• Biomolecules & Therapeutics
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• 제28권5호
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• pp.443-455
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• 2020

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

• 대한화장품학회지
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• 제47권4호
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• pp.333-340
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• 2021

본 연구에서 찔레꽃을 추출, 농축 및 동결 등을 통하여 시료화 하였다. 찔레꽃추출물과 ascorbic acid의 복합물과 단일 ascorbic acid의 항산화 효능을 비교하였다. 본 연구의 목적은 찔레꽃추출물과 ascorbic acid의 시너지 효과를 통한 항산화 효능을 분석하는 것이었다. 실험은 전자공여능, ABTS⁺ radical 소거능, SOD 유사활성, xanthine oxidase 저해 활성, 환원력, FRAP, 폴리페놀 함량 및 플라보노이드 함량을 측정하였다. 그 결과, 전자공여능 실험과 xanthine oxidase 저해 활성 실험에서 복합물이 대조군(ascorbic acid)보다 높은 항산화 활성을 보였다. 플라보노이드 함량 분석 실험의 경우, 100 ㎍/mL의 농도에서 RMW+A (272.1 mg QE/g), RME+A (90.6 mg QE/g), RMW+A (79.4 mg QE/g)이 대조군(19.0 mg QE/g)보다 함량이 더 높았다. 따라서 찔레꽃추출물과 ascorbic acid 복합물은 단독 사용한 경우에 비하여 시너지 효과를 발휘했다. 따라서 이 복합물은 항산화 화장품에 사용할 경우 제품의 안정화 및 피부노화 억제에 기여할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2683-2688
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• 2016

A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV-0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with $IC_{50}$ values of $94.9{\mu}M$ and $49.0{\pm}0.2{\mu}M$, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent.

• 한국식품영양과학회지
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• 제32권8호
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• pp.1233-1238
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• 2003

Chloride염 및 유기산 칼슘염을 농도별로 첨가하여 배양할 때 6종의 식중독 미생물에 대한 증식 억제 효과를 Bioscreen C(600 nm)를 이 용하여 시험 하였다. E. cereus는 sodium chloride 7% 또는 potassium chloride 9% 처리시 증식이 관찰되지 않았다. Calcium chloride는 3% 농도에서 E. coli O157:H7과 S. aureus의 증식이 관찰되지 않았다. Magnesium chloride는 5% 농도에서 B. cereus, S. Typhimurium 및 S.aureus의 증식을 억제하였다. 유기산 칼슘염의 식중독 미생물에 대한 증식 억제 효과는 calcium propionate>calcium acetate>calcium lactate 순으로 나타났다. S. Typhimurium은 calcium chloride 단독 처리 할 때는 5% 이상 농도에서 증식이 관찰되지 않았으나, calcium chloride 3%와 젖산 0.01%를 병용할 때 같은 효과가 나타나 단독 사용할 때 보다 병용에 따른 상승효과가 큰 것으로 나타났다.

• 약학회지
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• 제36권5호
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• pp.496-505
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• 1992

