• The Korea Journal of Herbology
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• v.22 no.2
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• pp.147-153
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• 2007

Objectives : Sophora flavescens (SF) is widely used in traditional herbal medicine in Korea and is well recognized for its anti-inflammatory effect. However, its effect on Tumornecrosis factor alpha (Tnf) production in BV2 microglial cell is not yet known. Methods : We investigated the effect of SF on the production and expression of Tnf, a well known inflammatory mediator, in lipopolysaccaride (LPS)-activated BV2 microglial cells. Results : The LPS-induced Tnf production was markedly reduced by treatment with SF (50 ${\mu}g/ml$). In reverse transcription polymerase chain reaction (RT-PCR) analysis, SF suppressed the LPS activated expression of Tnf mRNA. In addition, Western blot analysis confirmed that SF suppressed the expression of Tnf. Sophora flavescens also inhibited the LPS-induced phosphylation of extracellular signal-regulated kinases (ERK), which mediate the Tnfproduction signaling pathway whereas LPS-induced phosphylation of p38 mitogen activated protein kinase (p38 MAPK), and c-Jun NH2-terminal kinases (JNK) was not inhibited by SF, which implies that SF suppresses LPS-induced Tnf production via the ERK mediated pathway. Conclusion : Taken together, these findings indicated that SF inhibits LPS-induce Tnf production, and that this inhibitory effect is mediated via the ERK pathway.

• The Journal of Korean Medicine
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• v.41 no.2
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• pp.43-57
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• 2020

Objectives: The purpose of this study was to investigate the effect of Phellinus linteus cheonghyeol plus (PLCP) on antioxidant and inhibition of inflammatory factor expression associated with dyslipidemia in HUVEC. Methods: The scavenging activity of DPPH and ABTS radical of PLCP was measured in HUVEC. The expression levels of NF-κB, p-IκBα, ERK, JNK, and p38 proteins were measured after treating with TNF-α in HUVEC. The expression levels of MCP-1, ICAM-1, and VCAM-1 mRNA and biomarkers were measured after treatment with TNF-α in HUVEC Results: 1. PLCP increases DPPH and ABTS radical scavenging activity in a concentration dependent manner. 2. PLCP significantly decreased the concentration of NF-κB, p-IκBα, ERK, JNK protein compared to the control at concentrations of 100 ㎍/㎖ or more, and significantly decreased concentration of p38 protein at all concentrations. 3. PLCP significantly decreased MCP-1 mRNA expression levels at 100㎍/㎖ or more compared to the control. ICAM-1 and VCAM-1 mRNA expression levels were significantly reduced at all concentrations compared to the control. MCP-1, ICAM-1 protein expression levels were significantly reduced compared to the control at concentrations of 100 ㎍/㎖ or more, and VCAM-1 protein expression levels were reduced at all concentrations. Conclusions: These results suggest that PLCP has an antioxidant effect, and it has been experimentally confirmed that it can prevent or inhibit inflammatory diseases caused by dyslipidemia due to its inhibitory effect on inflammation-related factors in HUVEC.

• Biomedical Science Letters
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• v.12 no.3
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• pp.249-254
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• 2006

It has been reported that liver is a very important organ to xenotransplantation. Pig is known to be a most suitable species in transplantation of human organs. However, the physiological function of pig hepatocytes is not clear elucidated. Epidermal growth factor (EGF) is known to be a mitogen in various cell systems. Thus, we examined the effect of EGF on cell proliferation and its related signal cascades in primary cultured pig hepatocytes. EGF stimulates cell proliferation in a dose (>1ng/ml) dependent manner. EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by AG 1478 ($10^{-6}M$, an EGF receptor antagonist) genistein and herbymycin A (tyrosine kinase inhibitors, $10^{-6}M$), suggesting the role of activation and tyrosine phosphorylation of EGF receptor. In addition, EGF-induced increase of $[^3H]-thymidine$ incorporation was prevented by neomycin $(10^{-4}M)$, U73122 $(10^{-5}M)$ (phospholipase C [PLC] inhibitors), staurosporine ($(10^{-8}M)$, or bisindolylmaleimide I $(10^{-6}M)$ (protein kinase C [PKC] inhibitors), suggesting the role of PLC and PKC. Moreover, EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by PD 98059 (a p44/42 mitogen activated protein kinase [MAPK] inhibitor), SB 203580 (a p38 MAPK inhibitor), and SP 600125 (a JNK inhibitor). EGF increased the translocation of PKC from cytosol to membrane fraction and activated p42/44 MAPK, p38 MAPK and JNK. In conclusion, EGF stimulates cell proliferation via PKC and MAPK in cultured pig hepatocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.5
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• pp.288-294
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• 2019

