• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.485-496
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• 2002

Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.

• Journal of Life Science
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• v.24 no.12
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• pp.1339-1344
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• 2014

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

• Journal of Applied Biological Chemistry
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• v.64 no.2
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• pp.185-192
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• 2021

Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.43-51
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• 2022

Regulation of the hair follicle cycle in association with dermal papilla cells is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether steam-dried Betula platyphylla extracts (BPE) promote hair growth by upregulating in vitro and in vivo responses of dermal papilla cells. The data showed that BPE3 contained high amounts of phenolic compounds with higher antioxidant effects and increased hair growth-related genes, including fibroblast growth factor7 and Wnt7b, in dermal papilla cells. Notably, BPE3 effectively enhanced the formation of hair follicles by increasing FGF7, Wnt7b, and vascular endothelial growth factor in C57BL/6N dorsal skins. Additionally, BPE3 significantly decreased the expression of inflammatory repertoires, inducible nitric oxide synthase, interleukin-6, and cyclooxygenase 2. Several small molecules, such as betulin and unsaturated fatty acids, support the pharmacological activity of BPE3. In conclusion, BPE3 effectively promoted hair growth by activating dermal papilla cells and enhancing hair follicle cycles by attenuating the inflammatory environment in the scalp.

• Journal of Acupuncture Research
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• v.22 no.3
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• pp.155-167
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• 2005

Objectives : The purpose of this study was to investigate the anti-inflammatory effect of Cobrotoxin on binding affinity of cobrotoxin with P50, $IKK{\alpa}$ and $IKK{\beta}$, activities of NF-${\kappa}B$, Cell viability of astrocyte, expressions of protein molecules of NF-${\kappa}B$ such as P50, P-$1{kappa}B$, $1{\kappa}B$ and iflammation related genes such as Cox-2, iNOS, cPLA2 in the SNP or LPS induced Inflammatory pathway of Rats' astrocytes. Methods : In this study, The expression of cytosolic phospholipase A2, Nitric oxcide, Cyclooxygenase-2 and inducible nitrogen oxide synthase was determined by western blotting with corresponding antibodies, and the generation of NF-${\kappa}B$ was assayed by EMSA method in astrocytes of rats. The Cell viability of astrocytes was determined by MTT assay, and Binding affinity of Cobrotoxin with P50, $IKK{\alpha}$ and $IKK{\beta}$ was assayed by Surface plasmon resonance analysis, and NF-${\kappa}B$ dependent luciferase activity was determined by luciferase analysis, and Uptake of cobrotoxin in astrocytes was identified by Confocal laser scanning microscope Results : 1. Compared with control, LPS-induced NF-${\kappa}B$ DNA binding activity was decreased significantly by 0.1, $0.5{\mu}g/m{\ell}$ of Cobrotoxin in Astrocyte. 2. Compared with control, LPS-induced NF-kB dependent luciferase expression was decreased significantly by 0.1, 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin in Astrocyte. 3. Compared with control, SNP induced P50, $I{\kappa}B$ expressions in astrocyte were decreased significantly by 0.1, 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin and P-$1{\kappa}B$ expression was decreased significantly by 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin. 4. Compared with control, LPS induced P50, $1{\kappa}B$ expressions in astrocyte were decreased significantly by 0.5 and $1{\mu}g/m{\ell}$ of Cobrotoxin. 5. Compared with control, SNP induced Cox-2, iNOS, CPLA2 expressions in astrocyte were decreased significantly by $1{\mu}g/m{\ell}$ of Cobrotoxin. 6. Compared with control, LPS induced Cox-2, cPLA2 expressions in astrocyte were decreased significantly by 0.1, 0.5, $1{\mu}g/m{\ell}$ of Cobrotoxin and iNOS expression was decreased significantly by 0.5, $1{\mu}g/m{\ell}$ of Cobrotoxin. 7. Compared with $0.5{\mu}g/m{\ell}$ of Cobrotoxin, SNP-induced NF-${\kappa}B$ DNA bindins activity in astrocyte was increased significantly by Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 1mM and Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 5mM. 8. Compared with $0.5{\mu}g/m{\ell}$ of Cobrotoxin, LPS-induced NF-${\kappa}B$ DNA binding activity in astrocyte was increased significantly by Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 1mM, Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 5mM, Cobrotoxin $0.5{\mu}g/m{\ell}$with GSH 1mM and Cobrotoxin $0.5{\mu}g/m{\ell}$ with GSH 5mM 9. Compared with $0.1{\mu}g/m{\ell}$ of cobrotoxin, SNP induced P50 expressions in astrocyte were increased significantly by Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 1mM, Cobrotoxin $0.5{\mu}g/m{\ell}$ with DTT 5mM Cobrotoxin $0.5{\mu}g/m{\ell}$ with GSH 1mM and Cobrotoxin $0.5{\mu}g/m{\ell}$ with GSH 5mM. 10. The uptake of the labeled cobrotoxin into the cells was shown under a confocal laser scanning microscope. cobrotoxin was uptaken into the membrane and nucleus of astrocytes. Conclusions : In summary, the present results demonstrate that cobrotoxin directly binds to sulfhydryl group of p50 and IKKS resulting In the reduction of translocation of p50 and IkB release, thereby inhibits activation of NF-${\kappa}B$, and suggest that pico to nanomolar range of cobrotoxin could inhibit the expression of genes in the NF-${\kappa}B$ signal pathway.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• Journal of Life Science
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• v.30 no.4
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• pp.359-369
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• 2020

