• Asian-Australasian Journal of Animal Sciences
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• v.20 no.3
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• pp.432-439
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• 2007

Thiazolidinediones (TZDs) act as potent activators of the adipose differentiation program in established preadipose cell lines. TZD's have also been investigated in diabetic patients and reported to act as PPAR-${\gamma}$ ligands. In this report, the effects of TZDs on the differentiation pathway of myoblasts have been investigated. C2C12 mouse myoblasts were grown in Dulbecco's Modified Eagles medium for 4-5 days until they reached almost 100% confluency. Post-confluent cells (day 0) were further exposed to adipogenic induction medium along with TZDs for 48 hours. Thereafter, cells were exposed only to TZDs every 48 h until day 10. The control was provided with differentiation medium without any treatment. Alterations in the cells during the differentiation programme were analyzed on the basis of fusion index, oil-red-o staining, adipocyte index, adipocyte stain uptake measurement, immuno-histochemistry and western blotting. Exposure of C2C12 mouse myoblasts to TZDs prevented the expression of myosin heavy chain with parallel increase in the expression of C/EBP-${\alpha}$ and PPAR-${\gamma}$ and acquisition of adipocyte morphology, thus abolishing the formation of multinucleated myotubes. TZDs exert their adipogenic effects only in non-terminally differentiated myoblasts; myotubes were insensitive to the compound. Continuous exposure (at least 4-5 doses) to inducers after the growth arrest was essential to provide a sustained environment to the cells converting to fully matured adipoctyes. The results indicate that TZDs specifically converted the differentiation pathway of myoblasts into that of adipoblasts.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.199-205
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• 2015

Background: Ginsenoside Rb1 (G-Rb1), the major active constituent of ginseng, improves insulin sensitivity and exerts antidiabetic effects. We tested whether the insulin-sensitizing and antidiabetic effects of G-Rb1 results from a reduction in ectopic fat accumulation, mediated by inhibition of lipolysis in adipocytes. Methods: Obese and diabetic db/db mice were treated with daily doses of 20 mg/kg G-Rb1 for 14 days. Hepatic fat accumulation was evaluated by measuring liver weight and triglyceride content. Levels of blood glucose and serum insulin were used to evaluate insulin sensitivity in db/db mice. Lipolysis in adipocytes was evaluated by measuring plasma-free fatty acids and glycerol release from 3T3-L1 adipocytes treated with G-Rb1. The expression of relevant genes was analyzed by western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay kit. Results: G-Rb1 increased insulin sensitivity and alleviated hepatic fat accumulation in obese diabetic db/db mice, and these effects were accompanied by reduced liver weight and hepatic triglyceride content. Furthermore, G-Rb1 lowered the levels of free fatty acids in obese mice, which may contribute to a decline in hepatic lipid accumulation. Corresponding to these results, G-Rb1 significantly suppressed lipolysis in 3T3-L1 adipocytes and upregulated the perilipin expression in both 3T3-L1 adipocytes and mouse epididymal fat pads. Moreover, G-Rb1 increased the level of adiponectin and reduced that of tumor necrosis factor-${\alpha}$ in obese mice, and these effects were confirmed in 3T3-L1 adipocytes. Conclusion: G-Rb1 may improve insulin sensitivity in obese and diabetic db/db mice by reducing hepatic fat accumulation and suppressing adipocyte lipolysis; these effects may be mediated via the upregulation of perilipin expression in adipocytes.

• Korean Journal of Medicinal Crop Science
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• v.24 no.2
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• pp.115-120
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• 2016

