• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.738-742
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• 2005

This study was designed to investigate the anti-dementia effects of acorn (Quercus acutissima CARR.) in brain of the mouse. Dementia model was induced by administration of scopolamin (30 mg/kg BW) Male ICR mouse $(30{\pm}2g\;BW)$ were fed basal diet (control group), and experimental diets (AP-5 and AP-10 groups) added $5\%\;and\;10\%$ of dried acorn powder to basal diet for 8 months. Acetylcholine content significantly increase in AP-5 and AP-10 groups ($4.2\%\;and\;11.3\%$, respectively) compared with control group. Acetylcholinesterase activities were significantly inhibited ($13.5\%\;and\;17.6\%$, respectively) in brain of AP-5 and AP-10 groups. Monoamine oxidase-B (MAO-B) activities were significantly inhibited ($10.0\%\;and\;12.7\%$, respectively) in brain of AP-S and AP-10 groups. These results suggest that acorn (Q. acutissima CARR.) may play an effective role in an attenuating various age-related changes such as dementia including learning and memory impairments in brain.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.36-42
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• 2002

Diesel exhaust (DE) has been recognized as a noxious mutagen and/or carcinogen, because its components can form DNA adducts. Mechanisms governing the susceptibility to DE and the efficiency of such DNA adduct formation require clarification. The transcription factor Nrf2 is essential for inducible and/or constitutive expression of a group of detoxification and antioxidant enzymes, and we hypothesized that the nrf2 gene knockout mouse might serve as an excellent model system for analyzing DE toxicity. To address this hypothesis, lungs from nrf2(-/-) and nrf2(+/-) mice were examined for the production of xenobiotic-DNA adducts after exposure to DE (3 $mg/m^{3}$ suspended particulate matter) for 4 weeks. Whereas the relative adduct levels (RAL) were significantly increased in the lungs of both nrf2(+/-) and nrf2(-/-) mice upon exposure to DE, the increase of RAL in the lungs from nrf2(-/-) mice exposed to DE were approximately 2.3-fold higher than that of nrf2(+/-) mite exposed to DE. In contrail, cytochrome P4501Al mRNA levels in the nrf2(-/-)mouse lungs were similar to those in the nrf2(+/-) mouse lungs even after exposure to DE, suggesting that suppressed activity of phase II drug-metabolizing enzymes is important in giving ise to the increased level of DNA adducts in the Nrf2-null mutant mouse subjected to DE. Importantly, severe hyperplasia and accumulation of the oxidative DNA adduct 8-hydroxydeoxyguanosine were observed in the bronchial epidermis of nrf(-/-) mite following DE exposure. These results demonstrate the increased susceptibility of the nrf2 germ line mutant mouse to DE exposure and indicate the nrf2 gene knockout mouse nay represent a valuable model for the assessment of respiratory DE toxicity.

• The Journal of Internal Korean Medicine
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• v.41 no.3
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• pp.339-349
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• 2020

Objective: This study aimed to evaluate anti-inflammatory and antitussive expectoration effects of Friltillariae Thunbergii Bulbus (FTB) in a mouse model. Materials and Methods: To evaluate the anti-inflammatory effects of the FTB, we conducted in vitro experiments using RAW264.7 cells. An MTT assay and enzyme-linked immunosorbent assay (ELISA) were carried out to examine the anti-inflammatory effects of FTB. The expectorant effect on phenol red secretion, the antitussive effect on cough induced by ammonia solution, and leukocyte increased inhibition effects in acute airway inflammation in the animal model were confirmed. Results: FTB did not show cytotoxicity in the experimental group at 10, 30, 50, 100, 300, or 500 ㎍/ml and significantly inhibited the increase of NO, TNF-α and IL-6 in the experimental groups at 30, 50, 100, 300, and 500 ㎍/ml concentrations. In sputum, cough, and acute airway inflammation animal models, FTB significantly increased phenol red secretion in the 400 mg/kg administration group. FTB significantly reduced the number of coughs and significantly increased cough delay time in both 200 and 400 mg/kg dose groups. FTB decreased the white blood cell count in BALF (bronchoalveolar lavage fluid) in the 400 mg/kg administration group. Conclusion: Our study revealed that FTB elicits antitussive and expectorant effects by inhibiting inflammatory cytokines, increasing sputum secretion, suppressing cough, and reducing inflammatory cells. We concluded that FTB is a highly promising agent for respiratory tract infection with therapeutic opportunities.

• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.656-668
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• 2018

Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

• Journal of Applied Biological Chemistry
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• v.64 no.2
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• pp.165-170
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• 2021

In this study, the antioxidant effects of mineral-containing deep sea water (DSW) on kidney function was confirmed using a cell model. DSW samples were prepared with different mineral concentrations including calcium and magnesium-the main minerals found in DSW-to derive the following sample groups: trace minerals (TM), high magnesium (HM), high magnesium, low salt (HMLS) and high magnesium, high calcium (HMHC). The purpose of this preparation was to determine the optimal calcium/magnesium ratio in DSW. Human embryonic kidney (HEK293) cells were exposed to sodium chloride (NaCl) for 2 h to induce release of reactive oxygen species (ROS). Thereafter, the cells were treated with the respective DSW samples before ROS concentrations, as well as antioxidant enzyme activity and protein levels, were measured. Among the water samples, HMLS showed the most protective effect against ROS, whereas the intracellular glutathione content was highest in cells from the HMLS- and HMHC-treated groups. However, TM- and HMHC-treated cells showed similar tendencies to the control group, in terms of mRNA expression of antioxidant genes. These results suggested that DSW may aid in preventing renal oxidative stress caused by excessive sodium intake. Furthermore, it was determined that HMLS and HMHC water samples displayed good antioxidant effects in the kidney cell model, based on the combined results of ROS concentration and antioxidant marker measurements.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

