• Journal of Ginseng Research
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• 제42권4호
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• pp.512-523
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• 2018

Background: 20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. Methods: MEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. Results: A Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient $r^2=0.929-0.947$). Conclusion: The MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

• 약학회지
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• 제58권3호
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• pp.171-180
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• 2014

To enhance the in vitro permeation of lovastatin through excised hairless mouse and human cadaver skins, solubility was determined in various hydrophilic and lipophilic vehicles, and the effects of vehicles and penetration enhancers on the skin permeation from solution formulations were investigated. Solubility of lovastatin was highest in N-methyl-2-pyrrolidone (NMP) ($278.2{\pm}10.1$ mg/ml) and dimethyl sulfoxide (DMSO) ($162.2{\pm}9.7$ mg/ml). Among different pure vehicles used, NMP, DMSO, propylene glycol and isopropyl myristate provided some drug permeation ($6.9{\pm}1.1$, $5.9{\pm}1.6$, $3.0{\pm}0.5$ and $2.2{\pm}0.3{\mu}g/cm^2$ at 24 hr, respectively) through hairless mouse skin. The addition of oleic acid, linoleic acid and oleyl alcohol to DMSO showed the maximum permeation at around 5 v/v%, however, capric acid and caprylic acid had no enhancing effect. The increase of enhancer concentrations showed bell-shaped permeation rate, suggesting the presence of optimal concentration in lovastatin penetration. Increasing donor concentration from 10 mg/ml to 80 mg/ml in DMSO and a cosolvent of DMSO, NMP and DGME (3 : 3 : 4 v/v) did not show significant dose dependent permeation in both hairless mouse and human cadaver skins. The maximum lovastatin flux through human cadaver skin was found to be $0.87{\pm}0.46{\mu}g/cm^2$/hr with 5 v/v% linoleic acid and donor dose of 4 mg/0.64 $cm^2$ in the cosolvent. These results suggest that transdermal delivery of lovastatin would be feasible by establishing the optimal concentrations of donor dose and unsaturated fatty acids in appropriate vehicles.

• 한방안이비인후피부과학회지
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• 제37권1호
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• pp.17-28
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• 2024

Objectives : This study was conducted to reveal the scientific mechanism of the anti-skin aging activity of Kyung-Ok-Ko(KOK), which is highly useful as a Korean traditional medicine and functional food. Methods : The skin wrinkle and aging inhibitory activity of KOK was confirmed through in vitro experiments of human dermal fibroblast neonatal cell(HDFn) and in vivo of C. elegans, and hairless mouse(SKH-1). Results : The amount of the C-terminus of the collagen precursor in the HDFn cell culture medium treated with KOK using an enzymes-linked immunoassay kit. The group treated with KOK 200㎍/㎖ was a 28.3% increase of collagen precursor compared to the control group. KOK showed inhibitory activity of MMP-1 compared to the control group at a concentration of 200㎍/㎖. In addition, KOK 200㎍/㎖ showed significant inhibitory activity of thermal stress and an oxidative stress compared to the control group in C. elegans. Furthermore, KOK showed a concentration-dependent(100mg/kg and 500mg/kg) anti-wrinkle formation effect in UV-irradiated hairless mouse(SKH-1). Additionally, when KOK was administered to UV-irradiated hairless mice, an increase in procollagen -1 and -3 genes expression was observed, and mmp-1 and mmp-9 genes, which increase collagen decomposition, decreased with the administration of KOK. Conclusions : The skin aging inhibition mechanism of Kyung-Ok-Ko(KOK) is presumed to be achieved through suppressing thermal stress and oxidative stress, suppressing mmp-1 and mmp-9 genes, and increasing procollagen-1 and procollagen-3.

