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Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies
원해단,김정태,김성훈,정성현 고려인삼학회 2012 Journal of Ginseng Research Vol.36 No.1
Panax ginseng exhibits pleiotropic benefi cial effects on cardiovascular system, central nervous system, and immune system. In the last decade, numerous preclinical fi ndings suggest ginseng as a promising therapeutic agent for diabetes prevention and treatment. The mechanism of ginseng and its active components is complex and is demonstrated to either modulate insulin production/secretion, glucose metabolism and uptake, or infl ammatory pathway in both insulin-dependent and insulin-independent manners. However, human studies are remained obscure because of contradictory results. While more studies are warranted to further understand these contradictions, ginseng holds promise as a therapeutic agent for diabetes prevention and treatment. This review summarizes the evidences for the therapeutic potential of ginseng and ginsenosides from in vitro studies, animal studies and human clinical trials with a focus on diverse molecular targets including an AMP-activated protein kinase signaling pathway.
전사체 프로파일을 이용한 고려 홍삼의 항당뇨 기전 연구
원해단,신은정,정성현,Yuan, Hai-Dan,Shin, En-Jung,Chung, Sung-Hyun 대한약학회 2008 약학회지 Vol.52 No.5
This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.
고지방 식이로 유도된 비만 쥐에서 HPJ 추출물의 항비만 효과
원해단(Hai-Dan Yuan),임방호(Bang-Ho Lim),김성집(Sung-Jib Kim),권해연(Hai-Yan Quan),장아(Ya Zhang),신대희(Dae-Hee Shin),정성현(Sung-Hyun Chung) 대한약학회 2009 약학회지 Vol.53 No.5
In this study, we investigated the anti-obese activity of HPJ extract in C57BL/6J mice. The C57BL/6J mice were randomly divided into five groups: normal control group (Con), high fat diet control group (HFD), treatment groups with HPJ at 125 mg/kg (HPJ125), 250 mg/kg (HPJ250), or 500 mg/kg (HPJ500). To induce an obesity, mice were fed by a high fat diet for 6 weeks, and mice were administered with HPJ extract once a day for 8 weeks. At the end of treatment, we examined the effect of HPJ extract on body weight, plasma lipid, and lipogenic enzymes. HPJ extract was found to lower whole body and epididymal adipose tissue weights and lowered plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), non-esterified fatty acid (NEFA) and leptin, compared to those in HFD group. Histological analyses of the liver and fat tissues of mice treated with HPJ extract revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the HFD group. In addition, HPJ extract preserved the morphological integrity of pancreatic islets. To elucidate an action mechanism of HPJ extract, Western blot and RT-PCR were performed using epididymal adipose tissues. HPJ extract up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylasse (ACC). HPJ extract also attenuated lipogenic gene expressions of sterol regulatory element-binding protein 1α (SREBP1α), fatty acid synthase (FAS), sterol-CoA desaturase 1 (SCD1) and glycerol-3-phosphate acyltransferase (GPAT) in dose-dependent manners. In contrast, expressions of lipolytic genes such as peroxisome proliferator-activated receptor-α (PPAR-α) and CD36, and fatty acid β-oxidation gene, carnitine palmitoyltransferase-1 (CPT-1) were increased. These results suggest that HPJ extract ameliorates obesity through inhibiting synthesis of lipogenic enzymes as well as stimulating fatty acid oxidation resulting from activation of AMPK, and HPJ extract could be developed as a potential therapeutic agent for obese patients.
흰쥐에서의 Dextran Sulfate Sodium-유발 궤양성 대장염에 대한 Curcumin의 효과
강주섭,원해단,지옥화,김신희,김현진,엄애선,이윤식,백승삼,김종욱 대한암예방학회 2006 Journal of cancer prevention Vol.11 No.2
Ulcerative colitis (UC), one of the inflammatory bowel diseases (IBD), tends to increase in Korea every year, but their causes and pathogenesis is still unknown. Sulfasalazine and corticosteroid are regularly used to treat IBD, but they have many side effects during long-term use and none therapeutic effect for some patients. So it is important to explore new agents that are more effective and have fewer side effects. Curcuma is the main component of turmeric, has anti-carcinogenic, anti-oxidative and anti- inflammatory activities. The aim of this study was to evaluate the effect of curcumin on UC induced by dextran sulfate sodium (2% DSS for 4 weeks) in the rat. The experiment animals were divided into four groups: control (normal), DDS-induced colitis rats, high-dose (100 mg/kg/day, po) and low dose (10 mg/kg/day, po)-treated groups that treated for 7 weeks during 4 weeks with 2% DDS and 3 weeks alone. We evaluated pathologically disease activity index (DAI) and the colon mucosa damage index (CMDI) and biochemically malondialdehyde (MDA), prostaglandin E2 (PGE2) in colon mucosa. The DAI and CDMI in DDS-induced colitis rats were more severe and the content of MDA and PGE2 level in DDS-induced rat were also higher than control and curcumin-treated rats, respectively. Curcumin may be alleviating some abnormality of disease index in a dose-depended manner. (Cancer Prevention Res 11, 137-143, 2006)
DMN-유발 간섬유화 동물에서 혈류 의존성 약물인 Verapamil의 약물동태에 대한 간질환의 영향
강주섭,박윤영,원해단,김현진,이주원,지옥화,엄애선,이상구,이윤식,신인철,이민호,홍정욱 대한암예방학회 2005 Journal of cancer prevention Vol.10 No.1
The purpose of this study was to determine the effect of hepatic disease severities on pharmacokinetics of flow-limited verapamil in dimethylnitrosamine (DMN)-induced cirrhotic rats. Hepatic cirrhotic rats (SD rats, 200~250 g) were induced by intraperitoneal injection with 1% DMN solution at a dose of 10μg/g by 3 days/week as experimental groups and same dose of saline as control for 4 weeks. The serum verapamil concentrations were quantified at zero, 10 min, 30 min, 1, 2 and 3 hrs after bolus injection of 3 mg/kg of verapamil by a column-switching HPLC method and pharmacokinetic parameters such as Co, MRT, AUC, Vdss, t1/2 (β) and CLp were determined in each group. And then some hepatic tissue was obtained and subjected to analysis of the hepatic 4-hydroxyproline content and were inspected by light microscope after hematoxylin and eosin staining. The serum concentrations and pharmacokinetic parameters such as Co, AUC, MRT and t1/2 (β) were significantly increased (p<0.01) and Vdss and CLp were significantly decreased (p<0.01) in hepatic cirrhotic rats according to DMN-treated period. The 4-hydroxyproline content was also gradually increased propertionally to DMN-treated period. The pharmacokinetic parameters of verapamil were seemed to change gradually to depend on the hepatic fibrotic severity. Therefore, we suggested that flow-limited drug as like verapamil dosage adjustment is necessary according to hepatic function severity. (Cancer Prev Res 10, 34-47, 2005)
흰쥐에서의 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxine 유발 지질 과산화 반응에 대한 Leucocyanidins(Vitis vinifera L.)의 효과
지옥화 ( Ok Hwa Jhee ),이주원 ( Joo Won Lee ),김신희 ( Shin Hee Kim ),원해단 ( Hei Dan Won ),김현진 ( Hyun Jin Kim ),박윤영 ( Yun Young Park ),강민정 ( Min Jeong Kang ),박성국 ( Sung Kug Park ),엄애선 ( Ae Sun Om ),백승삼 ( Seung 한국식품영양학회 2005 韓國食品營養學會誌 Vol.18 No.4