• The Korea Journal of Herbology
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• 제35권3호
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• pp.47-54
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• 2020

Objective : Infectious diseases are a growing problem worldwide by Methicillin-resistant Staphylococcus aureus (MRSA). Daehwangmokdan-tang is one of the oriental medicine prescriptions contained in Principles and Practice of Eastern Medicine. This study investigated the antibacterial activity of EtOH 70% extracts of Daehwangmokdan-tang (DMT) which prescription is composed of oriental medicine against MRSA. Methods : The antimicrobial activity and active concentration of MRSA were verified by measuring the minimum inhibitory concentration (MIC) of DMT. In addition, the effects of the disease were checked by treating the existing antibiotics and large ethanol extract in parallel, and the extent of growth suppression was checked over time. In addition, cell membrane permeability experiment confirmed the effect of large DMT on the immunity mechanism of MRSA. Results : TThe minimum inhibitory concentration of DMT against MRSA is 500 ~ 2000 ㎍/㎖ by broth dilution method. In the checkerboard method, the combinations of DMT with antibiotics has partial synergistic effect or synergy effect and DMT markedly reduced the MICs of the antibiotics oxacillin (OX), gentamicin (GEN) against MRSA. In the inhibition of resistance mechanism of DMT against MRSA, the expression of resistance gene and protein about β-lactam antibiotic was reduced. Also, we observed the effect of DMT about cell membrane permeability against MRSA, and confirmed that DMT suppressed growth of strains by increasing cell membrane permeability and energy metabolism. Conclusion : Basis on the result, we speculate that DMT may be useful for the treatment of MRSA infections when used in combination with β-lactam antibiotic.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.27-39
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• 2023

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

• The Korean Journal of Pesticide Science
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• 제13권1호
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• pp.54-61
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• 2009

EPN-resistant diamondback moth were tested the developmental characteristics, longevity, fecundity and synergistic effect with synergists when treated with the bistrifluron, an inhibitor of chitin synthesis. Inhibition rate of egg hatch was below at the recommended concentration (50 ppm) to the EPN-resistant strain than EPN-non selected strain, however, mortality within 24hr after hatching was showed as 50-60%. They did not show the difference between two strains. Mortality of larval instars were showed effective to two strains with no difference. Inhibition rate of emergence did not show any effect when treated with pupae. Moreover, they did not affect to the longevity and fecundity. When bistrifluron was treated at 50 ppm to the adult, however, longevity and fecundity was decreased with no difference between two strains. Bistrifluron to the EPN-resistant strain showed synergistic effect as high as 137.7 and 73.1 folds with synergist such as PBO (microsomal oxidase inhibitor) and polyoxin B (chitin synthetase inhibitor), respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4353-4358
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• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• Microbiology and Biotechnology Letters
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• 제33권2호
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• pp.130-135
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• 2005

To investigate the antimicrobial effect of the Patrinia scabiosaefolia extracts against food-borne pathogens, we extracted the P. scabiosaefolia with methanol at room temperature and the fractionation of the methanol extracts was carried out by using petroleum ether, chloroform, ethyl acetate, and methanol, respectively. The antimicrobial activity of the P. scabiosaefolia extracts was determined by using a paper disc method against food-borne pathogens and food spoilage bacteria. The ethyl acetate extracts of P. scabiosaefolia showed the highest antimicrobial activity against Escherichia coli and Shigella sonnei. Synergistic effect in inhibition was observed when P. scabiosaefolia extract was mixed Forsythiae fructus extract as compared to each extracts alone. Finally, the growth inhibition curves were determined by using ethyl acetate extracts of P. scabiosaefolia against Staphylococcus epidermidis and Shigella sonnei. The ethyl acetate extract of P. scabiosaefolia had strong antimicrobial activity against S. sonnei at the concentration of 4,000 ppm. At this concentration, the growth of S. Sonnei was retarded more than 72 hours and up to 48 hours for S. epidermidis. These results suggest that the ethyl acetate extracts of P. scabiosaefolia can be used for the efficient material against the growth of S. epidermidis and S. sonnei.

