• The Korea Journal of Herbology
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• v.29 no.4
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• pp.35-44
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• 2014

Objectives : Evodia rutaecarpa (Juss.) Benth.(ER) and Chaenomeles sinensis Koehne (CS) have multiple applications and were known to have anti-inflammatory effects. In the current study, we investigated to clearly understand the mechanism of therapeutic role for CS, ER and their combination in CIA model mice. Methods : DBA/1OlaHsd mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CS, ER and their combination once a day for 7 weeks. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN) using ELISA and FACS analysis. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Result : Oral administration of CS, ER and their combination (150 mg/kg) significantly suppressed the progression of CIA, and significantly suppressed the progression of CIA and inhibited the production of TNF-${\alpha}$ and IL-6 in serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CS plus ER. Conclusion : These result suggest that CS plus ER significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-${\alpha}$, IL-6 and collagen II specific antibody in serum.

• Proceedings of the Korean Environmental Health Society Conference
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• 2004.06a
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• pp.185-187
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• 2004

The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP showed significant organ weight changes in liver, spleen exposed during lactational periods. But the dams exposed during lactational periods showed significant organ weight changes not only in liver, spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However no clear synergistic effects of BPA and BBP could be found. Estrogen receptor ${\alpha}$ expression by BPA and BBP in the uterus(dam, F1 female) and testis(F1 male) were studied. There was no significant different $ER{\alpha}$ expression pattern between control and treated groups. But $ER{\alpha}$ expression were increased in F1 male testis and female uterus. F1 male showed distinct $ER{\alpha}$ expression, especially in the group of lactational combined exposure. Synergistic $ER{\alpha}$ expression was found by combined treatment of BPA and BBP.

• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.16-22
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• 2003

BBP (Butyl benzyl phthalate), a widely used plasticizer. can enter the food and environment as consequence of its manufacture, use, and disposal. BBP was found to be developmental and teratogenic or endocrine disrupting chemical in rats. The effects of BBP were investigated in female rats (P) and second generation (F1) via lactations. Sprague-Dawley were given BBP by oral administration at 0, 5, 10, 100, 1000 mg/kg on day 0 to 21 of lactation period. The results were as follows : At maternal findings, there were some significant changes (p<0.05) in relative organ weight, especially liver and uterus weight by BBP administration. In estrous cycle, high treated group was inclined to be proestrus or estrus compared to control group. BBP indues estrous cycle earlier than the control group. At fetal findings, there were some significant changes in relative liver and spleen weight, especially 100, 1000 mg/kg administered groups. The relative weight of ventral prostate was decreased, so it was represent to dose-response tendency. Parent rats (P) were detected monobenzyl phthalate (MBeP) 3.21~5.81 $\mu\textrm{g}$/ml in 100, 1000 mg/kg dose groups. MBeP of male and female fetuses (F1) were detected at the level of 1.21~2.63 $\mu\textrm{g}$/ml of serum. Male serum concentration oi MBeP was higher than the females'. Estrogen receptor $\alpha$ expression by BBP and bisphenol A in uterus and testis of F1 were studied. The ER$\alpha$ expression were increased in F1 male testis and female uterus. F1 male showed distint ER$\alpha$ expression, especially in the combined exposrue. Synergistic ER$\alpha$ expression was found by combined treatment group of BBP and bisphenol A. From the above results, it could be concluded that the effects of dams and F1 by BBP administration during lactation period were estrogenic, and BBP can transfer to F1 via lactation, and make estrogenic at F1 reproductive organs.

• Bulletin of the Korean Chemical Society
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• v.35 no.9
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• pp.2781-2786
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• 2014

Human ${\alpha}_1$-antitrypsin (${\alpha}_1$-AT) is a natural inhibitor of neutrophil elastases and has several dozens of genetic variants. Most of the deficient genetic variants of human ${\alpha}_1$-AT are unstable and cause pulmonary emphysema. However, the most clinically significant variant, Z-type ${\alpha}_1$-AT, exhibits retarded protein folding that leads to accumulation of folding intermediates. These aggregate within the endoplasmic reticulum (ER) of hepatocytes, subsequently causing liver cirrhosis as well as emphysema. Here, we studied the role of an ER folding assistant protein Cpr5p on Z-type ${\alpha}_1$-AT folding. Cpr5p was induced > 2-fold in Z-type ${\alpha}_1$-AT-expressing yeast cells compared with the wild type. Knockout of CPR5 exacerbated cytotoxicity of Z-type ${\alpha}_1$-AT, and re-introduction of CPR5 rescued the knockout cells from aggravated cytotoxicity caused by the ${\alpha}_1$-AT variant. Furthermore, Cpr5p co-immunoprecipitated with Z-type ${\alpha}_1$-AT and facilitated its protein folding. Our results suggest that protein-folding diseases may be suppressed by folding assistant proteins at the site of causal protein biosynthesis.