Although many studies on immune modulatory materials have used RAW 264.7 cells, few have used T cell-derived TK-1 cell lines. Moreover, although some studies have investigated the efficacy of plant-derived β-sitosterol, few have examined the immunomodulatory activity of its analogue, daucosterol. In this study, β-sitosterol and daucosterol were isolated from D. batatas and identified by nuclear magnetic resonance spectroscopy. To evaluate the immune-enhancing or inhibitory effects of the isolated phytosterols, the expression levels of the inflammatory response genes COX-2, TNF-α, IL-6, and iNOS were analyzed by RT-PCR. The relative expression levels of TNF-α and iNOS in RAW 264.7 cells were increased more than threefold with β-sitosterol treatment comparing to those of untreated control. In the case of TK-1 cells, the expression level of TNF-α was decreased and the expression level of iNOS was increased in a β-sitosterol concentration-dependent manner. The expression levels of COX-2, TNF-α, and IL-6 increased by approximately 0.7-1.2 times in RAW 264.7 cells treated with daucosterol compared to those of untreated control, but iNOS expression decreased by 0.8-0.18 times. In the case of daucosterol-treated TK-1 cells, the expression levels of TNF-α, IL-6, and iNOS were markedly reduced from those of TK-1 cells treated only with lipopolysaccaride. As a conclusion, β-sitosterol treatment increased TNF-α and iNOS expression levels in RAW 264.7 cells, thus exerting an immune- boosting effect. However, in TK-1 cells, iNOS expression increased while TNF-α expression decreased, indicating an immunosuppressive activity of β-sitosterol. Daucosterol appears to exert an immunosuppressive effect in both macrophages and T cell lines by inhibiting iNOS expression in RAW 264.7 cells and greatly inhibiting the expression of TNF-α, IL-6, and iNOS in TK-1 cells.

• Journal of the Korean Chemical Society
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• v.51 no.6
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• pp.536-542
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• 2007

Behcet's disease (BD) is a chronic inflammatory disorder, involving several organs. Inflammation in the disease is thought to be mediated by cytokines derived from T-helper type 1 (Th1) lymphocytes. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC (major histocompatibility complex) and non-MHC genes, are implicated in the pathogenesis of BD. This study tries to determine whether HLA-B51, IL-18, SLC11A1 and TNF-α polymorphisms are associated with susceptibility to Behcet's disease in Koreans. As a results, HLA-B51 was a genetic factor with the strongest association with BD. But it is still uncertain whether this HLA molecule is directly involved in the pathogenesis of BD. Although the IL-18 gene polymorphisms were not associated with a susceptibility to BD in the Korean population, the patients carrying the GG genotype at position 137 had a higher risk of developing the ocular lesions. This study suggests that the allele 3 and the genotype allele 3 / allele 3 of 5'-promoter (GT)n polymorphism in the SLC11A1 gene may have a protective effect for the development of BD in the Korean population. There were no evidences for genetic association conferred by the TNF-α gene with respect to susceptibility to BD.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.767-774
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• 2011

