorescent protein; BHI: Brain heart infusion medium

The Effect of Various Penetration Enhancers on the Octyl Methoxycinnamate Permeability: Mechanisms of Action Study

Octyl methoxycinnamate is one of the ingredients in sunscreen products. The main aim of this study was to investigate the effect of different enhancers of in vitro skin permeability of Octyl methoxycinnamate. Octyl methoxycinnamate permeability parameters were evaluated through the whole skin of the rat with and without chemical enhancers including eucalyptus oil, urea, menthol and olive oil by Franz cell diffusion. The effects of enhancers on skin structure were also studied using DSC and FT-IR techniques. The skin prevented the permeability of Octyl methoxycinnamate so that after 24 hours less than 3% of the substance passed through the skin. The results of this study showed that by increasing the time, it is possible to increase the skin permeation and the highest rate of skin absorption were corresponded to olive oil (ERflux=63.074), eucalyptus oil (ERflux=48.78) and menthol (ERflux=33.5), respectively while the least amount of skin absorption was related to urea (ERflux=29.53). Chemical penetration enhancers are substances that interfere with the complex structure of the skin and protein lipids. Two endothermic transitions were obtained at about 67 (Tm1) and 112 ° C (Tm2) in thermogram of the hydrated whole rat skin. Tm1 and Tm2 seems to be due to the melting of the lipids and the irreversible intracellular keratin or melting of the lipid-protein (keratin) complex, respectively. The amount of Tm1, ΔH1 and ΔH2 were decreased by all penetration enhancers compared to the hydrated skin. The FT-IR results suggested the mechanism of increasing absorption effect by lipid fluidization and lipid extraction. All of penetration enhancers used in this study significantly increased the skin permeability of Octyl methoxycinnamate.

Waste Cooking Oil for Wax Esters Synthesis Using Candida Rugosa Lipase Immobilized on Fe3o4@oa Nanoparticles

Wax ester is an important skin conditioning agent derived from the esterification of fatty acids with alcohols. It is widely used in cosmetic as it has a composition similar to that of natural skin lipids. This study presents the synthesis of wax esters from hydrolyzed WCO in presence of cetyl alcohol and Candida rugosa lipase immobilized on Fe3O4@OA. The effects of the reaction time and cycles of reuse were investigated. The wax ester conversion has been monitored for 24 h. High conversion of ~ 89.3 % was observed already at 12 hours of synthesis. No significant reduction, during four cycles of use, of the lipase activity occurs.

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes’ effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.

A systematic approach to determination of permeation enhancer action efficacy and sites: Molecular mechanism investigated by quantitative structure−activity relationship

The present study was to systematically evaluate the enhancement action efficacy and sites of chemical permeation enhancer (CPEs), which provided references for the reasonable application of CPEs and the formula optimization of transdermal patch. Enhancement action efficacy was characterized using an indicator of comprehensive enhancement effect (ERcom). In addition, enhancement action sites were evaluated using a novel enhancement action parameter (βR/P), which was derived from the release enhancement effect (ERrelease) and skin permeation enhancement effect (ERpermeation) using seven CPEs with different physicochemical properties. Then the molecular mechanism was revealed by quantitative structure−activity relationship. Hydrophilic CPEs obtained highest ERrelease indicated that its enhancement action site was polymer matrix according to βR/P value (>1), due to CPEs formed the strongest hydrogen bonds with polymer, thereby undermined drug-polymer interaction according to the results of FT-IR, MDSC and molecular docking. CPEs with high log P, molecular weight and polarizability showed highest ERpermeation, which indicated that its enhancement action site was skin according to its βR/P value <1, due to it interacted with skin lipid strongly and obtained the lowest diffusion rate in skin. Thus, it increased the disruption level of highly ordered arrangement of intercellular lipid bilayers, which was characterized by ATR-FTIR, Raman, confocal laser scanning microscopy and molecular dynamics simulation. In conclusion, physicochemical properties of CPEs determined its enhancement action efficacy and sites in transdermal drug delivery process, which permitted rational selection of CPEs and the development of safer and more efficacious transdermal patch.

