ginsenoside-rg3 and Diabetes-Mellitus--Type-2

Type 2 diabetes is known to abrogate the vascular response. Combination of two commonly consumed ginseng species, American ginseng (AG) and a Korean Red ginseng (KRG), enriched with ginsensoide Rg3, was shown to concomitantly improve glucemic control and blood pressure. We evaluated the hypothesis that improvements in central hemodynamics, vascular function and stiffness markers are involved in observed benefits of co-administration.. In this randomized, placebo controlled, two-center trial, patients with type 2 diabetes and hypertension were assigned to either 2.25 g ginsenoside Rg3-enriched KRG&AG co-administration or a control 3 times daily for 12-weeks, treated by standard of care. The effects on central hemodynamics, pulse wave velocity (PWV) and endothelial function over the 12-week administration were analyzed.. In intent-to-treat analysis of 80 individuals, a reduction in central systolic BP (-4.69 ± 2.24 mmHg, p = 0.04) was observed with co-administration of Rg3-KRG + AG relative to control at 12-weeks, which was characterized by a decrease in end-systolic pressure (-6.60 ± 2.5 mmHg, p = 0.01) and area under the systolic/diastolic BP curve (-132.80 ± 65.1, p = 0.04, 220.90 ± 91.1, p = 0.02, respectively). There was no significant change in reactive hyperemia index (0.09 ± 0.11, p = 0.44), PWV (-0.40 ± 0.28 %, p = 0.17), and other related pulse wave analysis components.. Co-administration of complementary ginseng species improved central systolic BP and components of pulse waveform without a direct effect on endothelial function, when added to background pharmacotherapy in individuals with diabetes. These data support potential utility of ginseng for modest blood pressure benefit to broaden its role in diabetes management.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Ginsenosides; Humans; Hypertension; Male; Middle Aged; Panax; Plant Extracts

Diabetic nephropathy (DN) is a major complication of diabetes. The kidney disease develops in nearly 20%-40% of type 2 diabetes (T2D) patients. Ginseng is the root of Panax ginseng C. A. Meyer and has been used in prevention and treatment of diseases for more than 2000 years as a traditional oriental medicine. The 20(R)-ginsenoside Rg3, an active saponin isolated from ginseng, can prevent and treat many diseases. The object of this research was to explore the alleviative effects of 20(R)-Rg3 on DN in mice.. The T2D animal model was induced by continuous access to a high fat diet (HFD) combined with a single injection of 100 mg/kg streptozotocin (STZ) in C57BL/6 mice. The mice were treated by oral gavage of the 20(R)-Rg3 (10, 20 mg/kg) for 8 weeks. Functional and histopathological analyses of the kidneys were then performed. Protein expression levels of MAPKs and NF-κB signal pathways in the kidney were evaluated by western blotting. The expressions of HO-1 and NF-κB in the kidney were measured by fluorescent labeling staining. Other assessments including fasting blood glucose (FBG) levels, blood lipids, oxidative indicators, and inflammatory factors were all performed.. Abnormally elevated FBG levels were observed in HFD/STZ mice, contributing significantly to the occurrence of DN. Simultaneously, HFD/STZ mice showed the rise of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the decrease in high density lipoprotein cholesterol (HDL-C). DN was evidenced by the overproduction of malondialdehyde (MDA), decreased levels of superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, high levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Simultaneously, the results of the immunofluorescence assay showed an increased expression level in NF-κB p65 while a decrease in antioxidant enzyme HO-1 was observed. Herein, 20(R)-Rg3 treatment for 8 weeks not only attenuated FBG levels and advanced glycation end products (AGEs) levels but also improved insulin (INS) level, blood lipids, oxidative stress, and renal function by regulating MAPKs and NF-κB signal pathways in DN mice.. Taken together, the findings from the present study explicitly confirmed that 20(R)-Rg3 exerted ameliorative effects on DN mice via improving anti-oxidative activity and reducing renal inflammation.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diet, High-Fat; Ginsenosides; Heme Oxygenase-1; Hypoglycemic Agents; Kidney; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidative Stress; Signal Transduction; Streptozocin; Transcription Factor RelA

Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes.. An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry (UPLC/Q-Orbitrap MS).. The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1-M5) of glimepiride were found, and they were named 3N-hydroxyglimepiride, hydroxyglimepiride, 1,2-epoxy ether-3-hydroxyglimepiride, 1N-hydroxyglimepiride and 1N,2C,S,O,O-epoxy ether-3-hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2.. An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.