• Molecules and Cells
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• v.20 no.3
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• pp.378-384
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• 2005

Estrogen metabolites are carcinogenic. The comparative mitogenic activities of $17{\beta}$-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2), $16{\alpha}$-hydroxyestrone ($16{\alpha}$-OHE1) and 2-methoxyestradiol (2-ME), were determined in estrogen receptor(ER)-positive MCF-7 human breast cancer cells. Each of the E2 metabolites caused proliferation of the MCF-7 cells, but only E2 and $16{\alpha}$-OHE1 induced a greater than 20-fold increases in transcripts of the progesterone receptor (PR) gene, a classical ER-mediated gene. This suggests that the mitogenic action of E2 and $16{\alpha}$-OHE1 could result from their effects on gene expression via the ER. E2 metabolites altered the expression of E2-regulated proteins including heat shock proteins (Hsps). $16{\alpha}$-OHE1 and 2-ME as well as E2 increased levels of Hsp56, Hsp60, $Hsp90{\alpha}$ and Hsp110 transcripts, and the patterns of these inductions resembled that of PR. Hsp56 and Hsp60 protein levels were increased by all the E2 metabolites. Levels of the transcripts of 3 E2-upregulated proteins (XTP3-transactivated protein A, protein disulfide isomerase-associated 4 protein and stathmin 1) and an E2-downregulated protein (aminoacylase 1) were also affected by the E2 metabolites. These results suggest that the altered expression of Hsps (especially Hsp56 and Hsp60) by E2 metabolites such as E2, $16{\alpha}$-OHE1 and 2-ME could be closely linked to their mitogenic action.

• Toxicological Research
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• v.33 no.1
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• pp.71-77
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• 2017

Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

• Journal of Life Science
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• v.20 no.12
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• pp.1820-1828
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• 2010

Cobalt(II) chloride, a chemical compound with the formula$CoCl_2$, has been widely used in the treatment of anemia, as a chemical agent for the induction of hypoxia in cell cultures, and is known to activate hypoxic signaling. However, excessive exposure to cobalt is associated with several clinical conditions, including asthma, pneumonia, and hematological abnormalities, and can lead to tissue and cellular toxicity. It is also known to induce apoptosis. One of the questions was that of whether $CoCl_2$ might induce apoptosis via endoplasmic reticulum (ER) stress in neurons. To address this question, first, the level of DNA fragmentation was measured for assay of apoptotic rates using $CoCl_2$ with neuron PC12 cells. After confirmation of apoptosis inductions, under the same conditions, the expression levels of ER stress associated factors [ER chaperones Bip, calnexin, ERp72, ERp29, PDI, and ER membrane kinases (IRE1, ATF6, PERK)] were examined by RT-PCR and Western blotting. These results indicated that apoptosis is induced through activation of ER membrane kinases via ER stress. In conclusion, during induction of apoptosis through $CoCl_2$-induced hypoxia in neuron PC12 cells, ER membrane kinase of IRE1 was dominantly up-expressed, and, consecutively, TRAF2, which has been suggested to be one of the links connecting apoptosis and ER stress, was strongly up-expressed.

• Journal of Food Hygiene and Safety
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• v.21 no.2
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• pp.100-106
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• 2006

The use of underarm and body care cosmetics with oestrogenic chemical excipients (particularly the parabens) and the hypothesized association with breast cancer incidence, particularly in women. It is noted that the type of cosmetic product is irrelevant (e.g. antiperspirant/deodorant versus body lotion, moisturizers or sprays versus creams) and attention must focus on issues of actual exposure to chemicals through continued dermal application of body care products and the endocrine/hormonal activity and toxicity of the chemicals in the formulations. To evaluate the estrogenic activities of parabens such as ethylparaben, butylparaben, propylparaben, isobutylparaben and isopropylparaben, we used recombinant yeasts containing the human estrogen receptor [Saccharomyces cerevisiae ER+LYS 8127], human breast cancer MCF-7 cell lines and human estrogen receptor ${\alpha}\;and\;{\beta}$. In E-screen assays, isopropylparaben is the most estrogenic paraben, and in ER competition assay, isobutylparaben is the most estrogenic paraben. We evaluated isopropylparaben was most active in the recombinant yeast assay, followed by propylparaben, ethylparaben, isobutylparaben and butylparaben. Results from this study demonstrate that parabens are observed in human endocrine system. Therefore, we have shown that the parabens is induced the estrogenic activities similar to $17{\beta}$-estradiol and Bisphenol-A.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4949-4954
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• 2015

The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

• Transactions on Electrical and Electronic Materials
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• v.12 no.5
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• pp.213-217
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• 2011

The nonlinear electrical properties and degradation behavior against an impulse-current of 400 A in the ZnO-$Pr_6O_{11}$-CoO-$Cr_2O_3$-$Y_2O_3$-$Er_2O_3$ (ZPCCYE) varistors were investigated with different $Y_2O_3/Er_2O_3$ ratios. The $Y_2O_3/Er_2O_3$ mole ratio has a significant effect on nonlinear electrical properties and impulse degradation behavior of the ZPCCYE varistors. The varistors added with $Y_2O_3/Er_2O_3$ = 0.5/0.5 exhibited the best nonlinear properties with 39 in nonlinear coefficient (${\alpha}$) and the best clamp characteristics, in which the clamping voltage ratio (K) was in the range of K = 1.62-2.18 at an impulse-current of 1-50 A. The varistors added with $Y_2O_3/Er_2O_3$ = 0.25/0.5 exhibited the best electrical stability, with $%{\Delta}E_{1mA/cm^2}$=-5.6%, $%{\Delta}{\alpha}$ = 6.7%, and $%{\Delta}J_L$ = -14.6% against an impulse-current of 400 A. On the contrary, the varistors added with $Y_2O_3/Er_2O_3$ = 0.5/0.5 were destroyed applying an impulse-current of 400 A.