• Journal of Ginseng Research
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• v.44 no.6
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• pp.799-807
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• 2020

Background: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. Methods: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. Results: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. Conclusions: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.

• The Korea Journal of Herbology
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• v.38 no.3
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• pp.19-26
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• 2023

Objectives : Agrimoniae Herba is a herbal medicine widely distributed in Asia and contains flavonoids including catechin, quercitrin, rutin, hyperoside, and quercetin. This study aimed to investigate the anti-oxidant activity and skin barrier function of different solvent fractions (Hexane; methylene chloride, MC; ethyl acetate, EA; n-butanol, Bu; Water) obtained from Agrimoniae Herba. Methods : Anti-oxidant activity of different solvent fractions obtained from Agrimoniae Herba was investigated through total polyphenol contents, total flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity measurements. Then, filament aggregating protein (Filaggrin), Type I collagen, ceramide synthase (CERS) 3, and CERS4 were analyzed to evaluate the skin barrier strengthening effect of different solvent fractions obtained from Agrimoniae Herba on UVB-stimulated HaCaT cells. Results : As a result of measuring total polyphenol contents, total flavonoid contents, DPPH free radical scavenging activity, and ABTS radical scavenging activity, antioxidant activity was found to be excellent in the order of EA > Bu > MC > Hexane > Water. As a result of measuring mRNA gene expression of Type I collagen, Filaggrin, CERS3, and CERS4 after UVB-stimulated was applied to HaCaT cells treated with different solvent fractions obtained from Agrimoniae Herba, it was found to increase significantly in the Bu-treated group. Conclusion : Our findings show that the Bu sample obtained from Agrimoniae Herba has excellent anti-oxidant ability, which increases Type I collagen, Filaggrin, and ceramide synthetase in UVB-stimulated HaCaT cells to control the skin barrier improvement effect.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.4
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• pp.323-330
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• 2023

The skin's barrier structure is formed through the differentiation process of epidermal keratinocytes. It consists of corneocytes that are composed of keratin proteins and lipids that fill the spaces between them. During this process, the lipids such as phospholipid that made up the membrane of the basal layer cells of the epidermis are decomposed and replaced with newly synthesized components like ceramide. In this study, the effect of ginsenoside Rg3 components on the packing of the intercellular lipid structure of the skin barrier and the barrier function was confirmed. To confirm this, Rg3 components were treated during the differentiation process of 3D epidermal cells. The FT-IR and TEWL analysis on 3D epidermis showed an enhancement in the orthorhombic lipid packing and an improvement in barrier function. Additionally, in HaCaT cells, an increase in the expression of EVOL1 and EVOL4, which synthesize long-chain lipids, was detected, along with a decrease in CERS6, which synthesizes short-chain ceramide, and an increase in ACER6, which decomposes ceramide using phytosphingosine. This suggests the possibility that Rg3 affects lipid synthesis during the epidermal differentiation process, resulting in changes in barrier function.

• Journal of Veterinary Clinics
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• v.25 no.5
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• pp.330-339
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• 2008

Ceramide, cholesterol and free fatty acids are the major intercellular lipids, maintaining the integrity of the skin barrier. However, the roles of these lipids in canine skin barrier function are little known. The aim of this study was to evaluate the repairing effects of 2% ceramide (CER), 2% cholesterol (CHO), 2% linoleic acid (LIN) and 2% intercellular lipid mixture (ILM) on damaged canine skin barrier by 1.25% sodium lauryl sulphate (SLS). Transepidermal water loss (TEWL), skin hydration, skin pH and skin thickness were assessed. Histological profiles and transmission electron microscopic (TEM) profiles were assessed on day 12. SLS effectively induced the canine skin barrier damage. TEWL was significantly decreased by topical application of CER and ILM in SLS and vehicle-treated skin on day 8 and 12, respectively (p < 0.05, p < 0.0 I). By end of the experiment all lipids significantly decreased the TEWL as compared with SLS and vehicle control, but CER and ILM more significantly decreased the TEWL than UN and CHO, respectively (p < 0.01). Skin hydration was significantly increased by CER and ILM during experimental periods (p < 0.01). Skin pH was significantly decreased by CER, LIN and ILM. In histological profiles, the thickness of the stratum corneum (SC) was significantly increased by the SC lipids as compared with vehicle and SLS (p < 0.01). Especially, CER and ILM showed more prominent improvement of barrier recovery. In TEM of the SC, SLS induced exfoliations of corneodesmosomes in the SC, and CER and ILM effectively protected exfoliations of corneodesmosomes on SLS-damaged canine skin. These results indicated that topical application of CER and ILM dramatically improved damaged-skin barrier function by SLS. Also, it was considered that the use of CER or ILM was recommended for the management of skin barrier dysfunction by irritant and inflammatory skin disorders such as atopic dermatitis.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.99-114
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• 2007

