• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.861-868
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• 2013

This study investigated the effects of Opuntia ficus-indica and other natural resources (OF) in db/db and C57 mice. Plasma triglycerides, cholesterol, alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, fecal bile acid excretion, the histopathological appearance of the liver, and cholesterol-related mRNA expression were determined. Mice (12 db/db mice and 12 C57 mice) were assigned to diabetic-control (db-C), diabetic-OF treatment (db-OF), normal-control (C57-C), and normal-OF treatment (C57-OF) groups. Animals in the control group were fed an AIN-76 recommended diet and animals in the OF group were fed an experimental diet containing 5% of OF for 4 weeks. Concentrations of total plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, and very low density lipoprotein (VLDL)-cholesterol decreased with the administration of OF. In contrast, high density lipoprotein (HDL)-cholesterol levels were minimally affected by the experimental diet. Plasma AST and ALT showed lower activities in the db-OF group, and the fecal excretion of bile acid was reduced in the db-OF group. Histopathological analysis of the liver showed that fatty liver conditions in the db-OF group were more improved than db-C. Low-density lipoprotein receptor (LDL-R) and cholesterol 7${\alpha}$-hydroxylase (CYP7A1) mRNA expression were increased in the db-OF group as well. However, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R) mRNA expression was lower in the db-OF group. These results provide experimental evidence about improved lipid metabolism of the OF feeding in the db/db mice.

• Toxicological Research
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• v.18 no.4
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• pp.331-339
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• 2002

Phenoxy compounds, 2,4-Dichlorophenol acetoxy acid (2,4-D) and 2,4-dichlorophenol (DCP), are widely used as a hormonal herbicide and intermediate for pesticide manufacturing, respectively. In order to assess the potential of these compounds as endocrine disruptors, we studied the androgenicity of them wing in vivo and in vitro androgenicity assay system. Administration of 2,4-D (50 mg/kg/day, p.o.) or DCP (100 mg/kg/day, p.o.) to rats caused an increase in the tissue weight of ventral prostate, Cowpers gland and glands penis. These increase of androgen-dependent tissues were additively potentiated when rats were simultaneously treated with low dose of testosterone (1 g/kg, s.c.). 2,4-D increased about 350% of the luciferase activity in the PC cells transiently cotransfected phAR and pMMTV-Luc at concentration of $10^{-9}$ M. In 2,4-D or DCP-treated castrated rats, testosterone 6$\beta$-hydroxylase activity was not significantly modulated even when rats were co-treated with testosterone. In vitro incubation of 2,4-D and DCP with microsomes at 50 $\mu$M inhibited testosterone 6$\beta$-hydroxylase activity about 27% and 66% in rat liver microsomes, about 44% and 54% in human liver microsomes and about 50% and 45% in recombinant CYP3A4 system, respectively. The amounts of total testosterone metabolites were reduced about 33% and 75% in rat liver microsomes, 69% and 73% in human liver microsomes and 54% and 64% in recombinant CYP3A4 by 2,4-D or DCP, respectively. Therefore, the additive androgenic effect of 2,4-D or DCP by the co-administration of the low dose of testosterone may be due to the increased plasma level of testosterone by inhibiting the cytochrome P450-mediated metabolism of testosterone. These results collectively suggested that 2,4-D and DCP may act as androgenic endocrine disrupter by binding to the androgen receptor as well as by inhibiting the metabolism of testosterone.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.531-538
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• 2004

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-a, IL-1$\beta$, IL-2, IL-6, IL-12, IFN-${\gamma}$ and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1$^{st}$-5$^{th}$ days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7-2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.d.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.12
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• pp.1695-1704
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• 2014

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2939-2946
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• 2015

Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.243-248
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• 2009

The purpose of this study was to investigate the effects of morin, an antioxidant, on the bioavailability of doxorubicin (DOX) in rats. Thus, DOX was administered intravenously (10 mg/kg) or orally (50 mg/kg) with or without oral morin (0.5, 3 and 10 mg/kg). In the presence of morin, the total area under the plasma concentration-time curve (AUC) of DOX was significantly greater than that of the control. In the presence of 3 and 10 mg/kg of morin, the peak concentration $C_{MAX}$) was significantly higher than that of the control. Consequently, the absolute bioavailability (AB) of DOX in the presence of morin was 3.7-8.3%, which was significantly enhanced compared with those of the control group (2.7%). The relative bioavailability (RB) of DOX was 1.36 to 3.02 times higher than those of the control group. Compared to the intravenous control, the presence of morin increased the AUC of DOX, but was not significantly affected. The enhanced bioavailability of oral DOX by oral morin may be due to the inhibition of both P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A in the intestine and/or liver by morin. This result may suggest that the development of oral DOX combination with morin is feasible, which is more convenient than the i.v. dosage forms. The present study raised the awareness about the potential drug interactions by concomitant use of DOX with morin.

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.53-61
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• 2007

Objectives: Our previous studies have clearly demonstrated that the scavenging activity of reactive oxygen species (ROS), protective effect of lipid peroxidation (LPO), and inhibition of cytochrome P450 isozymes (CYPs) from the Circium japonicum aqua-acupuncture solution (CJAS). But, Circium japonicum water extracted solution (CJWS) was weakly reported in cardiovascular diseases such as oxidative stress-mediated atherosclerosis or its value evaluated. Methods: CJWS was assessed to determine the mechanism of its scavenging activity of ROS and inhibitory effect of CYP 2E1. Results: CJWS exhibited a concentration-dependent scavenger of DPPH and superoxide anions radicals using different assay systems. In addition, CJWS showed dose-dependent free radical scavenging activity, including hydroxyl radicals, peroxynitrite, and nitric oxide. The CJWS was also found to be effective in protecting rat liver homogenate against LPO. Futhermore, the CJWS showed significant inhibition of CYP 2E1 induced by pyrazol in a rat liver microsome. Conclusion : ROS and CYPs may play a role in several diseases, such as cardiovascular disease and heart failure. Our study demonstrated that the CJWS has excellent scavenging activity of ROS. Hence, it is worthwhile to investigate the potential effectiveness of CJWS in preventing oxidative stress-mediated cardiovascular diseases.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.370-378
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• 2018

Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.65 no.4
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• pp.274-283
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• 2020

Seed dormancy is an adaptive trait in which seeds do not germinate under unfavorable environmental conditions. Low dormancy seeds are easily germinated under optimal environmental conditions, and these characteristics greatly reduce the yield and quality of crops. In the present study, we compared the pre-harvest sprouting (PHS) rate of two cultivars, Joun and Jopyeong, using the Winkler scale after heading day and temperature of the test. The PHS rate increased as the Winkler scale after heading day increased from 700℃ to 1100℃ and the temperature of the test increased. In all conditions, the PHS rate of Jopyeong was higher than that of Joun. RNA-sequencing was used to analyze the cause of the high PHS rate. We analyzed the biological metabolic processes related to the abscisic acid (ABA) metabolite pathway using the KEGG mapper with selected differentially expressed genes in PHS seeds. We found that the expression of ABA biosynthesis genes (OsNCEDs) was down-regulated and that ABA catabolic genes (OsCYP707As) was up-regulated in PHS seeds. However, the quantitative real-time PCR results showed that Joun had a higher expression of OsNCEDs than that of Jopyeong, but OsCYP707As did not yield a significant result. Joun displayed higher ABA content than that of Jopyeong not only during ripeness time but also during PHS treatment. Taken together, we provided evidence that the ABA content remaining in the seed is important to the PHS rate, which is determined by the expression level of the ABA biosynthesis gene OsNCEDs.