Topics: Animals; Chromatography, Liquid; Cytochrome P-450 Enzyme Inhibitors; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Drug Synergism; Ginsenosides; Hypoglycemic Agents; Male; Microsomes, Liver; Molecular Structure; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization; Streptozocin; Sulfonylurea Compounds; Tandem Mass Spectrometry

Ginsenosides can be classified on the basis of the skeleton of their aglycones. Here, we hypothesized that the sugar moieties attached to the dammarane backbone enable binding of the ginsenosides to the sweet taste receptor, eliciting glucagon-like peptide-1 (GLP-1) secretion in the enteroendocrine L cells. Using the human enteroendocrine NCI-H716 cells, we demonstrated that 15 ginsenosides stimulate GLP-1 secretion according to the position of their sugar moieties. Through a pharmacological approach and RNA interference technique to inhibit the cellular signal cascade and using the Gαgust(-/-) mice, we elucidated that GLP-1 secreting effect of Rg3 mediated by the sweet taste receptor mediated the signaling pathway. Rg3, a ginsenoside metabolite that transformed the structure through a steaming process, showed the strongest GLP-1 secreting effects in NCI-H716 cells and also showed an anti-hyperglycemic effect on a type 2 diabetic mouse model through increased plasma GLP-1 and plasma insulin levels during an oral glucose tolerance test. Our study reveals a novel mechanism where the sugar moieties of ginsenosides Rg3 stimulates GLP-1 secretion in enteroendocrine L cells through a sweet taste receptor-mediated signal transduction pathway and thus has an anti-hyperglycemic effect on the type 2 diabetic mouse model.

Topics: Animals; Cell Line, Tumor; Diabetes Mellitus, Type 2; Enteroendocrine Cells; Enzyme-Linked Immunosorbent Assay; Gene Expression; Ginsenosides; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hyperglycemia; Immunoblotting; Mice, Inbred C57BL; Mice, Knockout; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transducin

20(S)-ginsenoside Rg3 is an active component of Panax ginseng. It is known that 20(S)-ginsenoside Rg3 has a protective effect against hyperglycemia, obesity and diabetes in vivo, but the precise mechanisms of these actions have not yet been entirely elucidated.. A urinary metabonomics method based on rapid-resolution liquid chromatography/mass spectrometry (RRLC/MS) was developed to investigate the effect of 20(S)-ginsenoside Rg3 on type 2 diabetic rats.. With multivariate statistical analysis, a clear separation between type 2 diabetic rats and those treated with 20(S)-ginsenoside Rg3 was achieved. Six potential biomarkers were found and identified.. This work shows that the mechanism of the effect of 20(S)-ginsenoside Rg3 on type 2 diabetes may be involved with the regulation of nucleic acid metabolism, energy metabolism and gut flora metabolism.

Topics: Animals; Chromatography, Liquid; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Ginsenosides; Male; Mass Spectrometry; Metabolomics; Panax; Rats; Rats, Wistar

Ginsenosides, the active component of Panax ginseng, have been shown to evidence a variety of biological activities associated with hyperglycemia, obesity and type 2 diabetes mellitus. This study evaluated the effects of the ginsenosides, Rg3 and Re, on glucose uptake and the glucose transport system in mature 3T3-L1 cells. The results demonstrated that the glucose uptake of ginsenosides Rg3 and Re at concentrations of 1-10 µM significantly increased by approximately ∼10% and ∼12%, respectively. Furthermore, the glucose transporter 4 (GLUT4) mRNA expression of ginsenosides Rg3 and Re at 10 µM was increased by approximately ∼1.73 and 1.43 fold, respectively. It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS-1) and the expression of phosphatidylinositol 3-kinase (PI3K)-110α protein, which is involved in downstream events in the insulin signaling pathway. These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS-1. Further, our results suggest that both of these ginsenosides might prove useful as effective antidiabetic and antihyperglycemic agents.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Biological Transport; Diabetes Mellitus, Type 2; Ginsenosides; Glucose; Glucose Transporter Type 4; Hyperglycemia; Insulin Receptor Substrate Proteins; Mice; Panax; Phosphatidylinositol 3-Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction