• 동의생리병리학회지
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• 제18권3호
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• pp.868-873
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• 2004

Renal dysfunction could be developed as the secondary disease of liver cirrhosis. Delayed or suppresed lipid peroxidation by the treatment with physiological active substances could be explained as the antioxidative and protective effect in tissue damage. In this study, we investigated an antioxidative effect and renal function improvement of Hovenia dulcis in liver fibrosis(cirrhosis) induced rats. The female Sprague-Dawley rats (180∼210 g) were divided into 3 groups (Normal, AC: CCl₄ mixture treated group, AC-HV: CCl₄ mixture+ Hovenia dulcis treated group) and renal damage was developed by CCl₄ mixture administration in 4 weeks (0.8 ㎖/rat). The tissue of kidney and liver and sera were used for quantitative measurement of enzyme activity, MDA and Hyp. The histological change and gene expression of collagen α1(III) mRNA and a1(IV) mRNA were observed by Masson's trichrome staining and RT-PCR. As a result, the clinical biochemical parameters of liver function (AST and ALT) in sera of AC-HV group showed significantly 46.4% and 104.8% lower (p<0.005), and the level of ALP and BUN as the parameter of protein urine and azotemia showed 17.8 % and 25.8 % lower than in AC group. In AC-HV group, the concentration of MDA in kidney and liver was decreased significantly 15.8% and 21.3% when compared with AC group (p<0.01 -0.005). The content of Hyp in kidney of AC-HV group is merely higher than in AC group, in contrast to liver tissue. The expression of collagen α1(III) mRNA and collagen α1(IV) mRNA was decreased in AC, but both of collagen mRNA in normal and AC-HV group expressed fast similar. More massive lipid droplets, thicker collagen fiber bundles in portal triads and more formation of portal central septum were observed in the liver of AC group than in AC-HV group. In conclusion, CCl₄ mixture intoxication could be developed not only liver fibrosis(cirrhosis) but also renal dysfunction by the massive lipid peroxidation and suppression of interstitial collagen and basement membrane collagen synthesis. And the water extract of Hovenia dulcis may be possessed the antioxidative and protective effect and improvement of kidney function in renal dysfunction induced rats.

• 한국임상수의학회지
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• 제28권1호
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• pp.20-27
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• 2011

Hovenia dulcis Thunb (HDT) has been known folk medicine and has been used as therapeutic drug in the treatment of liver disease. Also it has been used as a detoxifying agents for alcoholic poisoning and promoting diuresis. However, there has not been any study on therapeutic effect of Hovenia dulcis extract on $CCl_4$ induced liver and kidney damage in rats. In this study, we report on therapeutic effects of Hovenia dulcis extract on $CCl_4$ induced liver and kidney damage in rats. Rats were divided into four groups of eighteen animals. Control group (DW) was administrated with distilled water 2.5 mL/kg per peritonial administration and then $CCl_4$ group (CCl) was administrated $CCl_4$ 2.5 mL/kg per peritonial administration, $CCl_4$+HDT extract group ($CCl_4$+HDT) was administrated HDT extrat (100 mg/kg) after $CCl_4$ 2.5 mL/kg administration, $CCl_4$+Silymarin group ($CCl_4$+Sily) was administrated Silymarin (50 mg/kg) after $CCl_4$ 2.5 mL/kg administration. The complete blood cell (CBC) count of RBC, WBC, PCV, Hb, MCH, MCV, MCHC and blood chemistry profile of AST, ALT, GGT, ALP, Total choloesterol, Tryglyceride, Total bilirubin, Amylase, Glucose, BUN, Creatinine, Lipase and pathologic changes were observed for 7 days after administration of D.W., $CCl_4$, $CCl_4$+HDT extract, $CCl_4$+Silymarin. The results are as follows : 1. RBC and PCV were significantly (p < 0.01) increased in all groups compared to D.W. but hemoglobin, MCH, MCV and MCHC were not showed significant difference during experimental periods. 2. AST, ALT, T-cholesterol, T-bilirubin, TG were significantly (p < 0.05) increased in all groups on day 3 compared to D.W. and were normal on day 7. 3. ALP was significantly (p < 0.05) decreased in $CCl_4$+HDT group on day 3 but Amylase was not showed significant difference during experimental periods. 4. BUN was significantly (p < 0.05) increased in $CCl_4$ group on day 7, but $CCl_4$+HDT group and $CCl_4$+Sily group were normal. Creatninie was significantly (p < 0.05) increased in $CCl_4$ group on day 3 and normal on day 7 but $CCl_4$+HDT group and $CCl_4$+Sily group were not showed significant difference during experimental periods.

