• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.2
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• pp.18-30
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• 2018

Objective: This study was designed to investigate the anti-cancer effects of AAH on ovarian cancer in vitro and by using allograft model in vivo. Methods: In this experiment, the effects of AAH on proliferation rates, cell morphology, cell death type, cell cycle, caspase activities and p38 mitogen-activated protein kinase (MAPK) pathway were investigated in A2780, human ovarian cell line. Results: AAH inhibited proliferation of A2780 cells in a dose dependent manner. In addition, AAH induced apoptosis but did not affect cell cycle of A2780 cells. AAH also effectively inhibited caspase 3 and caspase 9 activities respectively. In allograft tumor model, AAH reduced tumor volume and expanded life span in a dose dependent manner. Conclusion: It can be inferred that AAH can induce apoptosis in ovarian cancer cells and has possibility as an anticancer agent for ovarian cancer.

• Journal of Environmental Science International
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• v.28 no.2
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• pp.249-257
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• 2019

Ulmus davidiana Nakai (UDN) has been traditionally used as a herbal medicine to treat inflammatory diseases in Korea. In the present study, we investigated the anti-ecotoxic potential of a 116 kDa glycoprotein isolated from UDN (UDN glycoprotein) in human intestinal epithelial INT-407 cells. We demonstrated that UDN glycoprotein ($20{\mu}g/mL$) could inhibit the production of lactate dehydrogenase (LDH) induced by toluene, an ecotoxic substance. Additionally, we found that the toluene-induced intestinal cytotoxicity was mediated by the phosphorylation of p38 Mitogen-Activated Protein Kinase (MAPK) via the production of intracellular Reactive Oxygen Species (ROS). The UDN glycoprotein significantly decreased the levels of ROS production and p38 MAPK activation in toluene-stimulated INT-407 cells. Moreover, the UDN glycoprotein inhibits the phosphorylation of nuclear factor-kappa B ($NF-{\kappa}B$), which is responsible for the production of LDH, in toluene-stimulated INT-407 cells. Collectively, our data indicate that UDN glycoprotein is a natural antioxidant and a modulator of ecotoxicity signaling pathways in human intestinal epithelial cells.

• The Journal of Korean Medicine
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• v.43 no.4
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• pp.20-32
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• 2022

Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG's anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and Iκ-Bα by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of Iκ-Bα but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1β, IL-6, and TNF-α via the deactivation of JNK, p38 and nuclear factor (NF)-κB on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

• Journal of the Korean Dietetic Association
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• v.25 no.3
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• pp.217-228
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• 2019

There have been no published studies concerning the anti-inflammatory effects of corn silk on colon cancer cells. Thus, this study was conducted to investigate the effect of corn silk extract containing high levels of maysin on inflammation and its mechanism of action in colon cancer cells. SW 480 human colon cancer cells were treated with $1{\mu}g/mL$ of lipopolysaccharide (LPS) to induce inflammation, and next they were treated with different concentrations of corn silk extract (0, 5, 10 and $15{\mu}g/mL$). The concentrations of nitric oxide (NO) were determined. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1beta ($IL-1{\beta}$) and interleukin-6 (IL-6), were determined. Western blot analysis was performed to determine the protein expressions of nuclear factor-kappa B ($NF-{\kappa}B$) and mitogen-activated protein kinases, and the latter consists of extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 MAP kinase (p38). The concentration of NO and the mRNA expression of iNOS were significantly and dose-dependently decreased in the corn silk-treated groups (P<0.05). The mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were significantly increased in the LPS-treated group (P<0.05), but these expressions were significantly and dose-dependently decreased in the corn silk treated groups (P<0.05). The protein expressions of $NF-{\kappa}B$ (in a dose-dependent fashion), ERK (at 10 and $15{\mu}g/mL$), JNK (at $15{\mu}g/mL$) and p38 (at 10 and $15{\mu}g/mL$) were significantly decreased with corn silk treatments (P<0.05). In conclusion, corn silk extract containing high levels of maysin seems to inhibit the LPS-induced inflammatory responses in SW480 colon cancer cells via the $NF-{\kappa}B$ pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.3
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• pp.293-300
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• 2012

Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important inflammatory mediators implicated in pathogenesis of inflammation and certain types of human cancers. The present study was designed to determine whether Red Ginseng (RG) could modulate $I{\kappa}B$-kinase, iNOS and COX-2 gene expression and immune responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). RG extract suppressed the expression of LPS-induced $I{\kappa}B$, iNOS, COX-2, and immune responses in a dose-dependent manner. It also showed an anti-inflammatory effect by inhibiting NF-${\kappa}B$ immune response induced by LPS treatment. Inhibitory effect of RG on LPS-induced inflammation was mediated by suppressed phosphorylation of ERK, JNK and p38 through the regulation of the mitogen-activated protein kinase (MAPK) pathway leading to a decreased production of NO, iNOS, COX-2 and NF-${\kappa}B$. The results implied the role of RG as an inflammation regulator and its possible application for curing inflammatory diseases.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.152-165
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• 2008

Purpose: It is the purpose of this study to investigate the anti-inflammatory effects and mechanism of cheukbaekjurpihwan(CBJPH) extract on LPS (lipopolysaccharide)-induced inflammatory mediators in murine peritoneal macrophages. Methods: To evaluate anti-inflammatory effects of CBJPH extract, the production of cytokines(TNF-${\alpha}$(tumor necrosis factor-alpha), IL(interleukin)-6, IL-12) and NO(nitric oxide) was measured in vitro and in vivo. And western blot analysis has been done to look into the mechanism. Results: CBJPH extract reduced LPS-induced NO, TNF-${\alpha}$ and IL-6, IL-12 productions in peritoneal macrophages. CBJPH extract inhibited the activation of JNK(c-Jun N-terminal kinase), but didn't inhibit the activation of MAPKs (mitogen-activated protein kinases) such as p38, ERK1/2(extracelluar signal-regulated kinase1/2) and the degradation of $I_{\kappa}B-{\alpha}$(inhibitory kappa B-alpha) in the LPS-stimulated peritoneal macrophages. CBJPH extract suppressed LPS-induced endotoxin shock and the productions of TNF-${\alpha}$, but not of IL-6, after an oral administration of CBJPH extract Conclusion: CBJPH extract suppressed the productions of LPS-induced NO and cytokines by preventing JNK from phosphorylation, which may provide a clinical basis for anti-inflammatory properties of CBJPH.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.28 no.1
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• pp.31-41
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• 2002

The production of matrix matalloproteinases(MMPs) by the UV irradiated skin fibroblast and the degradation of extracellular matrix(ECM) by these enzymes is known as one of the main reasons of photoaging. Recently, Fisher group showed that the MMP expression is mainly regulated by the mitogen-activated protein(MAP) kinas family, such as extracellular signal-regulated kinase(ERK), c-Jun amino-terminal kinase(JNK) and p38, each of which forms a signaling pathway. In this work we first examined the effect of nitric oxide (NO) on the production of MMP-1 and MMP-2 by the human dermal fibroblasts (HDFs). NO is a multifunctional messenger molecule generated from L-arginine and involved in many kinds of signaling pathway. We found that the treatment of HDF with NO donor, sodium nitroprusside (SNP) enhanced the expression of MMPs with or without UV irradiation and the treatment with nitric oxide synthase (NOS) inhibitors resulted in the significant decrease of MMPs production. From these results, we concluded that the production of MMPs by the UV irradiated HDF is regulated through the signaling pathway involving NO and cyclic GMP.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.463-469
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• 2022

Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A₂ generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca²⁺ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser¹⁷⁵⁶), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A₂ generation and associated signaling molecules, including cytosolic phospholipase A₂ and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β₃) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• BMB Reports
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• v.45 no.8
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• pp.482-487
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• 2012

To identify the novel inhibitors of endoplasmic reticulum stress-induced cell death, we performed a high throughput assay with a chemical library containing a total of 3,280 bioactive small molecules. Cyclosporine A and bromocriptine were identified as potent inhibitors of thapsigargiin-induced cell death (cut-off at $4{\sigma}$ standard score). However, U74389G, the potent inhibitor of lipid peroxidation had lower activity in inhibiting cell death. The inhibition effect of cyclosporine A and bromocriptine was specific for only thapsigargin-induced cell death. The mechanism of inhibition by these compounds was identified as modification of the expression of glucose regulated protein-78 (GRP-78/Bip) and inhibition of phosphorylation of p38 mitogen activated protein kinase (MAPK). However, these compounds did not inhibit the same events triggered by tunicamycin, which was in agreement with the cell survival data. We suggest that the induction of protective unfolded protein response by these compounds confers resistance to cell death. In summary, we identified compounds that may provide insights on cell death mechanisms stimulated by ER stress.

• BMB Reports
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• v.52 no.6
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• pp.385-390
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• 2019

Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway.