• Molecules and Cells
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• v.37 no.7
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• pp.547-553
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• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

• Herbal Formula Science
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• v.24 no.2
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• pp.80-99
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• 2016

Objectives : Instrumental chemical analysis was utilized to investigate the effect of Add-Omit-Saenghyeoryunbu-eum(AO-SHU) on diabetic treatment. One of the most exciting, yet also controversial, arguments is the safety and biological mechanisms of the natural medicine on human body. Therefore, the aim of this study is to provide a better understanding on bioactive chemical components, hazards of heavy metal contamination and biological mechanism of the diabetic medicine composed of 12 different natural herbs. Methods : To study bioactive compound and metallic component in the diabetic medicine in detail, LC-MS/MS (Liquid Chromatography-Mass/Mass), GC (Gas Chromatography) and ICP (Inductively Coupled Plasma) were utilized to characterize the extract of the diabetic medicine and the result was compared with 18 marker substances selected from literature survey. In addition, in vitro assay experiments including GPR 119 activity and human DGAT-1 inhibition, and OGTT (Oral Glucose Tolerance Test) were performed to verify the effectiveness of this medicine on diabetic treatment. Results : Out of 18 marker substances, 9 bioactive compounds were identified from LC-MS/MS analysis which include Citruline, Catalpol, Berberine, Ginsenoside Rb1, Ginsenoside Rg1, Oleanolic acid, β-Sitosterol, Mangiferin, and Schizandrin. ICP study on 245 residual pesticides revealed that 239 species were not detected but 6 species, Dimethomorph, Trifloxystrobin, Pyraclostrobin, Isoprocarb, Carbaryl and Flubendiamide, while the amounts are trace levels, below permitted concentrations. The biological activity was observed in vitro assay and Oral Glucose Tolerance Test(OGTT), which are consistent with a preliminary clinical test result, a drop in blood sugar level after taking this herbal medicine. Conclusions : Instrumental chemical analysis using LC-MS/MS, GC, and ICP was conducted successfully to identify bioactive compounds in AO-SHU for the treatment of diabetes, finding 9 bioactive compounds. Furthermore, in vitro assay experiments and OGTT show that AO-SHU has its biological activities, which imply that it can be a candidate for the future diabetes remedy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.6
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• pp.1042-1049
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• 2000

Irradiation-induced volatile flavor compounds in irradiated (1, 3, 5, 10 kGy) beef were analyzed by liquid liquid continuous extraction (LLCE) and gas chromatography/mass spectrometry (GC/MS) methods. One hundred fifty volatile compounds were detected in irradiated beef. These compounds were composed mainly of 71 hydrocarbons, 35 aromatic compounds, 15 aldehydes, 7 ketones, 4 acids, 6 esters and 12 miscellaneous compounds. Among these, only 6 volatile compounds including (E) -2-hexenal, nonene, 2-nonenal, cyclodecene, dodecene and cyclododecene were detected as irradiation-induced volatile flavor compounds, comparing with unirradiated beef meat. However, 4 volatile compounds, such as cyclodecene (r=0.88), (E)-2-hexenal (r=0.85), nonene (r=0.74) and 2-nonenal (r=0.70), having a positive correlation coefficient with the increment of irradiation dose, were considered as marker compounds for detecting irradiation dosages in irradiated beef.

• Journal of Life Science
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• v.27 no.7
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• pp.812-816
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• 2017

Although amaranth, a red-colored tar dye, is usually used in foods, cosmetics, and pharmaceutics, its bioavailability and intestinal absorption have not previously been investigated. Therefore, the purpose of this study was to investigate the pharmacokinetics properties and intestinal permeability of amaranth in rats following the intravenous and oral administration of this dye. Amaranth rapidly disappeared from the plasma following the intravenous injection, with a half-life of 38.8 minutes. However, the plasma concentration of amaranth was increased to 400 minutes following the oral administration of amaranth, and the absorption time and bioavailability of amaranth were calculated to be 356 minutes and 55.6%, respectively. This suggests that once amaranth exists in the gut, this dye may be efficiently and effectively absorbed. Consistent with this result, the intestinal permeability of amaranth was comparable to atenolol, a marker compound of moderate permeability, and to one-third of caffeine's intestinal permeability (a highly permeable compound). In conclusion, a significantly long absorption time and substantial intestinal absorption of amaranth was observed following the oral administration of amaranth at a dose of 300 mg/kg in rats, despite the rapid elimination of this dye from the plasma. These results may suggest the necessity of a careful and limited use of amaranth dye when it is added to food, lip-care cosmetics, and orally administered pharmaceutics.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.2
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• pp.145-152
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• 2016

