• Journal of the Society of Cosmetic Scientists of Korea
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• v.29 no.2 s.43
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• pp.205-232
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• 2003

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol 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 ONA 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, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured . The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h more than $20\%$ compared to vehicle treated group (p<0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. 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 f week without TEWL alteration (p<0.005). EM examination using RuO4 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 thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via $PPAR\;\alpha$. Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either $ONA\;(10{\mu}M)$ or UA $(10{\mu}M)$ for 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via $PPAR\;{\alpha}$. Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

• The Korean Journal of Physiology
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• v.8 no.2
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• pp.75-78
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• 1974

It was planned to investigate, by observing incorporation of $[^3H]$ thymidine into liver cells, the influence of Panax Ginseng upon hepatic DNA synthesis in mice that received ACTH. Thirty male mice $(body\;weight:\;18{\sim}20\;g)$ were divided equally into the ginseng-ACTH and the saline-ACTH groups. Each animal of the ginseng-ACTH and the saline-ACTH groups received every day (subcutaneously) 0.05 m1/10 g body weight of ginseng extract (4 mg of ginseng alcohol extract in 1 ml of saline) and the same amount of saline, respectively, for 5 days. On the 5th experimental day, all animals received 0.01 unit of ACTH intraperitoneally one hour. after the last medication, and $1{\mu}Ci/g$ body weight of $[^3H]$ thymidine after one more hour. Five animals, at a time, of each group were sacrificed 1, 10, and 24 hours after thymidine administration, and their hepatic radioactivity was measured autoradiographically in terms of the % number of radioactive cells in 1,000 cell counts (Radioactive Index, R.1.). Following results were obtained: 1. The hepatic radioactive indices obtained from the saline-ACTH group 1, 10, and 24 hr after $[^3H]$ thymidine administration were $1.50{\pm}0.32,\;2.16{\pm}0.33\;and\;2.79{\pm}0.31\;(mean{\pm}S.D.)$, respectively. 2. The corresponding values obtained from the ginseng-ACTH group $(2.71{\pm}0.22,\;3.85{\pm}0.29,\;and\;5.06{\pm}0.31)$ were significantly higher than the values of the saline-ACTH group. It is inferred from the above results that the ginseng tends to prevent reduction in hepatic DNA synthesis caused by ACTH administration.

• The Korean Journal of Physiology
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• v.8 no.2
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• pp.45-48
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• 1974

It was planned to investigate, in mice that received ACTH, the influence of Panax Ginseng upon DNA synthesis of submandibular gland by observing incorporation of $[^3H]$ thymidine into the tissue cells. Thirty male mice $(body\;weight:\;18{\sim}20\;g)$ were divided equally into the ginseng-ACTIH and the saline-ACTH groups. Each animal of the ginseng-ACTH and the saline-ACTH groups received every day (subcutaneously) 0.05 m1/10 g body weight of ginseng extract(4 mg of ginseng alcohol extract in 1 ml of saline) and the same amount of saline, respectively, for 5 days. On the 5th experimental day, all animals received 0.01 unit of ACTH intraperitoneally one hour after the last medication, and $1\;{\mu}Ci/g$ body weight of $[^3H]$ thymidine after one more hour. Five animals, at a time, of each group were sacrificed 1, 10, and 24 hr after $[^3H]$ thymidine administration, and the radioactivity of cells in their mandibular gland was measured autoradiographically in terms of the % number of radioactive cells in 1,000 cell counts (Radioactive Index, R.1.). Results obtained were as follows: 1. The radioactive indices obtained from submandibular gland of the saline-ACTH group 1, 10 and 24 hr after $[^3H]$ thymidine administration were $15.2{\pm}0.32,\;20.1{\pm}0.30,\;and\;24.5{\pm}0.52(mean{\pm}S.D.)$ in the mucous cells, $13.0{\pm}0.22,\;10.2{\pm}0.05,\;and\;7.5{\pm}0.42$ in the serous cells. and $10.5{\pm}0.40,\;13.6{\pm}0.32,\;and\;15.9{\pm}0.42$ in the duct cells, while the $mean{\pm}S.D.$ of the values obtained from the 3 cell types 1, 10 and 24 hr after $[^3H]$ thymidine were $10.9{\pm}0.28,\;12.4{\pm}0.31,\;and\;10.0{\pm}0.39.$ Thus the radioactive indices obtained from the ginseng-ACTH group were generally lower than those obtained from the saline-ACTH group. It is inferred from the above results that the ginseng tends to promote the suppressive action of ACTH upon DNA synthesis of cells in the mandibular gland.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5405-5408
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• 2012

