• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.570-577
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• 2003

The importance of cornified envelope (CE)-bound lipids to epidermal barrier function is increasingly being recognized. In the present study, we intentionally damaged the cornified layer of hairless mice by ultraviolet irradiation and sodium dodecyl sulfate (SDS) treatment, and assessed the changes in epidermal barrier function by measuring Trans Epidermal Water Loss (TEWL). We also measured changes in the amount of CE-bound lipids using thin layer chromatography (TLC). The results showed that both treatments increased TEWL and decreased CE-bound lipids (omega-hydroxy cerami de and omega-hydroxy acid). In addition, investigation of the chronological changes in TEWL revealed an inverse relationship between TEWL and CE-bound lipids, and a correlation between CE-bound lipids and epidermal barrier function. We then measured the amount of CE-bound lipids in the cheek and the medial side of the upper arm in humans. The results showed that because the cheek receives external stimulation on a daily basis, the amount of CE-bound lipids was significantly lower, while the level of TEWL was higher. These observations, together with those from the animal study, indicate that CE-bound lipids are related to epidermal barrier function.

• Korean Journal of Food Science and Technology
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• v.40 no.6
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• pp.686-690
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• 2008

Recent research has shown that curcumin has beneficial effects in a variety of skin diseases, including scleroderma, psoriasis, and skin cancer. In this study, we assessed the effects of curcumin on epidermal permeability barrier function in vivo and in vitro. In order to evaluate the effects of curcumin on epidermal permeability barrier function in vivo, hairless rats were exposed to UVB irradiation, and curcumin was administered orally at a dosage of 150 mg/kg per day for 8 weeks. Transepidermal water loss (TEWL) and epidermal thickness were measured at the end of the experiment. The expression of filaggrin, a marker of keratinocyte differentiation, and serine palmitoyltransferase (SPT), a marker of the formation of the stratum corneum lipid barrier, in human HaCat keratinocytes were analyzed. The in vivo results showed that an 8 week administration of curcumin markedly prevented the UVB-induced increase in TEWL. The UV-induced increase in epidermal thickness was also reduced significantly by curcumin treatment. The in vitro results demonstrated the concentration-dependent effects of curcumin on the expression of both filaggrin and SPT in HaCat cells, reflecting the notion that curcumin can induce epidermal keratinocyte differentiation and can improve the recovery of skin barrier functions. These results show that curcumin is a promising candidate for the improvement of epidermal permeability barrier function.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.34 no.1
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• pp.1-8
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• 2008

Epidermis is one of the most dynamic organs in the human body. Multiple layers of keratinocytes in the epidermis continuously undergo proliferation, differentiation, and desquamation cycles, which is the bases of maintaining the epidermal homeostasis. Epidermal homeostasis eventually leads to establish and maintain permeability barrier homeostasis, the most important function of the epidermis. The permeability barrier is located in the stratum corneum. Tightly coordinated regulations are required for the sustained normal barrier function. Extensive studies have established that several nuclear hormone liposensors, including peroxisome proliferator-activated receptor a PPARa, PPARb/d, PPARg and LXRs are expressed in keratinocyte. Activation of PPARs and LXRs could provide a mechanism to coordinate the formation of the corneocytes and extracellular lipid membranes that constitute the stratum corneum. Topical application of PPAR/LXR ligands to murine skin results in the increased expression of keratinocyte differentiation-related proteins, such as involucrin, loricrin, profilaggrin, and trans-glutaminase 1, which would stimulate cornified envelope formation. In conclusion, topical application of ligands or activators of PPAR/LXR as an epidermotherapy would be a promising option to deal dry skin conditions such as atopy.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.29 no.2 s.43
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• pp.205-232
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• 2003

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured . The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h more than $20\%$ compared to vehicle treated group (p<0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from f week without TEWL alteration (p<0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent $(ONA{\geq}UA>Vehicle)$. LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via $PPAR\;\alpha$. Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either $ONA\;(10{\mu}M)$ or UA $(10{\mu}M)$ for 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via $PPAR\;{\alpha}$. Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.765-779
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• 2003