• Journal of Pharmaceutical Investigation
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• 제28권1호
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• pp.15-23
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• 1998

Extract of Centella asiatica(ECA), which is poorly water-soluble extract from the Centella asiatica is known to express excellent wound healing properties. $ECA-{\beta}-cyclodextrin$ $(asiaticoside-{\beta}-cyclodextrin\;and\;genin-{\beta}-cyc1odextrin)$ solid dispersion system, which was prepared by freezedrying method, was formulated as gels containing poloxamer 407 and propylene glycol, and evaluated with respect to their viscosity, stability, skin permeation and drug amount in the skin of hairless mouse. The average molar ratio $asiaticoside-{\beta}-CD$ and $genin-{\beta}-CD$ was 1:1.7 and 1:22, respectively. When the molar ratio of genin and ${\beta}-CD$ was 1:5, madecassic acid made 100% solid dispersion system and asiatic acid about 65%. In dissolution study, >99% of asiaticoside from $asiaticoside-{\beta}-CD$ was dissolved in 5 minutes, and >99% madecassic acid and >64% asiatic acid from $genin-{\beta}-CD$. The apparent viscosity of poloxamer 407 gels with $ECA-{\beta}-CD$ solid dispersion system increased in proportion to poloxamer 407 and propylene glycol concentration. In the accelerated stability test, all $ECA-{\beta}-CD$ poloxamer 407 gels showed that asiaticoside was most stable and madecassic acid stable and asiatic acid similar to stability of gel with free ECA. The permeation amount of asiaticoside in poloxamer gels through hairless mouse skin decreased as the concentration of poloxamer 407 increased. When propylene glycol was added at the level of 10%, the permeation amount of asiaticoside at poloxamer gels through hairless mouse skin increased but from 15% it decreased. The permeation of asiaticoside into the skin of hairless mouse was estimated to be about $0.10\;{\mu}g/cm^2$.

• Toxicological Research
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• 제35권4호
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• pp.353-359
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• 2019

The purpose of this study was to investigate the effect of $7-MEGA^{TM}$ 500 on the improvement of skin aging in an UVB-induced photo-aging model of hairless mice. The dorsal skin of hairless mice was exposed to UVB three times a week for 12 weeks to induce skin wrinkle. After inducing the wrinkle, $7-MEGA^{TM}$ 500 was orally administered once a day for 4 weeks. Skin thickness, skin barrier function, and wrinkle indicators were improved by treatment with $7-MEGA^{TM}$ 500. Both gene and protein expression levels of MMP-3 and c-Jun in skin were significantly decreased by $7-MEGA^{TM}$ 500. Therefore, the intake of $7-MEGA^{TM}$ 500 is thought to have a positive effect on the improvement of skin aging, although further studies are needed.

• 한국식품위생안전성학회지
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• 제16권2호
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• pp.117-124
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• 2001