Curcumin (CM), a biphenyl compound, possesses anti-inflammatory, antioxidant and antimicrobial activity. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression and the molecular mechanisms of several biological processes. Liver fibrosis is a major cause of hepatic dysfunction and cancer and there are few effective therapies emphasizing the need for new approaches to control. The present study was conducted to investigate the effect of curcumin (CM) on liver fibrosis through modulating the expression level of miRNAs (199 and 200), the main miRNAs associated with liver fibrosis. Induction of liver fibrosis by carbon tetrachloride ($CCL_4$) was confirmed by histopathological examination. Mice were divided into 3 groups: group 1 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by 4 weeks with olive oil only. Group 2 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by curcumin (5 mg/mouse/day) once daily for the next 4 weeks. The third group was injected with olive oil. The expression level of miR-199 and miR-200 and some of their targeted genes were measured by real time PCR. miRNA (199 and 200) levels were significantly elevated in liver fibrotic tissues compared to control groups. Curcumin was significantly returned the expression levels of mir-199 and -200 with their associated target gene nearly to their normal levels. This is the first study that highlighted the effect of curcumin on liver fibrosis through regulation of miRNAs.

• Journal of Microbiology and Biotechnology
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• v.23 no.9
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• pp.1197-1205
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• 2013

Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis. Targeting the excessive activation of this system as well as the proliferation of the tumor vascular endothelial cell would be expected to prevent tumor neovasculature and halt the tumor development. In this regard, the amino-terminal fragment (ATF) of urokinase has been confirmed as effective to inhibit the proliferation, migration, and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Previous studies indicated that ATF expressed in Escherichia coli was mainly contained in inclusion bodies and also lacked posttranslational modifications. In this study, the biologically active and soluble ATF was cloned and expressed in Pichia pastoris. The recombinant protein was purified to be homogenous and confirmed to be biologically active. The yield of the active ATF was about 30 mg/l of the P. pastoris culture medium. The recombinant ATF (rATF) could efficiently inhibit angiogenesis, endothelial cell migration, and tumor cell invasion in vitro. Furthermore, it could inhibit in vivo xenograft tumor growth and prolong the survival of tumor-bearing mice significantly by competing with uPA for binding to cell surfaces. Therefore, P. pastoris is a highly efficient and cost-effective expression system for large-scale production of biologically active rATFs for potential therapeutic application.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.477-481
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• 2012

The rhizomes of Acorus gramineus have frequently been used in traditional medicine mainly for sedation as well as enhancing brain function. In this study, the anti-allergic activity of A. gramineus was investigated. The 70% ethanol extract of the rhizomes of A. gramineus was found to inhibit the allergic response against 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and ${\beta}$-hexosaminidase release from RBL-2H3 cells with $IC_{50}$'s of 48.9 and > $200{\mu}g/ml$, respectively. Among the 9 major constituents isolated, ${\beta}$-asarone, (2R,3R,4S,5S)-2,4-dimethyl-1,3-bis (2',4',5'-trimethoxyphenyl)tetrahydrofuran (AF) and 2,3-dihydro-4,5,7-trimethoxy-1-ethyl-2-methyl-3-(2,4,5-trimethoxyphenyl)indene (AI) strongly inhibited 5-LOX-catalyzed LT production in A23187-treated RBL-1 cells, AI being the most potent ($IC_{50}=6.7{\mu}M$). Against ${\beta}$-hexosaminidase release by antigen-stimulated RBL-2H3 cells, only AI exhibited strong inhibition ($IC_{50}=7.3{\mu}M$) while ${\beta}$-asarone and AF showed 26.0% and 39.9% inhibition at $50{\mu}M$, respectively. In addition, the ethanol extract of A. gramineus showed significant inhibitory action against the hapten-induced delayed hypersensitivity reaction in mice by oral administration at 200 mg/kg. Therefore, it is suggested that A. gramineus possesses anti-allergic activity and the constituents including ${\beta}$-asarone and AI certainly contribute to the anti-allergic activity of the rhizomes of A. gramineus.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.24 no.3
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• pp.17-23
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• 1998

