• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.785-791
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• 2005

Corydalis Tuber has traditionally been used for the treatment of water retention in the body. Administration of the aqueous extract of Corydalis Tuber has been known to be effective for the control of pain and treatment of arthritis. It was reported that Corydalis Tuber possesses anti-inflammatory activity and modulates the intestinal immune system. The effect of Corydalis Tuber against LPS-stimulated expressions of COX-2, iNOS, and $IL-1{\beta}$ in cells of the murine RAW 264.7 macrophages was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), $PGE_2$ immunoassay, and NO detection. The aqueous extract of Corydalis Tuber was shown to suppress $PGE_2$ production by inhibition on the LPS-stimulated enhancement of COX-2 enzyme activity, $IL-1{\beta}$, and iNOS expression in the RAW 264.7 macrophages. Present results suggest that Corydalis Tuber exerts anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ expressions, resulting in inhibition of $PGE_2$ synthesis. Corydalis Tuber has anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ mRNA expressions, resulting in inhibition of $PGE_2$ and NO synthesis.

• Korean Journal of Veterinary Research
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• v.58 no.1
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• pp.1-7
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• 2018

Genus Artemisia occurs as a hardy plant and has a wide range of culinary and medicinal features. In this study, we aimed to describe the melanin inhibitory activity of one Artemisia species, i.e., Artemisia capillaris Thunb. Ethanol extracts of fermented Artemisia capillaris (Art.EtOH.FT) and non-fermented Artemisia capillaris (Art.EtOH.CT) were tested for their ability to inhibit tyrosinase activity and melanin pigmentation. Both extracts showed dose-dependent inhibition against ${\alpha}$-melanocyte stimulating hormone-stimulated melanin formation and tyrosinase activity, without cytotoxicity. At $100{\mu}g/mL$, both extracts showed greater inhibition than kojic acid, the positive control. Protein expressions of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2) at the transcriptional level were determined by using real-time and semi-quantitative polymerase chain reaction. To complete the mechanistic study, presences of upstream elements of MITF, the phosphorylated-extracellular signal-regulated kinase (p-ERK), and phosphorylated-mitogen-activated protein kinase kinase (p-MEK) were confirmed by using western blot analysis. Expressions of p-TYR, p-TRP-1 and p-TRP-2, downstream factors for p-ERK and p-MITF, were translationally inhibited by both extracts. Art.EtOH.FT induced more potent effects than Art.EtOH.CT, especially signal transduction effects. In summary, Artemisia capillaris extracts appear to act as potent hypopigmentation agents.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.1
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• pp.31-45
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• 2020

Objectives In this study, we investigated the antimicrobial activity of a 70% ethanol extract of Maneung-hwan (MEH), which is prescribed by practitioners of oriental medicine for use against methicillin-resistant Staphylococcus aureus (MRSA). Methods The antibacterial activity of MEH against MRSA strains was evaluated using the disc diffusion method, broth microdilution method (minimal inhibitory concentration, MIC), checkerboard dilution test, and time-kill test. The mechanism of action of MEH was investigated by bacteriolysis using detergents or ATPase inhibitors Additionally, mRNA and protein expression were investigated by quantitative reverse transcription-polymerase chain reaction and western blot assay, respectively. Results The MIC of MEH was 25~1,600 ㎍/mL against all the tested bacterial strains. We showed that MEH extract exerts strong antibacterial activity. In the checkerboard dilution test, the fractional inhibitory concentration index of MEH in combination with antibiotics indicated synergism or partial synergism against S. aureus. The time-kill study indicated that the growth of the tested bacteria was considerably inhibited after a 24-h treatment with MEH and selected antibiotics. To measure the cell membrane permeability, MEH (3.9 ㎍/mL) was combined with Triton X-100 (TX) at various concentrations N,N-dicyclohexylcarbodimide (DCCD) was also tested as an ATPase inhibitor. TX and DCCD cooperation against S. aureus exhibited synergistic action. Accordingly, the antimicrobial activity of MEH in the context of cell membrane rupture and ATPase inhibition was assessed. Additionally, the expression of genes and proteins associated with resistance was reduced after exposing MRSA to MEH. Conclusions These results suggest that MEH possesses antibacterial activity and acts as a potential natural antibiotic against MRSA.