Gardenia jasminoides is an herbal medicine that treats obesity and dampness-phlegm. This study aimed to investigate the efficacy of Gardenia jasminoides on insulin resistance induced by Non-alcoholic fatty liver disease (NAFLD). 8-week-old C57BL/6 male mice were divided into three groups: control group (Ctrl), high-fat diet group (HFF), and high fat diet with Gardenia jasminoides extract administration group (GJT). Each 10 mice was allocated to each group (a total of 30 mice). All mice were allowed to eat fat-rich diet freely throughout the experiment. To examine the effect of Gardenia jasminoides, we observed weight changes, lipid blot distributions, PPAR-${\gamma}$, p-IkB, p-JNK in liver tissue, total cholesterol, and glucose levels in serum. Comparing of body weight measurements between 3 groups, in the GJT group, weight gain was significantly suppressed compared to the HFF group. The distribution of lipid blots and positive reaction of PPAR-${\gamma}$ were significantly lower in GJT group. The expression levels of p-$I{\kappa}B$ and p-JNK that plays critical roles in the development of insulin resistance were significantly decreased by GJ treatment. Total cholesterol and glucose levels in serum were also significantly lower in GJT group. Gardenia jasminoides has the effect of improving non - alcoholic fatty liver induced insulin resistance through the regulation of lipid metabolism.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.4
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• pp.1-12
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• 2018

Objectives Bangpungtongsungsan is an herbal medicine that treats obesity and dampness-phlegm. The aim of this study was to investigate the efficacy of Bangpungtongsungsan on insulin resistance induced by non-alcoholic fatty liver disease. Methods Male 6-week-old C57BL/6 male mice were divided into four groups: control group (Ctrl), high fat diet group (HFF), high fat diet with Bangpungtongsungsan extract administration group (BT1), and high fat diet with double concentration of Bangpungtongsungsan extract administration group (BT2). Each 10 mice were allocated to each group (total of 40 mice). All mice were allowed to eat fat rich diet freely throughout the experiment. To examine the effect of Bangpungtongsungsan, we observed weight changes, lipid blot distributions, PGC-1, $p-I{\kappa}B$, 8-OHdG, p-JNK, total cholesterol and glucose levels. Results Comparing of body weight measurements between 4 groups, weight gain was significantly lower in BT1 and BT2 group than the HFF group. The distribution of lipid blots and positive reaction of PGC-1 were significantly lower in BT1 and BT2 group. The positive reaction of $p-I{\kappa}B$ and 8-OHdG in hepatic tissues was significantly lower in BT1 and BT2 group. The positive reaction of p-JNK in hepatic tissues was significantly lower in BT1 and BT2 group. Total cholesterol and glucose levels were significantly lower in BT1 and BT2 group. Conclusions Bangpungtongsungsan has the effect of improving non-alcoholic fatty liver induced insulin resistance through regulation of lipid metabolism.

• Herbal Formula Science
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• v.27 no.1
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• pp.53-63
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• 2019

Objectives : In this study, we investigated the combination effects of Cinnamomi cortex Ethanol Extract (CcEE) and hyperthermia in the human AGS gastric cancer cell line. Methods : AGS cells were treated with the indicated concentrations of CcEE (0, 50 or $60{\mu}g/mL$) for 1h prior to hyperthermia. And then incubated for a further 30 min at the indicated temperatures (37, 42 or $43^{\circ}C$) in a humidified incubator containing 5% $CO_2$ or a thermostatically controlled water bath for hyperthermia. The cell viability was measured by MTT assay, Morphology assay and Trypan blue assay. To investigate the possible molecular signaling pathways, the activation of mitogen-activated protein kinase (MAPK) proteins (ERK, p38 and JNK) and expression of various anti-apoptotic proteins such as Caspase-3, Caspase-9, p53, Cyclin D1 and MMP-2 were assessed by Western blot analysis. In addition, Annexin V and 7-amino-actinomycin D (7-AAD) staining was performed to examine the apoptotic mechanism. Results : Combination of CcEE with hyperthermia effectively suppressed the cell viability and changed cellmorphology compared with CcEE or hyperthermia treatment alone. Combined treatment also abated the expression of Caspase-3, Caspase-9, Cyclin D1 and MMP-2. Whereas, the expression level of p53 was up-regulated by co-treatment. Moreover, combination treatment enhanced phosphorylation of ERK, p38 and JNK. In addition, this combination increased anti-cancer effect by inducing cell death through the apoptosis. Conclusions : Taken together, all these findings suggest that the combination treatment with CcEE and hyperthermia may have therapeutic potential as a promising approach to patients with stomach cancer.

