• 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.

• Preventive Nutrition and Food Science
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• v.7 no.2
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• pp.113-118
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• 2002

Alpha-lipoic acid is a known hypoglycemic agent that may be useful in the treatment of diabetes. The objective of this study was to investigate the fate of glucose in isolated muscles incubated with lipoic acid by determining its direct effects on specific metabolic and signaling pathways. Soleus muscles from healthy rats were incubated with lipoic acid in the absence or presence of insulin. Glucose transport, glycogen synthesis, glucose oxidation and lipid synthesis were determined and affects on major pathways associated with insulin signaling were evaluated. Glucose transport was not significantly altered by the addition of lipoic acid to the incubation medium. However, lipoic acid decreased glycogen synthesis in comparison to controls. Glucose oxidation was moderately increased while de-novo lipid synthesis from glucose was inhibited. Wortmannin repressed insulin stimulation of glucose incorporation into glycogen, an effect that was augmented by the combined treatment of wortmannin and lipoic acid. Basal and insulin-stimulated serine phosphorylation of Akt was not changed by the addition of lipoic acid to the incubation medium. These data show that in this in vitro model, lipoic acid did not significantly affect glucose uptake but dramatically modified pathways of glucose metabolism within muscle tissue.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.312-319
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• 2018

Background: Previous studies have shown that both ginseng root and ginseng berry exhibit antiobesity and antidiabetic effects. However, a direct comparison of the efficacy and mechanisms between the root and the berry after oral administration remains to be illuminated. Methods: In this study, we observed the effects of fermented ginseng root (FGR) and fermented ginseng berry (FGB) on obesity and lipid metabolism in high-fat diet induced obese mice. Results: FGR and FGB significantly inhibited the activity of pancreatic lipase in vitro. Both FGR and FGB significantly suppressed weight gain and excess food intake and improved hypercholesterolemia and fatty liver, while only FGR significantly attenuated hyperglycemia and insulin resistance. Both FGR and FGB significantly inhibited the mRNA expression of Ldlr and Acsl1 while FGR also significantly inhibited expression of Cebpa and Dgat2 in liver. FGR significantly decreased the epididymal fat weight of mice while FGB significantly inhibited the mRNA expression of genes Cebpa, Fas, Hsl, Il1b, and Il6 in adipose tissue. Conclusion: Saponin from both FGR and FGB had a beneficial effect on high-fat diet-induced obesity. Compared to FGB, FGR exhibited more potent antihyperglycemic and antiobesity effect. However, only FGB significantly inhibited mRNA expression of inflammatory markers such as interleukins $1{\beta}$ and 6 in adipose tissue.

• The Korean Journal of Mycology
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• v.30 no.2
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• pp.124-130
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• 2002

The inductions of phase II enzymes, such as NAD(P)H : quinone reductase (QR), glutathione S-transferase (GST), glutathione (GSH) level and the inhibition of polyamine metabolism were tested for the chemopreventive potentials of the extracts from the soybean fermented with Agrocybe cylindracea (AC) or Phellinus igniarius (PI). The soybean fermented with AC or PI was potent inducer of QR activity in murine hepatoma Hepa1c1c7 cells. GST activities of the extracts from soybean fermented with AC or PI were higher than that of the extract from soybean not fermented with basidiomycetes. In addition, GSH levels of the extracts from soybean fermented with AC or PI were increased about 1.2 fold or 1.4 fold, respectively. In addition, proliferation of Acanthamoeba castellanii in a broth medium was inhibited by the extracts from soybean fermented with AC or PI at the both concentration of 20 and 40 mg/3 ml. These results suggest that soybean fermented with AC or PI may have chemopreventive potentials by inducing QR activity, increasing GSH and GST levels and inhibiting polyamine metabolism.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.135-140
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• 1994

Over past decades, numerous in vitro model has been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as : 1. the characterization of main biotransformation reactions. 2. the identification of phase I and phase II isozymes involved in such reactions 3. the evaluation of interspecies differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles 4. the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions 5. the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obstained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers.

• Development and Reproduction
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• v.25 no.2
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• pp.75-82
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• 2021

We studied steroid metabolites produced from red-spotted grouper ovarian follicles during maturation. Oocytes with 350-500 ㎛ diameter were in vitro incubated in the presence of [³H] 17α-hydroxyprogesterone as a precursor. Steroid metabolites were extracted from incubated media and oocytes. The extracts were separated and identified using thin layer chromatography, high performance liquid chromatography and gas chromatography-mass spectrometry. The identified metabolites were androstenedione (A₄), testosterone (T) and estrone (E₁). The metabolites of A₄ was dominant in all size of oocytes and it was the highest in 480 ㎛ diameter oocytes. The metabolites of two progestins, 17α,20β-dihydroxy-4-pregnen-3-one and 17α,20α-dihydroxy-4-pregnen-3-one were detected in the oocytes less than 480 ㎛ diameter although they were not identified definitely. In the oocytes of 480 ㎛ diameter, metabolite of progestin was the highest, and germinal vesicle (GV) was still in the middle of cytoplasm. In the oocytes of 500 ㎛ diameter, GV was began to migrate and the major metabolites were A₄ and E₁. The metabolite of E₁ was detected in all size of oocytes and it was higher than that of E₂. These results suggest that oocytes of 480 ㎛ diameter are the transitional stage involving steroidogenic shift to final oocyte maturation and potential function of E₁ during maturation process.