The correlation between GABA receptors($GABA_A$ and $GABA_B$ receptor) and benzodiazepine receptor on the saline infusion-induced micturition reflex contraction was studied in the female rat. To investigate the effect of ${\gamma}-aminobutyric$ acid(GABA) on the micturition reflex, exogenous GABA(10 mg/kg) and GABA transaminase inhibitor(aminooxyacetic acid; AOAA $1\;{\mu}g$) were administered intravenously(i.v.) and intracerebroventriculary(i.c.v.), respectively. In result, both GABA and AOAA inhibited the saline induced micturition reflex contraction. This AOAA induced inhibition of micturition reflex was blocked by both bicuculine. $GABA_A$ receptor antagonist, and Ro 15-1788, benzodiazepine receptor antagonist. Muscimol, $GABA_A$ receptor antagonist($0.1\;{\mu}g$ i.c.v., $3\;{\mu}g$ intrathecal; i.t., 1 mg/kg i.v.) and baclofen, $GABA_A$ receptor agonist($1\;{\mu}g$ i.c.v., $3\;{\mu}g$ i.t., 1 mg/kg i.v.) also inhibited the bladder contraction. Pretreatment of bicuculline($1\;{\mu}g$ i.c.v.), but not of 5-aminovaleric acid(AVA, $1\;{\mu}g$ i.c.v.), $GABA_B$ receptor antagonist blocked the central inhibition of muscimol. These inhibitory effects were reversed by Ro15-1788 but were potentiated by flurazepam, benzodiazepine receptor antagonist. On the other hand, the inhibitory effects of baclofen were not affected by Ro 15-1788. Diazepam and flurazepam also inhibited the micturition reflex contraction when they were administered $3\;{\mu}g$ i.c.v., $10\;{\mu}g$ i.t., $10\;{\mu}M$, $30\;{\mu}M$ transurethrally, respectively. In conclusion, these results suggest that the micturition reflex is mediated by $GABA_A$, $GABA_B$ receptor and benzodiazepine receptor. The bezodiazepines increase the receptor binding of GABA to the $GABA_A$ receptor, so that the benzodiiazepines show the synergistic effect on the inhibition of the micturition reflex contraction, but not to the $GABA_B$ receptor.

• 치위생과학회지
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• 제23권1호
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• pp.51-59
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• 2023

Background: Tea tree oil has antiviral, antimicrobial and antifungal effects and Mastic oil has antifungal and anticancer effects. For synergistic effects of oils, blending oil containing a mixture of two to three oils is recommended. This study aimed to determine the antibacterial effects of Tea tree oil, Mastic oil, and Blending oil containing the two oils in a mixture, to verify and suggest the potential use of these oils as a substance to prevent dental caries. Methods: Tea tree oil, Mastic oil, and Blending oil with a 1:1 blend of the two oils were diluted in liquid medium to 0% (negative control), 0.5%, 1.0%, and 2.0%. Streptococcus mutans was applied to each experimental group of the three diluted oils and after 8 h culture, the optical density (OD) was measured and the growth inhibition rate for S. mutans was estimated. Results: Tea tree oil had significantly low OD values across all concentrations (p<0.05) without significant variation among different concentrations (p>0.05). Mastic oil did not significantly vary in OD compared to the negative control across all concentrations (p>0.05) without significant variation among different concentrations (p>0.05). Blending oil, compared to the negative control, did not significantly vary in OD at 0.5% (p>0.05) but significant variation was found as the concentration increased (p<0.05). Additionally, for Tea tree oil and Mastic oil, the growth inhibition rate showed no significant variation according to concentration (p>0.05), whereas for Blending oil, the growth inhibition rate for S. mutans showed a significant difference at 1.0% (p<0.05) and at higher concentrations. Conclusion: Blending oil containing a Tea tree oil and Mastic oil demonstrated a significant growth inhibition effect on S. mutans from the concentration of 1.0%, which suggested its potential use as an effective antibacterial agent for dental caries.

• Food Science and Biotechnology
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• 제16권5호
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• pp.753-758
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• 2007

This study was conducted to investigate the antioxidant activity of paprika in the lard-pork model system adding ground fresh paprika (3%) and paprika powders (5%). Paprika powders were obtained through 4 drying methods (freeze, vacuum, far infrared-ray, and hot-air). In the lard and meat-fat mixture (containing lard 30%) containing paprika powders, the rate of increase in the peroxide value (POV) and thiobarbituric acid (TBA) value decreased notably during the refrigerated storage ($4^{\circ}C$) compared to the control without paprika. Therefore, paprika powders showed potent antioxidant activity and especially the freeze dried paprika powder revealed the most effective activity among them. However, its antioxidant activity was still lower than that of the fresh paprika because the addition of fresh paprika in the lard and meat-fat mixture merely increased the POV and TBA value. In linoleic acid oxidation, the addition of capsanthin 500 ppm to mixed linoleic acid and 10 ppm of $FeCl_3$ (LF) inhibited the formation of peroxides by 15.2% compared to LF, showing its iron scavenging ability. When mixed antioxidants (${\beta}$-carotene 200 ppm + ascorbic acid 100 ppm, capsanthin 200 ppm + ascorbic acid 100 ppm) were added in LF, synergistic effects were obtained with 57.7 and 60.4% of inhibition of peroxide formation, respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1163-1169
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• 2014