Objectives : Atopic dermatitis has a close relationship with damage of skin barrier function. To investigate the effects of Bangpungtongsungsan(BT) extract to the skin damage on mice model after atopic dermatitis elicitation, this study was done through forcing injury to mice's skin. Methods : The BALB/c mice were distributed into three groups: control(CON) group, atopic dermatitis(AD)-elicited group, Bangpungtongsungsan(BT)-treated group. AD-elicited and BT-treated group were caused AD according to the method of Christophers E., Mrowietz and Minehiro. The BT extract was administered for 48 hours to BT-treated group. We observed changes of external dermal formation, eosinophils in vasculature, lipid formation in stratum corneum, distribution of ceramide, distribution of capillary, $I{\kappa}B$ kinase(IKK) and induce nitric oxide synthase(iNOS) mRNA expression. We used the statistical methods of student t-test(p<0.05). Results : After dispensing BT extract into the AD-elicited group, the number of eosinophil as an atopic index in mice noticeably decreased and dermal injury decreased. Also the decrease of hyperplasia, degranulated mast cells, angiogenesis and substance P were shown. The lipid lamellae, lipid protect formation, were repaired and the distribution of ceramide which inhibit protein kinase C(PKC) activation increased, and the PKC caused inhibition of nuclear $factor(NF)-{\kappa}B$ activation. As a result of inhibition of $NF-{\kappa}B$ activation, iNOS production were inhibited and apoptotic cell were increased. Moreover the decrease of IKK and iNOS mRNA expression in BT-treated RAW 264.7 cell were noted. Conclusion : BT mitigated skin damage on mice model after atopic dermatitis elicitation through recovering skin barrier function and inhibiting nuclear $factor(NF)-{\kappa}B$ activation.

• 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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.2
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• pp.99-107
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• 2006

Objectives : This experimental study was performed to investigate the effects of the Hominis placenta extracts on skin barrier. Methods : Male hairless mice, average weight 20g, were divided into two groups, intact and treatment group(paired, n=15). Intact group was not applied YB-301(an ointment including Hominis placenta). Treatment group was applied YB-301(an ointment including Hominis placenta) two times a day for 8 days. We observed skin melanin, skin erythema, skin pH, skin humidity, transepidermal water loss. Statistical analysis was performed by using paired sample T-test. Statistical significance was achieved if the probability was less than 5%(p<0.05) or 1%(p <0.01) Results : 1. YB-301(an ointment including Hominis placenta) showed statistically significant effect on skin melamin, skin pH, skin humidity(p<0.05). 2. YB-301(an ointment including Hominis placenta) showed statistically significant inhibitory effect on transepidermal water loss(p<0.01). 3. YB-301(an ointment including Hominis placenta) showed statistically no significant effect on skin erythema(p<0.05). conclusions : YB-301(an ointment including Hominis placenta) was effective m skin melanin, skin pH, skin humidity, transepidermal water loss in our study, so we suggest that Hominis placenta can be used as a ointment ingredient for strengthening the function of skin barrier.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.46 no.1
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• pp.73-80
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• 2020

Psychological stress can affect the physiological condition of the skin and cause various cutaneous disorders. The stress hormone cortisol is secreted by various skin cells such as fibroblasts, keratinocytes, and melanocytes. Tight junctions (TJs) are cell-cell junctions that form a barrier in the stratum granulosum of mammalian skin. TJs can also affect other skin barriers and are affected by chemical, microbial, or immunological barriers. Stress can cause damage to the skin barrier. Interestingly, to our knowledge, there has not been any research demonstrating the involvement of TJs in this process. In this study, cortisol was used to treat keratinocytes to determine its role in regulating TJs. We found that cortisol damaged skin barrier function by regulating the gene expression and structure of TJ components. Cortisol also inhibited the development of the granular layer in a skin equivalent model. These results suggest that cortisol affects the skin barrier function by the regulation of TJs.

• 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.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.108-109
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• 2003

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol, prunol 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 ON A 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, hepatoprotective, anti-inflammatory, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. To clarify the effects of UA and ONA on skin barrier recovery, both flank skin of 8-12 weeks hairless mice were topically treated with samples (2mg/ml) after tape stripping, then measured recovery rate using TEWL on hairless mice. The recovery rate increased in UA and ONA treated groups at 6h more than 20% compared to vehicle treated group (p <0.05). 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 1 week without TEWL alteration (p<0.005). EM examination using Ru04 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 stratum corneum was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Vehicle). Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber increasing by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory experiments were also confirmed in vivo findings. This result suggested that the effects of UA and ONA related to not only skin barrier but also collagen and elastic fibers. Taken together, UA and ONA can be relevant candidates to improve barrier function and pertinent agents for cosmetic applications.