• Journal of the Society of Cosmetic Scientists of Korea
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• v.41 no.1
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• pp.45-55
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• 2015

Ultraviolet B (UVB) irradiation induces both production of reactive oxygen species (ROS) and glucocorticoids (GCs)-mediated stress responses such as an increase of $11{\beta}$-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) activity in skin. In addition, ROS-induced inflammatory mediators and proinflammatory cytokines trigger skin inflammation. In this study, as $11{\beta}$-HSD1 inhibitor recovered a decrease of catalase expression, we investigated whether Trapa japonica (TJ) extract and its fractions could inhibit $11{\beta}$-HSD1/ROS-induced skin inflammation in HaCaT keratinocytes. TJ extract and its fractions inhibited expressions of $11{\beta}$-HSD1 as well as the increase of ROS in UVB-exposed HaCaT keratinocytes. Moreover, proinflammatory cytokines such as interleukin (IL)- ${\alpha}$, - ${\beta}$ and tumor necrosis factor (TNF)-${\alpha}$, and cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) as inflammatory mediators were also inhibited in both mRNA and protein levels. Finally, prostaglandin $E_2$ ($PGE_2$) produced by COX-2 was inhibited effectively by TJ extract and its fractions. Taken together, these results suggest that TJ extract could be a potential anti-inflammatory ingredient to inhibit UVB-induced inflammation in skin.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.321-330
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• 2014

Ultraviolet B (UVB) is a primary environmental factor that induces adverse effects on skin such as photoaging, skin burn and cancer. UVB also increases the expression of $11{\beta}$-hydroxysteroid dehydrogenase type 1 ($11{\beta}-HSD1$), which converts inactive cortisone to active cortisol in response to a variety of stressors in target tissues. Thus, we have screened new herbal extracts that suppress $11{\beta}-HSD1$ expression induced by UVB in human dermal fibroblasts. We also investigated whether Trapa japonica (TJ) extract and its fractions inhibit UVB-induced photoaging in Hs68 cells and 3D skin model. Results showed that TJ extract inhibited the increase of $11{\beta}-HSD1$ expression in UVB-exposed Hs68 cells significantly. TJ extract and its fractions not only inhibited $11{\beta}-HSD1$ expression, but also suppressed the increase of matrix metalloproteinases (MMP-1, 3, 9) and proinflammatory cytokines (IL-6, 8) in UVB-irritated Hs68 cells. TJ extract also inhibited MMP-1 expression in UVB-irritated 3D skin model. In addition, TJ extract recovered UVB-induced decreases of epidermal thickness and PCNA-positive cells in 3D skin model. Taken together, these results suggest that TJ extract and its fractions inhibit UVB-induced skin photoaging by interfering with $11{\beta}-HSD1$ and MMPs.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.2
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• pp.163-171
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• 2016

Steroid hormone, glucocorticoid (GC) has strong anti-inflammatory effects by binding to glucocorticoid receptor (GR) inhibiting the expression of inflammatory genes. Therefore, agents that activate the GR have been used for the treatment of dermatitis. However, the agents have side effects such as skin barrier dysfunction and dermal atrophy, inducing skin damage as well as skin aging. It has been reported that GC is activated by 11 beta-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) to increase the activity of the GR. This study aimed to identify natural materials that can effectively inhibit dexamethasone. We found that alpinetin isolated from Alpinia katsumadai extract has a significant effect on this. Alpinetin not only inhibited $11{\beta}$-HSD1 expression, but also suppressed the increase of phosphorylated GR and cortisol concentration. Alpinetin also recovered collagen expression in dexamethasone-treated dermal fibroblasts, and the reduction of dermal thickness in dexamethasnone-treated 3D skin model. These results suggest that alpinetin prevents skin aging induced by the increase of $11{\beta}$-HSD1 expression.

• Bulletin of the Korean Chemical Society
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• v.33 no.7
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• pp.2365-2368
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• 2012

The $11{\beta}$-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) enzyme is involved in modulation of glucocorticoid activity within target tissues. This enzyme may contribute to obesity and/or metabolic disease through its action in adipose or liver tissue. Inhibition of $11{\beta}$-HSD1 has major therapeutic potential for glucocorticoid-associated diseases, including obesity, diabetes (wound healing), and muscle atrophy. To develop such therapeutics, we performed a pharmacophore-based virtual screening (VS) for identification of novel $11{\beta}$-HSD1 inhibitors and found that the VS hit compounds show potent inhibition of $11{\beta}$-HSD1 enzyme activity. Further, we present a binding model for active compounds. The proposed pharmacophore may serve as a useful guideline for future design of new chemical entities as $11{\beta}$-HSD1-targeted antidiabetic agents.

• Journal of Nutrition and Health
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• v.50 no.3
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Korean Journal of Clinical Pharmacy
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• v.22 no.2
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• pp.153-159
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• 2012

Licorice is a very useful herbal medicine frequently prescribed, but glycyrrhizin, one of its components, can cause pseudoaldosteronism presenting hypokalemia, metabolic alkalosis and hypertension as a result of prolonging a biological half-life of systemic steroid by strongly inhibiting the enzyme $11{\beta}$-hydroxysteroid dehydrogenase type 2. The risk factors for this side effect are still unclear. Here, 479 hospitalized patients taking herbal medicines including licorice for more than five days were recruited to analyze their serum potassium levels, under following parameters ; age and gender of patient, dose and period of licorice, disease state such as hypertension and with or without diuretics. They were divided into the non-occurrence group (over 3.5 mEq/L) and the occurrence group (under 3.5 mEq/L) of hypokalemia based on serum potassium levels during hospitalization. The average ages of the non-occurrence group and the occurrence group were $52.6{\pm}17.8$ and $68{\pm}10.5$, respectively (p < 0.001). But there were no noticeable differences in the daily dose of licorice, days of taking, and total dose between groups. Regression analysis showed that odd ratio of age (>60) and taking diuretics inducing hypokalemia was 3.5 (95%CI 1.5-8.1), 4.6 (95%CI 2.0-10.9) that indicates significant correlation with hypokalemia. Based upon this analysis, it is imperative to monitor regularly the risk of pseudoaldosteronism or hypokalemia not only when administered licorice of high dose for long period but also when combined it with diuretics causing hypokalemia to the elderly patients over 60 year old.