• The Journal of Pediatrics of Korean Medicine
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• v.33 no.2
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• pp.12-21
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• 2019

Objectives Coptidis Rhizoma and Glycyrrhiza Uralensis are herbs that treat obesity and dampness-phlegm. The aim of this study is to investigate the efficacy of Coptidis Rhizoma and Glycyrrhiza Uralensis on lipid deposition with nonalcoholic fatty liver disease (NAFLD). Methods Male 6-week-old C57BL/6 male mice were divided into three groups: control group (Ctrl), high fat diet group (HFF), and high fat diet with Coptidis Rhizoma and Glycyrrhiza Uralensis extract administration group (CGT). Each 10 mice were allocated to each group (total of 30 mice). All mice were allowed to eat fat rich diet freely throughout the experiment. To examine the effect of Coptidis Rhizoma and Glycyrrhiza Uralensis, we observed weight changes, total cholesterol and glucose levels, lipid blot distributions, PGC-1, p-$I{\kappa}B$, and p-JNK. Results Body weights for all mice were measured and analyzed the difference between the groups. Weight gain was significantly lower in CGT group than the HFF group. Total cholesterol and glucose levels were significantly lower in CGT group. The distribution of lipid blots and positive reaction of PGC-1 were significantly lower in CGT group. The positive reaction of p-$I{\kappa}B$ in hepatic tissues was significantly lower in CGT group. The positive reaction of p-JNK in hepatic tissues was significantly lower in CGT group. Conclusions Coptidis Rhizoma and Glycyrrhiza Uralensis have the effect of improving non - alcoholic fatty liver induced insulin resistance through regulation of lipid metabolism.

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.2
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• pp.243-254
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• 2002

For the purpose of evaluating the biocompatability of 3 kinds of metallic materials frequently used in pediatric dentistry (stainless steel crown, orthodontic band, orthodontic wire), cellular and molecular studies, including cell growth and proliferation, screening of cell death with determination of types whether necrosis or apoptosis and changes in expressions of related signaling molecules were examined, using cultured human gingival fibroblasts (HGF-1), HGF-1 was cultured in Dulbecco's modified Eagle's medium. among which the 3rd to 6th generations of HGF-1 were used. The specimen were divided into stainless steel crown (R), band (B) and wire (W). The immunocytochemical study was done for the detection of anti-PCNA (proliferating cell nuclear antigen) labeling. With extracted protein, western blot was done for the detection of ERK1/2, JNK, and p38, using individual antibodies. Cultured cells proliferated, remarkably till 7 day and slightly at 11 day. There was no statistical significance in the counts of proliferating HGF-1 between control and experimental groups (p>0.05). Relative growth rates were no statistically significant difference between control and experimental groups (p>0.05). PCNA labeling indexes showing similar patterns in control and experimental groups. The expressions of ERK1 and ERK2, p38 were similar in control and experimental groups. The expression of JNK increased at 1st day, slightly decreased at 4th day and markedly increased at 7th and 11 day. Although the patterns of control and experimental groups were similar, the increased expressions of JNK at late period suggest a possible stress due to inhibited cell growth and proliferation, and worse culture condition. Conclusively, the 3 kinds of metal specimens used in this study did not induce cellular and molecular hazards during short term culture of HGF-1. But, for the better clinical stability, the establishment of long period culture and animal experiment was thought necessary.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.91-97
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• 2017

Although anti-aging activities of melatonin, a hormone secreted by the pineal gland, have been reported in senescence-accelerated mouse models and several types of cells, its impact and mechanism on the senescence of human dental pulp cells (HDPCs) remains unknown. In this study, we examined the impact of melatonin on cellular premature senescence of HDPCs. Here, we found that melatonin markedly inhibited senescent characteristics of HDPCs after exposure to hydrogen peroxide ($H_2O_2$), including the increase in senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal)-positive HDPCs and the upregulation of p21 protein, an indicator for senescence. In addition, as melatonin attenuated $H_2O_2$-stimulated phosphorylation of c-Jun N-terminal kinase (JNK), while selective inhibition of JNK activity with SP600125 significantly attenuated $H_2O_2$-induced increase in SA-beta-gal activity. Results reveal that melatonin antagonizes premature senescence of HDPCs via JNK pathway. Thus, melatonin may have therapeutic potential to prevent stress-induced premature senescence, possibly correlated with development of dental pulp diseases, and to maintain oral health across the life span.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.152.2-153
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• 2003

${\beta}Although$ it has been demonstrated that $p2l^{WAFl/Cip1}$, a well known cell cycle inhibitor, could be induced by $TGF-{\beta}$ in a p53-independent manner, the detailed signal transduction pathways still remain poorly understood. In this study, we show that ERK is required for $TGF-{\beta}$ induction of $p21^{WAF1/Cip1}$, but JNK or p38 MAPK is not. ERK activation by $TGF-{\beta}$ significantly attenuated by treatment with ROS scavenger such as NAC or catalase, indicating that ROS, mainly $H_2O_2$, generation by $TGF-{\beta}$ might stimulate ERK signaling pathway to require the induction of $p21^{WAF1/Cip1}$. (omitted)