• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8259-8263
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• 2016

Background: Nano-therapy has the potential to revolutionize cancer therapy. Chrysin, a natural flavonoid, was recently recognized as having important biological roles in chemical defenses and nitrogen fixation, with anti-inflammatory and anti-oxidant effects but the poor water solubility of flavonoids limitstheir bioavailability and biomedical applications. Objective: Chrysin loaded PLGA-PEG-PLGA was assessed for improvement of solubility, drug tolerance and adverse effects and accumulation in a gastric cancer cell line (AGS). Materials and Methods: Chrysin loaded PLGA-PEG copolymers were prepared using the double emulsion method (W/O/W). The morphology and size distributions of the prepared PLGA-PEG nanospheres were investigated by 1H NMR, FT-IR and SEM. The in vitro cytotoxicity of pure and nano-chrysin was tested by MTT assay and miR-34a was measured by real-time PCR. Results: 1H NMR, FT-IR and SEM confirmed the PLGA-PEG structure and chrysin loaded on nanoparticles. The MTT results for different concentrations of chrysin at different times for the treatment of AGS cell line showed IC50 values of 68.2, 56.2 and $42.3{\mu}M$ and 58.2, 44.2, $36.8{\mu}M$ after 24, 48, and 72 hours of treatment, respectively for chrysin itslef and chrysin-loaded nanoparticles. The results of real time PCR showed that expression of miR-34a was upregulated to a greater extent via nano chrysin rather than free chrysin. Conclusions: Our study demonstrates chrysin loaded PLGA-PEG promises a natural and efficient system for anticancer drug delivery to fight gastric cancer.

• 한국식품영양과학회지
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• 제40권1호
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• pp.94-101
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• 2011

본 연구는 오징어 가공부산물인 내장에 koji를 첨가하여 속성 발효한 천연조미료 소재 개발을 목적으로 결과를 요약하면 다음과 같다. 휘발성 염기질소량과 trimethylamine은 대조군이 가장 급격하게 증가하였고, 식염이 많이 첨가될수록 서서히 증가하였다. pH는 대조군이 가장 급격한 변화를 보였으며, 식염이 많이 첨가될수록 pH의 변화량이 적었다. 반면, 산도는 pH 감소와 반비례하여 증가하였다. 아미노질소는 식염 5% 첨가군이 가장 짧은 기간에 최고값을 나타내었으며, 식염 10, 15% 첨가군은 식염 5% 첨가군과 비슷한 값을 보였으나 발효기간이 길어 적합하지 않았다. 따라서 이상의 결과를 고려할 때, 식염 5% 첨가군이 조미료를 만들기에 가장 적합하다고 판단하였다. 식염 5%의 농도에 14일 간 발효시킨 오징어 내장 발효생성물의 일반성분은 조단백이 가장 많았으며, 유리아미노산 조성은 단맛을 내는 아미노산인 alanine과 감칠맛을 내는 아미노산인 glutamic acid의 함량이 가장 많았다. 항산화와 항대장암 활성은 농도 의존적으로 증가하는 것을 확인하였으나, positive control에 비하여 활성이 떨어졌다. 관능검사 결과는 시판 천연조미료와 비교하여 관능적으로 큰 차이가 없었다. 이상의 결과를 고려할 때 오징어 내장 발효생성물은 천연조미료 등 식품첨가제로써 활용이 가능하다고 판단된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.98-98
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• 2003