• Food Science and Preservation
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• v.20 no.6
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• pp.840-845
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• 2013

This study investigated the effects (i.e., the acetylcholinesterase activity, lipid peroxidation, and neuronal survival) of 20 kinds of medicinal water extracts. The water extracts of three medicinal plants - Cornus officinalis, Glycyrrhiza glabra, and Angelica gigas - were found to be the most effective on acetylcholinesterase inhibitory activity. In the lipid peroxidation-generating system induced by $H_2O_2/FeSO_4$ in rat brain homogenates, Perilla frutescens, Polygonum multiflorum, Cinnamomun cassia, and G. glabra exhibited protective activity against lipid peroxidation. The neuronal cell death induced by L-glutamate in PC12 was suppressed by the water extracts of G. glabra, Cinnamomun cassia, Platycodon grandiflorum, and Mentha arvensis at the concentration of $100{\mu}g/mL$. Taken together, these results showed that the water extract of G. glabra has the potential anti-dementia activity, which suggests that it might provide an effective strategy for improving dementia.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.8
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• pp.1102-1110
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• 2016

The mammalian target of rapamycin (mTOR) regulates cellular processes such as cell growth, metabolism, transcription, translation, and autophagy. Rapamycin is a selective inhibitor of mTOR, and induces autophagy in various systems. Autophagy contributes to clearance and recycling of macromolecules and organelles in response to stress. We previously reported that vitrified-warmed mouse oocytes show acute increases in autophagy during warming, and suggested that it is a natural response to cold stress. In this follow-up study, we examined whether the modulation of autophagy influences survival, fertilization, and developmental rates of vitrified-warmed mouse oocytes. We used rapamycin to enhance autophagy in metaphase II (MII) oocytes before and after vitrification. The oocytes were then subjected to in vitro fertilization (IVF). The fertilization and developmental rates of vitrified-warmed oocytes after rapamycin treatment were significantly lower than those for control groups. Modulation of autophagy with rapamycin treatment shows that rapamycin-induced autophagy exerts a negative influence on fertilization and development of vitrified-warmed oocytes.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.336-336
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• 1994

In order to develope the in vitro short term screen-ing method for carcinogen, we studied a purification method for thymine glycol in oxidaized DNA. Thymine glycol (5,6-dihydroxy-5, 6-dihydrothymine) is the major stable radiolysis poduct in thymine by chemical oxidants and ionzing radiation and it is a useful biomarker among oxidized DNA adducts, related with carcinogenests. Standard thymine glycol was prepared by oxidation of 〔$^3$H〕 thymine with KMnO$_4$ followed by purification with HPLC-LSC system and it was assayed by TLC and gas chromatography-MSD. 〔$^3$H〕 DMA adducts was isolated from E. coli (wild type ) treated with oxidative agents such as benzo(a)pyrene, adriamycin, aflatoxin B$_1$ and KBrO$_3$. These oxidative agents generated free radicals in cells by oxidative metabolism. As a result, thymine glycol was produced in cultured E. coli by four chemicals. This result shows that this methodology should be useful tool in screening oxidative carcinogen.

• Animal Bioscience
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• v.34 no.3_spc
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• pp.393-404
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• 2021

Objective: This study compared the catechin composition of different tea byproducts and investigated the effects of dietary supplementation with green tea byproducts on the accumulation of abdominal fat, the modulation of lipid metabolism, and the inflammatory response in red feather native chickens. Methods: Bioactive compounds were detected, and in vitro anti-obesity capacity analyzed via 3T3-L1 preadipocytes. In animal experiments, 320 one-day-old red feather native chickens were divided into 4 treatment groups: control, basal diet supplemented with 0.5% Jinxuan byproduct (JBP), basal diet supplemented with 1% JBP, or basal diet supplemented with 5×106 colony-forming unit (CFU)/kg Bacillus amyloliquefaciens+5×106 CFU/kg Saccharomyces cerevisiae (BA+SC). Growth performance, serum characteristics, carcass characteristics, and the mRNA expression of selected genes were measured. Results: This study compared several cultivars of tea, but Jinxuan showed the highest levels of the anti-obesity compound epigallocatechin gallate. 3T3-L1 preadipocytes treated with Jinxuan extract significantly reduced lipid accumulation. There were no significant differences in growth performance, serum characteristics, or carcass characteristics among the groups. However, in the 0.5% JBP group, mRNA expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were significantly decreased. In the 1% JBP group, FAS, ACC and peroxisome proliferator-activated receptor γ levels were significantly decreased. Moreover, inflammation-related mRNA expression levels were decreased by the addition of JBP. Conclusion: JBP contained abundant catechins and related bioactive compounds, which reduced lipid accumulation in 3T3-L1 preadipocytes, however there was no significant reduction in abdominal fat. This may be due to a lack of active anti-obesity compounds or because the major changes in fat metabolism were not in the abdomen. Nonetheless, lipogenesis-related and inflammation-related mRNA expression were reduced in the 1% JBP group. In addition, dietary supplementation with tea byproducts could reduce the massive amount of byproducts created during tea production and modulate lipid metabolism and the inflammatory response in chickens.