• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.55-64
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• 2017

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal ${\beta}$-amyloid ($A{\beta}$) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a $A{\beta}_{1-42}$-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the $A{\beta}_{1-42}$-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of $A{\beta}$-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.478-489
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• 2020

BACKGROUND/OBJECTIVES: Morusin, a marker component of Morus alba L., possesses anti-cancer activity. The objective of this study was to determine autophagy-inducing effect of morusin in non-small cell lung cancer (NSCLC) cells and investigate the underlying mechanism. SUBJECTS/METHODS: Autophagy induction and the expression of autophagy-related proteins were analyzed by LC3 immunofluorescence and western blot, respectively. The role of autophagy and AMP-activated protein kinase (AMPK) was determined by treating NSCLC cells with bafilomycin A1, an autophagy inhibitor, and compound C, an AMPK inhibitor. Cytotoxicity and apoptosis induction were determined by MTT assay, trypan blue exclusion assay, annexin V-propidium iodide (PI) double staining assay, and cell cycle analysis. RESULTS: Morusin increased the formation of LC3 puncta in the cytoplasm and upregulated the expression of autophagy-related 5 (Atg5), Atg12, beclin-1, and LC3II in NSCLC cells, demonstrating that morusin could induce autophagy. Treatment with bafilomycin A1 markedly reduced cell viability but increased proportions of sub-G1 phase cells and annexin V-positive cells in H460 cells. These results indicate that morusin can trigger autophagy in NSCLC cells as a defense mechanism against morusin-induced apoptosis. Furthermore, we found that AMPK and its downstream acetyl-CoA carboxylase (ACC) were phosphorylated, while mammalian target of rapamycin (mTOR) and its downstream p70S6 kinase (p70S6K) were dephosphorylated by morusin. Morusin-induced apoptosis was significantly increased by treatment with compound C in H460 cells. These results suggest that morusin-induced AMPK activation could protect NSCLC cells from apoptosis probably by inducing autophagy. CONCLUSIONS: Our findings suggest that combination treatment with morusin and autophagy inhibitor or AMPK inhibitor might enhance the clinical efficacy of morusin for NSCLC.

• Molecules and Cells
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• v.38 no.7
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• pp.638-642
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• 2015

Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than $10{\mu}M$ inhibited 143B proliferation, while $5{\mu}M$ quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, $5{\mu}M$ quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.31-31
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• 2017

Understanding the mechanism(s) to overcome or prevent seed ageing deterioration during storage is of fundamental interest to seed physiologists. Vitamin E (tocols) is known as a key metabolite to efficiently scavenge lipid peroxy radicals which cause membrane breakdown resulting in seed ageing. However, in rice research this hypothesis has been tested for very few lines only without considering intraspecific variation in genomic structure. Here, we present a correlation study between tocols and seed longevity using a diverse rice panel. Seeds of 20 rice accessions held in the International Rice Genebank at the International Rice Research Institute, representing aus, indica, temperate japonica and tropical japonica subpopulations, were used for tocols analysis (quantification of ${\alpha}$-, ${\beta}$-, ${\gamma}$-, ${\delta}$-tocopherol/tocotrienol by ultra performance liquid chromatography) and storage experiments at $45^{\circ}C$ and 10.9% seed moisture content (sample taken for germination testing every 3 days up to 60 days). To examine interactions between DNA sequences and phenotype, the 700k high-density single-nucleotide polymorphism marker data-set was utilized. Both seed longevity (time for viability to fall to 50%; $p_{50}$) and tocols content varied across subpopulations due to heterogeneity in the genetic architecture. Among eight types of tocol homologues, ${\alpha}$-tocopherol and ${\gamma}$-tocotrienol were significantly correlated with $p_{50}$ (negatively and positively, respectively). While temperate japonica varieties were most abundant in ${\alpha}$-tocopherol, indica varieties recorded 1.3 to 1.7-fold higher ${\gamma}$-tocotrienol than those of other subpopulations. It was highlighted that specific ratio of tocol homologues rather than total tocols content plays an important role in the seed longevity mechanism.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.138-147
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• 2003

Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{\alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{\kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{\gamma}{\;}(rIFN-{\gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{\gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{\kappa}B$. The $NF-{\kappa}B$ activation was increased in rIFN-{\gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{\gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{\;}(N^{G}MMA){\;}N^{\alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{\gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{\alpha}$ production. PDTC decreased CM-induced $TNF-{\alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{\alpha}{\;}by{\;}rIFN-{\gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.2
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• pp.101-108
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• 2016

