• Journal of Ginseng Research
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• 제44권6호
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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.

• 대한본초학회지
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• 제38권3호
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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.

• 대한화장품학회지
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• 제49권4호
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• pp.323-330
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• 2023

피부의 장벽 구조는 표피의 각질 형성세포의 분화과정에 의해서 생성된다. 이 구조는 케라틴 단백질로 구성되는 각질세포와 그 사이를 채우고 있는 세포간 지질로 구성된다. 이때 표피의 기저층의 세포의 막을 이루던 인지질 등의 성분은 분해되어 없어지고, 세라마이드 등이 성분이 신규로 합성되어 각질층의 세포간 지질을 구성한다. 본 연구에서는 피부 장벽의 세포간 지질 구조의 패킹과 장벽기능에 진세노사이드 Rg3성분이 미치는 영향을 확인하였다. 이를 위해 3D피부 세포의 분화과정에 Rg3성분을 처리하였다. 3D피부를 대상으로 FT-IR 및 TEWL를 분석한 결과, 각질 세포간 지질의 orthorhombic패킹이 강화되고 장벽기능이 강화되는 것을 확인하였다. 또한 HaCaT세포에 Rg3를 처리한 경우, 긴 체인 길이의 지질을 합성하는 EVOL1 및 EVOL4의 발현 증가와 짧은 길이의 세라마이드의 합성을 당하는 CERS6의 감소 그리고 피토스핑고신을 사용하는 세라마이드를 분해시키는 ACER6의 증가를 검출하였다. 이를 통해 Rg3가 표피 분화 과정 중 지질의 합성에 영향을 주어 장벽 기능 변화를 가져올 가능성을 제시하였다.

• 한국임상수의학회지
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• 제25권5호
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• pp.330-339
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• 2008

세라마이드, 콜레스테롤, 자유지방산은 각질세포간 주요 지질로써 피부장벽의 생성과 유지에 있어 중요한 역할을 담당한다. 그러나, 개에서 각질세포간 지질에 대한 역할은 거의 알려져 있지 않다. 본 연구는 개에서 1.25% sodium lauryl sulphate (SLS)에 의한 피부 장벽손상 유발후 2% 세라마이드, 2%콜레스테롤, 2% 리놀레익산과 이들 세가지 지질의 혼합제 (혼합제)의 장벽손상 복구를 평가하고자 실시하였다. 피부장벽기능은 표피경유수분소실(TEWL), 피부 수화도, 피부 산도, 피부 두께 측정을 통하여 평가하였고 최종적으로 조직학적 분석과 투과 전자 현미경 (TEM)을 통하여 피부 장벽구조를 평가하였다. SLS는 개의 피부에 효과적으로 피부장벽 손상을 유발하였다. 표피경유수분소실은 세라마이드와 혼합제 적용부위에서 계면활성제 및 대조군과 비교하여 유의적인 감소를 나타내었다 (p<0.05, p<0.01). 표피경유수분소실은 12일째에 모든 지질 적용군에서 유의적으로 감소하였으나 특히 세라마이드와 혼합제에서 콜레스테롤과 리놀레익산보다 유의적으로 감소하였다 (p<0.01). 실험 기간 동안, 피부 수화도는 세라마이드와 혼합제에서 유의적 증가를 보였다 (p<0.01). 조직학적 분석에서도 각각의 지질들은 피부손상을 회복시켰다. 특히 세라마이드와 혼합제의 효과가 탁월하였고 각질층의 두께도 대조군에 비해 유의적으로 증가되었다. 피부 산도는 세라마이드, 리놀레익산, 혼합제에서 유의적으로 감소하였다 (p<0.05). 따라서 세라마이드와 혼합제의 국소적용은 계면활성제에 의한 피부 장벽 손상에 효과가 탁월함을 확인하였으며 아토피와 같은 염증성 피부염과 외부 자극에 의한 피부 장벽 손상시에도 세라마이드 또는 혼합제의 병용이 효과적일 것으로 사료된다.

• 한방안이비인후피부과학회지
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• 제20권1호통권32호
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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.

• 대한화장품학회지
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• 제34권1호
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• pp.1-8
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• 2008

피부장벽을 포함한 표피층은 인체의 조직 가운데에서도 가장 역동적인 기관이다. 다시 말해서 끊임없이 새로운 표피세포의 형성, 분화 및 탈각과정이 반복되면서 표피항상성(epidermal homeostasis)을 유지한다. 표피항상성은 피부기능 가운데 가장 주요한 기능인 permeability barrier homeostasis의 확립으로 연결된다. Permeability barrier homeostasis는 각질층에서 이루어지며 이를 형성하고 유지하기 위해 매우 정교하게 조절되어야 한다. 표피항상성을 조절하는 핵심 조절인자로서 nuclear hormone receptor(NHR)가 중심에 있음이 최근 다양한 연구를 통해 입증되었다. 이들은 각질세포 특이적인 단백질, 즉, involucrin, loricrin 및 trans-glutaminase 1(TG 1) 등의 발현을 유전자 수준에서 조절할 뿐 아니라 표피 지질성분의 생합성을 증가시키는 등 피부장벽을 구성하는 brick 및 mortar의 생성과 유지에 핵심적 역할을 하는 것으로 알려졌다. NHR 가운데 peroxisome proliferator activator receptor(PPAR)와 liver X receptor(LXR)의 activator/ligands가 리놀레인산 등 지방산, leukotriene, prostanoid 및 oxygenated sterol 등이 지질대사과정에서 형성된 지질 종류인 까닭에 liposensor로도 알려지고 있다. 따라서 liposensor들을 비롯한 PPAR과 LXR activator/ligands들은 피부장벽기능이 저해된 아토피성 피부를 포함하여 건조피부를 관리하는 epidermotherapy의 수단으로서 잠재적 가능성이 있다고 생각된다.

• 한방안이비인후피부과학회지
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• 제19권2호
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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.

• 대한화장품학회지
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• 제46권1호
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• pp.73-80
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• 2020

심리적 스트레스는 피부의 생리적 상태에 영향을 미치고 다양한 피부 질환을 일으킬 수 있다. 스트레스 호르몬인 코티솔은 섬유질, 케라틴세포, 멜라노사이트와 같은 다양한 피부세포에 의해 분비된다. 밀착연접(tight junction, TJ) 은 포유류 피부의 과립증에서 장벽을 형성하는 세포 접합부위이다. TJ은 다른 피부 장벽기능에도 영향을 미칠 수 있으며 화학, 미생물 또는 면역학적 피부장벽에게 영향을 받는다. 스트레스로 인한 피부 장벽 손상에 관한 보고는 있지만 사람피부에서 코티솔이 TJ을 조절한다는 보고는 없다. 스트레스 호르몬 코티솔이 TJ을 조절하는 기능을 확인하기 위해 각질형성세포에 코티솔을 처리하였다. 코티솔은 TJ 구성 성분의 유전자 발현과 구조를 조절하여 피부 장벽 기능을 손상시켰다. 또한 코티솔은 인공피부 모델에서 과립층 형성을 억제하였다. 이러한 실험결과를 통해 스트레스 호르몬 코티솔이 TJ를 조절함으로써 피부 장벽 기능에 손상을 일으키는 것을 확인할 수 있었다.

• Journal of Ginseng Research
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• 제46권1호
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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.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book II
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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.