• Journal of Ginseng Research
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• v.30 no.1
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• pp.1-7
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• 2006

Ceramide has been involved in celt death and acted as a lipid mediator of stress responses. Elevation of ceramide level was reported to occur in oxidative stress and lead to cell death in many cell types. This study was undertaken to elucidate a protective role of ginsenoside Rgl in cell death induced by oxidative stress. When LLC-PK1 cells were treated with $H_2O_2$ at a concentration of $400{\mu}M$ for 5 hr, cell death was observed and a released LDH activity indicative of cytotoxicity was Increased. $H_2O_2$ exposure to LLC-PK1 cells was shown to elevate the content of total ceramide by approximately 200% compared to control cells. Ceramide level was hypothesized to be a key to a reversal of cell death to survival. Ginsenoside Rgl at the concentrations ranging from 12.5 to $250{\mu}M$ protected LLC-PK1 cells from cell death induced by $H_2O_2\;at\;400{\mu}M$ for 5 hr, and decreased the ceramide level relative to $H_2O_2$. Ginsenoside Rgl inhibited neutral human ceramidase by 71% of controls, while sphingomyelinase was not inhibited. These results suggest that ginsenoside Rgl show the protection against cell death via the modulation of ceramide metabolism, and ceramide may be a promising therapeutic target for human diseases related to cell death.

• Journal of Integrative Natural Science
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• v.4 no.4
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• pp.273-277
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• 2011

It's a threat for the public health that H1N1 (Influenza virus A) causes disease and transmits among humans. WHO (world health organization) declared that the infections caused by the new strain had reached pandemic proportions. The approved neuraminidase inhibitors (Zanamivir and Oseltamivir) and related investigative drug (BCX-1812) are potent, specific inhibitors of influenza A and B viruses. These drugs are highly effective to prevent influenza A and B infections. Early therapeutic use reduces illness duration and respiratory complications. Recently, we found one of the potent inhibitor of erystagallin A ($IC_{50}$ of 2.04 ${\mu}M$) for neuraminidase target, this inhibitor shows most similar structure to its natural substrate, sialic acid. Therefore, we chose 1l7f to get the receptor structure for docking study among many crystal structures. A docking study has been performed in Surflex-Dock module in SYBYL 8.1. In the present study, we attempt to compare the docking studies of pterocarpin and erystagallin A with neuraminidase receptor structure. In the previous report, the methoxy group of pterocarpin had H-bonding with Arg residues. The present docking results for erystagallin A showed the backbone of hydroxyl group shows significant H-bonding interactions with Arg152 and Arg292. The results showed that erystagallin A interacts more favorably with distinctive binding site rather than original active site. Therefore, we tried to reveal plausible binding mode and important amino acid for this inhibitor using docking and site id search calculations of Sybyl. The results obtained from this work may be utilized to design novel inhibitors for neuraminidase.

• Korean Journal of Medicinal Crop Science
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• v.28 no.2
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• pp.85-94
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• 2020

Background: Alzheimer's disease (AD) is caused by various factors, such as cholinergic dysfunction, regulation of neurotrophic factor expression, and accumulation of amyloid-beta. We investigated whether or not a combination of Carthamus tinctorius L. seed and Taraxacum coreanum (CT) has a protective effect on scopolamine-induced memory impairment in a mouse model. Methods and Results: Mice were orally pretreated with CT (50, 100 and 200 mg/kg/day) for 14 days, and scopolamine (1 mg/kg/day) was injected intraperitoneally before subjecting them to behavior tests. CT-administered mice showed better novel object recognition and working memory ability than scopolamine-treated control mice. In T-maze and Morris water maze tests, CT (100 and 200 mg/kg/day) significantly increased space perceptive ability and occupancy to the target quadrant, respectively. In addition, 100 and 200 mg/kg/day of CT attenuated cholinergic dysfunction through inhibition of butyryl cholinesterase in brain tissue. Furthermore, CT-administered mice showed higher cyclic adenosine monophosphate-response element-binding protein (CREB) levels and lower amyloid precursor protein (APP) levels compared to scopolamine-treated control mice. Conclusions: CT improved scopolamine-induced memory impairment through inhibition of cholinergic dysfunction, up-regulation of CREB, and down-regulation of APP. Therefore, CT could be a useful therapeutic agent for AD with protective effects on cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.467-472
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• 2015

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I ($AT_1R$) inhibitor, valsartan ($10{\mu}M$), but not by the $AT_2R$ inhibitor, PD123319. TSA ($1{\sim}10{\mu}M$) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing $AT_1R$. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through $AT_1R$.