• Journal of Korean Medicine for Obesity Research
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• v.15 no.2
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• pp.104-110
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• 2015

Objectives: The herb of Agastache rugosa (AR) is a traditional herbal medicine used for colds, vomiting and furuncles. However, there are few reports to investigate the inhibitory effects of AR on obesity. In this study, the effects of AR on high fat diet (HFD)-induced obesity and its mechanism of actions were investigated in experimental animals. Methods: The mice were fed HFD for 4 weeks to induce obesity. After randomly divided into normal fat diet, HFD and AR groups, 200 mg/kg of AR was administrated for 4 weeks with continuous HFD feeding while vehicle was orally treated to HFD group. Food intake and body weight were recorded weekly. Results: Increased body weight by HFD was improved by AR treatment. AR administration inhibited an increase of visceral fat weight as well as adipocyte hypertrophy. Hepatic steatosis was ameliorated in AR-treated mice. In addition, treatment of AR attenuated the expression of adipogenic transcription factor, peroxisome proliferator-activated receptor (PPAR)-gamma in the epididymal adipose tissue. Also the increased serum leptin level by HFD was maintained in AR group, leading to inhibition of food intake. Conclusions: AR treatment showed inhibitory effects on HFD-induced obesity by inhibition of PPAR-gamma and reduction of food intake. AR could be an alternative treatment for obesity.

• Journal of Microbiology and Biotechnology
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• v.22 no.6
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• pp.806-813
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• 2012

Adipocyte differentiation is strongly associated with obesity, which causes metabolic disorders. In this study, we investigated the inhibitory effects of widdrol on 3T3-L1 preadipocyte growth and differentiation. Widdrol decreased lipid droplet accumulation and down-regulated adipogenic transcription factors such as C/$EBP{\alpha}$, C/$EBP{\beta}$, and $PPAR{\gamma}$. Widdrol blocked preadipocyte proliferation and differentiation through the inhibition of mitotic clonal expansion, which was accompanied by the failure of degradation of p21, a cyclin-dependent kinase inhibitor. Cell-cycle analysis clearly indicated that widdrol actively induces cell-cycle arrest at the G1-S phage transition, causing cells to remain in the preadipocyte state. Moreover, widdrol increased p21 expression and inhibited Rb phosphorylation in preadipocyte incubated in a hormone medium. Therefore, these findings clearly suggest that widdrol blocks preadipocyte growth and differentiation through the inhibition of mitotic clonal expansion by p21-and Rb-dependent G1 arrest and can be developed as a potent anti-adipogenic agent for reducing obesity.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.1836-1844
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• 2016

Adipogenesis is one of the cellular processes and a highly controlled program. Nowadays, inhibition of adipogenesis has received attention as an effective way to regulate obesity. In the current study, we investigated the inhibition effect of a chloroform extract of Pleurotus eryngii var. ferulae 'Beesan No. 2' (CEBT) on adipogenesis in 3T3-L1 murine preadipocytes. Pleurotus eryngii var. ferulae is one of many varieties of King oyster mushroom and has been reported to have various biological activities, including antitumor and anti-inflammation effects. Biological activities of 'Beesan No. 2', a new cultivar of Pleurotus eryngii var. ferulae, have not yet been reported. In this study, we found that CEBT suppressed adipogenesis in 3T3-L1 cells through inhibition of key adipogenic transcription factors, such as peroxisome proliferatoractivated receptor ${\gamma}$ and CCAAT/enhancer binding protein ${\alpha}$. Additionally, CEBT reduced the expression of the IRS/PI3K/Akt signaling pathway and its downstream factors, including mammalian target of rapamycin and p70S6 kinase, which stimulate adipogenesis. Furthermore, ${\beta}-catenin$, a suppressor of adipogenesis, was increased in CEBT-treated cells. These results indicate that Pleurotus eryngii var. ferulae 'Beesan No. 2' effectively inhibited adipogenesis, so this mushroom has potential as an anti-obesity food and drug.

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.224-231
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• 2003

The aim of this study was to investigate the effect of resveratrol on the oxidative stress-induced inhibition of gap junctional intercellular communication in HaCaT keratinocytes. Anti-oxidative activity of resveratrol was measured by $\alpha,\alpha$-diphenyl-$\beta$-picrylhydrazyl assay and dichlorodihydrofluorescein diacetate oxidation assay. Gap junctional intercellular communication in HaCaT keratinocytes was assessed using the scrape loading/dye transfer technique. Western blots and reverse transcription-polymerase chain reaction were also analyzed for connexin 43 protein and mRNA expression, respectively. Resveratrol scavenged directly the stable $\alpha,\alpha$-diphenyl-$\beta$-picrylhydrazyl radical over a concentration range of 4 mg/ml ($78.2{\pm}2.7$% of control) to 500 mg/ml ($29.9{\pm}4.2$% of control) and decreased the intracellular reactive oxygen species induced by ultraviolet A (UVA) irradiation ($89.3{\pm}1.1$% of UVA group), ultraviolet B (UVB) irradiation ($70.9{\pm}1.7$% of UVB group) and 12-0-tet-radecanoylphorbol-13-acetate (TPA, $48.3{\pm}1.1$% of TPA group), respectively. UVA irradiation and TPA markedly reduced gap junctional intercellular communication, which was restored by resveratrol. There were no significant differences in the level of connexin 43 protein and mRNA expression among any of the experimental groups. Our data suggests that resveratrol has the protective effect on the oxidative stress-induced inhibition of gap junctional intercellular communication in HaCaT keratinocytes, and this protection is likely due to the scavenging of reactive oxygen species.