${\beta}$-(1,3)-D-Glucans have been known to exhibit antitumor and antimicrobial activities. The presence of dectin-1,${\alpha}$, ${\beta}$-glucan receptor of dendritic cell, on macrophage has been controvertial. RT-PCR analysis led to the detection of dectin-1${\alpha}$ and ${\beta}$ in murine macrophage Raw264.7 cell line. Among the various organs of mouse, dectin-1${\alpha}$ and ${\beta}$ were detected in the thymus, lung, spleen, stomach and intestine. To analyze gene expression modulated by ${\beta}$-glucan treated murine Raw264.7 macrophage, total mRNA was applied to cDNA microarray to interrogate the expression of 7,000 known genes. cDNA chip analysis showed that ${\beta}$-glucan of P. osteatus increased gene expressions of immunomodulating genes, membrane antigenic proteins, chemokine ligands, complements, cytokines, various kinases, lectin associated genes and oncogenes in Raw 264.7 cell line. When treated with ${\beta}$-glucan of P. osteatus and LPS, induction of gene expression of TNF-${\alpha}$ and IFN-R1 was confirmed by RT-PCR analysis. Induction of TNF-R type II expression was confirmed by FACS analysis. IL-6 expression was abolished by EDTA in ${\beta}$-glucan and LPS treated Raw264.7 cell line, indicating that ${\beta}$-glucan binds to dectin-l in a Ca$\^$＋＋/ -dependent manner. To increase antitumor efficacy of ${\beta}$-glucan, ginsenoside Rh2 (GRh2) was co-treated with ${\beta}$-glucan in vivo and in vitro tests. IC$\sub$50/ values of GRh2 were 20 and 25 $\mu\textrm{g}$/$m\ell$ in SNU-1 and B16 melanoma F10 cell line, respectively. Co-treatment with ${\beta}$-glucan and GRh2 showed synergistic antitumor activity with cisplatin and mitomycin C both in vitro and in vivo. Single or co-treatment with ${\beta}$-glucan and GRh2 increased tumor bearing mouse life span. Co-treatment with ${\beta}$-glucan and GRh2 showed more increased life span with mitomycin C than that with cisplatin. Antitumor activities were 67% and 72 % by co-injection with ${\beta}$-glucan and GRh2 in the absence or presence of mitomycin C, respectively.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.347-354
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• 2014

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

• 생약학회지
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• 제25권4호통권99호
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• pp.382-387
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• 1994

Antineoplastic activity against human gastric and colon carcinoma cell lines was measured in 49 extracts from 46 plants using MTT (3-[4, 5-dimethyl thiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) method. Six extracts from five plants have been reported to have antineoplastic effect. Extracts from remaining 41 plants failed to show significant cytotoxic effect at the concentration of less than $230\;{\mu}g/ml$.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.125-131
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• 2015

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first-level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were $0.1-1.0{\mu}g/ml$, $0.001-0.01{\mu}g/ml$ and $0.01-0.1{\mu}g/ml$, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the $0.01-1.0{\mu}g/ml$ had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.

• 대한한의학회지
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• 제38권2호
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• pp.15-30
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• 2017

Objectives: Hwangryunhaedok-tang (HHT; Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for treating inflammation, hypertension, gastritis, liver dysfunction, cerebrovascular diseases, dermatitis and dementia. The objective of this study was to assess the sub-acute toxicity of HHT in Sprague-Dawley (SD) rats, and its effect on the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs). Methods: Male and female SD rats were orally administered HHT once daily at doses of 0, 500, 1000 and 2000 mg/kg for 4 weeks. We analyzed mortality, clinical observations, body weight, food consumption, organ weights, urinalysis, hematology, serum biochemistry, and histopathology. The activities of major human CYP450s (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were assessed using in vitro fluorescence- and luminescence-based enzyme assays, respectively. Results: No toxicologically significant changes related to the repeated administration of HHT were observed in both male and female SD rats. The no observed adverse effect level (NOAEL) value was more than 2000 mg/kg/day for both sexes. HHT inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2D6, and CYP2E1, whereas it weakly inhibited the activities of CYP2B6, CYP2C9, CYP3A4, and UGT1A1. In addition, HHT negligibly inhibited the activities of human microsomal UGT1A4 and UGT2B7 with $IC_{50}$ values in excess of $1000{\mu}g/mL$. Conclusions: Our findings indicate that HHT may be safe for repeated administration up to 4 weeks. In addition, these findings provide information on the safety and effectiveness of HHT when co-administered with conventional drugs.

• Radiation Oncology Journal
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• 제8권1호
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• pp.115-124
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• 1990

고 에너지 23MV광자선의 특성 중 임상적용에 중요한 심부선량 백분율, 조직-최대선량비 (TMR), 산란-최대선량비 (SMR), 표면선량 및 출력선량 보정계수등의 변수가 이온전리 (IC-10)함 및 평행 평판전리 (PS-033)함에 의해 측정 조사되었다. 명목상의 23 MV X-선에 대한 가속에너지는 $18.5\pm0.5$ MV로 측정되었다. Mevatron KD 8067의 23 MV X-선의 중심선속의 반가층이 기하학적인 좁은 선속으로 측정되었으며 반가층의 두께는 $24.5\;g/cm^2$이었다. 조직-최대선량비는 심부선량백분율표에서 구해졌으며, 실측치와 비교한 결과 각 조사면의 크기와 깊이에서 약간의 차이를 보였으나 평균 $0.7\pm0.5$의 오차를 나타내고 있어 계산에 의한 TMR 값과 잘 일치함을 보였다. 조사면 $0\times0\;cm^2$의 TMR 값은 zero 조사면의 유효감약계수에 의한 값과, 각 조사면의 조직-최대 선량비로 부터 비선형최소자승법에 의해 구해진 유효선흡수계수 및 반가층 측정에 의한 유효선흡수 계수에 의한 값들로 비교되었으며, $\mu=0.0283{\pm}0,0002cm^{-1}$을 보였고, 세 방법 모두 오차범위내에서 잘 일치됨을 보였다. 한편, 불규칙 조사면의 선량계산에 이용될 SMR은 조사면의 반경 50cm까지 계산되어 대형 조사 면에서도 선량율 산출이 이루어지도록 하였다. Mevatron KD 8067의 23 MV X-선의 조직 표면선량은 SSD 100 cm, 1$10\times10\;cm^2$의 조사면에서 최대조직선량율의 $9.6\%,\;25\times25\;cm^2$에서는 $25.4\%$를 보였다.

