• Food Science and Biotechnology
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• v.17 no.4
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• pp.745-750
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• 2008

Anti-inflammatory potential of the enzymatic extract prepared by Kojizyme (ECK), a component of brown seaweeds Ecklonia cava (Alariaceae, Phaeophyta) in vivo was investigated. For the application of mouse ear edema model, 12-O-tetradecanoylphorbol acetate (TPA) was used, a topical inducer of a long-lasting inflammatory response. Our results demonstrated that ECK inhibited ear edema when topically applied to mouse ear skin. In histological evaluation, the inhibition activity of ECK on TPA-induced inflammation is similar to that of dexamethasone, although less strong. In addition, the mRNA expression levels of IL-$1{\beta}$, IFN-$\gamma$, TNF-$\alpha$, and cyclooxygenase-2 (COX2) and the immunoreactivity to inducible nitric oxide synthase (iNOS) and COX2 expressed mainly in inflammatory cells were down-regulated by ECK. These results indicate that ECK has anti-inflammatory effects through the inhibition of Th1 cytokines and 2 inducers of inflammation in TPA-induced ear skin edema.

• Annals of dermatology
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• v.30 no.6
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• pp.694-700
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• 2018

Background: Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid known to have a wide range of pharmacological activities. The 3-OH group in flavonoids has been reported to determine antioxidant activities. Objective: We tested whether kaempferol can affect the expression of integrins and the stem cell fate of interfollicular epidermal stem cells. Methods: Skin equivalent (SE) models were constructed, and the expression levels of stem cell markers and basement membrane-related antigens were tested. The immunohistochemical staining patterns of integrins, p63, and proliferating cell nuclear antigen (PCNA) were compared between kaempferol- and apigenin-treated SE models. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of integrins. Results: Kaempferol increased the thickness of the epidermis when added to prepare SEs. In addition, the basal cells of kaempferol-treated SEs appeared more columnar. In the immunohistological study, the expression of integrins ${\alpha}6$ and ${\beta}1$ and the numbers of p63- and PCNA-positive cells were markedly higher in the kaempferol-treated model. However, apigenin showed no effects on the formation of three-dimensional skin models. RT-PCR analysis also confirmed that kaempferol increased the expression of integrin ${\alpha}6$ and integrin ${\beta}1$. Conclusion: Our findings indicated that kaempferol can increase the proliferative potential of basal epidermal cells by modulating the basement membrane. In other words, kaempferol can affect the fate of interfollicular epidermal stem cells by increasing the expression of both integrins ${\alpha}6$ and ${\beta}1$. These effects, in particular, might be ascribed to the 3-OH group of kaempferol.

• BMB Reports
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• v.52 no.11
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• pp.647-652
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• 2019

G protein-coupled estrogen receptor (GPER) is known to play an important role in hormone-associated cancers. G-1, a novel synthetic GPER agonist, has been reported to exhibit anti-carcinogenic properties. However, the chemotherapeutic mechanism of GPER is yet unclear. Here, we evaluated GPER expression in human gastric cancer tissues and cells. We found that G-1 treatment attenuates GPER expression in gastric cancer. GPER expression increased G-1-induced antitumor effects in mouse xenograft model. We analyzed the effects of knockdown/overexpression of GPER on G-1-induced cell death in cancer cells. Increased GPER expression in human gastric cancer cells increased G-1-induced cell death via increased levels of cleaved caspase-3, -9, and cleaved poly ADP-ribose polymerase. Interestingly, during G-1-induced cell death, GPER mRNA and protein expression was attenuated and associated with ER stress-induced expression of PERK, ATF-4, GRP-78, and CHOP. Furthermore, PERK-dependent induction of ER stress activation increased G-1-induced cell death, whereas PERK silencing decreased cell death and increased drug sensitivity. Taken together, the data suggest that the induction of ER stress via GPER expression may increase G-1-induced cell death in gastric cancer cells. These results may contribute to a new paradigm shift in gastric cancer therapy.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.3
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• pp.145-153
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• 2021

The role of transient receptor potential vanilloid receptor-1 (TRPV1) has been primarily investigated in pain sensory neurons. Relatively, little research has been performed in testicular cells. TRPV1 is abundantly expressed in Leydig cells of young adult mice. This study was conducted to determine the role of the TRPV1 channel in Leydig cells. TRPV1 modulators and testosterone were treated to the mouse Leydig cell line TM3 cells for 24 h. Capsaicin, a TRPV1 activator, dose-dependently induced cell death, whereas capsazepine, a TRPV1 inhibitor, inhibited capsaicin-induced cell death. Testosterone treatment reduced capsaicin-induced cell death. High concentrations of testosterone decreased TRPV1 mRNA and protein expression levels. However, TRPV1 modulators did not affect testosterone production. These results showed that capsaicin induced cell death of Leydig cells and that testosterone reduced capsaicin-induced cell death. Our findings suggest that testosterone may regulate the survival of Leydig cells in young adult mice by decreasing the expression level of TRPV1.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.643-655
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• 2018

Background/Aims Irritable bowel syndrome (IBS) is a common disease characterized by intestinal dysmotility, the mechanism of which remains elusive. We aim to determine whether the high-affinity choline transporter 1 (CHT1), a determinant of cholinergic signaling capacity, modulates intestinal motility associated with stress-induced IBS. Methods A rat IBS model was established using chronic water avoidance stress (WAS). Colonic pathological alterations were evaluated histologically and intestinal motility was assessed by intestinal transit time and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response to colorectal distension. RT-PCR, western blotting, and immunostaining were performed to identify colonic CHT1 expression. Contractility of colonic muscle strips was measured using isometric transducers. enzyme-linked immunosorbent assay was used to measure acetylcholine (ACh). We examined the effects of MKC-231, a choline uptake enhancer, on colonic motility. Results After 10 days of WAS, intestinal transit time was decreased and fecal water content increased. Visceromotor response magnitude in WAS rats in response to colorectal distension was significantly enhanced. Protein and mRNA CHT1 levels in the colon were markedly elevated after WAS. The density of CHT1-positive intramuscular interstitial cells of Cajal and myenteric plexus neurons in WAS rats was higher than in controls. Ammonium pyrrolidine dithiocarbamate partly reversed CHT1 upregulation and alleviated colonic hypermotility in WAS rats. Pharmacological enhancement of CHT1 activity by MKC-231 enhanced colonic motility in control rats via upregulation of CHT1 and elevation of ACh production. Conclusion Upregulation of CHT1 in intramuscular interstitial cells of Cajal and myenteric plexus neurons is implicated in chronic stress-induced colonic hypermotility by modulation of ACh synthesis via nuclear factor-kappa B signaling.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.40-50
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• 2018

Objectives: The aim of this study is to investigate anti-inflammatory effects of Kyungheechunggan-tang (KHCGT) on LPS- induced RAW 264.7 cells and LX-2 cells and anti-fibrotic effects of KHCGT on LX-2 cells. Materials and Methods: Three types of KHCGTs (KHCGT-A, -B, and -C) by narrowing down the number of constituent herbs from 9 (KHCGT-A) to 5 (KHCGT-B) and to 3 (KHCGT-C) were developed. To understand pharmacological effects of KHCGT, three types of KHCGTs were treated on RAW 264.7 cells and LX-2 cells. Anti-inflammatory activities of KHCGT were evaluated by ELISA assay for pro-inflammatory cytokines, IL-6, $TNF-{\alpha}$ and IL-10, in LPS-stimulated RAW 264.7 cells and for IL-6 production in LPS-induced LX-2 cells. In addition, anti-fibrotic effects of KHCGT were determined by quantitative real-time PCR assay for fibrosis-related genes, ${\alpha}-SMA$, collagen1A1, TIMP1, MMP-2, in LX-2 cells. Results: KHCGT-A and KHCGT-C showed inhibitory effects on secretion of IL-6 in LPS-stimulated RAW 264.7 cells and LX-2 cells. KHCGT-B and KHCGT-C exhibited inhibitory effects on the expression of pro-inflammatory cytokines such as IL-6, $TNF-{\alpha}$, and IL-10 in LPS-stimulated RAW 264.7 cells. The mRNA expression levels of collagen1A1 and MMP-2 were significantly reduced by KHCGT-C whereas TIMP-1 was suppressed by KHCGT-A and KHCGT-B in LX-2 cells. Among three different formulas, KHCGT-C demonstrated the most remarkable effects on inflammation and fibrosis. Conclusions: In this study, KHCGT showed both anti-inflammatory and anti-fibrotic effects which make it to be a prospective agent for chronic liver diseases with inflammation and fibrosis.

