• Journal of Life Science
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• v.23 no.9
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• pp.1118-1125
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• 2013

Naringenin, a naturally occurring citrus flavonone, is a potentially valuable candidate for cancer chemotherapy. However, the cellular and molecular mechanisms responsible for its anticancer activity are largely unknown. In the present study, we attempted to elucidate the mechanisms responsible for naringenin-induced apoptosis in human leukemic U937 cells. We found that naringenin markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis, which was associated with the activation of caspases. A pan-caspase inhibitor, z-VAD-fmk, significantly inhibited naringenin-induced U937 cell apoptosis, indicating that caspases are key regulators of apoptosis in response to naringenin in U937 cells. Although the levels of antiapoptotic Bcl-2 and proapoptotic Bax proteins remained unchanged in naringenin-treated U937 cells, Bcl-2 overexpression attenuated naringenin-induced apoptosis. Furthermore, combined treatment with naringenin and HA14-1, a small-molecule Bcl-2 inhibitor, effectively increased the apoptosis through enhancement of XIAP down-regulation, Bid cleavage, and caspase activation, suggesting that the synergistic effect was at least partially mediated through the death receptor-mediated apoptosis pathway.

• Microbiology and Biotechnology Letters
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• v.44 no.2
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• pp.218-226
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• 2016

Helicobacter pylori primarily colonizes the human stomach. Infection by this bacterium is associated with various gastric diseases, including inflammation, peptic ulcer, and gastric cancer. Although there are antibiotic regimens for the eradication of H. pylori, the resistance of this species against antibiotics has been continuously increasing. The natural compound plumbagin has been reported as an antimicrobial and anticancer molecule. In this study, we analyzed the inhibitory effect of plumbagin on H. pylori strain ATCC 49503 as well as the expression of various molecules associated with H. pylori growth or virulence by immunoblotting and reverse transcription polymerase chain reaction (RT-PCR) analyses. We demonstrated the minimal inhibitory concentration of plumbagin on H. pylori through the agar dilution and broth dilution methods. Furthermore, we investigated the effect of plumbagin treatment on the expression of the RNA polymerase subunits and various virulence factors of H. pylori. Plumbagin treatment decreased the expression of RNA polymerase subunit alpha (rpoA), which is closely associated with bacterial survival. Moreover, the mRNA and protein levels of the major CagA and VacA toxins were decreased in plumbagintreated H. pylori cells. Likewise, the expression levels of urease subunit alpha (ureA) and an adhesin (alpA) were decreased by plumbagin treatment. Collectively, these results suggest that plumbagin may inhibit the growth, colonization, and pathogenesis of H. pylori by the mechanism demonstrated in this study.

• Journal of Life Science
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• v.30 no.10
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• pp.851-859
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• 2020

Saururus chinensis has white roots, leaves, and flowers and is known to have antibacterial activity and anti-cancer efficacy. The aim of this study was to investigate the effect of the ethyl acetate fraction of a methanol extract of Saururus chinensis (SCEA) on antioxidant activity and melanin synthesis. SCEA at 64 ㎍/ml showed 62% of the DPPH radical scavenging activity of vitamin C, and its reducing power was 33% greater than that of vitamin C. Tyrosinase activity was 26% higher and melanin synthesis was 44% higher in the presence of SCEA at 64 ㎍/ml than in a blank group in a dopa oxidation assay. MTT assay showed that SCEA displayed cytotoxicity above 0.5 ㎍/ml, and SCEA at 1 ㎍/ml increased melanin synthesis by 69% in live B16F1 cells. SCEA was also separated into 13 fractions by silica column chromatography, and fraction 2 (Fr. 2) showed the highest DPPH radical scavenging activity, reducing power, and melanin synthesis. SCEA also promoted melanin production in live cells. LC-MASS analysis showed that Fr.2 had a molecular weight of 239, and these findings suggest that SCEA could be available for the promotion of melanin synthesis in black hair.