Background: This study examined the hypoglycemic and kidney protective effect of black ginseng in streptozotocin-induced diabetic mice. Methods and Results: Diabetes was induced by treating mice with streptozotocin (STZ) for four weeks. In vivo studies were performed in order to investigate the hypoglycemic effect of the black ginseng prosapogenin (GBG05-FF) extract. The body weight and blood glucose level were measured. Moreover, after the mice were sacrificed, the kidneys were isolated and histological changes were observed with hematoxylin and eosin staining. Blood urea nitrogen and creatinine levels were also measured. The results showed that administration of black ginseng increased body weight. Compared to blood glucose levels in STZ mice, blood glucose levels were reduced by 48% in STZ mice supplemented with 300 mg/kg of black ginseng, and by 69% in STZ mice supplemented with 900 mg/kg. Furthermore, histopathological examination of STZ mouse kidneys revealed, changes in the kidneys, epithelial cell damages, inflammatory cell infiltration and glomerulus hypertrophy. However, a significant reduction of glomerular water droplets (indicative of glomerulus hypertrophy) was observed in the kidneys of STZ mice supplemented with black ginseng extract. Conclusions: These results suggest that black prosapogenin (GBG05-FF) ginseng extract has a significant hypoglycemic effect and can be used as an anti-diabetic substance and renal protective agents as part of dietary supplements or novel drugs.

• BMB Reports
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• v.40 no.5
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• pp.670-677
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• 2007

Although polysaccharide is believed to play an important role in the medicinal effect of Dendrobium chrysotoxum Lindl (DCL), its role as an antioxidant and in anti-hyperglycemic induction was not reported. In this study, polysaccharide with molecular weight of approximately 150 kDa, herein named DCLP, was isolated from the stem of DCL, and its antioxidative, hypoglycemic and immune stimulating effects were evaluated using various in vitro and in vivo assay systems. DCLP inhibited hydroxyl radicals ($^{\cdot}$OH)-mediated deoxyribose degradation by scavenging hydroxyl radicals directly as well as by chelating iron ions. DCLP also showed dose-dependent scavenging activity on superoxide anions ($O_2^{{\cdot}-}$) and offered significant protection (p < 0.001) against glucose oxidase-mediated cytotoxicity in Jurkat cells. DCLP had immune stimulating effects, as evidenced by the DCLP-mediated increases in the level of DNA synthesis, viability, and cytokine secretion in mouse lymphocytes. Moreover, oral administration of DCLP produced a significant reduction in blood glucose level in alloxan-induced diabetic mice. These findings suggest that DCLP has a potential utility in treating patients who require enhanced antioxidation, immune function and/or hypoglycemic activity.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.150-157
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• 1997

Capsaicin cream has been used to attenuate the pain associated with diabetic neuropathy, rheum-atoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, local irritation, limits the use of it and there is still a need for a new analgesic devoid of this side effect. This study was conducted to compare the local irritant effect of DA-5018, a new capsaicin derivative, with that of capsaicin in various animal models and human beings. Capsaicin, applied topically to the mouse ear, produced dose-dependent increase of ear volume and the frequency of ear scratching behavior in mice. Neither ear volume nor scratching behavior was affected by DA-5018. In eye wiping test of rat, DA-5018 was 10 times less irritant than capsaicin. Capsaicin administered intradermally into the rat paw elicited paw lick/lift response with a potency which was three times that of DA-5018. Zostrix-HP (0.075% capsaicin cream), but not DA-50180.3% cream, increased ear volume of rat and induced thermal hyperalgesia in normal and carrageenan inflamed paws. Six day-treatment of Zostrix-HP failed to develop tolerance against this thermal hyperalgesia. In human beings, Zostrix-HP produced burning sensation and itching in more than 90% of volunteers involved and its maximum irritant effect was significantly higher than that of DA-5018 cream. These results suggest that local irritation and burning sensation produced by DA-5018 is much less than capsaicin.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.27-37
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• 1998

