• The Korea Journal of Herbology
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• v.25 no.3
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• pp.1-9
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• 2010

Objectives : This study was undertaken to verify the effects of Gyeongshingangjeehwan18 (GGEx18) on obesity using ob/ob male mice. Methods : Eight-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as lean control and obese ob/ob mice were randomly divided into 5 groups: obese control, GGEx15, GGEx16, GGEx17, and GGEx18. After mice were treated with several kinds of GGEx for 11 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism. Results : 1. Compared with obese controls, GGEx-treated mice had lower body weight gain and feeding efficiency ratio, the magnitudes of which were prominent in GGEx16 and GGEx18. 2. Consistent with their effects on body weight gain, GGEx16 and GGEx18 not only decreased plasma triglycerides levels, but also increased HDL-cholesterol concentration. 3. CT analysis revealed that visceral fat areas were decreased in all treatment groups compared with obese control mice. The decrease in visceral fat area was prominent in GGEx16 and GGEx18, although they were not statistically significant. 4. The size of adipocytes were significantly decreased by GGEx18, whereas the adipocyte number per unit area was significantly increased, suggesting that GGEx18 decreased the number of large adipocytes. Hepatic lipid accumulation was decreased by GGEx16 and GGEx18, and the inhibitory effect was most effective in GGEx18. 5. Plasma GOT and GPT concentrations were significantly lower following GGEx16 and GGEx18 treatment compared with obese controls. Organ weights were not changed by GGEx treatment, indicating GGEx do not show any toxic effects. Conclusions : These results suggest that GGEx may regulate obesity. Of the 4 compositions, GGEx18 seems to be most effective in improving obesity and lipid disorders.

• The Korea Journal of Herbology
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• v.26 no.1
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• pp.65-74
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• 2011

Objectives : This study was undertaken to verify the modulation mechanism of Gyeongshingangjeehwan18 (GGEx18) in ob/ob male mice. Methods : Eight-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as lean control and obese ob/ob mice were randomly divided into 5 groups : obese control, GGEx15 (Ephedra sinica Stapf + Rheum palmatum L.), GGEx16 (Ephedra sinica Stapf + Laminaria japonica Aresch), GGEx17 (Rheum palmatum L. + Laminaria japonica Aresch), and GGEx18 (Ephedra sinica Stapf + Laminaria japonica Aresch + Rheum palmatum L.). After mice were treated with several kinds of GGEx for 11 weeks, the mRNA expression of peroxisome proliferator-activated receptor (PPAR) target genes and uncoupling protein (UCP) were measured. In addition, $PPAR{\alpha}$ and $PPAR{\beta}$ transactivation was examined in NMu2Li hepatocytes, C2C12 myocytes, and 3T3-L1 preadipocytes using transient transfection assays. Results : 1. Hepatic $PPAR{\alpha}$ target genes, such as ACOX and VLCAD mRNA levels were significantly increased by GGEx18 compared with obese controls. In skeletal muscle, LCAD mRNA expression was stimulated by GGEx16, GGEx17, and GGEx18, whereas MCAD mRNA expression by GGEx17 and GGEx18. $PPAR{\beta}$ target LPL mRNA levels were also increased by GGEx16, GGEx17, and GGEx18 in skeletal muscle, but adipose LPL mRNA levels were decreased. In addition, GGEx18 upregulated UCP mRNA expression in skeletal muslce. 2. $PPAR{\alpha}$ reporter gene expression was increased by GGEx18 in NMu2Li cells compared with vehicle. $PPAR{\alpha}$ and $PPAR{\beta}$ reporter activities were also increased by all GGEx treatments in C2C12 and 3T3-L1 cells. Conclusions : These results suggest that GGEx can act as $PPAR{\alpha}$ and $PPAR{\beta}$ activators, and that GGEx may regulate obesity by stimulating $PPAR{\alpha}$, $PPAR{\beta}$, and UCP activity. Of the 4 compositions, GGEx18 seems to be most effective in improving obesity and lipid disorders.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.39-44
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• 2013

Objectives : Gambigyeongsinhwan 16 (GGEx16), gambigyeongsinhwan 18 (GGEx18) and gambitongseong capsule are shown to be involved in the regulation of obesity. Therefore, the aim of this study was to compare the reporter activity of anti-obesity genes such as peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and $PPAR{\delta}$ by GGEx16, GGEx18 and gambitongseong capsule. Methods : After NMu2Li liver cells, C2C12 skeletal muscle cells and 3T3-L1 preadipocytes were treated with GGEx16 (1 ${\mu}g/ml$), GGEx18 (1 ${\mu}g/ml$) and different concentrations of gambitongseong capsule, the transactivation of $PPAR{\alpha}$ and $PPAR{\delta}$ was measured by a luciferase reporter gene assay. Results : $PPAR{\alpha}$ reporter gene activity in NMu2Li liver cells and 3T3-L1 preadipocytes was significantly increased by GGEx16, GGEx18 and gambitongseong capsule compared with control, whereas $PPAR{\alpha}$ reporter gene activity in C2C12 skeletal muscle cells was significantly increased by GGEx18 only compared with control. Similarly, $PPAR{\delta}$ reporter gene activity in 3T3-L1 preadipocytes was also significantly increased by GGEx18 compared with control. $PPAR{\delta}$ reporter gene activity in C2C12 skeletal muscle cells was significantly increased by GGEx16 and GGEx18 compared with control although $PPAR{\delta}$ reporter gene activity in NMu2Li liver cells was not changed by these three formulas. Conclusions : These results suggest that all three formulas have the ability to stimulate $PPAR{\alpha}$ and $PPAR{\delta}$ transactivation in animal cell lines with high metabolic rates. In particular, this effects were most prominent in GGEx18-treated cells. In addition, it is likely that GGEx18 may be used as an effective anti-obesity composition.

