Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function.

Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We investigated whether topical applications containing an NHE1 activator could improve skin barrier functions. We screened plant extracts to identify NHE1 activators in vitro and found Melissa officinalis leaf extract. Rosmarinic acid, a component of Melissa officinalis leaf extract, significantly increased NHE1 mRNA expression levels and NHE1 production. Immunofluorescence staining of NHE1 in 3D-cultured skin revealed greater upregulation of NHE1 expression by NHE1 activator cream, compared to vehicle cream. Epidermal lipid analysis revealed that the ceramide level was significantly higher upon application of the NHE1 activator cream on 3D-cultured skin, compared to application of a vehicle cream. In a clinical study of 50-60-year-old adult females (n = 21), application of the NHE1 activator-containing cream significantly improved skin barrier functions by reducing skin surface pH and transepidermal water loss and increasing skin hydration, compared to patients who applied vehicle cream and those receiving no treatment. Thus, creams containing NHE1 activators, such as rosmarinic acid, could help maintain or recover skin barrier functions.

Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation.

BACKGROUND: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted. OBJECTIVE: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function. METHODS: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro. RESULTS: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased. CONCLUSION: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals.

Erratum: Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation.

[This corrects the article on p. 432 in vol. 30, PMID: 30065583.].

Identification of a possible susceptibility locus for UVB-induced skin tanning phenotype in Korean females using genomewide association study.

A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain-containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P-value = 1.16 × 10(-4) ). To understand the functional consequences of this locus located in the non-coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV-induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV-induced tanning ability in individuals.

Smad-induced alterations of matrix metabolism by a myristoyl tetra peptide.

Regulation of extracellular matrix (ECM) components is essential for tissue homeostasis and function. We screened a small peptide that induces ECM protein synthesis for its usefulness in protecting keratinocytes. In this report, we demonstrate that myristoyl tetrapeptide Ala-Ala-Pro-Val (mAAPV) stimulates the expression of ECM proteins and inhibits the expression of metalloproteinases (MMPs) that degrade ECM proteins in Hs68 human fibroblast cells. In order to elucidate the underlying molecular mechanisms for the effects of mAAVP, we investigated the changes in gene expression in the presence of mAAPV using a cDNA microarray. Treatment with mAAPV resulted in decreased expression of MMP-related genes such as MMP1, MMP3, TIMP1 and TIMP3 and increased expression of collagen genes, including COL1A1, COL1A2, COL3A1, COL5A1 and COL6A3. The pattern of gene expression regulated by mAAPV was very similar to that of gene expression induced by transforming growth factor (TGF)-ß, indicating that the TGF-ß signaling pathway is crucial for simultaneous activation of several ECM-related genes by mAAPV. We examined whether the activation of SMAD, a downstream protein of TGF-ß receptor, is involved in the signal transduction pathway induced by mAAPV. The results demonstrate that mAAVP directly activates SMAD2 and induces SMAD3 to bind to DNA. In conclusion, our results demonstrate that mAAPV both enhances the expression of collagen and inhibits its degradation via production of protease inhibitors that prevent enzymatic breakdown of the ECM. The results suggest that mAAPV would be a useful ECM-protecting agent.

Cardamonin suppresses melanogenesis by inhibition of Wnt/beta-catenin signaling.

Wnt/beta-catenin signaling plays important roles in many developmental processes, including neural crest-derived melanocyte development. Here we show that cardamonin, a calchone from Aplinia katsumadai Hayata, inhibited pigmentation in melanocytes through suppression of Wnt/beta-catenin signaling pathway. Cardamonin significantly suppressed the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, which are melanocyte differentiation-associated markers, in human normal melanocytes, thereby decreasing intracellular melanin production. In addition, cardamonin promoted the degradation of intracellular beta-catenin that was accumulated by Wnt3a-conditioned medium (Wnt3a CM) or bromoindirubin-3'-oxime (BIO), a glycogen synthase kinase-3beta (GSK-3beta) inhibitor, in HEK293 reporter cells and human normal melanocytes. Our findings indicate that cardamonin may be a potential whitening agent for use in cosmetics and in the medical treatment of hyperpigmentation disorders.