• Journal of Acupuncture Research
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• 제31권1호
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• pp.111-119
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• 2014

Objectives : I investigated whether Bee Venom can synergistically strengthen the cytotoxic effects of NK-92 cells, enhancing the inhibition of the growth of Lung Cancer Cells including A549 and NCI-H460 through induction of death receptor dependent extrinsic apoptosis and NO generation in the Nitro-oxide pathway. Methods : Bee Venom inhibited cell proliferation of A549 or NCI-H460 Human Lung Cancer Cells as well as NK-92 Cells. Moreover, when they were co-punctured with NK cells and concomitantly treated by 3 ${\mu}g/ml$ of Bee Venom, more influence was exerted on inhibition of proliferation of A549 or NCI-H460 Human Lung Cancer Cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2, DR3, DR6 in A549 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells and treatment of 3 ${\mu}g/ml$ of Bee Venom, compared to co-culture of NK-92 cells alone, whereas the expression of Fas, TNFR2, DR6 in NCI-H460 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells, representing no synergistic effects in the co-culture of NK-92 cell and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom. Coincidently, caspase-8, a expression of pro-apoptotic proteins in the extrinsic apoptosis pathway demonstrated same results as the above. Meanwhile, In NO generation, there is little change of NO generation in co-culture of NK-92 cells with A549 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, whereas increase of NO generation was shown in co-culture of NK-92 cells with NCI-H460 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, although synergistic effects by Bee Venom was not found. Conclusions : These present data provide that Bee Venom could be useful candidate compounds to enhance lung cancer growth inhibiting ability of NK-92 cells through DR expression and the related apoptosis.

• Korean Journal of Clinical Laboratory Science
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• 제54권1호
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• pp.38-48
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• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.

• Tuberculosis and Respiratory Diseases
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• 제75권1호
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• Journal of the Korean Society of Food Science and Nutrition
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• 제36권1호
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• pp.1-7
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• 2007

Antimutagenic and in vitro anticancer effects of doenjangs added with green tea extract and/or using bamboo salt were studied by Ames test using Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) TA100 and 3-(4,5-dimethylthiazol) -2,5-diphenyltetrazolium bromide (MTT) assay on PC-3 and DU145 human prostate cancer cells, respectively. At the 1.25 mg/plate concentration, 1% green tea extract (GTE) added doenjang exhibited 85% antimutagenicity against aflatoxin $B_1$ ($AFB_1$), while the control doenjang revealed 63% antimutagenicity, showing increased antimutagenic effect by the addition of green tea extract during doenjang fermentation. GTE added doenjang also increased antimutagenic effect against MNNG. The inhibition rate of the control doenjang showed 34% at 0.625 mg/plate, while 1% and 2% GTE added doenjangs inhibited by 56% and 73% at the 0.625 and 1.25 mg/plate, respectively (p<0.05). In MTT assay, GTE added doenjangs caused 70% $\sim$ 77% inhibition on the proliferation of PC-3 human prostate cancer cells at 0.5 mg/mL while the control doenjang exhibited 46% inhibition. However, 2% GTE added doenjang showed 91% inhibition at 1.0 mg/mL. The trend of the inhibition rate was similar in DU14S human prostate adenocarcinoma cells. When bamboo salt was used instead of natural sea salt, the antimutagenicity against MNNG and in vitro anticancer effect on the prostate cancer cells greatly increased. From these results, it can be concluded that green tea extract addition to doenjang and the use of bamboo salt during doengjang preparation increased the antimutagenic and in vitro anticancer activities of the doenjang and showed a synergistic effect.

• Korean Journal of Weed Science
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• 제10권4호
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• pp.277-284
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• 1990

The response of rice (Oryza sativa L.) cultivars to mixtures of 2, 4-D(2, 4-dichlorophenoxyacetic acid) and other herbicides was investigated to determine if there was an interaction between them. When 2, 4-D was applied, shoot growth of Taipei 309 was more affected than that of IR28 at all concentrations used. In contrast, when thiobencarb (S-[(4-chlorophenyl)methyl]diethylcarbamothioate), butachlor [N-(buthoxymethyl) -2-chloro-N-(2, 6-diethylphenyl) acetamide], and glyphosate [N-(phosphonomethyl)glycine] were applied, the shoot growth of Taipei 309 was less affected than that of IR28 at all herbicide concentrations. Combination of 2, 4-D and the lowest thiobencarb concentration was antagonistic for shoot length for both cultivars, but at higher concentrations, it was synergistic. Synergism for shoot fresh weight between 2, 4-D and thiobencarb was observed with IR28 at all concentrations but, for Taipei 309, synergism was observed only at lower 2, 4-D concentrations. Mixing 2. 4-D with butachlor resulted in greater inhibition in shoot length and fresh weight of IR28 than Taipei 309 at all concentrations indicating a synergistic interaction. With combinations of 2, 4-D and glyphosate, an antagonistic interaction for shoot length was observed for both cultivars. A synergistic interaction for shoot fresh weight was observed with IR28 when combinations of the highest concentration of glyphosate and 2, 4-D were applied but there was an antagonistic interaction with Taipei 309.