• The Korea Journal of Herbology
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• v.21 no.1
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• pp.1-7
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• 2006

Objectives: To find out the effects GGT1, an antiobestic drug widely used clinics, has on the amount of feed intake, the amount of change in the body weight and the food efficiency ratio using the data from the hGHTg obese male rats. Also, to evaluate in terms of antiobestic effects, the difference between GGT1 and reductil (sibutramine), which has been approved by the FDA of the United States. Methods: We measured the change in body weight and the amount of feed intake for 8 weeks by categorizing the hGHTg obese male rats into three groups: the control group, the GGT1 group, and the reductil (RD) group. We also evaluated the antiobestic effect by calculating the food efficiency ratio, which is the increase of bodyweight divided by the amount of feed intake. Results: In case of body weight, moderate slope of the curve in the graph of GGT1 group could mean that the weight is decreasing as time flows. In case of food efficiency ratio, the p-value was 0.745 in a test for determining if an interaction exists between the group and the point of measurement, meaning that it does not exist; also, the p-value in a test for the effect of level of repetition in food efficiency ratio according to the point of measurement equaled 0.002. Conclusion: The drug-treated groups had a greater inhibitory effect in feed intake than the control group. The results showed the food efficiency ratio had a tendency to decrease. The GGT1 group in particular was under a greater effect than the RD group.

• Herbal Formula Science
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• v.13 no.2
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• pp.1-16
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• 2005

Objectives: To find out the effects GGTl, an antiobestic drug widely used in clinics, has on the blood-antiobestic index and the toxicity index using the data from the hGHTg obese male rats. We looked closely into both of the two indices because GGTl antiobestic effect can happen not only by pharmacological action, but also by its toxicity. Also, we verified the difference in effect between GGTl and reductil (sibutramine), which has been approved by the FDA of the United States. Methods: After performing the experiments for 8 weeks on the hGHTg obese male rats divided into three groups: the control group, the GGTl group, and the reductil (RD) group, we anesthetized the rats with Diethyl ether and took a 3ml blood sample from the heart. Then, after coagulating the blood in room temperature by using the plasma separator, we centrifuged it for 25 minutes in 3,000rpm using the high-speed refrigerated centrifuge. We kept the separated plasma in a deep freezer at $-80^{\circ}C$, and repeatedly measured the antiobestic index and the toxicity index twice using the hematology biochemistry analyzer. Also, in order to judge the indirect toxicity index, we separated liver from kidney and observed them. Results: When we looked at the results of the analysis of covariance on the measuring elements related to the antiobestic index (TC, HDL, LDL, TG, and GLU), there was no significant difference among the groups in all measuring elements. Also, the results of the analysis of covariance on the two roups (RD group and GGTl group) showed that the p-values had no significant difference under the level of significance 0.05. When we looked at the result of the analysis of covariance on the measuring elements related to the toxicity index (GOT, GPT, GGT, CREA, UA, ALB, and TP), we could see that the p-values in GPT, ALB, and TP have a significant difference among the groups. Also, the results of the analysis of covariance about the measuring elements related to the toxicity index on both groups, RD group and GGTl group, showed no significant difference in the p-values of all of the measuring elements in the two groups, RD and GGTl group. Conclusions: In conclusion, through this experiment, the safety of GGTl has been approved, and although the verification on its medical effect has not been clearly approved, when we consider the fact that it belongs to the same group as reductil, an antiobestic drug approved by the FDA of the United States, we could indirectly verify that GGTl has an antiobestic effect. We believe that when doing a sample design for a future experiment, it needs to be performed on a greater sample size based on the power analysis that needs to be performed primarily in experiments, and a more accurate verification is needed through more systematic experiment plans.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.383-387
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• 2006

To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.93-97
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• 2006

