Ryong Kong

Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle

ETHNOPHARMACOLOGICAL RELEVANCE Ginseng (Panax ginseng C. A. Meyer, Araliaceae) has been used as a traditional medicine for thousands of years for the treatment of a wide variety of diseases, including diabetes. Processed ginseng named Black ginseng exhibits more potent biological activities than white and red ginseng. The aim of this study was to investigate the effects of black ginseng extract (GBG05-FF) on hyperglycemia and glucose tolerance in streptozotocin (STZ)-induced diabetic mice. MATERIALS AND METHODS Black ginseng was produced by a repeated steaming and drying process, subsequent extraction with 70% ethanol, filtration, and lyophilization. The effect of GBG05-FF on glucose uptake and related protein expression and phosphorylation were determined in C2C12 cells. Furthermore, we evaluated the anti-diabetic effects of GBG05-FF in STZ-induced diabetic mice. RESULTS GBG05-FF significantly (p<0.05) increased glucose uptake in C2C12 myotubes via AMPK, Sirt1 and PI3-K pathway. In addition, GBG05-FF improved the fasting blood glucose levels and glucose tolerance in STZ-induced diabetic mice. GBG05-FF decreased blood parameters such as glycated hemoglobin, triglyceride and total cholesterol. Quantitative RT-PCR assay revealed that in the STZ-induced diabetic mice treated with GBG05-FF, the expression of hepatic genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase)), glycogenolysis (liver glycogen phosphorylase (LGP)) and glycogenesis (glycogen synthase (GS)) was suppressed, while the expression of the genes involved in glucose uptake (glucose transporter (GLUT) 1, GLUT4) and β-oxidation (acyl-CoA oxidase (ACO), carnitine palmitoyl transferase 1a (CPT1a), mitochondrial medium chain acyl-CoA dehydrogenase (MCAD)) in muscle were increased. GBG05-FF delayed diabetes-associated muscle atrophy by activating mTOR. The major bioactive compounds including ginsenoside Rg1, Rg3(S), Rg3(R), Rg5, Rk1 and Rh4 were evaluated for glucose uptake effect in C2C12 myotubes; the data indicated that Rh4 significantly (p<0.05) increased glucose uptake. CONCLUSION Collectively, the results suggested that GBG05-FF is a potentially useful agent for treatment of diabetes by increasing glucose uptake.

Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.

The inhibition effect of Chlorpromazine against the β-lactam resistance of MRSA.

OBJECTIVE To investigate the gene related to β-lactam resistance and to confirm the mechanism about a synergy effect between CPZ and β-lactam antibiotics. METHODS To measure antibacterial activity, we performed a minimum inhibitory concentration (MIC) and synergy test. Transmission electron microscopy (TEM) was used in morphological analysis. To analyze gene expression, we conducted reverse transcriptase polymerase chain reaction (PCR). RESULTS We confirmed a synergy effect between CPZ and β-lactam antibiotics. Furthermore, we observed that CPZ affect the cell envelope of MRSA by using TEM. At the gene level, CPZ reduced the expression of resistance genes. CONCLUSIONS Through this result, we hypothesize that a decrease of resistance factor expressions was caused by CPZ because it disrupts the activity of a sensor protein located in the cell membrane.

Anti-diabetic effect of black ginseng extract by augmentation of AMPK protein activity and upregulation of GLUT2 and GLUT4 expression in db/db mice

BackgroundBlack ginseng (Panax ginseng C. A. Meyer), three to nine times-steamed and dried ginseng, has biological and pharmacological activities. In this study, the anti-diabetic effects of the black ginseng ethanol extract (GBG05-FF) in typical type 2 diabetic model db/db mice were investigated.MethodsThe effect of GBG05-FF in Type 2 diabetic mice was investigated by their blood analysis, biological mechanism analysis, and histological analysis.ResultsThe mice group treated with GBG05-FF showed decreased fasting blood glucose and glucose tolerance compared to that of the nontreated GBG05-FF group. In the blood analysis, GBG05-FF decreased main plasma parameter such as HbA1c, triglyceride, and total-cholesterol levels related to diabetes and improved the expression of genes and protein related to glucose homeostasis and glucose uptake in the liver and muscle. The histological analysis result shows that GBG05-FF decreased lipid accumulation in the liver and damage in the muscle. Moreover, GBG05-FF increased the phosphorylation of the AMPK in the liver and upregulated the expression of GLUT2 in liver and GLUT4 in muscle. Therefore, the mechanisms of GBG05-FF may be related to suppressing gluconeogenesis by activating AMPK in the liver and affecting glucose uptake in surrounding tissues via the upregulation of GLUT2 and GLUT4 expression.ConclusionThese findings provided a new insight into the anti-diabetic clinical applications of GBG05-FF and it might play an important role in the development of promising functional foods and drugs from the viewpoint of the chemical composition and biological activities.

Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillin

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that is cross-resistant to most β-lactam antibiotics. We investigated whether oxacillin, which is a β-lactam antibiotic, alone or in combination with punicalagin can affect the penicillin binding protein 2a (PBP2a)-mediated resistance of MRSA. Susceptibility testing of punicalagin with oxacillin was performed using the microdilution and checkerboard assay and the growth curve assay. Binding affinity of punicalagin for cell wall peptidoglycan (PGN) was confirmed by an increased concentration of PGN in bacterial cultures containing punicalagin. The level of PBP2a was analyzed by western blotting. Punicalagin exhibited antimicrobial activity in the viability assay and increased the susceptibility of MRSA to oxacillin. PGN interfered with the antimicrobial activity of punicalagin and prevented the synergistic activity of punicalagin and oxacillin. Increasing the concentration of punicalagin and maintaining a constant concentration of oxacillin resulted in synergistic suppression of the expression of the mec operon (mecA, mecI, and mecR1). The production of PBP2a was suppressed by the addition of punicalagin to oxacillin. Our findings demonstrate that punicalagin potentiates the effect of oxacillin on MRSA by reducing the transcription of mecA (a gene marker for methicillin resistance), which resulted in a reduced level of PBP2a.

The Anti-Diabetic Effects and Nephroprotective Effect of Black Ginseng Prosapogenin Extract in Streptozotocin-Induced Mice

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.