• Proceedings of the PSK Conference
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• 2002.10a
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• pp.253.1-253.1
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• 2002

DA-8159 is a new PDEV inhibitor, synthesized by Dong-A Pharm, as an oral agent to treat male erectile dysfunction. DA-8159 and sildenafil are mainly metabolized by cytochrome P450 enzyme CYP 3A4. In this study. we compared the metabolism of DA-8159 with sildenafil in vitro and in vivo. First, we quantified the remaining gatio of original compound, DA-8159 and sidenafil., after we incubated drugs for 30 minutes with human liver microsome cytochrome P 450 3A4. (omitted)

• Journal of Korean Medicine for Obesity Research
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• v.22 no.1
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• pp.77-85
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• 2022

While the Coronavirus disease 2019 (COVID-19) pandemic is gradually turning into an endemic disease, concerns about post COVID-19 conditions (Long COVID) are emerging. Obesity is a major risk factor for severe complications of COVID-19, and COVID-19 has a wide range of effects on obesity and metabolic function. This paper aims to examine the interaction between COVID-19 and obesity, the effects and mechanisms of long COVID on obesity, and the role of Korean medicine on long COVID-related obesity. Obesity may worsen with cardiometabolic damage and psychosocial insecurity during COVID-19 and long COVID-induced neuroinflammation, systemic inflammation, mitochondrial dysfunction, and hypoxia also may aggravate obesity. Korean Medicine treatments, which have been widely used to treat obesity, have the potential to improve obesity in the era of long COVID by intervening in these mechanisms.

• The Journal of Korean Medicine
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• v.44 no.4
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• pp.163-169
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• 2023

Methods: This study presents a comprehensive case study of an elderly male diagnosed with acute kidney injury (AKI) resulting from severe dehydration, supported by an extended follow-up with laboratory findings. Results: An 83-year-old male patient experienced severe diarrhea overnight, leading to hospitalization due to symptoms of dehydration and hypotension. His laboratory results displayed a typical AKI pattern, including a significant increase in creatinine levels (5.19 mg/dL) and the presence of hyperkalemia and hyponatremia. Following general treatments, including the administration of an herbal drug (Bulhwangeumjeonggi-san), the estimated glomerular filtration rate (eGFR) improved from 10 ml/min (Stage 5) to 34 ml/min (Stage 3) within five days when he was discharged. Although subsequent eGFR tests, conducted one and two months later as an outpatient, revealed an improvement of 42 ml/min, the patient still experienced mild chronic dysfunction as a consequence. Conclusion: This study presents a noteworthy case of acute kidney injury attributed to severe dehydration, emphasizing the importance of medical awareness regarding diarrhea-induced kidney function impairment, especially in the elderly population.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.392-402
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• 2017

Background: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. Methods: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides. $H_2O_2$ productions, glutathione contents, lactate dehydrogenase activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations, caspase-3/-7 activities, transferase dUTP nick end labeling (TUNEL) staining, and immunoblot analysis were performed to elucidate the molecular mechanism responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP-activated protein kinase (AMPK)-related signaling pathway was examined using a chemical inhibitor and small interfering RNA (siRNA) transfection. Results and conclusion: Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-$\text\tiny L$-cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased the phosphorylation of AMPK, and compound C prevented 20S-PPD-induced cytotoxicity and mitochondrial dysfunction. Moreover, 20S-PPD increased the phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise, transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20S-PPD. Thus, 20S-PPD appears to induce HSC apoptosis by activating LKB1-AMPK and to be a therapeutic candidate for the prevention or treatment of liver fibrosis.

• Korean Journal of Clinical Pharmacy
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• v.31 no.1
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• pp.44-52
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• 2021

Background: Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. Methods: Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. Results: Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. Conclusions: In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.