• Natural Product Sciences
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• 제20권3호
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• pp.137-145
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• 2014

The biological activities of licorice F1 (Glycyrrhiza glabra ${\times}$ G. uralensis) lines (G) were investigated, revealing strong radical scavenging activity targeting 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl (${\cdot}OH$) radicals. At a concentration of $100{\mu}g/mL$, most of the licorice F1 lines scavenged DPPH and ${\cdot}OH$ by more than 80%. Gs-1, -2, and -6 can be considered good scavengers of DPPH radical and G-7 have higher antioxidant activity against ${\cdot}OH$ radical. In addition, licorice F1 lines exerted effective anti-microbial activities against Escherichia coli (Gs-12, -17, and -18) and Staphylococcus aureus (Gs-3, -4, -5, -21, and -26). Moreover, Gs-2, - 20, -31, and -32 effectively inhibited the growth of Helicobacter pylori. Among licorice F1 lines, Gs-25 exhibited high anti-inflammatory effects on nitric oxide produced by lipopolysaccharide- and interferon-${\gamma}$-activated RAW 264.7 cells. Furthermore, Gs-1, -12, and -20 inhibited the growth of AGS human gastric adenocarcinoma cells by more than 60% at a concentration of $100{\mu}g/mL$ and Gs-5, -11, -19, and -32 showed inhibitory effects against rat lens aldose reductase ($IC_{50}$ values, 1.69, 6.07, 6.12, and $4.54{\mu}g/mL$, respectively). The total content of glycyrrhizin (1), glycyrrhetinic acid (2), glabridin (3), and isoliquiritigenin (4) in licorice F1 lines was high in Gs-11, -15, and -30. The present study therefore indicated that Gs-2, -26, -31, and -32 of licorice F1 possessing strong anti-oxidative, anti-microbial, anti-inflammatory, anti-cancer, and aldose reductase inhibitory effects may be used as a possible source material for natural health supplements in the future.

• 한국식품과학회지
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• 제43권3호
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• pp.334-340
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• 2011

본 연구는 오징어 육에 발효촉진제를 첨가하여 발효한 오징어 조미료 소재 개발을 목적하며 결과를 요약하면 다음과 같다. Asp. oryzae koji를 10%첨가하여 발효하였을 때 아미노질소량이 가장 높았고 휘발성 염기질소량이 가장 낮았으며, pH의 감소량이 크고 산도가 높아 발효에 가장 알맞은 조건이었으며, 10일간 발효하였을 때 아미노질소량이 가장 높아 발효생성물을 제조하기에 가장 적합하였다. Asp. oryzae koji 10%의 농도에 10일간 발효한 오징어 육 발효생성물의 유리 아미노산 조성은 감칠맛을 내는 아미노산인 glutamic acid의 함량이 가장 많았고 핵산관련물질 중 감칠맛을 내는 IMP가 쓴맛을 내는 hypoxanthine보다 많아 식품 정미소재로 이용하기에 적합하였다. 항산화 및 ${\alpha}$-glucosidase 저해활성은 농도 의존적으로 증가하였으며, 항산화 및 소장에서 단당류의 생성을 억제하여 혈당을 낮출 수 있는 가능성이 있는 기능성 소재로서의 활용가능성도 있다고 보여진다. 오징어 발효생 성물에 부재료를 첨가하여 조미료를 제조한 결과 시판 천연조미료와 비교하여 관능적으로 큰 차이가 없었다. 이상의 결과를 고려할 때 오징어 육 발효생성물은 기능성 소재로의 활용에 대하여는 추가연구가 필요하지만, 천연조미료 등 식품 정미 소재로써 활용이 가능하다고 판단된다.