Epidermis is continuously regenerated by keratinocyte stem cells (KSCs) residing in basement membrane, which is critical to the survival of an organism. KSCs are believed to persist during the whole lifetime and generate an enormous number of keratinocytes, required for the maintenance of epidermis, through transit amplifying cells dividing definite times until they become differentiated. In this report, we have developed a phenolic compound, paeonol, purified from Moutan Cortex, as a KSC proliferation activator, by screening about 350 herbal compounds. The cell proliferation activation by paeonol is specific for KSC not for keratinocyte, and no significant difference in the expression of p63 protein, a KSC marker, in KSCs treated with paeonol was observed in FACS analysis with anti-p63 antibody. In the colony forming assay, paeonol-treated KSC showed improved colony forming activity more than 1.3 fold. In addition, the result of PCR array shows that the activity of paeonol is through several signal pathways involving stem cell functions. These results suggest that paeonol could enhance KSC proliferation activity without reduction in stemness and could be applied to cosmetics as a KSC activating ingredient.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6947-6951
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• 2015

Background: Oral carcinoma (OC) remains one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties against various human tumors. However, its mechanism of action remains to be addressed. The present study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of erb$\backslash$b2 as a main prognosticator tumor marker for OC in an animal model. Materials and Methods: A total of 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500mg/kg body weight doses of Hesa-A 3 times a day. The other two groups were considered as treated and untreated control groups. At the end of the experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results showed that compared to the control group, erb$\backslash$b2 was over-expressed ~ 30% in the carcinoma group. After treatment with 250mg/kg and 500mg/kg body weight of Hesa-A, erb$\backslash$b2 levels dropped by 24.1% and 3.4 % respectively compared to the control carcinoma group (p<0.01, p<0.0001). Moreover, there was a significant relation between erb$\backslash$b2 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insight into mechanism(s) by which Hesa-A may improve clinical outcome of oral carcinoma by affecting oncogene erb$\backslash$b2 expression and suggest Hesa-A as an effective chemotherapeutic agent in treatment of HER+tumors.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.3
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• pp.443-452
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• 1994

This study describes the effects of novel1, 25-dihydroxyvitamin D$_3$ analong[1,25(OH)$_2$-16ene-23yne-26, 27-F6-D$_3$] on proliferation of the human histiocytic lymphoma cell line U937 in vitro. We also examined the expression of c-myc oncogene in U937 cells was apparently inhibited to 62% and 87% of the control level after 4 days in the presence of 10-8M and 10-7 M of this analog, respectively. This compound morpholgically and functionally differentiated U937 cells to nonocyte-macrophage phenotype showing the increase of adherence ability to surface and a decrease of N/C ratio in Giemsa staining . Especially, nonspecific esterase activity which is a marker of cell differentiation to monocyte-macrophage was positive, and production of the positive stained cells increased in a dose dependent fashion . The expression of c-myc oncogene by 1, 25(OH)$_2$D$_3$ analog(10-7 M) was reduced by 60% at the mRNA level as determined by Northern blotting. The effects of this novel analog on cell proliferation and cell differentiation may open op new therapeutic strategies for human disorders such as psoriassis and may provide a tool to understand the mechanism of action of vitamin D$_3$ seco-steroids in malignancy.

