• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.159-169
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• 2023

Purpose : Though other Citrus spp. have reported their anti-inflammatory and antioxidative activities in previous studies, the biological activity of Kiyomi (Citrus unshiu × C. sinensis) has not been reported yet. Therefore, this study attempted to analyze the anti-inflammatory mechanisms of Kiyomi leaf ethanol extract (KLEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : The cytotoxic effect of KLEE in RAW 264.7 cells was determined by WST-1 assay. Bacterial endotoxin, the concentration of nitric oxide (NO) was analyzed by the Griess reaction. In addition, Western blot analysis was applied to measure the protein expression level of inducible NO synthase (iNOS). The phosphorylated status of the critical inflammatory transcription factor, nuclear factor (NF)-𝜅B, and its upstream signaling molecules, phosphoinositide 3-kinase (PI3K)/Akt as well as mitogen-activated protein kinases (MAPKs), were also measured by Western blot analysis. Results : KLEE was not cytotoxic up to a concentration of 200 ㎍/㎖, and protein expression levels of iNOS and cyclooxygenase (COX)-2, enzymes that counteract NO and prostaglandin (PG) E2 production, were inhibited by KLEE treatment. The phosphorylated status of PI3K/Akt as well as MAPKs including extracellular regulated kinase (ERK), c-jun NH2kinase (JNK), and p38, were significantly attenuated by KLEE treatment in LPS stimulated RAW 264.7 cells. Moreover, one of phase II enzymes, heme oxygenase (HO)-1 which has known for its anti-inflammatory capacity, was strongly induced by KLEE treatment. Conclusion : Consequently, KLEE treatment significantly attenuated the production of NO as well as the expression levels of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-𝜅B, as well as its upstream signaling molecules, PI3K/Akt and MAPKs, were also diminished by KLEE treatment with statistical significance in LPS-stimulated RAW 264.7 cells. These results suggest that KLEE might be a promising candidate for the attenuation of inflammatory disorders.

• The Korea Journal of Herbology
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• v.24 no.2
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• pp.49-56
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• 2009

Objectives : Inflammation is important event in the development of vascular diseases including hypertension, atherosclerosis, and restenosis. Bodusan (BDS) was a traditional Korean herbal medicine and widely used in treatment of gastrointestinal complaint and stomach ulcer. The aim of this study was to determine whether BDS and its components inhibit production of nitrite, PGE2 and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Methods : Cytotoxic activity of BDS and its components on RAW 264.7 cells was using 5-(3caroboxymcrophages. eth-oxyphenyj)-2H-tetra-zolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were detected by western blot. Results : Our results indicated that BDS and its components significantly inhibited the LPS-induced NO and PGE2 production. Moreover. BDS and its components inhibited iNOS and COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-11${\beta}$, IL-6 and MCP-1 formation in macrophages. Conclusions: These results indicate that BDS and its components have potential as an anti-inflammatory agent.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.543-551
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• 2023

Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, coimmunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-β1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-b1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.589-601
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• 2023

Purpose: Baicalein, a natural flavone found in herbs, exhibits diverse biological activities. Nonalcoholic steatohepatitis (NASH) is an irreversible condition often associated with a poor prognosis. This study aimed to evaluate the effects of baicalein on the development of NASH in mice. Methods: Male C57BL/6J mice were randomly divided into four groups. Three groups were fed a methionine-choline-deficient (MCD) diet to induce NASH and were simultaneously treated with baicalein (at doses of 50 and 100 mg/kg) or vehicle only (sodium carboxymethylcellulose) through oral gavage for 4 weeks. The control group was fed a methionine-choline-sufficient (MCS) diet without the administration of baicalein. Results: The baicalein treatment significantly reduced serum levels of alanine aminotransferase and aspartate aminotransferase, suggestive of reduced liver damage. Histological analysis revealed a marked decrease in nonalcoholic fatty liver activity scores induced by the MCD diet in the mice. Similarly, baicalein treatment at both doses significantly attenuated the degree of hepatic fibrosis, as examined by Sirius red staining, and hepatocellular death, as examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Baicalein treatment attenuated MCD-diet-induced lipid peroxidation, as evidenced by lower levels of hepatic malondialdehyde and 4-hydroxynonenal, demonstrating a reduction in oxidative stress resulting from lipid peroxidation. Moreover, baicalein treatment suppressed hepatic protein levels of 12-lipoxygenase (12-Lox) induced by the MCD diet. In contrast, baicalein enhanced the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Additionally, baicalein treatment significantly reduced hepatic non-heme iron concentrations and hepatic ferritin protein levels in mice fed an MCD diet. Conclusion: To summarize, baicalein treatment suppresses hepatic lipid peroxidation, 12-Lox expression, and iron accumulation, all of which are associated with the attenuation of NASH progression.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.307-318
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• 2023