A study correlating between instrumental and consumers' subjective luster values in oriental hair tresses.

Hair luster has long been a key objective for consumers in the hair care market and many researchers have sought to quantitate the luster of hair fibers or tresses. Recently, a fast polarimetric video camera called SAMBA with a high polarization contrast was introduced that can effectively separate specular and diffuse light. Instrumental measurement of shine using SAMBA was conducted to quantitate the luster on phenyl trimethicone-treated hair tresses. We confirmed with atomic force microscopy that phenyl trimethicone's luster-enhancing effect was related to its reduction of hair surface. Panel tests by 15 untrained panelists were carried out to determine whether their assessment corresponded with instrumental results. The instrumental data showed an excellent correlation with subjective assessments from the 15 panelists. This study shows that SAMBA has utility as an instrumental technique for hair luster evaluation and is in good agreement with consumers' subjective evaluation of luster.

Improving lip wrinkles: lipstick-related image analysis.

BACKGROUND/PURPOSE: The appearance of lip wrinkles is problematic if it is adversely influenced by lipstick make-up causing incomplete color tone, spread phenomenon and pigment remnants. It is mandatory to develop an objective assessment method for lip wrinkle status by which the potential of wrinkle-improving products to lips can be screened. The present study is aimed at finding out the useful parameters from the image analysis of lip wrinkles that is affected by lipstick application. METHODS: The digital photograph image of lips before and after lipstick application was assessed from 20 female volunteers. Color tone was measured by Hue, Saturation and Intensity parameters, and time-related pigment spread was calculated by the area over vermilion border by image-analysis software (Image-Pro). The efficacy of wrinkle-improving lipstick containing asiaticoside was evaluated from 50 women by using subjective and objective methods including image analysis in a double-blind placebo-controlled fashion. RESULTS: The color tone and spread phenomenon after lipstick make-up were remarkably affected by lip wrinkles. The level of standard deviation by saturation value of image-analysis software was revealed as a good parameter for lip wrinkles. By using the lipstick containing asiaticoside for 8 weeks, the change of visual grading scores and replica analysis indicated the wrinkle-improving effect. As the depth and number of wrinkles were reduced, the lipstick make-up appearance by image analysis also improved significantly. CONCLUSION: The lip wrinkle pattern together with lipstick make-up can be evaluated by the image-analysis system in addition to traditional assessment methods. Thus, this evaluation system is expected to test the efficacy of wrinkle-reducing lipstick that was not described in previous dermatologic clinical studies.

Penetration enhancement in mouse skin and lipolysis in adipocytes by TAT-GKH, a new cosmetic ingredient.

Since the basic domain of human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) protein was reported to possess the ability to traverse biological membranes efficiently, various therapeutic proteins have been attached to TAT for the purpose of therapy. In this study, the tripeptide GKH (glycine-lysine-histidine) derived from parathyroid hormone (PTH), known as lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient in slimming products. TAT-GKH at 10(-5) M induced approximately 37.6% and 41.5% maximal lipolytic effects in cultured 3T3-L1 differentiated adipocytes and in epididymal adipocytes isolated from rats, respectively, compared with basal lipolysis. The lipolytic effect of GKH was not changed by TAT-GKH fusion. In cytotoxicity tests, there was no cytotoxicity in any dose concentration of TAT-GKH. We confirmed that TAT-GKH induced lipolytic activity by GKH without cytotoxicity and with the possibility of its use as a safe cosmetic ingredient. TAT-GKH elevated penetration into excised hairless mice skin 36 times more efficiently than GKH. TAT-GKH can be used as a cosmetic ingredient in slimming products, with both penetration enhancement and lipolytic effect without cytotoxicity.