To investigate whether GyeongshinhaeGihwan 1(GGT1), an anti-obesity herbal medicine widely used in oriental medicine, regulates the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese male rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), PPAR $\gamma$ (peroxisome proliferator activated receptor-gamma), PPAR$\delta$ (peroxisome proliferator activated receptor-delta), leptin, TNF$\alpha$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3- phosphate dehydrogenase) were analyzed by RT-PCR. PPAR$\gamma$ mRNA levels of liver and kidney were decreased in drug-treated groups compared with control group and the decrease of PPAR$\gamma$ expression was more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of adipogenesis and lipid storage by decreasing the PPAR$\gamma$ expression. In contrast, PPAR$\delta$ mRNA levels of adipose tissue and kidney were increased by RD and GGT1 , and the magnitudes of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating PPAR$\delta$ expression, Compared with control and RD groups, GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite. However, The mRNA levels of leptin, LPL, and TNF$\alpha$ were not changed by GGT1 and RD, compared with DW. These results demonstrate that GGT1 not only decreases PPAR$\gamma$ expression of liver and kidney, but also increases PPAR$\delta$ expression of adipose tissue and kidney, leading to the regulation of obesity and that these effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to prevent obesity by increasing the serum leptin levels.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.241-251
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• 2005

Objectives: This experimental study was designed to investig:ue the effects of Oryungsan-gagampang on leptin and leptin receptor levels and differentiation of 3T3-L1 adipocyte. Methods: After 3T3-L1 adipocytes were incubated with various concentrations of Oryungsan-gagampang and Reductil(r) for 7 days, leptin and leptin receptor levels in 3T3-Ll adipocytes were measured by ELISA. To elucidate the mechanism of inhibitory effects of Oryungsan-gagampang on obesity, the 3T3-L1 adipocytes after oil red 0 staining were taken by digital photo system. Results: 1. Oryungsan-gagampang $1,000{\mu}g/ml$ significantly increased leptin levels in 3T3-L1 adipocytes in comparison with the control group (p<0.05), and Oryungsan-gagampang 0.1 10, $1,000{\mu}g/ml$ significantly increased leptin receptor levels in 3T3-L1 adipocytes in comparison with the control group (p<0.05). 2. Oryungsan-gagampang inhibited of differentiation of 3T3-L1 adipocytes. Conclusions: Oryungsan-gagampang showed significant effects on inhibiting differentiation of 3T3-Ll adipocytes, and increasing leptin levels and leptin receptor levels in 3T3-L1 adipocytes. Therefore, Oryungsan-gagampang could be used to treat obesity, but further studies are required.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.15-21
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• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• The Journal of Korean Medicine
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• v.31 no.1
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• pp.30-46
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• 2010

Objectives: This study was performed to investigate the anti-obesity effects of Gambi-bang 4 (GBB4) on obesity-induced mice. Methods: C57BL/6 mice were divided into four groups (normal, high fat diet with control, high fat diet with Reductil, high fat diet with GBB4 extract) and fed for 8 weeks. We observed body weight change, the weight change of the adipocytes in body, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides, serum leptin level, expression of ${\beta}3AR$ and leptin genes in 3T3-L1 adipocytes and adipose tissue, and histological changes of adipose tissue and liver cells. Results: 1. Compared with the control group, the GBB4 group was significantly lower in body weight, weight of adipocytes, and amount of glucose. 2. The GBB4 group was significantly lower in the amount of total cholesterol, LDL-cholesterol and triglycerides, and HDL-cholesterol compared with the control. 3. Compared with the control group, the GBB4 group was significantly lower in the amount of serum leptin. 4. The GBB4 group was significantly higher in the revelation of ${\beta}3AR$ and leptin in 3T3-L1 adipocytes and primary adipose cells compared with the control. 5. Compared with the control group, the GBB4 group was smaller in the size of adipocytes in adipose tissue and the adipose vacuoles in liver tissue were decreased. Conclusions: These results suggested that GBB4 has inhibitory effects on obesity. GBB4 might be applied in treatment of obesity, so further studies analyzing its effects are needed.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.4
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• pp.79-93
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• 2009

