• 약학회지
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• 제54권6호
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• pp.488-493
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• 2010

Therapeutic manipulation of angiogenesis, the formation of new vascular sprouts from existing capillaries, is one of the promising strategies for treatment of human diseases such as cancer, arthritis, and cardiovascular disorder. In the present study, we examined the effects and molecular mechanism of tissue inhibitor of metalloproteinases-2 (TIMP-2) and endostatin on fibroblast growth factor-2 (FGF-2)-stimulated endothelial cell proliferation, migration and adhesion in vitro, and angiogenesis in vivo. TIMP-2 and endostatin showed potent anti-angiogenic activity in vitro and in vivo. These effects appear to be mediated through different angiogenic signaling pathways. Collectively, our findings demonstrate that TIMP-2 and endostatin strongly inhibit FGF-2-induced angiogenic responses, and the establishment of fast and reproducible evaluation system in vitro and in vivo for the development of anti-angiogenic biomaterials and therapeutics.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.71-76
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• 1993

It has been reported that d-limonene inhibits chemical-induced rat mammary cancer by the mechanism of increases in detoxification enzymes such as glutathione S-transferases and that cineole fails to exhibit significant suppressive effect on chemical-induced carcinogenesis. The present study was designed to compare the effects of d-limonene and cineole on the benzo(a)pyrene (BP)-induced mutagenicity, BP metabolism and lipid peroxidation. Modified Ames assay was employed to evaluate the inhibitory effect of d-limonene and cineole on the BP-induced mutagenicity. The number of revertant-bearing wells was decreased by 44~77% in the presence of both BP and d-limonene compared with that of BP alone whereas cineole decreased the number of revertant-bearing wells by 28~45% at the concentrations between $2{\mu}m$m.TEX> and 2 mM. d-Limonene suppressed BP metabolism by 16, 54 and 67% at 1, 10 and 100 mM, respectively while cineole inhibited the metabolism by 16, 26 and 55% at the same concentrations. The $EC_{50}$ values for d-limonene and cineole in inhibiting lipid peroxidation were 2.0 mM and 16 mM respectively, as assayed by thiobarbituric acid method. The present study showed that d-limonene and cineole have common antimutagenic effects although d-limonone appeared to be more effective than cineole in suppressing mutation and lipid peroxidation. The results suggest that the antimutagenic effects of d-limonene and cineole may be associated with alternation in enzyme activities and with inhibition of lipid peroxidation.

• BMB Reports
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• 제42권5호
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• pp.265-270
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• 2009

Due to their multiple biological activities, flavonoids have gained attention as potentially useful therapeutics for a variety of diseases including cancer, cardiovascular diseases, and autoimmune diseases. In this study, we demonstrated that several flavonoids, including kaempferol, quercetin, fisetin, and chrysin block TNF-$\alpha$ induced IL-8 promoter activation and gene expression in HEK 293 cells. In addition, phosphorylation and degradation of $I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ p65 were inhibited by these flavonoids in TNF-$\alpha$-stimulated HEK 293 cells. Furthermore, generation of reactive oxygen species (ROS) in response to TNF-$\alpha$ was reduced by the flavonoids. Moreover, although pretreatment with fisetin, quercetin, or chrysin decreased cell viability, kaempferol did not. Taken together, these findings suggest that kaempferol would be useful for the treatment of TNF-$\alpha$-induced inflammatory diseases.

• 대한암한의학회지
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• 제10권1호
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• pp.75-86
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• 2005

Disease associated with microorganisms are far from resolved by current therapeutics. One of effective approach to health maintenance and disease control is the use of dietary bacterial and carbohydrate supplements. This comprises use of probiotics and prebiotics. Probiotics mean the live microorganisms, which when administered in adequate amounts confer a health benefit on the host. Prebiotics mean a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria that can Improve the host health. Especially, probiotics has the relation which is close with innate immunity and adaptive immunity. And probiotics has the clinical value with many disease like lactose intolerance, constipation, acute gastroenteritis, food hypersensitivity and allergy, atopic dermatitis, crohn's disease, rheumatoid arthritis, pelvic radiotherapy, intestinal inflammation and chemical exposure, colon cancer, inhibitory effect of Helicobacter pylori and lowering the level of cholesterol. We use jointly korean medicine and probiotics and it has the more therapeutic effect in the many disease.