Defatted green tea seed was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether, ethyl acetate and butanol. The ethanol and butanol extracts showed greater increases in antiproliferation potential against liver cancer cells than petroleum ether, ethyl acetate, $H_2O$, and hot water extracts did. Thus, this study was carried out to investigate the anti-proliferative actions of defatted green tea seed ethanol extract (DGTSE) in HepG2 cancer cells. The DGTSE contained catechins including EGC ($1039.1{\pm}15.2\;g/g$), tannic acid ($683.5{\pm}17.61\;{\mu}g/g$), EC ($62.4{\pm}5.00\;{\mu}g/g$), ECG ($24.4{\pm}7.81\;{\mu}g/g$), EGCG ($20.9{\pm}0.96\;{\mu}g/g$) and gallic acid ($2.4{\pm}0.68\;{\mu}g/g$), but caffeic acid was not detected when analyzed by HPLC. The anti-proliferation effect of DGTSE toward HepG2 cells was 83.13% when treated at $10\;{\mu}g$/mL, of DGTSE, offering an $IC_{50}$ of $6.58\;{\mu}g$/mL. DGTSE decreased CYP1A1 and CYP1A2 protein expressions in a dose-dependent manner. Quinone reductase and antioxidant response element (ARE)-luciferase activities were increased about 2.6 and 1.94-fold at a concentration of $20\;{\mu}g$/mL compared to a control group, respectively. Enhancement of phase II enzyme activity by DGTSE was shown to be mediated via interaction with ARE sequences in genes encoding the phase enzymes. DGTSE significantly (p<0.05) suppressed prostaglandin $E_2$ level, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) protein expressions, and NF${\kappa}$B translocation, but did not affected nitric oxide production. From the above results, it is concluded that DGTSE may ameliorate tumor and inflammatory reactions through the elevation of phase II enzyme activities and suppression of NF${\kappa}$B translocation and TNF-${\alpha}$ protein expressions, which support the cancer cell anti-proliferative effects of DGTSE in HepG2 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.7
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• pp.1015-1021
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• 2013

Glycyrrhiza inflata Batal, an important species of licorice, is one of the most widely used medicinal plants for over 4000 years. Glycyrrhiza plant species has been well known for its various therapeutic activities such as anti-inflammatory, anti-allergic, and anti-ulcer. The purpose of this study was to determine the effects of Glycyrrhiza inflata Batal ethanol extracts (GBE) on adipocyte and osteoblast differentiation. Mesenchymal C3H10T1/2 cells were treated with sub-cytotoxic doses of GBE, and its effects on adipocyte differentiation were assessed. We found that GBE dose-dependently increased lipid accumulation and also induced the expression of adipocyte markers, such as $PPAR{\gamma}$ and its target genes, aP2, and adiponectin, in C3H10T1/2 cells. Consistently, similar effects of GBE on lipid accumulation were also observed in preadipocyte 3T3-L1 cells that further supports the pro-adipogenic activities of GBE. We also investigated the effects of GBE on osteoblast differentiation of mesenchymal C3H10T1/2 cells. As a results, we found that GBE increased the activity of alkaline phosphatase in a dose-dependent manner and also promoted the expression of osteoblast markers, such as ALP and RUNX2, during osteoblast differentiation of C3H10T1/2 cells. Similar pro-osteogenic effects of GBE were also observed in preosteoblast MC3T3-E1 cells. Finally, our data show that a major bioactive compound found in Glycyrrhiza inflata Batal, licochalcone A (LA) but not glycyrrhizic acid (GA), can mediate the pro-adipogenic and pro-osteogenic effects of GBE. Taken together, this study provides data to show the possibility of GBE and its bioactive component LA as putative strategies for type 2 diabetes and bone diseases.