Ginseng and Diabetes

Hai-Dan Yuan,Jung Tae Kim,Sung Hoon Kim,Sung Hyun Chung 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.

Protective Effect of Cinnamaldehyde on Streptozotocin-induced Damage in Rat Pancreatic β-Cells

Hai Dan Yuan,Bo Huang,정성현 한국식품과학회 2011 Food Science and Biotechnology Vol.20 No.5

Cinnamaldehyde (CNA) is a primary constituent found in cinnamon (Cortex cinnamomi). Although antidiabetic and anti-inflammatory activities of cinnamon extract have been investigated in recent years, whether CNA is responsible for these activities is yet to be explored. In the present study, we investigated the protective effect of CNA on streptozotocin (STZ)-induced β-cell dysfunction in RINm5F rat insulinoma cells. CNA markedly inhibited nitric oxide (NO) and prostaglandin E2(PGE2) productions in concentration-dependent manners. Parallel with these observations, the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes were inhibited by CNA in concentration-dependent manners. CNA also inhibited STZ-induced nuclear factor (NF)-κB activation via the prevention of inhibitory κBα (IκBα) phosphorylation and degradation. Moreover, CNA significantly suppressed STZ-induced phosphorylations of extracellular signalregulated kinase (ERK), c-Jun NH2-terminal kinase (JNK),and p38 mitogen-activated protein kinase (MAPK) in concentration-dependent manners. These results suggest that CNA is an active constituent of the cinnamon, and CNA protects against STZ-induced pancreatic β-cell damage by down-regulations of iNOS and COX-2 gene expression through blocking of NF-κB and MAPKs activities.

Anti-diabetic Effect and Mechanism of Korean Red Ginseng in C57BL/KsJ db/db Mice

Hai-Dan Yuan,Eun-Jung Shin,Sung-Hyun Chung 고려인삼학회 2008 Journal of Ginseng Research Vol.32 No.3

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 ㎎/㎏) and metformin group (MET, 300 ㎎/㎏), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMPactivated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

Anti-Diabetic Effect of Pectinase-Processed Ginseng Radix (GINST) in High Fat Diet-Fed ICR Mice

Hai Dan Yuan,Hai Yan Quan,Mi Song Jung,Su Jung Kim,Bo Huang,Do Yeon Kim,Sung Hyun Chung 고려인삼학회 2011 Journal of Ginseng Research Vol.35 No.3

In the present study, we investigate anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. The ICR mice were divided into three groups: regular diet group, high fat diet control group (HFD), and GINST-treated group. To induce hyperglycemia, mice were fed a high fat diet for 10 weeks, and mice were administered with 300 mg/kg of GINST once a day for 5 weeks. Oral glucose tolerance test revealed that GINST improved glucose tolerance after glucose challenge. Compared to the HFD control group, fasting blood glucose and insulin levels were decreased by 57.8% (p<0.05) and 30.9% (p<0.01) in GINST-treated group, respectively. With decreased plasma glucose and insulin levels, the insulin resistance index of the GINST-treated group was reduced by 68.1% (p<0.01) compared to the HFD control group. Pancreas of GINST-treated mice preserved a morphological integrity of islets and consequently having more insulin contents. In addition, GINST up-regulated the levels of phosphorylated AMP-activated protein kinase (AMPK) and its target molecule, glucose transporter 4 (GLUT4) protein expression in the skeletal muscle. Our results suggest that GINST ameliorates a hyperglycemia through activation of AMPK/GLUT4 signaling pathway, and has a therapeutic potential for type 2 diabetes.

Ginseng Leaf Extract Prevents High Fat Diet-Induced Hyperglycemia and Hyperlipidemia through AMPK Activation

Hai-Dan Yuan,Sung-Jip Kim,Hai-Yan Quan,Bo Huang,Sung-Hyun Chung 고려인삼학회 2010 Journal of Ginseng Research Vol.34 No.4

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 ㎎/㎏, and GLE-treated at 500 ㎎/㎏. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-α and CD36 were increased. In addition, phospho-α and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

Korean Red Ginseng Attenuates Hepatic Lipid Accumulation via AMPK Activation in Human Hepatoma Cells

Hai-Yan Quan,Hai-Dan Yuan,Do Yeon Kim,Ya Zhang,정성현 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.1

