• Title/Summary/Keyword: Hepatic

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Hypofractionated Radiotherapy for Small-sized Hepatocellular Carcinoma as Salvage Therapy: Sustained Local Control and Safety (작은 크기의 재발성 간세포암에 대한 구제치료로 소분할 방사선치료: 국소 제어율과 안전성)

  • Bae, Sun-Hyun;Park, Hee-Chul;Lim, Do-Hoon;Lee, Jung-Ae;Choi, Moon-Seok;Lee, Joon-Hyoek;Koh, Kwang-Cheol;Paik, Seung-Woon;Yoo, Byung-Chul
    • Radiation Oncology Journal
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    • v.28 no.2
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    • pp.85-90
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    • 2010
  • Purpose: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Materials and Methods: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. Results: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusion: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.

Inhibition of Lipopolysaccharide-Inducible Nitric Oxide Synthase, $TNF-{\alpha}$, $IL-1{\beta}$ and COX-2 Expression by Flower and Whole Plant of Lonicera japonica (금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향)

  • Lee, Dong-Eun;Lee, Jae-Ryung;Kim, Young-Woo;Kwon, Young-Kyu;Byun, Sung-Hui;Shin, Sang-Woo;Suh, Seong-Il;Kwon, Taeg-Kyu;Byun, Joon-Seok;Kim, Sang-Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.2
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    • pp.481-489
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    • 2005
  • Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

A Randomized, Double-Blind, Placebo-Controlled Trial of Early Ursodeoxycholic Acid Administration for Prevention of Total Parenteral Nutrition-Induced Hepatobiliary Complications (총정맥영양법의 간담도 합병증에 대한 Ursodeoxycholic Acid 조기투여의 이중맹검 위약대조군 연구)

  • Choe, Yon-Ho;Beck, Nam-Sun;Kim, Ji-Hee;Lee, Suk-Hyang;Park, Tae-Sung
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.5 no.2
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    • pp.174-180
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    • 2002
  • Purpose: Ursodeoxycholic acid (UDCA) is known to decrease hepatic injury by promoting the biliary secretion of retained toxic endogenous bile acids in hepatobiliary diseases complicated by total parenteral nutrition (TPN). However, most studies have focused on treatment for complications after TPN. We investigated the preventive role of early administration of UDCA in TPN-induced hepatobiliary complications by a randomized, double-blind, placebo-controlled trial. Methods: Between May 2000 and May 2002, thirteen patients, who were given TPN more than 10 days in the hospital, were assigned randomly to two groups. One was the case group (7 patients) who were given UDCA simultaneously with TPN regimen, and the other, the control group (6 patients) who were given placebo. Their age ranged from 1 day to 13 years. They were affected with diseases impossible for enteral nutrition, such as prematurity, cerebral palsy, chronic diarrhea, anorexia nervosa, pancreatitis, and cyclic vomiting. The duration of TPN ranged from 10 to 70 days. Hematologic parameters including liver function test were measured at regular intervals, and the duration, composition, administration rate, total calorie of TPN were recorded. The serum levels of total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase were compared between groups after cessation of the study. Results: The autoregressive coefficient of the control group was 0.4419 (p=0.0651) in bilirubin, -0.0431 (p=0.7923) in AST, 0.2398 (p=0.2416) in ALT, and 0.2459 (p=0.1922) in alkaline phosphatase by mixed procedure model when the parameters were referred to the case group. Conclusion: The serum level of total bilirubin did not increase in comparison with that of the control group, but statistically insignificant, when both TPN and UDCA were administered simultaneously from the beginning.

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AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III

  • Ko, Jung-Min;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.4 no.1
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    • pp.72-79
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    • 2007
  • Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.

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Effects of Pinacidil, a Potassium-Channel Opener, on Biodistribution of Thallium-201 in Tumor-Bearing Mice ($K^+$ 통로개방제 Pinacidil이 종양이식 생쥐에서 Tl-201의 체내분포에 미치는 영향)

  • Lee, Jae-Tae;Chun, Kyung-Ah;Lee, Sang-Woo;Kang, Do-Young;Ahn, Byeong-Cheol;Jun, Soo-Han;Lee, Kyu-Bo;Ha, Jeoung-Hee
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.4
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    • pp.303-311
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    • 2000
  • Purpose: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive $K^+$-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. Materials and Methods: Baltic mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. $100{\mu}g$ of pinacidil dissolved in $200{\mu}l$ DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq ($5{\mu}Ci$) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. Results: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice ($58{\pm}4%$ ), than in the control group ($67{\pm}3%$) at 24 hours after with injection of $100{\mu}g$ pinacidil. Conclusion: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.