In order to investigate the effect of lowering blood glucose level, 27 medications of Sagal part in Donguibogam and the contraindicated medications to Sogal including Ijintang, Dodamtang, Chukdamtang and other six medications which were used to treat Diabetes in the 6th I.M of Kyung Hee Oriental Medical Center were given to the Alloxan induced diabetic mouse and blood glucose level were observed in the 2nd and 4th day. The result of this stqdy are as follows: 1. The 17 medicatlons(63% of 27 medicine) of Sogal part decreased' the glucose level significantly.(Singihwan, Baekhotang, Jowiseunggitang, Yukamijihwangwon, Palmihwan, Kamijeonssibaekchultang, Insamsukgotang, Sacngjinyanghyultang, Insambokryungsan, Hwalhyulyunjosaengjineum, Chungsinbogitang, Hwanggitang, Hwangryunjihwangtang, Ojeupokchunhwan, Yongbongwon, Joosahwangryunwon, Kagambaekchulsan) 2. Dry herbs like Banha, Namsung are the contraindicated herbs in the Sogal part of Donguibogam but Ijintang and Dodamtang which include those herbs also decreased the blood glucose level significantly. 3. The three medications-Bangpungtongsungsan, Bohyulansintang, Bogantang from the six me dications which were used to treat Diabetes in the 6th I.M. of Kyung Hee Oriental Hospital also decreased the blood glucose level significantly.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.351-359
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• 2009

Etiological studies of diabetes and its complications showed that oxidative stress might play a major role, Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Mori Fructus extract has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs, The aim of this study was to investigate the effect of Mori Fructus extract in male ob/ob mouse with severe obesity, hyperinsulinemia, hyperglycemia, hyperlipidemia. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57BL/6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus extract per 1 kg of body weight for 14 days. The effects of Mori Fructus extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Western blotting was performed using anti-AGE, anti-RAGE respectively. Mori Fructus extract lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Mori Fructus extract treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the generation of ROS in the kidney. MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the expression of AGE, RAGE in the ob/ob mice. The results suggested that Mori Fructus exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging the ROS, decreasing the MDA+HAE level, increasing the GSH level and inhibiting the expression of AGE, RAGE in the ob/ob mice.

• Applied Microscopy
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• v.38 no.1
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• pp.1-10
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• 2008

Dandelion has been frequently used as a remedy for women's disease, inflammatory diseases and disorders of the liver and gallbladder. Dandelion extracts water extract, an herbal medication, may have an effect on the activity of hepatic antioxidant enzymes in diabetic rat. This study aims demonstrate the effect of dandelion extracts, one of the natural chelator, on the biochemical and enzyme activity changes in the mouse liver caused by $HgCl_2$. Mice approximately 30 gm in weight were grouped into the control, mercury chloride-treated, and the dandelion extracts-treated after mercury chloride groups. $HgCl_2$ (5 mg/kg) and dandelion extracts (3 g/kg) were delivered orally. Serum AST and ALT were measured, enzyme activity of liver were examined by spectrophotometer and ultrastructural alteration of liver were examined by light and electron microscopy. Dandelion extracts were decreased the increase of serum AST and ALT level induced by mercury. The catalase activity was decreased in the dandelion extracts group. The activity of SOD was dereased, but did not show significant differences. Mercury chloride-treated hepatic cell were irregular nucleus, enlarged and reduced number of mitochodria, enlarged rough endoplasmic reticulum, loss of ribosomes. Cells treated with dandelion extracts were similar to those of the control group. In conclusion, dandelion extracts may protect the mercury-induced toxicity on Liver.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• Korean Journal of Food Science and Technology
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• v.39 no.3
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• pp.330-335
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• 2007

This study was performed to investigate the anti-diabetic mechanism of crude polysaccharides isolated from the fruiting bodies of Grifola frondosa. We treated 3T3-L1 adipocyte cells to observe whether the crude polysaccharides isolated from Grifola frondosa would stimulate insulin sensitivity. Significant insulin sensitizing activity was observed in the 3T3-L1 adipocytes, and giving the crude polysaccharide of Grifola frondosa with 1 nM of insulin caused glucose uptake to increase to a similar level as giving 50 nM of insulin alone. To confirm the mechanism for the anti-diabetic effect of the crude polysaccharides, we performed further examinations within $KK-A^{y}$ mice, an animal model of type 2 diabetes. The crude polysaccharides reduced blood glucose levels in the $KK-A^{y}$ mice for 2 weeks after feeding, and also significantly lowered plasma insulin levels. These results suggest that the anti-diabetic mechanism of the crude polysaccharide of Grifola frondosa is related to the enhancement of insulin sensitivity.