• Biomolecules & Therapeutics
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• 제8권2호
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• pp.107-112
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• 2000

To investigate the alteration of airway mucin in airway disease patients, immunoassay procedures were employed using monoclonal antibodies HM02 and HM03 (Hybridoma, 18,457-463, 1999). Alteration of mucin release was determined by ELISA and the integrity of mucin was determined by Western blot. In ELISA, it was found that mucin release increased from pneumonia, chronic cough, bronchiectasis, eosinophilic pneumonia, lung cancer and bronchial asthma patients. In Western blot, the increase in immunoreactivity was observed in case of pneumonia, chronic cough, bronchiectasis and bronchial asthma. In bronchial asthma, there was no obvious degradation of mucin while in other diseases, varying degree of mucin degradation was observed. The data from the present study implicate that HMO2 and HM03 are suitable for the immunological analysis of mucin in airway disease patients. The role of increased mucin release and varying degree of mucin degradation on airway diseases should be further investigated in the future.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.134-139
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• 2011

Sphingosine kinase (SPHK) has a central role to control cell death and cell proliferation, which is suggested as a sphingolipid rheostat by regulating the levels between ceramide and sphingosine 1-phosphate (S1P). Therefore, physiological regulators of SPHK will be a good candidate to develop a new targeted drug. For this purpose, a series of synthetic pseudoceramides were tested by SPHK assay either cell-based or cell-free system. K10PC-5 strongly inhibited SPHK, while K6PC-5 activated SPHK in cell-free system. Specifically, K6PC-5 activated SPHK under the co-treatment with $50\;{\mu}M$ dimethylsphingosine (DMS), a SPHK inhibitor. Collectively, we developed a simple SPHK assay system to find SPHK regulatory pseudoceramide compounds, K10PC-5 and K6PC-5 which may be useful to cancer treatment or immune regulation like FTY720, a synthetic sphingolipid mimetic compound.

• Biomolecules & Therapeutics
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• 제22권1호
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• pp.35-40
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• 2014

Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits ${\alpha}$-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.62-69
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• 2009

Roots of Astragalus membranaceus (A. membranaceus) (Astragali Radix, AR) has been used as a herbal medicine for gastrointestinal disorders in China, Korea, Japan, and other Asia countries. In this study we investigated the effects of the AR 70% ethanol extract and compounds isolated from AR on gastritis in rats and growth of human gastric cancer cells. AR 70% ethanol extract showed the potent acid-neutralizing capacities and partly cytotoxicity of Helicobacter pylori and human AGS gastric cancers cell. Astragaloside I and daucosterol, which were isolated from AR, significantly inhibited HCl/ethanol-induced gastric lesions. In addition, daucosterol increased the mucus content to almost the same as the positive control. The results of this study suggest that astragaloside I and daucosterol may be good candidates for the development of new drugs or neutraceuticals which can be used for the treatment or prevention of gastritis.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.414-420
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• 2015

Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-${\alpha}$, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-${\kappa}B$. In agreement, the upstream phosphorylation events for NF-${\kappa}B$ activation, composed of Src, Syk, and I${\kappa}B{\alpha}$, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.210-215
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• 2013

Ionizing radiation can induce cellular oxidative stress through the generation of reactive oxygen species, resulting in cell damage and cell death. The aim of this study was to determine whether the antioxidant effects of the flavonoid fisetin (3,7,3',4'-tetrahydroxyflavone) included the radioprotection of cells exposed to ${\gamma}$-irradiation. Fisetin reduced the levels of intracellular reactive oxygen species generated by ${\gamma}$-irradiation and thereby protected cells against ${\gamma}$-irradiation-induced membrane lipid peroxidation, DNA damage, and protein carbonylation. In addition, fisetin maintained the viability of irradiated cells by partially inhibiting ${\gamma}$-irradiation-induced apoptosis and restoring mitochondrial membrane potential. These effects suggest that the cellular protective effects of fisetin against ${\gamma}$-irradiation are mainly due to its inhibition of reactive oxygen species generation.