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Synthesis of trans-(3R,5S)-Atorvastatin Ca and Curative Effect on Hyperlipidemia Induced by a High-Fat Diet in Rats (trans-(3R,5S)-Atorvastatin Ca의 합성 및 Rat에서 고지방식이로 유도된 고지혈증 치료효과)

  • Choi, Won-Sik;Nam, Seok-Woo;Lee, Gyung-Rak
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.11
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    • pp.4940-4950
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    • 2011
  • cis-(3R,5R)-Atorvastatin Ca (1) used for hyperlipidemia have four stereomers. However, It is very difficult to prepare stereoselective stereomers. In this paper, the reduction of 3,5-diketo atorvastatin ester (3) was performed using $Me_4NHB(OAc)_3$ in acetic acid as a reductant and showed excellent stereoselectivity in the double reduction of 3,5-diketo atorvastatin ester (3). As a result, reduction of compound 3 by $Me_4NHB(OAc)_3$ was purely obtained with cis-(3R,5R)-atorvastatin ester (4) of 1.5% and trans-(3R,5S)-atorvastatin ester (5) of 98.5%. Also, cis-(3R,5R)-atorvastatin Ca (1) and trans-(3R,5S)-atorvastatin Ca (7) were used to determine efficacy in the treatment of liver damage and hyperlipidemia induced by a high-fat diet in rats and to study the performance of the January 2010 experient was conducted. As a result, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels of compound 1 and 7 groups were $93.0{\pm}0.5$, $43.5{\pm}0.8$, $40.4{\pm}1.4$, $45.6{\pm}0.9\;mg/d{\ell}$ and $110.0{\pm}0.7$, $33.3{\pm}0.6$, $65.8{\pm}1.9$, $54.8{\pm}1.2\;mg/d{\ell}$, respectively. Atherogenic index (AI) and cardiac risk factor (CRF) in compound 1 and 7 were $1.14{\pm}0.05$, $2.14{\pm}0.05$ and $2.31{\pm}0.06$, $3.31{\pm}0.06$, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were $51.9{\pm}4.6$, $16.0{\pm}2.1\;IU/{\ell}$ and $75.8{\pm}4.4$, $35.1{\pm}9.7\;IU/{\ell}$. Taken together, while compound 1 treat against high-fat diet-induced hyperlipidemia by attenuating hepatic lipid depots and reducing oxidative stress, compound 7 group had a low curative effect on hyperlipidemia induced by a high-fat diet in rats. These findings suggest that new method about synthesis of stereoselective stereomers and indicate that it may consider using in a clinical trial.

Effects of Lespedeza Caneata ethanol extract on the liver of alcohol administered Mice (야관문(Lespedeza Caneata) Ethanol 추출물이 알코올 투여한 생쥐의 간장에 미치는 영향)

  • Cheong, Min-Ju;Chung, Kyoung-A
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.10
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    • pp.432-438
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    • 2016
  • This study was conducted to investigate the effects of Lespedeza caneata extract on the livers of alcohol-administered mice. The study subjects were divided into a control (Con), alcohol administration (AL), alcohol and Lespedeza Caneata extract 200 mg/kg administration (AL-LC 200), and alcohol and Lespedeza caneata extract400 mg/kg administration (AL-LC 400) group. Distilled water was administrated orally to control and alcohol groups for ten days, while Lespedeza caneata extract was administered orally to alcohol and Lespedeza caneata extract groups for ten days. All experimental groups were fasted for twelve hours seven days after the oral administration, after which distilled water was administered orally to Con five times at twelve-hour intervals. At the same time, 50% ethanol (MERCK, USA) at 10 g/kg concentration was administered orally to AL and AL-LC groups five times at 12-hour intervals. The AST, ALT enzyme activation in blood and histology of the liver were then evaluated. AST and ALT in AL-LC groups were lower than in the AL group. Particularly, the AL-LC 200 and AL-LC 400 groups had significantly lower AST activation than the AL group. Histological results showed that most of the subjects in the AL group had necrosis and deformation in their livers, while fat droplets were accumulated in hepatic cells around the central vein. AL-LC 200 group revealed that a portion of the central vein was swollen, liver cells were expanded, and small fat droplets were accumulated. In the AL-CL 400 group, the central vein was normal and small fat droplets were accumulated in some liver cells. However, most of the liver cells appeared normal in the AL-CL 400 group. These results suggest that the extracts of Lespedeza caneata prevented alcohol induced liver damage in mice and have great potential for use as natural health products.

Antioxidative and Antimutagenic Effects of Korean Buckwheat, Sorghum, Millet and Job기s Tears (한국산 메밀, 수수, 기장, 율무의 항산화효과 및 돌연변이억제효과)