• Journal of Preventive Medicine and Public Health
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• v.29 no.3 s.54
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• pp.669-678
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• 1996

Helicobacter pylori is now recognized as causative agent of chronic gastritis and peptic ulcer, and strongly associated with development of gastric carcinoma. With development of sensitive and specific serologic tests to identify individuals infected with Helicobacter pylori, the epidemiologic study of this diseases has been investigated. But it's transmission route is not established, yet. The purpose of this study is to measure the prevalence of Helicobacter pylori infection in healthy children and young adults and to evaluate related factors for Helicobacter pylori infection in Korea. The seroprevalence of Ig G antibodies to Helicobacter pylori was determined using a Enzyme Linked Immunosorbent Assay and we obtained the information, such as demographic characteristics, monthly household income, numbers of family members in the house, numbers of persons using same room, type of house, and type of drinking water through the questionnaire survey. The observed overall seropositivity rate was 25.7%. The rate is increased progressively from 5.8% in the age group $1\sim3$ years to 44.4% in the age group $20\sim29$years($\chi^2$ for trend, p<0.001). Especially, the rate increased steeply from 6.5% in the age group $4\sim6$ years to 20.8% in the age group $7\sim9$ years, and this suggested that elementary school age was the major acquisition time of Helicobacter pylori infection. In multivariate logistic regression model, age, numbers of family members in the house, and type of house was statistically significant variables for Helicobacter pylori infection. Each odds ratio(93% CI) were as follows; base to age group $1\sim9$ years, age group $10\sim19$ years $3.6(2.0\sim6.4)$, age group $20\sim29$ years $7.3(4.1\sim13.1)$ and base to group of $1\sim3$ family members, group of $4\sim5$ family members $2.1(1.1\sim4.0)$, group of 6 or more family members $2.7(1.3\sim5.4)$ and base to apartment, single and multihouse $1.9(1.1\sim3.5)$. Sex, monthly household income, numbers of persons using same room, and type of drinking water was not statistically significant for Helicobacter pylori infection.

• Journal of Life Science
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• v.15 no.1 s.68
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• pp.38-44
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• 2005

Infection with hepatitis B virus (HBV) is a major health problem worldwide. Although a tremendous amount has been known about HBV, there have been obstacles in the study of HBV due to the narrow host range of HBV limited to humans and primates. In the present study, we investigated the susceptibility to HBV infection of mouse hepatoma cell line, Hepa-1c1c7. In addition, based on that human hepatocytes infected by HBV increase the expression of the pro-inflammatory cytokine TNF-a, the inducibility of TNF-a expression by HBV in the cells was determined. HBV surface antigen (HBsAg) secretion was measured by the microparticle enzyme immunoassay and steady state mRNA expression was analyzed by quantitative competitive RT-PCR. Transient transfection of Hepa-1c1c7 cells with HBV expression vector resulted in a dose-dependent induction of TNF-a expression. Infection of Hepa-1c1c7 cells with the serum of HBV carrier also increased TNF-a mRNA expression. Both in the transfected and infected cells, HBV mRNA was expressed and significant HBsAg secretion was detected. There was no significant variation in $\beta-actin$ mRNA expression by HBV. These results demonstrate that HBV is infectious to Hepa-lc1c7 in vitro and the viral infection induces TNF-a expression, which suggests that Hepa-lc1c7, a mouse hepatoma cell line, may be a possible model system for analysis of various molecular aspects of HBV infection.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.144-149
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• 2009

Chondrocytes and synovial fluid derived markers are used to monitor for osteoarthritis(OA). Specific inhibitors, known as tissue inhibitors of metalloproteinases(TIMP), regulate the proteolytic activity of matrix metalloproteinases(MMP). This study investigated whether MMP and TIMP levels were altered in synovial fluid and cartilage following the experimental induction of OA in canines. Twenty mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and the medial collateral ligament as well as a medial meniscectomy. Matrix metalloproteinase-2 and MMP-9 levels were assayed using Western blot and TIMP-2 levels were measured with enzyme-linked immunosorbent assays four weeks after OA induction. Increased MMP-2 expression was observed in chondrocytes isolated from cartilage following OA induction, but MMP-9 expression decreased. Matrix metalloproteinase-2 and MMP-9 levels in synovial fluid from the OA induced joint significantly increased compared to those of the sham group. Tissue inhibitors of metalloproteinase-2 concentrations were higher in chondrocytes from the OA cartilage, yet TIMP-2 remained lower in the synovial fluid of OA. This suggests the elevated release of MMP-9 over MMP-2 into the synovial fluid following the cartilage degradation-related death of chondrocytes after OA. Osteoarthritis can be further deteriorated by increased MMP activity in the synovial fluid because TIMP-2 exist low concentration into the extracellular matrix. As a result, MMP activity, particularly MMP-9 activity, can be useful as a biomarker in diagnosing and monitoring the early stages of canine OA.