• Archives of Pharmacal Research
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• 제26권6호
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• pp.499-503
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• 2003

Because physiological changes that potentially alter pharmacokinetics occurs in diabetes mellitus patients, pharamacokinetics of drugs used in the treatment of hypertension was studied using acebutolol as a model anti-hypertensive drug. Thus, the pharmacokinetics of acebutolol was investigated after oral administration of acebutolol (15 mg/kg) to control rabbits and rabbits with acute or chronic diabetes mellitus induced by alloxan. Kidney and liver functions were documented for acute and chronic diabetes mellitus groups based on plasma chemistry data. After oral administration of acebutolol to acute and chronic groups, the plasma concentrations appeared higher; As a result, area under the plasma concentration-time curve from time zero to time infinity10575 and 8668 $\mu g\cdot$ h/mL for acute and chronic group, respectively. In comparison, the area was apparently smaller in the control group (i.e., 7132 $\mu g\cdot$ h/mL). The half-life in acute groups was significantly prolonged 8.45 h compared with the half-life in the control group (i.e., 6.30 h). Alteration in acebutolol pharmacokinetics was more pronounced in the acute group as evidenced by the significantly higher values the area under the plasma concentration time curve, absorption rate constant and maximum plasma concentration compared with chronic or control group. Therefore, these observations indicate that acebutolol pharmacokinetics may be affected in patients with diabetes mellitus, especially in the early stage of the disease.

• 한방비만학회지
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• 제20권1호
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• pp.31-39
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• 2020

Objectives: Obesity is becoming more popular disease worldwide. Because of the side effects of conventional obesity treatment modality, herbal medicine treatment is becoming more preferred. Gambihwan which including Ephedra sinica Staph is widely used in traditional Korean Medicine practice for obesity treatment. Garcinia cambogia is a kind of health functional food that has body fat reducing effect. Nowadays, ephedra and Garcinia cambogia are often used simultaneously in clinical practice of Korean Medicine. However, the effectiveness and safety of combination therapy in obesity treatment is not well established. Methods: We conducted retrospective observational study to explore effectiveness and safety of combination therapy. We evaluated effect of combined treatment of Gambihwan and Garcinia cambogia on body weight, body mass index, body fat mass, and waist hip ratio reduction. We also assessed safety via liver function test and adverse event. Results: Finally, 23 patients were included. In paired t-test, body weight significantly decreased from 64.50±14.50 kg to 62.94±13.85 kg (P<0.001) and body mass index were also significantly decreased from 24.43±3.79 kg/㎡ to 23.83±3.59 kg/㎡ (P<0.001). Body fat mass was also reduced. Aspartate transaminase and alanine aminotransferase were not significantly increased. There were no drug-induced liver injury and no severe adverse event. Conclusions: In our retrospective review, we found combination therapy of Gambihwan and Garcinia cambogia reduce body weight, body mass index and body fat mass. There were no severe adverse event and drug induced liver injury which indicated safety of combination therapy in obesity treatment.

• 대한임상검사과학회지
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• 제47권4호
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• pp.251-258
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• 2015