녹차의 주요 성분인 catechin은 항돌연변이, 항종양, 항균, 항바이러스 활성 및 콜레스테를 저하, 혈압 상승 억제, 해독, 방사선 차단 작용 등과 같은 다양한 생물학적 작용들이 보고되고 있다. 최근 환경 오염의 급증으로 인한 오존층의 파괴로 지표에 도달하는 자외선이 증가됨에 따라 피부노출 위험이 증가하고 있다. 따라서 피부암의 발생이 증가하는 추세이며 역학적 및 실험실적 연구에서 자외선 조사가 가장 큰 원인이라고 보고되고 있다. 이에 본 연구는 catechin이 UVB에 의해서 손상된 피부조직에 미치는 영향을 연구하였고 광발암과정에서 catechin의 억제효과가 apoptosis에 어떤 영향을 주어 작용하는지를 in vivo hairless mouse skin에서 연구하였다. 녹차잎에서 추출한 catechin을 hairless mouse를 대조군, catechin을 처리한 군, 자외선을 처리한 군, catechin과 자외선을 처리한 군으로 나누었으며 catechin의 농도는 3mg/mouse로 피부에 도포한 후 자외선을 100 mJ/$ extrm{cm}^2$ 조사하였다. 자외선에 의한 피부조직에 미치는 catechin의 영향을 H&E stain을 실시하여 확인하였고, apoptosis에 미치는 catechin의 보호효과를 알아보기 위해 DNA laddering 형성 여부와 TUNEL assay로 확인하였으며 western blot을 이용하여 apoptoic activity와 관련된 단백질인 p53연구하였다. 또한 자외선에 의한 세포증식에 미치는 catechin을 영향을 bromodeoxyuridine(BrdU) 면역염색방법을 이용하여 살펴보았다. 본 연구결과 자외선에 의하여 피부는 진피층의 교원섬유의 증가가 정상피부보다 2~3배 비후되었고, 염증세포의 침윤과 섬유화세포 등이 관탈되었으며 표피층은 두꺼워졌으나 상피세포가 소실되어 1~2층으로 되었다. UVB조사와 catechin을 2주간 처리한 후의 mouse의 피부는 표피층이 9~12층으로 이루어져 있었고, 세포의 핵은 과염색성을 보이며 커져있어 손상된 표피층 상피세포가 재생되고 있음을 확인하였다. Apoptosis에 미치는 결과에서 UVB 조사군은 apoptosis의 대표적 특징인 DNA fragmentation이 관찰되었고, UVB와 catechin을 처리한 군에서는 생성되지 않아 뚜렷한 보호효과를 나타내었다. TUNEL assay를 실시한 결과 UVB군과 catechin 군을 비교하였을 때 UVB+catechin군에서 apoptotic cells이 유의성 있는 차이(p<0.05)를 보였다. Apoptosis 관련 단백질인 p53발현을 살펴본 결과 대조군과 비교해볼 때 UVB군과 UVB와 catechin을 처리한 군간에서는 차이가 없었다. 자외선에 의한 세포증식에 미치는 catechin의 영향을 살펴본 결과 BrdU에서는 UVB군과 UVB+catechin군을 비교하였을 때 UVB+catechin군에서 BrdU 세포수가 유의성 있는(p<0.05) 감소를 보였다. 본 연구 결과에 의해 녹차의 주요성분인 catechin은 자외선에 의해 유도되는 세포증식 및 apoptosis를 억제하고, 세포손상, 세포증식 및 apoptosis를 억제시킴을 확인하였다.

• 한국식품과학회지
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• 제37권6호
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• pp.989-996
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• 2005

본 실험은 대두 추출물과 홍삼 농축액 분말 혼합물인 APB-03(AmorePacific Beauty-03)의 경구반복투여에 대한 피부주름개선 효과를 평가하기 위하여 hairless mouse에서 경구 반복투여 및 UV 반복조사를 통한 효능평가시험을 실시하였다. 정상군(Control group)과 UV 대조군(UV control group), UV/APB-03 저용량군(UV/APB-03(XI) group), UV/APB-03 중간용량군(UV/APB-03(X5) group)과 UV/APB-03 고용량군(UV/APB-03(X10) group)을 두고, 경구로 주 5회 반복 투여하며, 광노화를 유발하기 위하여 주 3회 UV를 조사가 병행되었다. 시험 기간 중 임상증상, 체중변화 및 사료 음수 섭취량 등을 관찰하고, 2회의 피부주형을 채취하여 영상 분석을 실시하였으며 실험 종료 후 피부조직을 채취하여 병리조직학적 검사를 실시하였다. 시험물질을 투여한 모든 동물에서 시험 전 기간을 통해 사망한 동물은 없었으며, 본 시험물질에 의한 것이라고 인정되는 임상증상, 행동이상 및 체중변화 등도 관찰되지 않았으며, 부검시에도 본 시험물질의 투여에 기인한 것으로 사료되는 어떠한 육안적 병변도 관찰되지 않았다. UV 조사 기간 중, 육안으로 관찰 시 정상군에 비해 UV 대조군의 피부주름 증가가 뚜렷하였으며, APB-03을 투여한 군은 UV 대조군에 비해 주름 증가가 현저히 감소하였으며, 정상군과 비슷할 정도로 피부주름 상태가 양호하였다. 8주 및 12주에 제작된 replica를 image analyzer 분석평가를 실시한 결과, APB-03을 경구 반복 투여한 실험군은 UV 대조군에 비해 전체적으로 주름이 감소하였으며, 실험 12주의 UV/APB-03 고용량군의 피부주름은 UV 대조군에 비해 통계적으로 유의성 있게 감소하는 것을 알 수 있었다(p<0.01). H&E(Hematoxylin & Eosin) stain을 실시한 결과, UV 조사에 의한 표피 및 진피, 피하지방층에서의 손상에 대해 APB-03의 치유능력을 관찰할 수 있었다. 이상의 실험 결과를 종합해 볼 때, 암컷 hairless mouse에서 APR-03의 경구 반복 투여 시 UV 조사로 유도된 광노화의 억제 및 피부주름예방효과가 확인되었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.206.2-206.2
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• 2000