• Herbal Formula Science
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• v.31 no.4
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• pp.265-281
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• 2023

Objectives : Ukgan-san plus Citri Pericarpium and Pinelliae Rhizoma (UCP) is used as a traditional herbal formula in Korea and Japan for treatment of fever, fever-induced convulsions, and liver dysfunction and so on. In this study, we investigated the cytoprotective effect and underlying mechanism of UCP against oxidative stress induced by cotreatment of arachidonic acid (AA) and iron. Methods : To evaluate the hepatoprotective effects of UCP against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The changes in intracellular reactive oxygen species (ROS), glutathione (GSH), and mitochondrial membrane permeability (MMP) were investigated against to the oxidative stress. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) and its downstream target genes were examined by immunoblot analysis. Results : Treatment of UCP increased the cell viability and altered the expression levels of apoptosis-related proteins such as PARP, caspase-9, caspase-3, Bcl-2. UCP also inhibited the GSH depletion, excessive ROS production and mitochondrial dysfunction induced by AA + iron. In addition, the Nrf2 and the Nrf2 target genes activation were increased by UCP. Conclusions : These results indicated that UCP has the ability to protect against oxidative stress-induced hepatocyte damage, which may be mediated with Nrf2 pathway.

• Journal of Life Science
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• v.19 no.8
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• pp.1152-1158
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• 2009

For the toxicological pathologic study of amanita muscaria, we have investigated single and repeated dose toxicity in Sprague-Dawley (SD) rats. Single dose toxicity study was identified as catalepsy, incline and tail pinch methods (control 0 mg/kg, low 3.3 mg/kg, middle 16.5 mg/kg, high 33.0 mg/kg). Repeated dose toxicity study was carried out in blood tests, serum tests and histopathological methods. Neurotoxicity - muscle paralysis, and convulsion and loss of movement - was observed at 33.0 mg/kg group in the single dose toxicity study. Dysfunction of liver and kidney were shown in the repeated oral administration of the amanita muscaria at 3${\sim}$4 weeks. Serum chemistry results revealed a marked increase of LDH [Lactate Dehydrogenase (3181.5 IU/L; normal 230-460 IU/l)], ALT [Alanine transaminase (124.0 IU/l; normal <40 IU/l)] but the kidney was normal. Histopathological results show interstitial edema and tubular epithelial necrosis in the kidney. These results suggest that amanita muscaria has a neurotoxic effect and causes dysfunction of liver and kidney in the SD rat.

• Nutritional Sciences
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• v.5 no.4
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• pp.234-244
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• 2002

This study was conducted to compare the rates of hyperlipidemia, hypertension, high blood glucose, and liver dysfunction, between 64 obese children (24 boys and 11 girls who were moderately obese, and 21 boys and 8 girls who were severely obese) and 45 normal weight children (31 boys and 14 girls) from 13 elementary schools in Kangnung city. Among the boys with severe obesity, the levels of serum triglycerides and LDL-cholesterol (133.60 $\pm$ 49.99 mg/dl and 105.00 $\pm$ 41.12 mg/dl( respectively) were significantly higher compared to the normal Weight group (81.16 $\pm$ 23.59 mg/dl and 87.74 $\pm$ 32.095 mg/dl, respectively) of moderately obese group (102.30 $\pm$ 36.03 mg/dl, 89.99 $\pm$ 32.10 mg/이, respectively). In girls, only serum triglycerides were significantly higher in the severely obese group (154.30 $\pm$ 46.84 mg/dl), compared with the normal weight group (80.00 $\pm$ 25.31 mg/dl) or moderately obese group (106.40 $\pm$ 41.73 mg/dl). In boys, blood pressure in the severely obese group (systolic: 120.5 $\pm$ 9.74 mmHg; diastolic: 80.95 $\pm$ 10.44 mmHg) was significantly higher compared with the groups of normal weight or moderately obese children. The rate of hypertriglyceridemia was significantly different among normal weight, moderately obese, and severely obese boys (9.7%, 41.7%, and 76.2%, respectively). The proportion of boys who had an Atherogenic Index(AI) higher than 3 was found to be significantly higher in the severely obese group (28.6%), compared to 6.5% in the normal weight group and 4.1% in the moderately obese group. Among boys, a significantly higher rate of hypertension was found in the severely obese group, which showed high systolic blood pressure and high diastolic pressure (81.0% and 81.0%), compared with the normal weight group (16.1% and 22.6%) and moderately obese group (33.3% and 33.3%). In conclusion, the diagnosis and management of obese children needs to be tailored to gender and the degree of obesity. Furthermore, a systematic management program needs to be developed for early screening and detection of obesity in order to minimize the risk of hyperlipidemia and hypertension, especially in severely obese children.

• Gut and Liver
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• v.12 no.6
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• pp.682-693
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• 2018

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.589-603
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• 2022

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.