• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.170.2-170.2
• /
• 2003

Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer, including the degrees of invasion and tumor recurrence. We previously showed that p38 MAPK is a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells (Cancer Res: 63, 5454-5461, 2003). In this study, we further investigated the role of p38 MARK pathway in the induction of metastatic potential in MCF10A cells as a "gain of function" study. (omitted)

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.117.1-117.1
• /
• 2002

• BMB Reports
• /
• 제51권6호
• /
• pp.308-313
• /
• 2018

Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$), and their upstream kinases, $I{\kappa}B$ kinase (IKK) ${\alpha}/{\beta}$, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates $NF-{\kappa}B$, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors.

• 한국한의학연구원논문집
• /
• 제17권3호
• /
• pp.77-85
• /
• 2011

Objectives : The purpose of this study was to develop a simulator which can analyze the anti-inflammatory effects of medical herbs based on e-cell concerning p38 MAPK signal pathway. Methods : We collected data concerning medical herbs with anti-inflammatory effects and the active compounds to provide as a fundamental databse and to validate the newly developed algorithm. At this time, we used the target database as pubmed and gathered the data by data mining tool, pathway studio. Also we have developed the web-based search system for confirming database related to anti-inflammation. We researched the mechanism of actions of proteins in p38 MAPK signal pathway when active compound has been inserted into the network. We reduced total network into TAK-MKK3-p38 and made the two types of mathematical model about active compounds' interaction. Results & Conclusion : We constructed the database which have 69 cases of medical herbs, 71 cases of active compounds, about 8,000 cases of URL(Uniform Resource Locator) related to papers and reports. We designed the ordinary differential equations for response of TAK, MKK3, p38 in e-cell's cytosol and nucleus. We used this formular as measure whether an active compound of medicinal plants which is inputted by an user would have an anti-inflammation effects. We developed the visualization program which could show the change of concentration over time.

• 대한약침학회지
• /
• 제27권2호
• /
• pp.131-141
• /
• 2024

Objectives: Polycystic ovary syndrome (PCOS) is one of the most common disorders and it shows up to 20% prevalence in reproductive-aged women populations, but no cures are available to date. We aimed to investigate the protective effects of Changbudodam-tang (CBD) on cell death signaling pathways, inflammation, and oxidative stress observed in Bone-Marrow derived human mesenchymal stem cell (BM-hMSC) by means of PCOS therapeutics in the future. Methods: BM-hMSCs were applied with cell deaths and injuries. Apoptosis and pyroptosis signals were quenched with their related signaling pathways using quantitative PCR, Western blot, and fluorescence image analysis. Results: Our data clearly displayed hydrogen peroxide- and nigericin-treated cell death signaling pathways via regulations of mitochondrial integrity and interleukin (IL)-1β at the cellular levels (p < 0.01 or 0.001). We further observed that pre-treatment with CBD showed protective effects against oxidative stress by enhancement of antioxidant components at the cellular level, with respect to both protein and mRNA expression levels (p < 0.05, 0.01 or 0.001). The mechanisms of CBD were examined by Western blot analysis, and it showed anti-cell death, anti-inflammatory, and antioxidant effects via normalizations of the Jun N-terminal kinase/mitogen-activated protein kinase kinase 7/c-Jun signaling pathways. Conclusion: This study confirmed the pharmacological properties of CBD by regulation of cellular oxidation and the inflammation-provoked cell death condition of BM-hMSCs, which is mediated by the MKK7/JNK/c-Jun signaling pathway.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 춘계학술대회 논문집
• /
• pp.72-72
• /
• 2003

Induction of glutathione S-transferases is associated with cancer chemoprevention. We reported that PD98059, an MKK1 inhibitor, induces glutathione Stransferase A2 (rGSTA2). This report comparatively examines the role of CCAAT/enhancer binding protein (C/EBP) and Nrf-2 in the induction of rGSTA2 by PD98059. PD98059 at the concentrations effective for the inhibition of MKKI increased the rGSTA2 protein and mRNA levels in H4IIE cells. (omitted)

• Journal of Yeungnam Medical Science
• /
• 제29권2호
• /
• pp.77-82
• /
• 2012

AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Its activation requires phosphorylation at Thr-172, which resides in the activation loop of the ${\alpha}1$ and ${\alpha}2$ subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKK${\beta}$ ($Ca^{2+}$/calmodulin-dependent protein kinase kinase${\beta}$). AMPK has been implicated in the regulation of physiological signals, such as in the inhibition of cholesterol fatty acid, and protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on the vascular function and improves vascular abnormalities. AMPK is modulated by numerous hormones and cytokines that regulate the energy balance in the whole body. These hormone and cytokines include leptin, adiponectin, ghrelin, and even thyroid hormones. Moreover, AMPK is activated by several drugs and xenobiotics. Some of these are in being clinically used to treat type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). I reviewed the precise mechanisms of the AMPK activation pathway and AMPK-modulating drugs.

• 약학회지
• /
• 제45권4호
• /
• pp.419-425
• /
• 2001

The neuronal cell death induced by excess glutamate (Glu) has been implicated in many acute and chronic neurodegenerative diseases including cerebral ischemia. Glu-induced elevation of intra-cellular $Ca^{2+}$ plays a critical role in the excitotoxicity, partly through the activation of a variety of $Ca^{2+}$ dependent enzymes. In the present study, we investigated the Glu-induced modulation of $Ca^{2+}$/calmodulin-dependent protein kinase IV (CaMK IV), a multifunctional enzyme abundantly present in the nuclei of neurons. The exposure of cultured rat cortical neurons to $100{\mu}$M Glu for 3 min dramatically increased CaMK IV activity up to 4.5-fold of the control-treated enzyme activity. The activation was very rapid, reaching peak at 3 min and then declined gradually. Under the same experimental conditions, time-dependent acute and delayed neuronal cell death was observed. Immunoblot analyses using specific antibodies showed that the expressions of CaMK IV and $CaMKK_{\alpha}$ were time-dependently modulated by Glu. Taken together, these results imply that the modulation of CaMK IV activity by Glu may be involved in the cascade of events resulting in neuronal cell death in cortical cultures.

• 대한한방내과학회지
• /
• 제34권2호
• /
• pp.204-214
• /
• 2013

Objectives : This study was designed to investigate the cellular and molecular mechanisms of anti-inflammatory activity of the water extract of Polygala tenuifolia Willd. (Pt-WE). Methods : Using lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells, we examined inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$). Also, the inhibitory effect of Pt-WE on the activity of activator protein 1 (AP-1) and upstream signaling molecules was evaluated. To assess the protective effect of Pt-WE on hydrochloride/ethanol (HCl/EtOH)-induced gastric ulcer in mice, we compared Pt-WE (200 mg/kg) with ranitidine (50 mg/kg) treated mice's gastric mucosa, based on gross observations. Results : Pt-WE inhibited LPS-induced production of NO, $PGE_2$ in a dose-dependent manner, without causing cytotoxicity. Pt-WE suppressed AP-1 activation by reducing generations of both c-Jun and c-Fos. In addition, Pt-WE inhibited the p-MKK 4/7 (mitogen-activated protein kinase kinase 4/7) and p-JNK (c-Jun N-terminal kinase) 1 in LPS-stimulated RAW264.7 cells. HCl/EtOH-induced gastric ulcer lesions were inhibited by pre-treatment of Pt-WE based on gross observations. In addition, Pt-WE decreased the phosphorylation level of JNK. Conclusions : These results demonstrate that Pt-WE has anti-inflammatory and gastroprotective effects. Thus, Pt-WE may be used widely in treatment of not only neurodegenerative diseases but also inflammatory diseases.

• Journal of Microbiology and Biotechnology
• /
• 제28권10호
• /
• pp.1626-1634
• /
• 2018

Ginseng (the root of Panax ginseng Meyer) fermented by Lactobacillus plantarum has been found to attenuate allergic responses in in vitro and in vivo experimental models. Ginseng has been reported to also possess various biological functions including anti-inflammatory activity. The present study was aimed at comparing the anti-allergic effect of ginseng and fermented ginseng extracts on IgE-mediated passive cutaneous anaphylaxis in vitro in a murine cell line and in vivo in mice. Fermented ginseng extract (FPG) showed higher inhibitory effect against in vitro and in vivo allergic responses when compared with ginseng extract (PG). The secretion of ${\beta}$-hexosaminidase and interleukin (IL)-4 from the IgE-DNP-stimulated RBH-2H3 mast cells were significantly (p < 0.05) inhibited by FPG treatment, and this effect was concentration-dependent. Further, MKK4 activation and subsequent JNK phosphorylation were attenuated by FPG treatment. The inhibitory effect of FPG on the in vitro allergic response was verified in vivo against IgE-DNP-induced passive cutaneous anaphylaxis in a mouse model. These data indicated that the fermentation of ginseng with L. plantarum enhanced its anti-allergic effects both in vitro and in vivo. We predict that compositional changes in the ginsenosides caused by the fermentation may contribute to the change in the anti-allergic effects of ginseng. The results of our study highlight the potential of the use of FPG as a potential anti-allergic agent.