• BMB Reports
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• v.52 no.3
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• pp.208-213
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• 2019

Chemoresistance is the primary obstacle in the treatment of locally advanced and metastatic nasopharyngeal carcinoma (NPC). Recent evidence suggests that the transcription factor forkhead box M1 (FoxM1) is involved in chemoresistance. Our group previously confirmed that FoxM1 is overexpressed in NPC. In this study, we investigated the role of FoxM1 in cisplatin resistance of the cell lines 5-8F and HONE-1 and explored its possible mechanism. Our results showed that FoxM1 and NBS1 were both overexpressed in NPC tissues based on data from the GSE cohort (GSE12452). Then, we measured FoxM1 levels in NPC cells and found FoxM1 was overexpressed in NPC cell lines and could be stimulated by cisplatin. MTT and clonogenic assays, flow cytometry, ${\gamma}H2AX$ immunofluorescence, qRT-PCR, and western blotting revealed that downregulation of FoxM1 sensitized NPC cells to cisplatin and reduced the repair of cisplatin-induced DNA double-strand breaks via inhibition of the MRN (MRE11-RAD50-NBS1)-ATM axis, which might be related to the ability of FoxM1 to regulate NBS1. Subsequently, we demonstrated that enhanced sensitivity of FoxM1 knockdown cells could be reduced by overexpression of NBS1. Taken together, our data demonstrate that downregulation of FoxM1 could improve the sensitivity of NPC cells to cisplatin through inhibition of MRN-ATM-mediated DNA repair, which could be related to FoxM1-dependent regulation of NBS1.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.51-58
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• 2021

Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H2O2 treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H2O2-treated cells; however, it recovered on G9a inhibition. H2O2-treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a. H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H2O2-treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H2O2-treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.190-197
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• 2017

BACKGROUND/OBJECTIVES: Gallus gallus domesticus (GD) is a natural mutant breed of chicken in Korea with an atypical characterization of melanin in its tissue. This study investigated the effects of melanin extracts of GD on osteoblast differentiation and inhibition of osteoclast formation. MATERIALS/METHODS: The effects of the melanin extract of GD on human osteoblast MG-63 cell differentiation were examined by evaluating cell viability, osteoblast differentiation, and expression of osteoblast-specific transcription factors such as bone morphogenetic protein 2 (BMP-2), small mothers against decapentaplegic homologs 5 (SMAD5), runt-related transcription factor 2 (RUNX2), osteocalcin and type 1 collagen (COL-1) by reverse transcription-polymerase chain reaction and western blotting analysis. We investigated the inhibitory effect of melanin on the osteoclasts formation through tartrate-resistant acid phosphatase (TRAP) activity and TRAP stains in Raw 264.7 cell. RESULTS: The melanin extract of GD was not cytotoxic to MG-63 cells at concentrations of $50-250{\mu}g/mL$. Alkaline phosphatase (ALP) activity and bone mineralization of melanin extract-treated cells increased in a dose-dependent manner from 50 to $250{\mu}g/mL$ and were 149% and 129% at $250{\mu}g/mL$ concentration, respectively (P < 0.05). The levels of BMP-2, osteocalcin, and COL-1 gene expression were significantly upregulated by 1.72-, 4.44-, and 2.12-fold in melanin-treated cells than in the control cells (P < 0.05). The levels of RUNX2 and SMAD5 proteins were higher in melanin-treated cells than in control vehicle-treated cells. The melanin extract attenuated the formation of receptor activator of nuclear factor kappa-B ligand-induced TRAP-positive multinucleated RAW 264.7 cells by 22%, and was 77% cytotoxic to RAW 264.7 macrophages at a concentration of $500{\mu}g/mL$. CONCLUSIONS: This study provides evidence that the melanin extract promoted osteoblast differentiation by activating BMP/SMADs/RUNX2 signaling and regulating transcription of osteogenic genes such as ALP, type I collagen, and osteocalcin. These results suggest that the effective osteoblastic differentiation induced by melanin extract from GD makes it potentially useful in maintaining bone health.