ginsenoside-m1 and Body-Weight

The prevalence of pre-diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre-diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha-cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti-hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12-month randomized controlled trial to investigate the metabolic effects of these two products in people with pre-diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow-up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre-diabetes to help reduce the risk of progression to type 2 diabetes.

Topics: Adult; alpha-Cyclodextrins; Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Female; Ginsenosides; Humans; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Triglycerides

Ginsenoside compound K (CK) is a hydrolysate of ginsenosides in the soil bacteria. This study evaluated the toxicity of CK as acute and the 26-week repeated-dose. The results of acute toxicity show that CK administered orally to rats and mice did not cause mortality or toxicity at the maximum dosage of 8 g/kg and 10 g/kg, respectively. In the toxicity study for 26-week, rats were administered with CK at doses of 13, 40, or 120 mg/kg, and were observed for 26 weeks and recovery periods of four weeks. Under the conditions, asthenia, hypoactivity, loss of fur and body weight reduction were transiently noticed in males of 120 mg/kg group. Hepatotoxicity and nephrotoxicity also were evident including the elevation of liver and kidney relative weight, along with focal liver necrosis as well as the increase in plasma enzymes (ALT and ALP) in male rats receiving CK (120 mg/kg), but this toxicity might be reversible. For 13 and 40 mg/kg CK groups, there was no significant variation in food habits, clinical signs, urine analysis, body weight, biochemical and hematological values, organ coefficient and histopathology examination. The NOAEL for male and female rats were observed to be 40 and 120 mg/kg, respectively.

Topics: Administration, Oral; Animals; Body Weight; Female; Ginsenosides; Kidney; Liver; Male; Mice; No-Observed-Adverse-Effect Level; Organ Size; Pilot Projects; Rats, Sprague-Dawley; Time Factors; Toxicity Tests, Acute

Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Ginsenosides; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipids; Male; Molecular Structure; Panax; Plant Roots; Rats; Rats, Wistar; Signal Transduction; Streptozocin

Investigation was conducted to understand the mechanism of action of diacylglycerol acyltransferase 1 (DGAT1) using small molecules DGAT1 inhibitors, compounds K and L.. Biochemical and stable-label tracer approaches were applied to interrogate the functional activities of compounds K and L on TG synthesis and changes of carbon flow. Energy homeostasis and gut peptide release upon DGAT1 inhibition was conducted in mouse and dog models.. Compounds K and L, dose-dependently inhibits post-prandial TG excursion in mouse and dog models. Weight loss studies in WT and Dgat1(-/-) mice, confirmed that the effects of compound K on body weight loss is mechanism-based. Compounds K and L altered incretin peptide release following oral fat challenge. Immunohistochemical studies with intestinal tissues demonstrate lack of detectable DGAT1 immunoreactivity in enteroendocrine cells. Furthermore, (13) C-fatty acid tracing studies indicate that compound K inhibition of DGAT1 increased the production of phosphatidyl choline (PC).. Treatment with DGAT1 inhibitors improves lipid metabolism and body weight. DGAT1 inhibition leads to enhanced PC production via alternative carbon channeling. Immunohistological studies suggest that DGAT1 inhibitor's effects on plasma gut peptide levels are likely via an indirect mechanism. Overall these data indicate a translational potential towards the clinic.

Topics: Animals; Body Composition; Body Weight; Chromatography, Liquid; Diacylglycerol O-Acyltransferase; Disease Models, Animal; Dogs; Enteroendocrine Cells; Feces; Gastrointestinal Tract; Ginsenosides; Hormones; HT29 Cells; Humans; Immunohistochemistry; Lactones; Male; Mice; Mice, Inbred C57BL; Orlistat; Postprandial Period; Tandem Mass Spectrometry; Triglycerides

Compound K, i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, is the main metabolite of the protopanaxadiol type of ginseng saponin produced by intestinal bacteria after oral administration of ginseng extract. In the present study, the toxicity of compound K was evaluated in male and female dogs after 90 days continuous intravenous infusion. Beagle dogs were treated with compound K at doses of 6.7, 20 and 60 mg/kg/day, and observed for 90 days followed by recovery periods. Measurements included clinical observations, body weight, food consumption, temperature, electrocardiogram (ECG), hematology, blood chemistry, urinalysis, gross necropsy, organ weight and histopathology. Under the conditions, the clinical condition of the animals, body weights, body weight gains and food consumption were unaffected by compound K administration relative to the control group. Hematology, ECG data and urinalysis parameters were also unaffected. However, the hepatotoxicity was evident from the observation of multiple parameters, including histopathological evaluation of liver tissue upon necropsy as well as large increases in plasma levels of liver enzymes (alanine aminotransferase, ALT, Gamma-glutamyltranspeptidase, γ-GT, alkaline phosphatase,ALP) in groups receiving compound K (20 or 60 mg/kg/day), and this hepatoxicity might be reversible. In addition, the NOAEL of compound K is 6.7 mg/kg/day in this 90 days toxicity study.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Body Weight; Dogs; Dose-Response Relationship, Drug; Eating; Electrocardiography; Female; Ginsenosides; Injections, Intravenous; Liver; Male; No-Observed-Adverse-Effect Level; Organ Size; Panax; Plant Extracts; Toxicity Tests, Chronic; Urinalysis

To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG) and its metabolite ginsenoside M1 (G-M1) on carbon tetrachloride (CCl(4))-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST) and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl(4)-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biotransformation; Body Weight; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Chronic Disease; Ginsenosides; Liver; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Organ Size; Protective Agents; Sapogenins; Snails; Spectrometry, Mass, Electrospray Ionization; Superoxide Dismutase; Tissue Extracts