Suppressive activity of mango aglycone on PTP1B and application thereof

A technology of mangiferin and inhibitors, which is applied in the field of biopharmaceuticals and can solve problems such as insulin sensitivity that have not yet been seen

Inactive Publication Date: 2010-03-17
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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However, there are no research reports on its inhibi

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  • Suppressive activity of mango aglycone on PTP1B and application thereof
  • Suppressive activity of mango aglycone on PTP1B and application thereof
  • Suppressive activity of mango aglycone on PTP1B and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1 Mangiferin aglycon is to the inhibitory activity determination of PTP1B (IC 50 Determination of value)

[0027] Mangiferin aglycon was dissolved in a small amount of DMSO and diluted with MOPS buffer, and 10 μl was added to a 100 μl reaction system (pH 7.0, 25 mM mops, 1 mM EDTA, 2 mM DTT, 0.1 M NaCl), so that the final concentrations were 1500, 150, 15, 1.5, 0.15 μM, add the substrate pNPP to 16mM, add 5ng of recombinant human PTP1B and place it at 37°C for 30min. Add 10 μl of 1M NaOH to terminate the reaction, place it on a microplate reader to measure the absorbance A at a wavelength of 405 nm, and use sodium metavanitate (NaVO 3 ) as a positive control, and without adding PTP1B as a blank control, the inhibition rate was calculated. Use the inhibition rate to plot the concentration to get the mangiferin aglycon IC 50 9.2 μM, sodium metavanate IC 50 is 0.32 μM.

Embodiment 2

[0028] Example 2 Determination of the inhibition kinetics of PTP1B by mangiferin aglycone

[0029] Different concentrations of pNPP (32, 16, 8, 4, 2mM) and different concentrations of NL solutions (1.25, 2.5, 5, 10, 20μM) were prepared respectively. Each NL concentration corresponds to 5 groups of pNPP concentrations for inhibitory activity determination, and V is calculated according to the change of OD405, and the corresponding substrate concentration is S, and the graphs are drawn according to the L-B equation. The results showed that the straight lines intersected on the Y axis, so it can be judged that NL is a competitive inhibitor of PTP1B.

Embodiment 3

[0030] Example 3 Effect of mangiferin on improving insulin sensitivity in normal mice

[0031] C57BL / 6 mice were randomly divided into 5 groups with 11 mice in each group, which were control group and NL administration group with different doses (100, 60, 40, 15 mg / kg). The treatment groups were intragastrically administered different concentrations of NL (suspended with 0.5% CMC-Na aqueous solution), and the control group were intragastrically administered 0.5% CMC-Na aqueous solution. Continuous administration for 7 days, fasting for 12 hours after the last administration, intraperitoneal injection of insulin at 1 U / kg, blood samples were taken at 0, 15, 30, 60, 90, and 120 minutes to measure blood glucose levels.

[0032] Insulin Tolerance Test (Insulin Tolerance Test, ITT) experiment shows that NL (5, 40mg / kg) can significantly improve the insulin sensitivity of C57BL / 6 mice, reduce its blood sugar, and there are significant differences in the last four time points (p< 0....

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Abstract

The invention belongs to the technical field of biological pharmacy, and in particular relates to suppressive activity detection of tetrahydroxy norathyriol on protein-tyrosine-phosphatase (PTP) 1B, improvement of resistance function of insulin and accpication in medicament for PTP1B related diseases. Proved by in vitro enzyme suppression experiments, the invention testifies that mango aglycone is the competitive suppressant of restructuring humanized PTP1B with IC50 value being 9.2 mu m; mango aglycone can ensure the sensitivity of C57BL/6 normal mouse and ob/ob diabetes model mouse on insulin to be obviously improved, and reduce blood sugar of experimental animals, which suggests that mango aglycone is a novel suppressant of PTP1B, and can be taken as potential lead compound to be applied in preparing medicament for curing insulin resistance related diabetes, obesity and other metabolic syndrome, tumor and other PTP1B related diseases.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and specifically relates to the inhibitory activity of mangiferin on protein tyrosine phosphatase 1B (PTP1B), the effect of improving insulin resistance, and the preparation and treatment of metabolic syndromes such as type II diabetes, obesity, tumors and other diseases. Drug application in PTP1B-related diseases. Background technique [0002] The phosphorylation level of protein tyrosine is an important regulator of intracellular signal transduction, which is regulated by protein tyrosine kinase (Proteintyrosine kinase, PTK) and protein tyrosine phosphatase (Protein tyrosine phosphatase, PTP), PTP1B (Protein tyrosine phosphatase 1B, PTP1B) belongs to the PTP family, is an important negative regulator in the insulin signaling pathway and participates in the signal transduction process of leptin, various growth factors, prolactin, integrin, platelet hemagglutinin, etc., and diabetes ,...

Claims

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Application Information

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IPC IPC(8): A61K31/352A61P5/48A61P3/10A61P3/04A61P3/00A61P35/00
Inventor 徐琛何凤霞张辰宇张昊邓小达周平张艳吴冬冬李佳李金波
Owner NANJING UNIV
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