Objectives: Bacterial biofilm is regarded as a significant threat to the production of safe food and the arise of antibiotic-resistant bacteria. The objective of this investigation is to evaluate the quorum sensing inhibitory effect of Nepeta curviflora methanolic extract. Methods: The effectiveness of the leaves at sub-inhibitory concentrations of 2.5, 1.25, and 0.6 mg/mL on the virulence factors and biofilm formation of P. aeruginosa was evaluated. The effect of N. curviflora methanolic extract on the virulence factors of P. aeruginosa, including pyocyanin, rhamnolipid, protease, and chitinase, was evaluated. Other tests including the crystal violet assay, scanning electron microscopy (SEM), swarming motility, aggregation ability, hydrophobicity and exopolysaccharide production were conducted to assess the effect of the extract on the formation of biofilm. Insight into the mode of antiquorum sensing action was evaluated by examining the effect of the extract on the activity of N-Acyl homoserine lactone (AHL) and the expression of pslA and pelA genes. Results: The results showed a significant attenuation in the production of pyocyanin and rhamnolipid and in the activities of protease and chitinase enzymes at 2.5 and 1.25 mg/mL. In addition, N. curviflora methanolic extract significantly inhibited the formation of P. aeruginosa biofilm by decreasing aggregation, hydrophobicity, and swarming motility as well as the production of exopolysaccharide (EPS). A significant reduction in AHL secretion and pslA gene expression was observed, indicating that the extract inhibited quorum sensing by disrupting the quorum-sensing systems. The quorum-sensing inhibitory effect of N. curviflora extract appears to be attributed to the presence of kaempferol, quercetin, salicylic acid, rutin, and rosmarinic acid, as indicated by LCMS analysis. Conclusion: The results of the present study provide insight into the potential of developing anti-quorum sensing agents using the extract and the identified compounds to treat infections resulting from quorum sensing-mediated bacterial pathogenesis.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.75-86
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• 1994

To assess the role of adrenal medulla and renin-angiotensin system in the regulation of sympathetic neurotransmission, the pressor response to PNS was evaluated in pithed SHR and normotensive WKY or SDR with or without adrenal demedullation and/or enalapril pretreatment. Three weeks after adrenal demedullation, MAP and the heart rate of demedullated rats were similar to their corresponding sham-operated groups. The pressor response to PNS was frequency-dependent, and blocked by prazosin. In contrast to the normotensive rats, in SHR, the pressor response to PNS was attenuated in demedullated rats as compared with sham-operated rats. However, the attenuation of PNS-induced pressor responses in demedullated SHR was not observed in enalapril-treated SHR. The adrenal demedullation in SHR did not affect the plasma and aortic catecholamine contents in spite of the decreased catecholamine contents of adrenal gland, nor ACE activity in aortic strips. But, in WKY rats, the aortic catecholamines, especially epinephrine, contents as well as ACE activity were increased by adrenal demedullation. These results suggest that the facilitatory role of adrenal medulla in sympathetic neurotransmission depends upon the activation of renin-angiotensin system, and that the compensatory regulation of renin-angiotensin system takes place in normotensive rats but not in SHR.

• Proceedings of the Korean Society of Marine Engineers Conference
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• 2011.06a
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• pp.235-235
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• 2011

Lau basin of south Pacific, as an active back arc basin, is promising area bearing seafloor massive hydrothermal deposit that is located in a subduction zone between the Pacific ocean plate and Indo-Australian continental plate. Korea Ocean Research and Development Institute tracked from 2004 to 2006 the hydrothermal activity to the extension of the northeast Lau Basin, targeting seamount. hydrothermal activity by tracking was found hydrothermal evidences. In this study, Marine seismic survey was carried out in the Lau basin seamount of the possibility of hydrothermal deposit. In particular, Marine magnetic survey and seismic survey was carried out at the same time in TA-12 seamount and noise characteristics were found in the seamount. the main process of data processing is Bandpass filter, FK filter, Deconvolution for noise attenuation such backscatter and multiple reflections. the migration is performed to compensate for reflection points followed by seamount of a slope. In this study, bedrock and upper strata could be identified and in the Future, the comparative method with Multi Beam Echo Sounder(MBES) are likely to derive the correct velocity model, the marine magnetic survey results should be considered.

• 한국지구물리탐사학회:학술대회논문집
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• 2008.10a
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• pp.97-100
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• 2008

Mount Fuji is the focus of intense study because of its potential hazard signaled by seismic, geologic and historical activity. Based on extensive seismic data recorded in the vicinity of Mt. Fuji, coda quality factor ($Q_c^{-1}$) using a single scattering model hypothesis, and intrinsic and scattering quality factor $(Q_i^{-1}$ and $Q_s^{-1})$ using the Multiple Lapse Time Window Analysis (MLTW) method was measured. To focus the study on the magmatic structure below Mt. Fuji, to the data were separated into two groups: a near-Fuji region of rays traversing an area with radius 5 km around the summit (R < 5 km), and a far-Fuji region of rays beyond a radius of 20 km around the summit (R > 20 km). The results of the study have a small error range due to the large data sample, showing that all $Q^{-1}$ values in near-Fuji area are greater than those of far-Fuji area, and $Q_i^{-1}$ for both the near and far-Fuji area is higher than $Q_s^{-1}$ at high frequencies. The $Q_i^{-1}$ values of the near-Fuji area are lower than those of the other volcanic areas considered, while values of $Q_s^{-1}$ are not. The low $Q_i^{-1}$ for the volcanic region of near-Fuji suggests that the magmatic activity, or percent of partial melt, at Mt. Fuji is not as active as hot spot volcanoes such as Kilauea, Hawaii.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.413-420
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• 2005

We previously demonstrated the ability of ginseng saponins (active ingredients of Panax ginseng) to enhance $Ca^{2+}$-activated $Cl^{-}$ current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of $Ca^{2+}$ from $IP_{3}-sensitive$ intracellular stores through the activation of PTX-insensitive $G\alpha_{q/11}$ proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates $IP_{3}$ receptor-mediated $Ca^{2+}$ release in both $Ca^{2+}-dependent$ and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current responses in Xenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement was dose- and time-dependent, with an $IC_{50} of 14.9\pm3.5 {\mu}M$. The inhibitory effect of CaM on saponin's activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be $16.7\pm4.3 h$. Intraoocyte injection of CaM inhibited $Ca^{2+}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement and also attenuated $IP_{3}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. $Ca^{2+}$/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. These results suggest that CaM regulates ginseng saponin effect on $Ca^{2+}$-activated $Cl^{-}$ current enhancement via $Ca^{2+}$-independent manner.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.199-207
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• 2018

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.