• Journal of Ginseng Research
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• 제32권1호
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• pp.48-56
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• 2008

Chronic ultraviolet (UV) exposure is the major cause of photoaging that causes skin wrinkling, roughness, dryness, laxity, and pigmentation. Recently, increasing efforts are being made to understand the relationship between foods and skin health. Ginsenosides are present in ginseng (Ginseng Radix Rubra) extract, and are known to have biomedical properties, such as, anti-oxidant and anti-inflammatory effects. In this study, we investigated whether KTNG0345 prepared from red ginseng extracts delivered orally reduces skin wrinkling and ultraviolet B (UVB)-induced wrinkle formation in hairless mouse skin. KTNG0345 was administrated orally to the mice (5 times a week) during the period of UVB-irradiation (3 times a week) for 8 weeks at three different doses of 300 mg/kg, 500 mg/kg and 1000 mg/kg (w/v). UV doses were increased weekly by 1 MED (1MED = 75 $mJ/cm^2)$ up to 4 MED and then maintained at this level. After the 8-week administration period, it was found that orally administered KTNG0345 significantly inhibited UVB-induced wrinkle formation in a dose-dependent manner. Increases in skin thickness caused by UVB were prevented by KTNG0345. Moreover, it also significantly inhibited matrix metalloproteinases (MMP) -13 and MMP-9 expressional inductions by UVB. In addition, KTNG0345 was observed to prevent UVB-induced water loss of epidermis in hairless mouse skin. Our results demonstrate that orally administered KTNG0345 has anti-wrinkling effects in hairless mouse skin, and suggest that dietary red ginseng and herbal mixture may be considered a functional beauty food for preventing UVB-induced skin wrinkles.

• BMB Reports
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• 제48권1호
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• pp.19-24
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• 2015

A mouse homozygous for the spontaneous mutation uncovered (Uncv) has a hairless phenotype. A 309-bp non-frameshift deletion mutation in the N-terminal cytoplasmic domain of iRhom2 was identified in Uncv mice ($iRhom2^{Uncv}$) using target region sequencing. The detailed molecular basis for how the iRhom2 mutation causes the hairless phenotype observed in the homozygous $iRhom2^{Uncv}$ mouse remains unknown. To identify differentially expressed proteins in the skin of wild-type and homozygous $iRhom2^{Uncv}$ littermates at postnatal day 5, proteomic approaches, including two-dimensional gel electrophoresis and mass spectrometry were used. Twelve proteins were differentially expressed in the skin in a comparison between wild-type and homozygous $iRhom2^{Uncv}$ mice. A selection of the proteomic results were tested and verified using qRT-PCR, western blot and immunohistochemistry. These data indicate that differentially expressed proteins, especially KRT73, MEMO1 and Coro-1, might participate in the mechanism by which iRhom2 regulates the development of murine skin.