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Water Extract of Potentilla discolor Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

ABSTRACT: Potentilla discolor Bunge, as a traditional Chinese medicine, exhibits many phytochemical activities. The aim of the present study was to investigate the effects of Potentilla discolor Bunge water extract (PDBW) and its underlying mechanisms on gluconeogenesis and glycogen synthesis in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice. LC-MS/MS analyses of PDBW identified 6 major compounds including apigenin-7-O-?-D-glucoside, epicatechin, quercetin 3-O-?-D-glucuronide, kaempferol-3-O-?-D-glucopyranoside, scutellarin, and quercitrin. In the study, a mouse model of type 2 diabetes was induced by 4-week HFD combined with STZ (40 mg/kg body weight) for 5 days. After oral administration of PDBW at 400 mg/kg body weight daily for 8 weeks, the mice with type 2 diabetes showed significant decrease in the levels of fasting blood glucose and glycated hemoglobin A1c (HbA1c), and increase in the insulin level. PDBW improved the glucose tolerance, insulin sensitivity and lipid profiles. Furthermore, PDBW inhibited the mRNA levels of key gluconeogenic enzymes [phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)] in liver. PDBW also promoted glycogen synthesis by raising the liver glycogen content, decreasing the phosphorylation of glycogen synthase (GS) and increasing the phosphorylation of glycogen synthase kinase3? (GSK3?). Besides, PDBW induced the activation of protein kinase B (Akt) and AMP-activated protein kinase (AMPK), which might explain changes in the phosphorylation of above enzymes. In summary, PDBW supplementation ameliorates metabolic disorders in a HFD/STZ diabetic mouse model, suggesting the potential application of PDBW in prevention and amelioration of type 2 diabetes.

SUBMITTER: Li T

PROVIDER: S-EPMC7522508 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Water Extract of Potentilla discolor Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

Li Tiange T Chang Rui R Zhang Huijuan H Du Min M Mao Xueying X

Frontiers in nutrition 20200915

Potentilla discolor Bunge, as a traditional Chinese medicine, exhibits many phytochemical activities. The aim of the present study was to investigate the effects of Potentilla discolor Bunge water extract (PDBW) and its underlying mechanisms on gluconeogenesis and glycogen synthesis in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice. LC-MS/MS analyses of PDBW identified 6 major compounds including apigenin-7-O-β-D-glucoside, epicatechin, quercetin 3-O-β-D-glucur ...[more]

PMID: 33043040

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Project description:Background/aim: Potentilla discolor Bunge (PDB) is an ancient herb of traditional Chinese medicine. Studies have suggested that extracts of PDB may ameliorate diabetes mellitus (DM). This study aimed to systematically assess the efficacy of PDB extracts on glycolipid metabolism and oxidative stress in animal models of diabetes and to provide evidence-based references for the use of PDB extracts. Methods: This study followed the PRISMA 2020 guidelines. Studies were searched from eight databases until January 2023. Statistical analysis was performed using StataSE 15.0 and RevMan 5.3. The standard mean difference (SMD) and 95% confidence intervals (CI) were computed using the random-effects model. SYRCLE's risk of bias tool was used to assess the risk of bias. Results: In total, 32 studies with 574 animals were included. The findings demonstrated that PDB extracts considerably lowered fasting blood glucose (SMD: -3.56, 95%CI: -4.40 to -2.72, p < 0.00001); insulin resistance (SMD: -3.19, 95% CI: -5.46 to -0.92, p = 0.006), total cholesterol (SMD: -2.18, 95%CI: -2.89 to -1.46, p < 0.00001), triglyceride (SMD: -1.48, 95% CI: -2.01 to -0.96, p < 0.00001), low-density lipoprotein cholesterol (SMD: -1.80, 95% CI: -2.58 to -1.02], p < 0.00001), malondialdehyde (SMD: -3.46, 95% CI: -4.64 to -2.29, p < 0.00001) and free fatty acid levels (SMD: -3.25, 95%CI: -5.33 to -1.16, p = 0.002), meanwhile, increased insulin sensitivity index (SMD: 2.51 95% CI: 1.10 to 3.92, p = 0.0005), body weight (SMD:1.20, 95% CI: 0.38 to 2.01, p = 0.004), and the levels of high-density lipoprotein cholesterol (SMD: 1.04, 95% CI: 0.40 to 1.69, p = 0.001), superoxide dismutase (SMD:2.63, 95% CI: 1.53 to 3.73, p < 0.00001), glutathione peroxidase (SMD:1.13, 95%CI: 0.42 to1.83, p = 0.002), and catalase (SMD:0.75, 95% CI: 0.11 to 1.40], p = 0.02). Conclusion: These findings suggest that PDB extracts can ameliorate DM by improving glycolipid metabolism and oxidative stress. PDB may be a promising medication for DM; however, due to significant heterogeneity between studies, these findings should be interpreted with caution. In addition, future well-designed trials should determine which components of the PDB play a major role in ameliorating DM and whether these benefits persist in humans. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, CRD42023379391.

Project description:PurposeType 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM.MethodsComponents and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments.ResultsNetwork pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; β-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and β-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM.ConclusionOur findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

Project description:BACKGROUNDWhile saturated fat intake leads to insulin resistance and nonalcoholic fatty liver, Mediterranean-like diets enriched in monounsaturated fatty acids (MUFA) may have beneficial effects. This study examined effects of MUFA on tissue-specific insulin sensitivity and energy metabolism.METHODSA randomized placebo-controlled cross-over study enrolled 16 glucose-tolerant volunteers to receive either oil (OIL, ~1.18 g/kg), rich in MUFA, or vehicle (VCL, water) on 2 occasions. Insulin sensitivity was assessed during preclamp and hyperinsulinemic-euglycemic clamp conditions. Ingestion of 2H2O/acetaminophen was combined with [6,6-2H2]glucose infusion and in vivo 13C/31P/1H/ex vivo 2H-magnet resonance spectroscopy to quantify hepatic glucose and energy fluxes.RESULTSOIL increased plasma triglycerides and oleic acid concentrations by 44% and 66% compared with VCL. Upon OIL intervention, preclamp hepatic and whole-body insulin sensitivity markedly decreased by 28% and 27%, respectively, along with 61% higher rates of hepatic gluconeogenesis and 32% lower rates of net glycogenolysis, while hepatic triglyceride and ATP concentrations did not differ from VCL. During insulin stimulation hepatic and whole-body insulin sensitivity were reduced by 21% and 25%, respectively, after OIL ingestion compared with that in controls.CONCLUSIONA single MUFA-load suffices to induce insulin resistance but affects neither hepatic triglycerides nor energy-rich phosphates. These data indicate that amount of ingested fat, rather than its composition, primarily determines the development of acute insulin resistance.TRIAL REGISTRATIONClinicalTrials.gov NCT01736202.FUNDINGGerman Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, Portugal Foundation for Science and Technology, European Regional Development Fund, and Rede Nacional de Ressonancia Magnética Nuclear.

Dataset Information

Water Extract of Potentilla discolor Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

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Water Extract of <i>Potentilla discolor</i> Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

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