• Journal of Life Science
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• v.13 no.5
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• pp.642-650
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• 2003

To develop a new approach to the treatment of neuroblastoma cells we evaluated the effect of cAMP on the Ewing's sarcoma cell line CHP-100. We observed that the proliferation-inhibitory effect of cAMP analogs was due to cell cycle arrest and induction of apoptosis, which was confirmed by observing the morphological changes and DNA fragmentation. DNA flow cytometric analysis revealed that cAMP arrested the cell cycle progression at the G1 phase, which effects were associated with inhibition of phosphorylation of retinoblastoma protein (pRB) and enhanced binding of pRB and the transcription factor E2F-1. cAMP also suppressed the cyclin-dependent kinase (Cdk) 2 and cyclin E-associated kinase activity without changes of their expressions. Furthermore, cAMP induced the levels of Cdk inhibitor $p21^{WAF1/CIP1$ expression and p21 proteins induced by cAMP were associated with Cdk2. Overall, our results identify a combined mechanism involving the inhibition of pRB phosphorylation and induction of p21 as targets for cAMP, and this may explain some of its anti-cancer effects.

• Journal of Periodontal and Implant Science
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• v.41 no.3
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• pp.149-156
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• 2011

Purpose: Globular adiponectin (gAd) is a type of adipocytokine, which is mainly produced by adipose tissue. It has been reported that gAd acts as a pro- as well as an anti-inflammatory factor. Interleukin (IL)-6 and IL-8 are pro-inflammatory cytokines. To investigate the role of gAd on periodontal tissues, the expression of adiponectin receptor 1 (AdipoR1) and the effect of gAd on the expression of IL-6 and IL-8 were investigated in periodontal ligament (PDL) and gingival fibroblasts. Methods: PDL and gingival fibroblasts were cultured from human periodontal tissues. gAd derived from Escherichia coli and murine myeloma cells were used. The expression of AdipoR1 was estimated by reverse transcription-polymerase chain reaction and western blot The expression of cytokines was measured by enzyme-linked immunosorbent assay. Results: PDL and gingival fibroblasts expressed both mRNA and protein of AdipoR1. gAd derived from E. coli increased the production of IL-6 and IL-8, but polymyxin B, an inhibitor of lipopolysaccharide (LPS), inhibited IL-6 and IL-8 production induced by gAd in both types of cells. gAd derived from murine myeloma cells did not induce IL-6 and IL-8 production in those cells. gAd derived from E. coli contained higher levels of LPS than gAd derived from murine myeloma cells. LPS increased production of IL-6 and IL-8 in PDL and gingival fibroblasts, but pretreatment of cells with gAd derived from murine myeloma cells did not inhibit LPS-induced IL-6 and IL-8 expression. Conclusions: Our results suggest that PDL and gingival fibroblasts express AdipoR1 and that gAd does not act as a modulator of IL-6 and IL-8 expression in PDL and gingival fibroblasts.

• Journal of Korean Medicine for Obesity Research
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• v.19 no.2
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• pp.106-112
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• 2019

Objectives: The aim of this study was to observe the reduction of lipid accumulation by treatment with Akkermansia muciniphila extract on 3T3-L1 adipocytes. Methods: After treating pasteurized Akk. muciniphila strains in HT-29 colorectal cancer cell, the relative expression of interleukin (IL)-8, tumor necrosis factor-α, IL-6, and IL-1β mRNA was analyzed by real time polymerase chain reaction, respectively. 27 strains of Akk. muciniphila which have anti-inflammatory effects were selected. 3T3-L1 pre-adipocytes were treated with Akk. muciniphila for 24 hr and then measured the toxicity using water soluble tetrazolium salt assay. The cells were incubated for 4 days and then differentiated into adipocytes using the medium including adipogenic reagents for 10 days. The Akk. muciniphila was treated when the medium was exchanged for differentiation medium at 4^th day and insulin medium at 6^th day. To observe the lipid accumulation, the cells were stained with Oil red O dye and were measured using a spectrophotometer. Results: In the cytotoxicity test, the cell viability of 3T3-L1 pre-adipocytes was significantly increased compared to the control group which untreated with Akk. muciniphila, and there was no cytotoxicity of Akk. muciniphila at 1×10⁷ CFU/mL. The results on Oil red O staining and absorbance measurements were showed a significant decrease in lipid accumulation in the group which was treated with Akk. muciniphila compared to the control group. Conclusions: In our results, Akk. muciniphila has the inhibitory effect of lipid accumulation in 3T3-L1 adipocytes. This suggests that Akk. muciniphila could be help to improve obesity.