Astragalus, a commonly used traditional Chinese medicine, has exhibited antitumor actions in patients. In this study, in vitro and in vivo antitumor effects of astragalus and synergistic antitumor efficacy in combination with pterostilbene were investigated. Melanoma cells were treated with pterostilbene (Pt), graduated doses of astragalus injection (AI), or these in combination. Cell viability was measured using a MTT assay. Released nucleosomes and caspase activity were measured using enzyme-linked immunosorbent assay. Growth inhibition in vitro and in vivo was also assessed. Analysis of variance and t tests were used for statistical analysis. Significant reduction (p<0.05) in cellular proliferation were observed with AI and AI-Pt in a time- and concentration-dependent manner. Apoptosis and caspase-3/7 activity were significantly increased by AI and AI-Pt treatment (p<0.05). In vivo, AI inhibited melanoma tumor growth, with inhibition rates ranging from 36.5 to 62.3%, by inducing apoptosis via up-regulation Bax expression and the Bax/Bcl-2 ratio and down-regulating Bcl-2 expression. AI significantly inhibits the growth of melanoma in vitro and in vivo by inducing apoptosis. These data suggest that combined treatment of astragalus with pterostilbene enhances antitumor efficacy.

• Archives of Pharmacal Research
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• 제20권4호
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• pp.379-383
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• 1997

Cyclosporin A, an potent immunosuppressant, has been known to be one of the modulators of drug resistance as well as a cytostatic drug. Despite many attempts to basic or clinical application of cyclosporin A, there are few reports on the inhibition of brain tumor cells. In the present experiment, the possibility of cyclosporin A as synergic adjuvant was investigated by MTT assay, $[^{3}H]$ thymidine uptake and through flowcytometric anaysis. Sole treatment of cyclosporin A on the CRT and CH235-MG glioma cell line revealed dose dependent cytotoxicity within a range of tested dose. Combined treatment of cyclosporin A with ACNU, BCNU and hydroxyurea on various glioma cancer cell line led to a significant synergistic cytotoxicity as well as inhibition of DNA synthesis with dose-dependency. In addition, cyclosporin A alone or combined treatment caused discernible changes of cell cycle in the tested cells. These data provide that cyclosporin A could potentiate the effect of nitrosourea compounds in vitro on human glioma cells.

• The Plant Pathology Journal
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• 제32권3호
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• pp.209-215
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• 2016

In this study, the treatment of pistachio nuts by Bacillus subtilis UTBSP1, a promising isolate to degrade aflatoxin B1 (AFB1), caused to reduce the growth of Aspergillus flavus R5 and AFB1 content on pistachio nuts. Fluorescence probes revealed that the cell free supernatant fluid from UTBSP1 affects spore viability considerably. Using high-performance liquid chromatographic (HPLC) method, 10 fractions were separated and collected from methanol extract of cell free supernatant fluid. Two fractions showed inhibition zones against A. flavus. Mass spectrometric analysis of the both antifungal fractions revealed a high similarity between these anti-A. flavus compounds and cyclic-lipopeptides of surfactin, and fengycin families. Coproduction of surfactin and fengycin acted in a synergistic manner and consequently caused a strong antifungal activity against A. flavus R5. There was a positive significant correlation between the reduction of A. flavus growth and the reduction of AFB1 contamination on pistachio nut by UTBSP1. The results indicated that fengycin and surfactin-producing B. subtilis UTBSP1 can potentially reduce A. flavus growth and AFB1 content in pistachio nut.