Systematic Investigation of the Effect of Non-Ionic Emulsifiers on Skin by Confocal Raman Spectroscopy-A Comprehensive Lipid Analysis.

Non-ionic emulsifiers are commonly found in existing pharmaceutical and cosmetic formulations and have been widely employed to enhance the penetration and permeation of active ingredients into the skin. With the potential of disrupting skin barrier function and increasing fluidity of stratum corneum (SC) lipids, we herein examined the effects of two kinds of non-ionic emulsifiers on intercellular lipids of skin, using confocal Raman spectroscopy (CRS) with lipid signals on skin CRS spectrum. Non-ionic emulsifiers of polyethylene glycol alkyl ethers and sorbitan fatty acid esters were studied to obtain a deep understanding of the mechanism between non-ionic emulsifiers and SC lipids. Emulsifier solutions and dispersions were prepared and applied onto excised porcine skin. Water and sodium laureth sulfate solution (SLS) served as controls. SC lipid signals were analysed by CRS regarding lipid content, conformation and lateral packing order. Polyethylene glycol (PEG) sorbitan esters revealed no alteration of intercellular lipid properties while PEG-20 ethers appeared to have the most significant effects on reducing lipid content and interrupting lipid organization. In general, the polyoxyethylene chain and alkyl chain of PEG derivative emulsifiers might indicate their ability of interaction with SC components. HLB values remained critical for complete explanation of emulsifier effects on skin lipids. With this study, it is possible to characterize the molecular effects of non-ionic emulsifiers on skin lipids and further deepen the understanding of enhancing substance penetration with reduced skin barrier properties and increased lipid fluidity.

Behavior of 1-Deoxy-, 3-Deoxy- and N-Methyl-Ceramides in Skin Barrier Lipid Models

Ceramides (Cer) are essential components of the skin permeability barrier. To probe the role of Cer polar head groups involved in the interfacial hydrogen bonding, the N-lignoceroyl sphingosine polar head was modified by removing the hydroxyls in C-1 (1-deoxy-Cer) or C-3 positions (3-deoxy-Cer) and by N-methylation of amide group (N-Me-Cer). Multilamellar skin lipid models were prepared as equimolar mixtures of Cer, lignoceric acid and cholesterol, with 5 wt% cholesteryl sulfate. In the 1-deoxy-Cer-based models, the lipid species were separated into highly ordered domains (as found by X-ray diffraction and infrared spectroscopy) resulting in similar water loss but 4–5-fold higher permeability to model substances compared to control with natural Cer. In contrast, 3-deoxy-Cer did not change lipid chain order but promoted the formation of a well-organized structure with a 10.8 nm repeat period. Yet both lipid models comprising deoxy-Cer had similar permeabilities to all markers. N-Methylation of Cer decreased lipid chain order, led to phase separation, and improved cholesterol miscibility in the lipid membranes, resulting in 3-fold increased water loss and 10-fold increased permeability to model compounds compared to control. Thus, the C-1 and C-3 hydroxyls and amide group, which are common to all Cer subclasses, considerably affect lipid miscibility and chain order, formation of periodical nanostructures, and permeability of the skin barrier lipid models.

피지선세포에서 SREBP-1 활성에 의한 우방자추출물의 지질 생성 촉진 작용

Arctii Lappa Fructus has the numerous health benefits, including antioxidant, anti-inflammatory, and anti-carcinogenic properties. Skin lipids are one of several factors that maintain epidermal barrier function. This study was to explore the lipogenic effect by ethanol extract of Arctii Lappa Fructus (EAF) in sebocytes. First, it was confirmed that EAF exhibited high antioxidant activity and collagenase activity inhibition. We found that cholesterol and triglyceride levels of cells by EAF were increased significantly in a dose-dependent manner. Moreover, EAF increased the expression of transcription factor sterol regulatory element-binding protein-1 (SREBP-1) in the cells. These results suggest that EAF induces lipogenesis in cells through the activation of SREBP-1.