• Korean Journal of Plant Resources
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• v.23 no.2
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• pp.172-178
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• 2010

This study was carried out to investigate abiotic and biotic environmental factors affecting homoharringtonine (HHT) contents of Cephalotaxus koreana, whereby, to provide basic information of high value-added industry production of HHT as a promising anti-cancer agent. For correlation between abiotic environmental factors (soil moisture, soil pH, habitat density and temperature) and HHT contents, the contents were highly correlated with soil moisture (0.77) and soil pH (-0.68). For multiple regression analysis of relationship between abiotic environmental factors (soil moisture and soil pH) and HHT contents, soil moisture appeared to be strongly affecting the contents relatively due to being significant at only its regression coefficient ($26.48^{***}$). For the effect of biotic environmental factors (damage index) affecting HHT contents, the contents was quadratic with equation of $H=278.23+1242D-398.87D^2$, also, damage index had strong effect on the contents. Finally, for the result of the most influencing an environmental factor on HHT contents, both damage index and soil moisture were suitable in second polynomial regression, also, damage index ($R^2=0.73^{***}$) was turned out to be more influencing factor than soil moisture ($R^2=0.67^{**}$) on HHT contents relatively. Therefore, we predict that HHT contents in the trees of Cephalotaxus koreana is produced as a chemical defense mechanism triggered by a stress-related damage of fungi or insects.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.170-180
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• 2008

Purpose : Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods : Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results : The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/Bcl-2 expression in geneticin-treated animal model. Conclusion : Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.53 no.3
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• pp.333-338
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• 2008

The tea has traditionally been used as a foodstuff by unique flavor, however recently not only the diversity of consumer demands but also the public interest in unique favorite and functional aspects have increased. It has been also reported that the main components contained in the leaves of tea (Camellia sinensis) include total nitrogen, free amino acids, polyphenols, and fiber, of which catechin has powerful bioactive effect such as anti-cancer, anti-aging, and anti-diabetic. (-)-Epigallocatechin gallate (EGCG) which is a major phenolic constituent of green tea extract has received considerable attention for a variety of important bioactivities. This study was carried out to obtain useful information for tea breeding programs, and to investigate the concentration of quality and functional related components in Korean indigenous tea germplasms. Korean indigenous tea lines were classified into three groups of sprout time, i.e, early, medium and late sprout time, and the ratio were 20%, 43% and 37%, respectively. There was a difference in characteristics among these Korean indigenous tea lines, leaf width of those ranged from 19.8 to 75 mm, leaf length was 35.5-160.0 mm, and leaf area was $660-8,400\;mm^2$. Experimental data on chlorophyll content (SPAD value) of Korean indigenous tea genetic resources ranged from 51.3 to 82.3. The concentrations of the total nitrogen, total free amino acids, and theanine were ranged 4.18-6.07%, 2.87-4.58%, and 1.64-2.66%, respectively. Also, catechin concentration showed from 11.54 to 15.07%, and concentration of caffeine was 2.82-4.23%. These results indicated indicated that it is possible to select elite lines with high concentration of quality related components and low concentration of caffeine from Korean domestic tea germplasms.