• Biomedical Science Letters
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• v.17 no.4
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• pp.273-281
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• 2011

Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) inhibits obesity and insulin resistance in obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We investigated whether GGEx may affect AMP-activated protein kinase ${\alpha}$ ($AMPK{\alpha}$) since $AMPK{\alpha}$ activation is known to stimulate fatty acid oxidation in skeletal muscle of obese rodents. After OLETF rats were treated with GGEx, we studied the effects of GGEx on $AMPK{\alpha}$ and acetyl-CoA carboxylase (ACC) phosphorylation, and the expression of $AMPK{\alpha}$, $PPAR{\alpha}$, and $PPAR{\alpha}$ target genes. The effects of GGEx on mRNA expression of the above genes were also measured in C2C12 skeletal muscle cells. Administration of GGEx to OLETF rats for 8 weeks increased phosphorylation of $AMPK{\alpha}$ and ACC in skeletal muscle. GGEx also elevated skeletal muscle mRNA levels of $AMPK{\alpha}1$ and $AMPK{\alpha}2$ as well as $PPAR{\alpha}$ and its target genes. Consistent with the in vivo data, similar activation of genes was observed in GGEx-treated C2C12 cells. These results suggest that GGEx stimulates skeletal muscle $AMPK{\alpha}$ and $PPAR{\alpha}$ activation, leading to alleviation of obesity and related disorders.

• Biomedical Science Letters
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• v.17 no.4
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• pp.283-289
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• 2011

Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) activates AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) critical for fatty acid oxidation in skeletal muscle and C2C12 skeletal muscle cells. Thus, we examined whether GGEx can reduce lipid accumulation in these cells and tissues. After obese and type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with GGEx, we studied the effects of GGEx on skeletal muscle lipid accumulation. The effects of GGEx and/or the AMPK inhibitor compound C on lipid accumulation and expression of AMPK and $PPAR{\alpha}$ were measured in C2C12 skeletal muscle cells. Compared with lean Long-Evans Tokushima Otsuka rats, obese OLETF rats had increased triglyceride droplets. However, administration of GGEx to OLETF rats for 8 weeks significantly decreased triglyceride droplets in skeletal muscle. Consistent with the $in$ $vivo$ data, GGEx inhibited lipid accumulation, the degree of which was comparable to Wy14,643, the potent activator of $PPAR{\alpha}$. GGEx also increased skeletal muscle mRNA levels of AMPK${\alpha}1$, AMPK${\alpha}2$, and $PPAR{\alpha}$. However, compound C inhibited these effects in C2C12 cells. These results suggest that GGEx suppresses skeletal muscle lipid accumulation and this process may be mediated by AMPK and $PPAR{\alpha}$ activation.

• Biomedical Science Letters
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• v.19 no.3
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• pp.206-212
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• 2013

The herbal composition Gyeongshingangjeehwan 18 (GGEx18), which is composed of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), has been used as an anti-obesity drug in Korean local clinics. Thus, we investigated whether GGEx18 regulates obesity by suppressing appetite in high fat diet-induced obese C57BL/6J mice. Administration of GGEx18 to obese mice for 9 weeks significantly decreased body weight gain, epididymal adipose tissue weight, and food efficiency ratio. GGEx18 also caused a significant decrease in the circulating levels of leptin, which were increased by about 450% in obese control mice compared with normal lean mice. Concomitantly, GGEx18 decreased mRNA levels of a potent appetite-stimulating hormone neuropeptide Y, but increased an appetite-suppressing hormone pro-opiomelanocortin mRNA levels. These results suggest that GGEx18 may prevent obesity through regulating appetite in nutritionally obese mice.

• Herbal Formula Science
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• v.16 no.2
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• pp.205-217
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• 2008