Physiological lipid mixtures comprised of cholesterol, ceramide and free fatty acid better maintain epidermal homeostasis and have been recently used for dermatoses induced by skin barrier damage, for example for atopic dermatitis and xerotic skin. Itching and dry atopic dermatitis of the skin may be related to altered skin barrier function. In a previous study, the use of multi-lamellar emulsion (MLE), which is a lipid mixtures containing cholesterol, pseudoceramide and free fatty acid, has been shown to accelerate the recovery of the epidermal permeability barrier. In this study, we assessed the efficacy of MLE compared with a currently used anti-itch moisturizer (AIM), the active ingredients of which are menthol and camphor, on barrier recovery after barrier disruption. To clarify the effect of MLE and AIM after acute barrier perturbation, we measured the relation between transepidermal water loss (TEWL) and the barrier recovery rate at 3, 6, 24, and 48 hours after tape stripping hairless mice and then observed changes in the stratum corneum (SC), including the intercellular lipid structure and secretion of lamellar bodies, by electron microscopy. MLE treated skin recover skin barrier function more rapidly, and AIM treated skin delayed barrier repair. Morphological changes in the epidermis, of MLE treated skin revealed well-conserved lipid multi-lamellar structures at 24 h after tape stripping, whereas AIM treated skin showed altered lamellar bilayers within the SC interstices at 48 h. In addition, MLE treated skin showed an increase in the number of LBs and in their secretions and a decrease in the number of SC layers versus AIM treated skin. These results suggest that MLE may accelerate the production of an epidermal permeability barrier in hairless mice by increasing the number and secretion of LB and improve the dryness and itch associated with an altered epidermal permeability barrier.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.115-125
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• 2022

Background: Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. Methods: GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. Results: Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. Conclusion: GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.553-561
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• 2019

Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.

• Journal of Ginseng Research
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• v.39 no.2
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• pp.135-140
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• 2015

Background: A leaf cuticle has different structures and functions as a barrier to water loss and as protection from various environmental stressors. Methods: Leaves of Panax ginseng were examined by scanning electron microscopy and transmission electron microscopy to investigate the characteristics and development of the epicuticular structure. Results: Along the epidermal wall surface, the uniformly protuberant fine structure was on the adaxial surface of the cuticle. This epicuticular structure was highly wrinkled and radially extended to the marginal region of epidermal cells. The cuticle at the protuberant positions maintained the same thickness. The density of the wall matrix under the structures was also similar to that of the other wall region. By contrast, none of this structure was distributed on the abaxial surface, except in the region of the stoma. During the early developmental phase of the epicuticular structure, small vesicles appeared on wallecuticle interface in the peripheral wall of epidermal cells. Some electron-opaque vesicles adjacent to the cuticle were fused and formed the cuticle layer, whereas electron-translucent vesicles contacted each other and progressively increased in size within the epidermal wall. Conclusion: The outwardly projected cuticle and epidermal cell wall (i.e., an epicuticular wrinkle) acts as a major barrier to block out sunlight in ginseng leaves. The small vesicles in the peripheral region of epidermal cells may suppress the cuticle and parts of epidermal wall, push it upward, and consequently contribute to the formation of the epicuticular structure.

• Journal of Nutrition and Health
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• v.45 no.3
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• pp.211-217
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• 2012

UV-irradiation is a major factor of photo-aged skin, by which pigmentation, wrinkles and laxity are increased. In addition, the epidermal barrier is disrupted, ultimately causing dryness in photo-aged skin. As an effort to search dietary sources for improving the dryness of UV irradiated skin, the dietary effect of red ginseng based functional foods on the epidermal level of ceramides, a major lipid maintaining epidermal barrier, was determined in this study. Albino hairless mice were fed either a control diet [group UV (UV-irradiated control)] or diets with 0.5% (group M0.5) or 1% (group M1.0) of red ginseng extracts mixed with Torilis fructus and Corni fructus (66.7% red ginseng) in parallel with UV irradiation for 5 wks. A normal control group (group C) was fed a control diet without UV irradiation for 5 wks. The epidermal level of ceramides in group UV was significantly lower than that in group C, in which ceramidase, an enzyme involved in ceramide degradation, was highly expressed. In group M0.5, the epidermal level of ceramide was significantly increased to the level even higher than in group C. In addition, protein expression of serine palmitoyl transferase (SPT), a key enzyme involved in de novo ceramide synthesis, was increased in group M0.5. However the epidermal levels of ceramides as well as of ceramidase protein expression in group M1.0 did not differ from those in group UV. In conclusion, we demonstrate that dietary supplementation of red-ginseng extracts mixed with Torilis fructus and Corni fructus at a level of 0.5% level in diet increased the epidermal level of ceramides coupled with the elevated expression of SPT protein.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.525-530
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• 2015

Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C ($50{\mu}g/ml$) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolicrelated enzymes, and as a result, could improve overall epidermal barrier function.