Inner nutshell of Castanea mollisima BL (chestnut) has been used as an anti-aging and anti-wrinkle agent from the ancient time in east Asia. In order to develop new anti-aging and anti-wrinkle, ethanolic extract of inner nutshell of Castanea mollisima BL (Cor-285) was prepared and various biological activities were evaluated. Cor-285 showed potent antioxidant activity, Especially, Cor-285 possessed potent free radical scavenging activity in vitro (IC50:7.6 g/ml) compared to gallic acid (IC50:12.5 g/ml), Cor-285 showed the preventive effect against UV-induced cytotoxicity of fibroblast at concentration of 25-250 g/ml. When Cor-285 was evaluated for its anti-allergic activity, it effectively inhibited histamine release from mast cells induced by compound 48/80 (86% inhibition at 10 mg/ml). The inhibitory activity was stronger than that of glycyrrhiznate. Cor-285 also showed in vivo inhibition against delayed hypersensitivity as well as croton-oil induced ear edema in mice when topically applied These results strongly suggest that Cor-285 may reduce immunoregulatory 1 inflammatory skin trouble. From the attempts to isolate the constituents, citropten (simple coumarin) and ellagic acid, a well known radical scavenger, were isolated. In a clinical trial of twenty healthy volunteers with aged skin,6 weeks application of Cor-285 (3% cream) decreased wrinkle about 26% and increased moisturizing 20% on the skin. All of these results indicate that Cor-285 may be an effective anti-aging and anti-wrinkle agent.

• Toxicological Research
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• v.35 no.1
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• pp.45-63
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• 2019

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

• The Korean Journal of Food And Nutrition
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• v.24 no.3
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• pp.273-281
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• 2011

Rice bran is byproducts of the hulling of rice, an important food resource in Korea. Various studies have been reported immune-enhancing effects of rice bran cultured with Lentinus edodes. In particular black rice bran contains anthocyanin, and the effects of antioxidant have been reported. The objective of the this study was to investigate the possible immune-enhancing effects of black rice bran substance extracted from a submerged culture of Lentinus edodes with black rice bran (crude fermentation-polysaccharide, CFP) and products(crude fermentation-polysaccharide-S. cerevisiae CFP-S, crude fermentation-polysaccharide-L. gasseri, CFP-L) which are of secondary fermentation of by using Saccharomyces cerevisiae and Lactobacillus gasseri in the Blab/c male mice. We found that supplementation of CFP, CFP-S and CFP-L enhanced macrophage and splenocyte proliferation compared to the control group(NC) in mice. Also, we measured the concentration of cytokines(IFN-${\gamma}$, TNF-${\alpha}$, IL-6) secreted by activated macrophage and splenocyte. The results of the experiment are that supplementation of CFP and CFP-S increased the macrophage and splenocyte proliferation compared to the control group but supplementation of CFP-L decreased the splenoyte proliferation compared to the control group(without mitogen and treated with LPS). When macrophage and splenocyte were stimulated by CFP and CFP-S supplementation, it was increased IFN-${\gamma}$, TNF-${\alpha}$ and IL-6 concentration compared with the control group. These results suggest that the capacity of CFP and CFP-S seem to act as a potent immune modulator causing augmentation of immune cell activity, and enhance the immue function through regulating cytokine production capacity by activated macrophage and splenocyte in mice.

• Korean Journal of Food Science and Technology
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• v.42 no.4
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• pp.488-493
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• 2010

We investigated the effect of Perilla frutescens (PF) ethanol extract powder (PF-E30) on the local allergic reaction activated by anti-DNP IgE and the mast cell-mediated immediate-type allergic reactions induced by compound 48/80 in a mouse model. One gram of PF powder extracted with 30% ethanol at $80^{\circ}C$ contained 12.3 mg of rosmarinic acid. Oral administration of PF-E30 (0.1 to 0.5 mg/kg body weight) significantly reduced plasma histamine levels and inhibited histamine release from peritoneal mast cells in mice activated by compound 48/80 or anti-DNP IgE. Moreover PF-E30 dose-dependently inhibited the production of antigen-induced IgE. These results indicate that the PF ethanol extract inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.