Objectives : We investigated the effects of Herba Ephedrae and Rhizoma Amorphophalli on high fat diet induced obese male mice. Methods : 8 weeks old, high fat diet induced obese male mice were divided into 5 groups: C57BL/6 normal control, obese vehicle control, GGEx55 (Herba Ephedrae), GGEx61 (Rhizoma Amorphophalli), GGEx62 (Herba Ephedrae + Rhizoma Amorphophalli). After mice were treated with GGEx for 8 weeks, we measured body weight gain, food intake, feeding efficiency ratio, rectal temperature, fat weight, plasma leptin and lipid levels. We also took micro-computerized axial tomography (micro-CT) on the mice. Results : 1. GGEx55 and GGEx62 groups significantly decreased body weight gain and feeding efficiency ratio compared with vehicle control. But they significantly increased rectal temperature. 2. Plasma total cholesterol and LDL-cholesterol concentrations were significantly increased by GGEx55 groups, whereas were significantly decreased by GGEx62 groups compared with vehicle control. 3. GGEx55 and GGEx62 groups significantly decreased total, subcutaneous and visceral fat as well as fat areas in micro-CT analysis of abdomen compared with vehicle control. 4. Plasma GOT and GPT concentrations were significantly increased by GGEx55 groups compared with vehicle control. Conclusions : These results demonstrate that GGEx55 and GGEx62 effectively reduces body weight gain, feeding efficiency ratio in high fat diet induced obese mice, leading to the modulation of obesity. In addition, GGEx55 and GGEx62 decreases visceral adipose tissue mass and improves plasma lipids, suggesting that GGEx55 and GGEx62 may act as a therapeutic agent for obesity.

• Herbal Formula Science
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• v.16 no.1
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• pp.169-183
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• 2008

In this study, we measured body mass index, visceral fat ratio and 6 parts of body, neck circumference, circumference of upper arm, chest circumference, abdomen circumference, hip circumference, and thigh circumference by bioimpedence analysis system, after taking Gyeongshingangjeehwan16 (GGEx16) in five months except the first period before taking GGEx16 on 49 women who are obesity or high-level obesity. In order to examine the significance test for the effect of obesity improvement of GGEx16, we practices repeated measure ANOVA with values of measurement variables in 6 monthly times. As a result of all measurement variables, there were significant difference (P-value=0.001). Therefore, we can say that GGEx16 is effective about obesity improvement. As it dramatically decreased between second measure period and first measure period for all measure variables, we can see that there were the most effect of GGEx16 in the first time after taking GGEx16. It is known that a important measurement variable to have a effect for obesity improvement about two variable which are body mass index and visceral fat ratio is waist circumference through correlation analysis. The result of whether there are differences to effect of obesity improvement for GGEx16 around the climacteric, there were significant difference for the effect of obesity improvement for GGEx16 around the climacteric about all parts of body (P-value=0.001). There were also powerfully difference in effect of obesity improvement for GGEx16 around the climacteric about all parts of body (P-value=0.001). Especially, the climacteric before is more effective than the climacteric after in the aspect of the effect of GGEx16.

• Biomedical Science Letters
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• v.24 no.4
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• pp.341-348
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• 2018

The polyherbal drug Gyeongshingangjeehwan 18 (GGEx18) from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) has traditionally been used as an antiobesity drug in Korean local clinics. This study investigates the effects of GGEx18 on pancreatic fibroinflammation in high-fat diet (HFD)-fed obese C57BL/6J mice and the molecular mechanism involved in this process. After HFD-fed obese C57BL/6J mice were treated with GGEx18 (125, 250, and 500 mg/kg) for 12 weeks, variables and determinants of obesity, pancreatic inflammation, and fibrosis were measured using histology, immunohistochemistry, and real-time polymerase chain reaction. Administration of GGEx18 at 500 mg/kg/day to obese mice decreased body weight gain, mesenteric adipose tissue mass, and adipocyte size. GGEx18 treatment not only reduced mast cells and CD68-immunoreactive cells, but also decreased collagen levels and ${\alpha}$-smooth muscle actin-positive cells in the pancreas of HFD-fed mice. Concomitantly, GGEx18 decreased the expression of genes for inflammation (i.e., CD68 and tumor necrosis factor ${\alpha}$) and fibrosis (i.e., collagen ${\alpha}1$ and transforming growth factor ${\beta}$) in the pancreas of obese mice. These results suggest that GGEx18 may inhibit visceral obesity and related pancreatic fibroinflammation in HFD-fed obese mice.

• Herbal Formula Science
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• v.14 no.2
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• pp.45-56
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• 2006

Objectives : We evaluated anti-hyperlipidemia effect of Gyeongshinganjeehwan (GGEx) in high fat induced obese male micro-pigs. Methods : 7 month-old micro-pigs are fed with normal (n = 3) or high fat diet (n = 18) for 12 weeks. The pig revealed obesity in high fat diet were divided into 2 groups (n = 5 each) and vehicle (OMP) and Gyeongshingangjeehwan (GGEx, 616.7 mg/kg/day) were administrated for 1 month. We monitored the changes in body weight and measured plasma cholesterol, triglyceride, free fatty acid, GOT and, GPT after 1 month. The visceral fat were measured with computerized tomography and weights of various organs were measured after sacrifice. Results : 1. GGEx group had significantly reduced body weight gain than obese control group in statistics. 2. GGEx group didn't significantly differ from obese control group in blood total cholesterol, blood LDL-cholesterol, blood triglyceride. but it's data were similar to normal control group. 3. GGEx group had prominantly reduced visceral fat than obese control group in computerized tomography. 4. Blood GOT and GPT didn't differ from between groups. The organ weight were not significant different. And it is normal in size and colour of visceral organs. Conclusions : It is concluded that GGEx has anti-hyperlipidemia effect by improving visceral fat and access to security.