• Journal of Animal Science and Technology
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• v.56 no.8
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• pp.33.1-33.8
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• 2014

Background: Sox 9 is a major marker of chondrocyte differentiation. When chondrocytes are cultured in vitro they progressively de-differentiate and this is associated with a decline in Sox 9 expression. The active form of vitamin D, 1, 25 $(OH)_2D_3$ has been shown to be protective of cartilage in both humans and animals. In this study equine articular chondrocytes were grown in culture and the effects of 1, 25 $(OH)_2D_3$ upon Sox 9 expression examined. The expression of the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine chondrocytes in vitro, we have previously shown, is inversely correlated with de-differentiation. The expression of these channels in response to 1, 25 $(OH)_2D_3$ administration was therefore also examined. Results: The active form of vitamin D (1, 25 $(OH)_2D_3$ when administered to cultured equine chondrocytes at two different concentrations significantly increased the expression of Sox 9 at both. In contrast 1, 25 $(OH)_2D_3$ had no significant effect upon the expression of either TRPV 5 or 6 at either the protein or the mRNA level. Conclusions: The increased expression of Sox 9, in equine articular chondrocytes in vitro, in response to the active form of vitamin D suggests that this compound could be utilized to inhibit the progressive de-differentiation that is normally observed in these cells. It is also supportive of previous studies indicating that $1{\alpha}$, 25-dihydroxyvitamin $D_3$ can have a protective effect upon cartilage in animals in vivo. The previously observed correlation between the degree of differentiation and the expression levels of TRPV 5/6 had suggested that these ion channels may have a direct involvement in, or be modulated by, the differentiation process in vitro. The data in the present study do not support this.

• Korean Journal of Pharmacognosy
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• v.50 no.4
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• pp.312-317
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• 2019

In order to obtain basic data on the shelf life of Epimedii Herba (EH), a physicochemical characteristics including weight loss rate, loss on drying, ash, acid-insoluble ash, and quantitative determination were evaluated to compare the data by packaging methods including general (G), general + silica gel (GS), alumium (AL), and alumium + silica gel (ALS) packaging and storage periods (0-66 months). All physicochemical analyzes were conducted using the method of "The Korean Pharmacopoeia (KP) 9^th edition". As a result, weight loss rate (%), loss on drying (%), ash (%), acid-insoluble ash (%) of EH according to the packaging methods and storage periods were -0.27-4.73%, 3.06-9.35%, 5.48-7.37%, and 0.45-0.99, respectively. In the quantitative analysis of icariin, the marker compound of EH using high-performance liquid chromatography, the initial content was 0.44% at 0 month in all packaging methods. After that, the result of analyzing the content of icariin every 6 months was detected 0.44-1.18%. All of the above results satisfied the acceptance criteria for loss on drying, ash, acid-insoluble ash, and quantification contained in the KP. This study can be used as a basic data for establishing the packaging method and shelf life of EH.

• Natural Product Sciences
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• v.14 no.3
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• pp.147-151
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• 2008

A high performance liquid chromatographic (HPLC) method for the simultaneous determination of marker constituents, baicalin and glycyrrhizin was established for the quality control of traditional herbal medicinal preparation, Eul-Ja-Tang (EJT). Separation and quantification were successfully achieved with a Waters XTerra RP18 column ($5{\mu}m$, 4.6 mm I.D. ${\times}$ 150 mm) by gradient elution of a mixture of acetonitrile and water containing 0.03% phosphoric acid (pH 2.03) at a flow rate of 1.0 mL/min. The diode-array UV/VIS detector (DAD) was used for the detection and the wavelength for quantification was set at 250 nm. The presence of baicalin and glycyrrhizin in this decoction was ascertained by retention time, spiking with each authentic standard and UV spectrum. Both baicalin and glycyrrhizin showed good linearity ($r^2$ > 0.999) in a relatively wide concentration ranges. The R.S.D. for intra-day and inter-day precision was less than 5% and the limits of detection (LOD) were about 30 ng. The mean recovery of each compound was 99.5 - 101.2% with R.S.D. values less than 4.0%. This method was successfully applied to the determination of contents of baicalin and glycyrrhizin in three commercial products of EJT, which resulted in the difference in the contents of these compounds. These results suggest that the developed HPLC method is simple, effective and could be readily utilized as a quality control method for commercial EJT products.