In this study, we examined Korean red ginseng (KRG) extract affects on the lipid metabolism in HepG2cells. Increase in AMP-activated protein kinase (AMPK)phosphorylation was observed when the cells were treated with KRG. Activation of AMPK was also demonstrated by measuring the phosphorylation of acetyl-CoA caboxylase (ACC), a substrate of AMPK. KRG down-regulated gene expressions of sterol regulatory element binding protein 1c (SREBP1c) and its target proteins, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD1) in time- and dose-dependent fashions. In contrast, gene expressions of peroxisome proliferator-activated receptor α(PPARα) and CD36 were increased. These effects were reversed in the presence of compound C, an AMPK inhibitor. However, there were no differences in gene expressions of SREBP2, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and low-density-lipoprotein receptor (LDLR). Taken together, KRG induced supression of SREBP1c and activation of PPARα via AMPK and these effects seem to be one of anti-hyperlipidemic mechanism of KRG in HepG2 cells.

Anti-Diabetic Effect of Pectinase-Processed Ginseng Radix (GINST) in High Fat Diet-Fed ICR Mice

Yuan, Hai Dan,Quan, Hai Yan,Jung, Mi-Song,Kim, Su-Jung,Huang, Bo,Kim, Do-Yeon,Chung, Sung-Hyun The Korean Society of Ginseng 2011 Journal of Ginseng Research Vol.35 No.3

In the present study, we investigate anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. The ICR mice were divided into three groups: regular diet group, high fat diet control group (HFD), and GINSTtreated group. To induce hyperglycemia, mice were fed a high fat diet for 10 weeks, and mice were administered with 300 mg/kg of GINST once a day for 5 weeks. Oral glucose tolerance test revealed that GINST improved glucose tolerance after glucose challenge. Compared to the HFD control group, fasting blood glucose and insulin levels were decreased by 57.8% (p<0.05) and 30.9% (p<0.01) in GINST-treated group, respectively. With decreased plasma glucose and insulin levels, the insulin resistance index of the GINST-treated group was reduced by 68.1% (p<0.01) compared to the HFD control group. Pancreas of GINST-treated mice preserved a morphological integrity of islets and consequently having more insulin contents. In addition, GINST up-regulated the levels of phosphorylated AMP-activated protein kinase (AMPK) and its target molecule, glucose transporter 4 (GLUT4) protein expression in the skeletal muscle. Our results suggest that GINST ameliorates a hyperglycemia through activation of AMPK/GLUT4 signaling pathway, and has a therapeutic potential for type 2 diabetes.

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.

Ginseng Leaf Extract Prevents High Fat Diet-Induced Hyperglycemia and Hyperlipidemia through AMPK Activation

Yuan, Hai-Dan,Kim, Sung-Jip,Quan, Hai-Yan,Huang, Bo,Chung, Sung-Hyun The Korean Society of Ginseng 2010 Journal of Ginseng Research Vol.34 No.4

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice.

Quan, Hai-Yan,Yuan, Hai-Dan,Jung, Mi Song,Ko, Sung Kwon,Park, Young Guk,Chung, Sung Hyun D.A. Spandidos 2012 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.29 No.1

<P>Ginsenoside Re is a protopanaxatriol-type saponin isolated from Panax ginseng berry. Although anti-diabetic and anti-hyperlipidemic effects of Re have been reported by several groups, its mechanism of action is largely unknown until now. Here, we examine anti-diabetic and anti-hyperlipidemic activities of Re and action mechanism(s) in human HepG2 hepatocytes and high-fat diet fed C57BL/6J mice. Re suppresses the hepatic glucose production via induction of orphan nuclear receptor small heterodimer partner (SHP), and inhibits lipogenesis via suppression of sterol regulatory element binding protein-1c (SREBP-1c) and its target gene [fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1)] transcription. These effects were mediated through activation of AMP-activated protein kinase (AMPK), and abolished when HepG2 cells were treated with an AMPK inhibitor, Compound C. C57BL/6J mice were randomly divided into five groups: regular diet fed group (RD), high-fat diet fed group (HFD) and the HFD plus Re (5, 10, 20 mg/kg) groups. Re treatment groups were fed a high-fat diet for 6 weeks, and then orally administered Re once a day for 3 weeks. The in vitro results are likely to hold true in an in vivo experiment, as Re markedly lowered blood glucose and triglyceride levels and protected against hepatic steatosis in high-fat diet fed C57BL/6J mice. In conclusion, the current study suggest that ginsenoside Re improves hyperglycemia and hyperlipidemia through activation of AMPK, and confers beneficial effects on type 2 diabetic patients with insulin resistance and dyslipidemia.</P>