• Journal of Microbiology and Biotechnology
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• v.28 no.8
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• pp.1401-1411
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• 2018

The serine-threonine kinase AKT plays a pivotal role in tumor progression and is frequently overactivated in cancer cells; this protein is therefore a critical therapeutic target for cancer intervention. We aimed to identify small molecule inhibitors of the pleckstrin homology (PH) domain of AKT to disrupt binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3), thereby downregulating AKT activity. Liposome pulldown assays coupled with fluorescence spectrometry were used to screen flavonoids for inhibition of the AKT PH-PIP3 interaction. Western blotting was used to determine the effects of the inhibitors on AKT activation in cancer cells, and in silico docking was used for structural analysis and optimization of inhibitor structure. Several flavonoids showing up to 50% inhibition of the AKT PH-PIP3 interaction decreased the level of AKT activation at the cellular level. In addition, the modified flavonoid showed increased inhibitory effects and the approach would be applied to develop anticancer drug candidates. In this study, we provide a rationale for targeting the lipid-binding domain of AKT, rather than the catalytic kinase domain, in anticancer drug development.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.283-288
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• 2013

The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.

• International Journal of Oral Biology
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• v.41 no.3
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• pp.125-131
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• 2016

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of $IL-1{\beta}$ in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, $IL-1{\beta}$ plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of $IL-1{\beta}$ is a potential therapeutic target for inflammatory TMJ pain.

• The Journal of the Korean dental association
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• v.53 no.7
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• pp.476-484
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• 2015

Purpose: This study intended to analyze the validity of clinical effectiveness data of clinical trials testing systemic titrated extract of Zea Mays L. unsaponifiable fraction chemotherapeutic agent. Material and Methods: Among 5 clinical trials claimed as proof of clinical effectiveness on the Web site of the manufacturer of this chemotherapeutic agent, a review of 4 clinical trials, written in either Korean or English, was conducted. Data were extracted from studies for the following variables: year of publication, age, sample size, follow-up period, combination with contemporary periodontal treatments, randomization, randomization check, blinded measurement, and statistical test type. Results: The study subjects' age intervals were too diverse to decide a common target population to generalize the findings. No study stated clearly the rationale for the sample size determination. Follow-up period to observe the start of clinical effectiveness was inconsistent and decided without any rationale of pathophysiological latent period. Randomization to make the comparisons on the same start line was performed but failed in a study. Randomization effect was not checked in 4 studies. Performance of blinded measurement of clinical outcomes to prevent bias was unclear in 2 studies. Type of statistical test was inappropriate in 3 studies. Conclusions: Based on the analysis of the validity of data on clinical and demographic variables, the four available clinical trials have not demonstrated compelling evidence of therapeutic effectiveness of systemic titrated extract of Zea Mays L. unsaponifiable fraction chemotherapeutic agent to improve prognosis of periodontal disease either with the contemporary periodontal treatment or without it.

• Genomics & Informatics
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• v.4 no.3
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• pp.97-102
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• 2006

In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. Methods: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. Results: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER<0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. Conclusion: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.

• Biomedical Science Letters
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• v.22 no.3
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• pp.83-97
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• 2016

The measurement of viral load in HIV-1 infected patients is essential for the establishment of a therapeutic strategy. Several commercial assays have shown shortcomings in quantifying rare genotypes of HIV-1 such as minor groups of N and O. In this study, the HIV-1 RT-qPCR assay was developed. The primers and probe of HIV-1 were designed to target the pol gene and to increase the detection efficiency of various subtypes including group N and O. The HIV-1 quantitative RT-qPCR assay was assessed for its analytical performance and clinical evaluation. The LoD was determined to 33.9 IU/ml. The LoD of several subtypes including A, C, D, CRF_01AE, F, CRF_02AG, G and H, were determined to less than 40 IU/ml. The HIV-1 quantitative RT-qPCR assay was evaluated using the China National Reference Panel of HIV-1 RNA to determine the analytical performance. The results were all within the acceptable range. The clinical evaluation was performed at Hunan CDC in China. The clinical evaluation results were compared with those of the China domestic commercial kit. A significant correlation (fresh samples; $R^2=0.84$, P<0.001, frozen samples; $R^2=0.76$, P<0.001) between the two systems was observed for 64 fresh samples and 76 frozen samples with viral loads, and the Bland-Altman plot showed good agreement (98.4%, 96.1%, respectively). In conclusion, the HIV-1 quantitative RT-qPCR assay had comparable analytical performance with several commercial kits. The study provides basic data for the research of HIV-1 diagnosis and the development of P < HIV-1 molecular diagnostic assay.