This study is conducted to investigate vasorelaxant effect of Corni Fructus(CF) on rabbit carotid artery. To determine vasorelaxant effect of CF on rabbit carotid artery, arterial sections with intact or removed endothelium were used in this organ bath study. After being contracted by phenylephrine(PE), arterial sections were treated with CF extract in a dose-dependent manner. To identity its mechanism, the contracted arterial sections by PE were pretreated with indomethacin(IM), tetraethylammonium chloride(TEA), Nω-nitro-L-arginine(L-NNA) or methylene blue(MB) and 1.0 ㎎/㎖ CF extract. We also studied to confirm the effect on influx of extracellular calcium chloride(Ca²⁺) of the CF extract in rabbit carotid artery. To measure the cytotoxicity of the CF extract, cell viability of human umbilical vein endothelial cell(HUVEC) was measured by MTT assay. Generation of nitric oxide(NO) was also measured by Griess reagent. The arterial sections with intact endothelium were relaxed significantly by CF extract, but this effect was inhibited in the arterial sections with damaged endothelium. The vasorelaxant effect was inhibited significantly when arterial sections were pretreated with IM, TEA, L-NNA, MB. In Ca²⁺-free krebs solution, increasing of arterial contraction by Ca²⁺ was also inhibited by CF significantly. The treatment of CF extract increased NO concentration in HUVEC. This study suggested that the vasorelaxant effect of CF extract would be related with endothelium derived relaxing factor(EDRF) such as NO, prostacyclin(PGI₂), endothelium derived hyperpolarization factor(EDHF).

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.624-629
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• 2010

Nardostachys jatamansi water extract (NJ) has long been used for the treatment of inflammation-and immune-mediated disorders in the oriental countries. However, its site of action and pharmacological mechanism are not fully investigated. In this study, the authors tried to explore the cytoprotective and anti-inflammatory actions of NJ. First of all, NJ has no harmful effects on viability of neuronal cell line HT22 cells in the dose range of 300 mg/ml. On the contrary, it shows cytoprotective effects on the cells treated with reactive oxygen species H2O2. Probably the cytoprotective effects of NJ might be caused by its ability to induce well known cytoprotective gene hem oxygenase-1 (HO-1). Furthermore, NJ shows inhibitory effects on the expression of inducible nitric oxide synthase (iNOS) and NO production which are known to destroy the integrity of both cells and tissues. It also inhibits potent proinflammatory cytokine tumor necrosis factor-alpha (TNF-a) production. The blocking effects of NJ on cytopathic and proinflammatory actions of LPS might be caused by the induction of cytoprotective and anti-inflammatory genes HO-1 in macrophages cell line RAW 264.7 cells. The results in this study suggest NJ could be used for the amelioration of inflammation which is underlying mechanism responsible for most chronic diseases.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.1 no.1
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• pp.25-39
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• 2003

This study proposed a new electrolytic reduction technology that is based on the integration of simultaneous uranium oxide metallization and Li$_2$O electrowinning. In this electrolytic reduction reaction, electrolytically reduced Li deposits on cathode and simultaneously reacts with uranium oxides to produce uranium metal showing more than 99% conversion. For the verification of process feasibility, the experiments to obtain basic data on the metallization of uranium oxide, investigation of reaction mechanism, the characteristics of closed recycle of Li$_2$O and mass transfer were carried out. This evolutionary electrolytic reduction technology would give benefits over the conventional Li-reduction process improving economic viability such as: avoidance of handling of chemically active Li-LiCl molten salt increase of metallization yield, and simplification of process.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.701-709
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• 2006

The Rhus verniciflua Stokes (乾漆-RVS) has been used in traditional East Asia medicine for the therapy of gastritis, stomach cancer, although the mechanism for the biological activity is unclear. In the present study aims to investigate RVS extract contributes to growth inhibitory effect and it's the molecular mechanism on the human gastric cancer cells. AGS (gastric cancer cells) and RIEI (normal cells) were treated to different concentrations and periods of RVS extract $(10{\;}{\sim{{\;}100{\;}ug/mil)$. Growth inhibitory effect was analyzed by measuring FACS study and MTS assay. Cell cycle inhibition was confirmed by measuring CDK2 kinase activity by immunoprecipitation and kinase assay. And apoptosis was confirmed by surveying caspase cascades activation using a pan caspase inhibitor Exposure to RVS extract (50 ug/mll) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces Gl -cell cycle arrest through the regulation of cyclins, the induction of p27kip1, and the decrease CDK2 kinase activity. And upregulated p27kip1 level is caused by protein stability increment by the reduction of S-phase kinase-associated protein 2 (Skp2), a key molecule related with p27kip1 ubiquitination and degradation, and do novo protein synthesis. Besides, 乾漆 extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces Gl -cell cycle arrest via accumulation of p27kip1 and apoptosis in human gastric cancer cells but not in normal cells, therefore we suggest that the extract can be used as a novel class of anti-cancer drugs.

• The Journal of the Korea Contents Association
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• v.14 no.9
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• pp.1-13
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• 2014

Apart from the physical realism, the implementation of various physical actions of an agent to respond to dynamically changing situations is essential for the design of an agent in a cyber world. To achieve a maximum diversity in actions, we develop a mechanism that allows composite actions to be constructed by reusing a set of primitive motions and enables an agent to instantly react to changes in the ambient states. Specifically we model an agent's body in terms of joints, and a primitive or composite motion is performed in a real time. To implement this mechanism, we produce an animation for basic joint movements and develop a method to construct overall motions out of the primitive motions. These motions can be assembled into a plan by which an agent can achieve a goal. In this manner, diverse actions can be implemented without excessive efforts. This approach has conspicuous advantages when constructing a parallel action, e.g., eating while walking, that is, two or more parallel actions can be naturally merged into a parallel action according to their priority. We implement several composite and parallel actions to demonstrate the viability of our approach.