  • 곽충실;임수진;김성애;박상철;이미숙
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.6
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    • pp.921-929
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    • 2004
  • Dietary intake of whole grains, vegetable and fruit is known to reduce the degenerative chronic diseases, such as cancer and cardiovascular diseases. Antioxidative and antimutagenic effects of the ethanol extract of Korean Millet, Buckwheat, Sorghum and Job's tears were examined by inhibition against iron-induced linoleate per-oxidation, DPPH (1,l-diphenyl-2-picrylhydrazyl) radical generation and MDA-BSA (malondialdehyde-bovine serum albumin) conjugation, and Ames test using Salmonella. Buckwheat showed the strongest antioxidative effect in three different systems among these four grains, but it showed the lowest antimutagenic effect. Sorghum was the second to Buckwheat in iron-induced linoleate peroxidation inhibition activity and DPPH radical scavenging activity, and showed very good direct-antimutagenic effect in 2-Nitrofluorene treated Salmonella Typhimurium TA98 and indirect-antimutagenic effect in 2-Anthramine treated Salmonella Typhimurium TA98 and TA100 with hepatic S9 mixture. Millet showed the strongest antimutagenic effect in Salmonella Typhimurium TA98 and TA 100 with or without S9. Buckwheat contained the highest total flavonoids and polyphenols, 1.14 mg/g and 3.71 mg/g, respectively. Total flavonoid content in these four grains was negatively correlated with $IC_{50}$/ for DPPH radical scavenging antioxidative effect significantly (r=-0.9924, p=0.0076), but not with antimutagenic effect.

Effects of Flower of Pueraria lobata on Lipid Peroxidation and Activities of Alcohol Metabolic Enzymes in Alcohol-treated Rats (갈화가 에탄올을 투여한 흰쥐의 지질과산화와 알코올 대사효소의 활성도에 미치는 영향)

  • 이정숙;김나영;이경희;김갑순;박희준;최종원;김석화
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.5
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    • pp.935-942
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    • 2000
  • This study was designed to investigate the effect of flower of Pueraria lobata on liped peroxidation and activities of alcohol metabolic enzymes in alcohol-treated rats. Male Spra gue-Dawley rats were given 25% ethanol (Alcohol), 25% ethanol and 5 mg tectorigenin/kg B.W.(Alc.-Tec), 25% ethanol and 5mg kaikasaponin III/kg B.W. (Alc-Kai). The contents of serum total lipid, triglyceride and phospholipid were increased by ethanol treatment and were lower in the Alc.-Tec and Alc.-Kai group than in the Alcohol group. Decreased serum HDL-cholesterol by alcohol treatment was recovered by tectorigenin and kaikasaponin III. Microsomal cytochrome P-450, aniline hydroxylase and aminopyrine N-demethylase activities were increased by ethanol and were lower in the Alc. Tec and Alc.-Kai group than in the Alcohol group. Activity of hepatic alcohol dehydrogenase was increased by ethanol and was higher in the Alc.-Tec and Alc.-Kai group than in the Alcohol group. Microsomal ethanol oxidizing system activity was higher in Alc.-Tec group than in the other group. No significant difference was found in catalase activity among treatment groups. These data indicate that tectorigenin and kaikasaponin III were effected alcohol metabolic enzyme system and the liver damage associated with chronic ethanol consumption.

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Effect of Pimpinella brachycarpa Extract on Lipid Metabolism in Rats Fed High Cholesterol Diet (참나물이 고콜레스테롤식이를 섭취한 흰쥐의 지질대사에 미치는 영향)

  • Lee, Jae-Joon;Choo, Myung-Hee;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.9
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    • pp.1151-1158
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    • 2006
  • This study was performed to investigate the effect of ethanol extract of Pimpinella brachycarpa (PB) on serum and liver lipid metabolism in rats. Male Sprague Dawley rats were administered 1% cholesterol and 0.25% sodium cholate to induce hypercholesterolemia. PB ethanol extract (200 mg/kg/day or 400 mg/kg/day) was also administered orally to rats with high cholesterol diet for 6 weeks. We divided 40 rats into five groups; normal diet group (NC), high cholesterol diet group (HC), normal diet and PB ethanol extract (200 mg/kg) administered group (NC-PB), high cholesterol diet and PB ethanol extract (200 mg/kg) administered group (HC-PBL), and high cholesterol diet and PB ethanol extract (400 mg/kg) administered group (HC-PBH). The growth rate and liver weight of the high cholesterol diet group was higher than those of the normal diet group, whereas those of the groups administered PB ethanol extract were gradually decreased. There was a signigicant increase in the activities of serum alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in the high cholesterol diet group. The administration of PB ethanol extract decreased serum ALT, AST and ALP activities in a dose-dependent manners. The high cholesterol diet group showed increased serum triglyceride, total cholesterol, free cholesterol and LDL-cholesterol levels, and decreased atherogenic index, HDL-cholesterol and phospholipid levels as compared with the normal diet group. PB ethanol extract administrated groups showed increased HDL-C/T-C, HDL-cholesterol and phospholipid levels, and decreased serum triglyceride, total cholesterol, free cholesterol, and LDL-cholesterol levels as compared with the high cholesterol diet group. There were no differences in the concentrations of serum triglyceride, phopholipid, LDL-cholesterol, HDL-cholesterol and free cholesterol between normal diet groups. The hepatic concentrations of total cholesterol and triglyceride were also lower in PB ethanol extract administrated groups than in the high cholesterol diet group. These results suggest that ethanol extract of PB exerts hypocholesterolemic effect by reducing serum and liver cholesterol contents.