커큐민(curcumin)은 강황 내 주요 폴리페놀 화합물의 한 성분으로 비만과 관련된 비알코올성 지방간염을 막아 주는 것으로 잘 알려져 있다. 이 연구의 목적은 고지방 식이로 키운 비만 마우스에서 사염화탄소($CCl_4$)로 유발한 간섬유증에 미치는 커큐민의 보호효과를 조사하기 위해 시도하였다. 군간 비교를 위해, 정상 식이와 고지방 식이로 키운 마우스에 7주간 $CCl_4$를 투여하면서 동시에 커큐민을 투여한 것과 투여하지 않은 군으로 나누었으며, 체중이나 혈당과 같은 대사 프로파일이나 지방세포의 크기 및 간섬유증의 변화를 조사하기 위해 혈청 생화학적 검사, 조직학적 검사 및 면역조직화학적 검사를 수행하였다. 또한 간세포 내자멸세포의 관찰을 위해 TUNEL 법을 사용하였다. 그 결과 고지방식이+$CCl_4$ 마우스에 커큐민을 투여한 군에서는 투여하지 않은 군에 비해 체중, 공복혈당 수치, 혈청 AST, ALT 수치가 낮았고, 지방조직 내의 지방세포 크기와 대식세포 및 비만세포 수가 감소하였다. 이와 반대로 정상식이+$CCl_4$ 마우스에 커큐민을 투여한 경우에는 투여하지 않은 군에 비해 체중과 비만세포 수 이외에는 통계학적인 차이가 없었다. 더욱이 커큐민은 간조직의 간실질세포의 자멸세포 수는 줄인 반면 활성 간성상세포 모양의 비실질세포의 자멸세포 수를 증가시켰다. 이 결과를 종합해 볼 때 커큐민은 비만 마우스의 간질환 진행에서 효과적인 항섬유 치료제로서 사용할 수 있을 것으로 사료된다.

• 대한한방내과학회지
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• 제32권2호
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• pp.170-187
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• 2011

Background : Obesity, the syndrome caused by a high fat diet, is a disease. At the same time, obesity causes diabetes mellitus, hyperlipidemia, and cardiovascular disease. Recently, its prevalence rate is increasing. Yagwan-cheunghyeoltang (YCT) used in this experiment is the prescription of Yagwanmoon added to Cheunghyeol-tang which is reported to be very effective in weight loss controlling and serum cholesterol. It is also reported that Yagwanmoon has significant antioxidant effects and YCT has a significant effect on blood glucose control. Objectives : This study was conducted to experimentally evaluate the effects of YCT on obesity in rats induced by high fat diet. Methods : The experiment was conducted with 4-week-old male rat s divided into 5 groups. They were a normal diet group, a high fat diet group, a positive drug control group, a 1% YCT group, and a YCT 3% group, and were tested for eight weeks. After four weeks of inducing obesity by a high fat diet, rats were allowed to lose weight by following the normal diet group, approximately 30% compared with 10 rats in each group were determined as still obese. Changes in body weight and organ weight and serum cholesterol, triglyceride, glucose-density, low density lipoprotein cholesterol, antioxidant activity were checked. Results : In the experimental groups, we observed weight loss and visceral fat reduction, improvement of liver function, reduction of serum glucose, activation of HMG-CoA reductase inhibitor, reduction of concentrations of leptin and it showed a significant effect on antioxidants and lipid peroxidation. Conclusions : YCT has significant effects on the regulation of hyperlipidemia and lipid peroxidation associated with obesity and has significant effects on, antioxidants and lipid peroxidation, too. Additional clinical studies are needed.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제17권2호
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• pp.98-103
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• 2014

Purpose: Gallbladder (GB) wall thickening can be found in various conditions unrelated to intrinsic GB disease. We investigated the predisposing etiologies and the outcome of acalculous GB wall thickening in children. Methods: We retrospectively analyzed 67 children with acalculous GB wall thickening who had visited our institute from June 2010 to June 2013. GB wall thickening was defined as a GB wall diameter > 3.5 mm on abdominal ultrasound examination or computed tomography. Underlying diseases associated with GB wall thickening, treatment, and outcomes were studied. Results: There were 36 boys and 31 girls (mean age, $8.5{\pm}4.8years$ [range, 7 months-16 years]). Systemic infection in 24 patients (35.8%), acute hepatitis in 18 (26.9%), systemic disease in 11 (16.4%), hemophagocytic lymphohistiocytosis in 4 (6.0%), acute pancreatitis in 3 (4.5%), and specific liver disease in 3 (4.5%) predisposed patients to GB wall thickening. Systemic infections were caused by bacteria in 10 patients (41.7%), viruses in 5 patients (20.8%), and fungi in 2 patients (8.3%). Systemic diseases observed were systemic lupus erythematosus in 2, drug-induced hypersensitivity in 2, congestive heart failure in 2, renal disorder in 2. Sixty-one patients (91.0%) received symptomatic treatments or treatment for underlying diseases. Five patients (7.5%) died from underlying diseases. Cholecystectomy was performed in 3 patients during treatment of the underlying disease. Conclusion: A wide range of extracholecystic conditions cause diffuse GB wall thickening that resolves spontaneously or with treatment of underlying diseases. Surgical treatments should be avoided if there are no definite clinical manifestations of cholecystitis.

• Archives of Pharmacal Research
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• 제20권4호
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• pp.318-323
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• 1997

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethyinitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life $(t_{1/2})$ in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL $(8.67{\pm}4.85%)$ decreased about four-folds, but in DMNA $(73.00{\pm}9.85%)$ similar result war observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.

• 대한한방내과학회지
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• 제44권6호
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• pp.1243-1255
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• 2023

Objective: This study aims to explore the pharmacological effects and mechanisms of enzyme (Viscozyme)-treated garlic extract (EG) in an animal model of acute enteritis induced by lipopolysaccharide (LPS). Methods: The experiment included four subgroups: normal, control, EG200 (treated with 200 mg/kg EG), and EG400 (treated with 400 mg/kg EG). Drug administration lasted 3 days, followed by the induction of acute enteritis in all groups (except normal) through the intraperitoneal administration of 20 mg/kg of LPS 1 h after the last oral dose. Autopsy was conducted 24 h later to collect serum and colon tissue. Serum was analyzed for reactive oxygen species (ROS) and C-reactive protein (CRP), while Western blotting was performed on the colon tissue. Results: After analyzing the ROS and CRP levels in serum, the EG treatment group exhibited a significant decrease compared with the control group. The EG treatment group exhibited a significant decrease in the activation of the mitogen-activated protein kinases (MAPKs)/nuclear factor-kappa B p65 (NF-κB) pathway compared with the control group. EG administration significantly regulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X, cysteine aspartyl-specific protease-3, and cytochrome C. Conclusions: EG treatment in mice with LPS-induced acute colitis reduced the ROS and CRP levels, suppressed the MAPKs/NF-κB pathway in the colon, and effectively alleviated acute enteritis by modulating apoptosis-related factors. Based on these findings, EG emerges as a promising candidate for the prevention and treatment of acute colitis, showing its potential therapeutic efficacy in this experimental model.

• 한국한의학연구원논문집
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• 제8권2호통권9호
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• pp.95-107
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• 2002

Yukmijihwang-tang(YM) is a noted herbal prescription in Chinese and Korean traditional medicines, and it has been known to reinforce the vital essence and has been widely used for a variety of disease such as stroke, osteoporosis, anti-tumor, and hypothyrodism. Regarding its traditional use, YM has been known to reinforce the Yin (vital essence) of liver and kidney. Also it has been known to reinforce nutrition and biological function in brain. Recently, studies suggested that YM increase antioxidant activities and exert the protective effect against oxidant-induced liver cell injury. We investigated the high-throughput gene expression analysis on the Yukmijihwang-tang administrated in SD rats. Microarray data were validated on a limited number of genes by semiquantitative RT-PCR and Western blot analyses. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes in drug discovery This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with herbal medicine. Total RNA from normal control brain and Yukmijihwang-tang administrated brain were hybridized to microarrays containing 10,000 rat genes. The 52 genes were found to be up-regulated(twice or more) excluding EST gene. The nine genes were found to be down-regulated(twice or more) excluding EST gene. Gene array technology was used to identify for the first time many genes expression pathway analysis that arecell cycle pathway, apoptosis pathway, electron transport chain pathway, cytoplasmic ribosomal protein pathway, fatty acid degradation pathway, and TGF-beta signaling pathway. These differentially expressed genes pathway analysis have not previously been iavestigated in the context of herbal medicine efficacy and represent novel factors for further study of the mechanism of herbal medicine efficacy.