• Journal of Cancer Prevention
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• 제21권3호
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• pp.135-143
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• 2016

Background: Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a coumarin derivative, has been reported to possess antioxidative, anti-inflammatory and neuroprotective effects. A number of recent observations suggest that the induction of heme oxygenase-1 (HO-1) inhibits inflammation and tumorigenesis. In the present study, we determined the effect of fraxetin on HO-1 expression in HaCaT human keratinocytes and investigated its underlying molecular mechanisms. Methods: Reverse transcriptase-PCR and Western blot analysis were performed to detect HO-1 mRNA and protein expression, respectively. Cell viability was measured by the MTS test. The induction of intracellular reactive oxygen species (ROS) by fraxetin was evaluated by 2′,7′-dichlorofluorescin diacetate staining. Results: Fraxetin upregulated mRNA and protein expression of HO-1. Incubation with fraxetin induced the localization of nuclear factor-erythroid-2-related factor-2 (Nrf2) in the nucleus and increased the antioxidant response element-reporter gene activity. Fraxetin also induced the phosphorylation of Akt and AMP-activated protein kinase $(AMPK){\alpha}$ and diminished the expression of phosphatase and tensin homolog, a negative regulator of Akt. Pharmacological inhibition of Akt and $AMPK{\alpha}$ abrogated fraxetin-induced expression of HO-1 and nuclear localization of Nrf2. Furthermore, fraxetin generated ROS in a concentration-dependent manner. Conclusions: Fraxetin induces HO-1 expression through activation of Akt/Nrf2 or $AMPK{\alpha}/Nrf2$ pathway in HaCaT cells.

• Natural Product Sciences
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• 제12권4호
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• pp.221-225
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• 2006

Phytochemical examination of the fruits of Actinidia arguta has led to the isolation three organic acids, one coumarin, and three flavonoids. Structures of these compounds were elucidated as protocatechuic acid (1), caffeic acid (2), $caffeoyl-\beta-D-glucopyranoside$ (3), esculetin (4), quercetin (5), quercetin $3-O-\beta-D-galactopyranoside$ (6), and quercetin $3-O-\alpha-L-rhamnopyranosyl$ $(1\rightarrow6)-O-\beta-D-glucopyranoside$ (7) by comparisons with previously reported spectral data. To investigate the anti-inflammatory and anti-oxidative effects of these compounds, nitric oxide production inhibitory activity in LPS-stimulated RAW 264.7 cells and DPPH radical scavenging activities were examined. Nitric oxide productions were reduced significantly by the addition of compounds $[1(IC_{50}=59.27{\mu}g/ml),\;2(IC_{50}=27.95{\mu}g/ml),\;3(IC_{50}=73.09{\mu}g/ml),\;4(IC_{50}=67.44{\mu}g/ml),\;5(IC_{50}=17.40{\mu}g/ml),\;6(IC_{50}=41.99{\mu}g/ml),\;7(IC_{50}=54.46{\mu}g/ml)]$, and extracts $(IC_{50}=56.21{\mu}g/ml)$ compared with positive control, L-NMMA $(IC_{50}=14.48{\mu}g/ml)$. The phenolic compounds also showed anti-oxidative activities. Especially, Compounds $1(IC_{50}=8.87{\mu}g/ml),\;4(IC_{50}=3.41{\mu}g/ml),\;and\;5(IC_{50}=6.06{\mu}g/ml),\;$, showed potent anti-oxidative activities similar to L-ascorbic acid $(IC_{50}=5.89{\mu}g/ml)$.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.479-488
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• 2021

This study aimed to develop docetaxel (DTX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC₅₀ values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

• 생약학회지
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• 제35권2호통권137호
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• pp.116-121
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• 2004

Seven compounds, euscaphic acid (1), nepehinol (2), ursolic acid (3), phytol (4), ${\beta}-amyrin$ (5), scopoletin (6), and rutin (7) were isolated from the aerial parts of Synurus excelsus which has been used as Korean traditional medicine to treat rheumatic arthritis and dysmenorrhea. Their structures were established by chemical and spectroscopic methods. All compounds were isolated for the first time from this plant.