Objectives : In order to investigate the effects of Gambibang-3(here in after referred to GBB3) on the obese gene and obese inhibitory, C57BL/6 mice were induced by high fat diet. Methods : C57BL/6 mice were divided into four groups(normal, high fat diet with control, high fat diet with Reductil(here in after referred to RDT), high fat diet with GBB3 extract) and fed for 8 weeks. And observed that, the weight change of the adipocytes in body and liver, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, glucose, leptin change in the serum, the expression of ${\beta}3AR$ and leptin gene in 3T3 cell and primary adipocyte cell. Results & conclusions : The following results were obtained in this study. 1. GBB3 and RDT group showed that the revelation of ${\beta}3AR$ in primary adipose cell and 3T3 cell were increased considerably, and that the revelation of leptin in primary adipose cell and 3T3 cell were decreased considerably. 2. GBB3 and RDT group showed that the weight of adipocyte and liver were not different with control group significantly. 3. GBB3 and RDT group showed that the amount of HDL-Cholesterol were increased considerably, the amount of glucose, LDL-Cholesterol and Triglyceride were decreased considerably. 4. GBB3 group showed that the amount of leptin in the serum were decreased considerably.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.35-50
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• 2010

Objectives : In order to investigate the effects of So-yangin Biman-bang(here in after referred to BM) on the obese gene and obese inhibitory, C57BL/6 mice were distinctively induced by high fat diet. Methods : C57BL/6 mice were divided into four groups(normal, high fat diet with control, high fat diet with Reductil(here in after referred to RDT), high fat diet with BM extract) and have been fed for 8 weeks. Through observing the process, the weight change of the adipocytes in body and liver, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, glucose, leptin change in the serum, the expression of ${\beta}3AR$ and leptin gene in 3T3-L1 cell and primary adipocyte cell. Results : The following results have been found in this study. 1. Losing weight have significantly been shown. 2. The weight change of the body adipocyte and liver have been decreased but no significance has been found. 3. With close observation on the change of blood, HDL-cholesterol has positively been increased in numbers but the level of glucose, LDL-cholesterol, triglyceride have distinctively been decreased. 4. The manifestation of ${\beta}3AR$ in 3T3-L1 cell and primary adipocyte cell have shown a definite increase in numbers but the manifestation of leptin has shown certain decrease in its amount. Conclusions : As results of this, So-yangin Biman-bang is thought to be effective in metabolic syndrom and lipid metabolism disorder that can possibly be occurred by obesity control and treatment. The clinical research will be needed in order to apply to So-yangin constitution in the future.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.2
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• pp.81-96
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• 2008

Objectives : This study was performed to investigate inhibitory effects of Gamipalmul-tang($jiaweibawu-t{\bar{a}}ng$) on the hematological and histological changes of obese mice. Methods : C57BL/6 mice were divided into four groups (normal group, high fat diet with normal saline, high fat diet with reductil, high fat diet with Gamipalmul-tang($jiaweibawu-t{\bar{a}}ng$) and fed for 8 weeks. Body weight change, final increase of body weight, ALT, AST, creatinine, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, glucose, cell viability by cytotoxicity, the expression of ${\beta}3AR$ in 3T3-L1 cell, the expression of leptin, ${\beta}3AR$ and serotonin in adipocyte tissue and size of adipocyte were observed in 8 weeks. Results : 1. In 3T3-L1 cell. the expression of ${\beta}3AR$ was increased significantly. 2. The final increase of body weight in obese-mouse were decreased significantly. 3. The level of AST, ALT were decreased significantly. 4. The level of LDL-cholesterol was decreased significantly and HDL-cholesterol was increased significantly. 5. The levels of triglyceride was decreased and leptin and glucose were decreased significantly. 6. In adipocyte tissue, the expression of ${\beta}3AR$ were increased significantly. 7. In adipocyte tissue, the expression of leptin and serotonin were decreased significantly. 8. The size of Adipocyte was decreased. Conclusions : On the basis of these results, we concluded that Gamipalmul-tang($jiaweibawu-t{\bar{a}}ng$) has inhibitory effects in rat.