• BMB Reports
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• v.52 no.6
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• pp.373-378
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• 2019

The nucleotide-binding and oligomerization domain (NOD) is an innate pattern recognition receptor that recognizes pathogen- and damage-associated molecular patterns. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) is a matrix degradation product found in the synovial fluids of patients with osteoarthritis (OA). We investigated whether NOD2 was involved in 29-kDa FN-f-induced pro-catabolic gene expression in human chondrocytes. The expression of mRNA and protein was measured using quantitative real-time polymerase chain reaction (qrt-PCR) and Western blot analysis. Small interfering RNAs were used for knockdown of NOD2 and toll-like receptor 2 (TLR-2). An immunoprecipitation assay was performed to examine protein interactions. The NOD2 levels in human OA cartilage were much higher than in normal cartilage. NOD1 and NOD2 expression, as well as pro-inflammatory cytokines, including interleukin-1beta (IL-$1{\beta}$) and tumor necrosis factor-alpha (TNF-${\alpha}$), were upregulated by 29-kDa FN-f in human chondrocytes. NOD2 silencing showed that NOD2 was involved in the 29-kDa FN-f-induced expression of TLR-2. Expressions of IL-6, IL-8, matrix metalloproteinase (MMP)-1, -3, and -13 were also suppressed by TLR-2 knockdown. Furthermore, NOD2 and TLR-2 knockdown data demonstrated that both NOD2 and TLR-2 modulated the expressions of their adaptors, receptorinteracting protein 2 (RIP2) and myeloid differentiation 88, in 29-kDa FN-f-treated chondrocytes. 29-kDa FN-f enhanced the interaction of NOD2, RIP2 and transforming growth factor beta-activated kinase 1 (TAK1), an indispensable signaling intermediate in the TLR-2 signaling pathway, and activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$), subsequently leading to increased expressions of pro-inflammatory cytokines and cartilage-degrading enzymes. These results demonstrate that 29-kDa FN-f modulated pro-catabolic responses via cross-regulation of NOD2 and TLR-2 signaling pathways.

• Food Science of Animal Resources
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• v.39 no.2
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• pp.179-196
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• 2019

We investigated the effect of high density lipoprotein from egg yolk (EYHDL) on serum, hepatic and fecal lipid and fatty acids (FAs) levels and on gene expression involved in FAs metabolism. Male KM mice were fed either normal diet (ND; n=20), high fat diet (HFD; n=20), or high fat diet containing EYHDL (EYHDL; 0.6 mg/g, every day by oral gavage, n=20) for 100 days. At the end of the experiment, the effects of treatments on biochemical parameters, FAs profiles and involved gene expression were analyzed. Our results revealed that EYHDL markedly suppressed the body weight gain, accumulation of abdominal fat tissues, serum concentrations of LDL-cholesterol (LDL-C) and triglycerides, hepatic triglycerides and cholesterol accumulation, while increased serum concentration of HDL-cholesterol (HDL-C). EYHDL intake also increased total cholesterol (TC) excretions compared with HFD group. Moreover, it alleviated the severity of fatty liver and improved glucose and insulin tolerance compared with HFD. More importantly, EYHDL partially normalized FAs profiles in serum, liver and fecaces and neutralized the HFD-induced upregulation of SREBP-1c, Acaca, Fasn, GPAT and Scd1. In conclusion, our findings indicate that EYHDL may have the potential to improve metabolic disturbances that occur in HFD mice and can be considered as an appropriate dietary recommendation for the treatment of metabolic syndrome (MetS).

• The Korea Journal of Herbology
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• v.36 no.5
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• pp.59-67
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• 2021

Objectives : Hibiscus (Hibiscus sabdariffa L.) is rich in antioxidants such as flavonoids and anthocyanins and is known to have anti-inflammatory activity and anti-aging function of the skin, but there is no study on its effect on the skin barrier. This study aim to investigate the positive effect on the skin barrier by confirming the effect of water extracts of Hibiscus sabdariffa L. (WEHS) on the tight junction-related gene expression. Methods : The antioxidant efficacy of WEHS was investigated through ABTS and DPPH assays, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium was performed to examine the effect on cell viability. quantitative Reverse transcription polymerase chain reaction and immunoblot analysis were performed to confirm the effect of WEHS on the expression of tight junction-related genes, and immunofluorescence microscopy was used to confirm the movement of Claudin 1 protein into tight junctions. Results : WEHS showed strong antioxidant activity and induced an increase in both mRNA and protein expression levels of Claudin 1 among tight junction-related genes. The strong localization of Claudine 1 protein increased by WEHS to the tight junction was confirmed by immunofluorescence microscopy. Conclusions : Hibiscus was confirmed through this study to show antioxidant activity and the function of promoting the expression of the tight junction Claudin 1 gene, suggesting that Hibiscus can be used as a material for the prevention and treatment of skin moisturizing and atopy, which have an important influence on tight junction.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1115-1122
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• 2021

Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1β (IL-1β), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.