• Natural Product Sciences
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• 제8권2호
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• pp.58-61
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• 2002

Five coumarins and a pyrimidine were isolated from the roots of Angelica gigas. Their structures were elucidated as bergapten (1), decursinol angelate (2), decursin (3), nodakenetin (4), uracil (5) and nodakenin (6) by spectral analysis. Among them, bergapten (1) and uracil (5) were isolated for the first time from this plant part.

• Archives of Pharmacal Research
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• 제8권3호
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• pp.187-190
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• 1985

A cytotoxic coumarin against L1210 cell was isolated from the unripe fruit of Poncirus trifoliata ($ED_{5}$) = 10.2 $\mu$ g/ml. Its structure was identified as aurapten, 7-geranyloxycoumarin. Hydrolysis of the substance gave umbelliferone and geraniol. Only geraniol showed the cytotoxic activity ($ED_{53}$ = 6.5 $\mu$g/ml) while umbelliferone and its methyl or allyl derivatives were not active.

• 약학회지
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• 제50권5호
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• pp.338-344
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• 2006

A novel series of 4-senecioyloxymethyl-6,7-dimethoxycoumarin, isolated from Crinum latifolium, was prepared by reacting 4-bromomethyl or 4-bromomethyl-6,7- dimethoxycoumarin with various carboxylic acids and examined for their anti-angiogenic activities in human umbilical vein endothelial cells (HUVECs). Among them, 4e, 4f, 4g and 4i with noncyclic moiety exhibited potent anti-angiogenic activity. However, compounds with cyclic moiety such as phenyl, pyridinyl, thiophenyl and furanyl group did not exhibit any anti-angiogenic activity. Also, compounds 4f and 4g which exhibited strong anti-angiogenic activity in a dose-dependent manner showed antitumor activity.

• 한국정보디스플레이학회:학술대회논문집
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• 한국정보디스플레이학회 2007년도 7th International Meeting on Information Display 제7권2호
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• pp.1433-1436
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• 2007

Using a blue emitting DPVBi material and red dopant DCJTB, WOLEDs with and without green emitter C6 added in ETL or HTL have been fabricated. The chromaticity color index of WOLEDs without C6 depends strongly on the doping concentration. In addition, manipulating thickness of emitting layer is similar effect such as controlling weight concentration of dopant. While the white color of WOLEDs with C6 added in ETL or HTL depend on position of C6. WOLED of three colors added green dye have been shown turn-on voltage of 3.25V, and EL efficiency 3.05cd/A @9V, $8102\;cd/m^2$, CIE coordinates (0.30, 0.32).

• Archives of Pharmacal Research
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• 제27권10호
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• pp.1016-1019
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• 2004

The chromatographic separation of a methylene chloride extract of Artemisia rubripes led to the isolation of a new sesquiterpene lactone (3), together with four known compounds, a coumarin (2) and three terpenes (1, 4, and 5). Their structures were characterized to be $1{\beta},6{\alpha}$- dihydroxy-4(15)-eudesmene (1), scopoletin (2), $1{\alpha},4{\beta}-dihydroxy-8{\alpha}$-acetoxy-guaia-2,10(14), 11(13)-triene-6,12-olide (3), $1{\alpha},4{\beta}$ -dihydroxy-8${\alpha}$-acetoxy-guaia-2,9,11(13)-triene-6,12-olide (4), and $\beta$ -sitosterol-3-O-${\beta}$-D-glycoside (5) by spectroscopic means.

• Bulletin of the Korean Chemical Society
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• 제5권6호
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• pp.219-223
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• 1984

The 8-methoxypsoralen$<^{4',5'}_{5',6}>$ thymidine monoadducts are isolated from the irradiation mixture of 8-methoxypsoralen and thymidine in a dry film state by a flash column followed by lobar column chromatography. Some physical properties of the adducts were determined. The fluorescence maximum and quantum yield of the monoadduct are dependent on the solvent polarity and the phosphorescence to fluorescence quantum yield ratio was 2.10 which was significantly increased by external heavy atoms. The phosphorescence lifetime was 1.2s which is relatively large compared to other coumarin derivatives. Accurate spectral data of the monoadducts are presented.