• Journal of Ginseng Research
• /
• v.42 no.4
• /
• pp.512-523
• /
• 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.

• YAKHAK HOEJI
• /
• v.58 no.3
• /
• pp.171-180
• /
• 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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.37 no.1
• /
• pp.17-28
• /
• 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
• /
• v.28 no.1
• /
• pp.15-23
• /
• 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
• /
• v.35 no.4
• /
• pp.353-359
• /
• 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.

• Journal of Food Hygiene and Safety
• /
• v.16 no.2
• /
• pp.117-124
• /
• 2001

The main constituent of green tea, catechins have been reported to have numberous biological anti-vites including antimutagenic, antibacterial, hypocholesterolemic, antioxidant and antitumor properties. In the present study, we examined the protective effect of catechin on UVB-induced skin damage. Catechin (3 mg/mouse) was topically treated to dorsal area of SHK-1 hairless mouse daily for 2 weeks. UVB (100 mJ/$\textrm{cm}^2$) was also treated soon after application of catechin alone or with catechin for 2 weeks. Catechin reduced UVB-induced infiltration of inflammatory cells, fibrosis of cells and collagen-fiber formation. In addition, catechin also prevented UVB-induced DNA fragmentation and apoptosis cell number, but not changed p53 level. Furthermore catechin inhibited UVB-induced cell proliferation. There results showed that catechin have preventive effect aganinst UVB-induced skin damages. and these effects could contribute to the antitumor promoters activity.

• Korean Journal of Food Science and Technology
• /
• v.37 no.6
• /
• pp.989-996
• /
• 2005

Ultraviolet (UV) induces photo aging, erythema, sunburn, photo-toxicity, photo-allergy, and skin tumor, To investigate photo-protective effects of AmorePacific Beauty-03 (APB-03; mixture of red ginseng extract powder and soybean extract powder) on UV-induced damaged skins, 40 SKH hairless female mice were orally administered APB-03 or saline five times a week and irradiated with UV three times per week far up to 12 weeks. Visible skin changes and skin damage in dermis and epidermis by replica image analysis and histological analysis. In APB-03-treated group, better skin, negative replica appearance and less wrinkle formation were observed compared to the UV control group. These results demonstrate oral administration of APB-03 have photo-protective effects on UV-damaged hairless mouse skin.

• Proceedings of the PSK Conference
• /
• 2000.04a
• /
• pp.206.2-206.2
• /
• 2000

• Journal of Ginseng Research
• /
• v.32 no.1
• /
• pp.48-56
• /
• 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
• /
• v.48 no.1
• /
• pp.19-24
• /
• 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.