Application of low-dose ursolic acid as medicament for treating diabetic early nephropathy

A technology for kidney disease and preparation of drugs, which is applied in drug combinations, urinary system diseases, and pharmaceutical formulations, etc.

Inactive Publication Date: 2011-10-05
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the animal level, especially without affecting non-fasting blood glucose levels, whether low-dose ursolic acid can significantly inhibit diabetes-induced glomerular hypertrophy and accumulation of type IV collagen in glomeruli and be used as a treatment for early diabetic nephropathy drugs, no studies have reported

Method used

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  • Application of low-dose ursolic acid as medicament for treating diabetic early nephropathy
  • Application of low-dose ursolic acid as medicament for treating diabetic early nephropathy
  • Application of low-dose ursolic acid as medicament for treating diabetic early nephropathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: Effects of Oral Ursolic Acid on Various Physiological Characteristics of Diabetic Mice

[0031] After feeding the diabetic mice with ursolic acid for 3 months, the body weight of the mice in each experimental group was measured, and blood was taken from the tail vein to determine the blood sugar level. The kidney weight of each group of mice was weighed, and the kidney weight / body weight was calculated, and the results are shown in Table 1.

[0032] Table 1. Experimental results of physiological characteristics of mice

[0033] Group (sample size)

weight(g)

Blood sugar (mmol / dl)

Kidney weight (mg)

Kidney weight / body weight (%)

Diabetic group (10)

22.9±1.6 a

27.2±5.6 a

178.6±19.6 a

0.78±0.10 a

Diabetic group + oral ursolic acid (10)

24.2±1.2 a

23.0±4.4 a

177.6±14.4 a

0.74±0.07 a

Non-diabetic group (10)

27.5±2.3

11.2±1.4

163.8±20.3

0.60±0.07

...

Embodiment 2

[0036] Embodiment 2: Inhibition of oral ursolic acid on glomerular hypertrophy caused by diabetes

[0037] The glomerulus is the most important ultrafiltration organ in the kidney. It maintains a low concentration of protein in the blood and urine to ensure the normal function of the body. In diabetes, the glomeruli are overloaded with ultrafiltration, resulting in pathological hypertrophy of the glomeruli.

[0038]After the kidneys of the mice in each experimental group were fixed with 10% neutral formaldehyde, they were routinely embedded in paraffin. Kidney sections were stained with PASH. 25-35 glomeruli were randomly selected from each mouse kidney section, and the area of ​​each glomerulus was measured using ImagePlus 6.0 software after photographing with an Olympus BX60 microscope equipped with a CCD under a field of view of 400 times magnification. The volume of the glomerulus is calculated using the following formula: volume of the glomerulus (Vg) = β / k [area of ​​t...

Embodiment 3

[0040] Embodiment 3: The inhibitory effect of oral ursolic acid on the accumulation of type IV collagen caused by diabetes in glomeruli

[0041] The accumulation of extracellular matrix proteins in the glomerulus is one of the main causes of glomerulosclerosis and renal failure in post-diabetes. Type IV collagen is one of the major proteins of the kidney extracellular matrix protein. The expression of type IV collagen in the kidney was determined by immunohistochemical method. Conventional kidney paraffin sections were rehydrated with xylene and different concentrations of ethanol, and then 3% hydrogen peroxide was used to block the activity of endogenous peroxidase. After the sections were blocked with 2% goat serum, they were incubated overnight at 4°C with an antibody to type IV collagen (Rockland, USA). Washed with PBST, incubated with the corresponding secondary antibody at room temperature for 1 hour. The signal was amplified by the ABC kit (Vector Laboratories, USA),...

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Abstract

The invention discloses an application of a low-dose ursolic acid as a medicament for treating diabetic early nephropathy. The administration mode of the ursolic acid is oral administration, and the administration dose is 50-70mg / kg weight. The invention verifies that the oral administration of the low-dose ursolic acid has a remarkable inhibition action for the activation of ERK1 / 2 and JNK accesses in an MAPK access in a renal cortex induced by diabetes and the phosphorylation level of STAT3 tyrosine and can markedly lower the expression of iNOS in the renal cortex induced by the diabetes, and more importantly, the oral administration of the ursolic acid can inhabit the glomerular hypertrophy caused by the diabetes and the accumulation of type IV collagen at glomerulus, thereby indicating that the oral administration of the ursolic acid has a remarkable therapeutic effect on the diabetic early nephropathy.

Description

technical field [0001] The invention relates to the use of low-dose ursolic acid as a medicine for treating diabetic complications, in particular to the use of a medicine for treating early diabetic nephropathy. Background technique [0002] Diabetic nephropathy is one of the microvascular complications of diabetes, and is the main cause of chronic kidney disease and end-stage renal failure in diabetic patients. There are many reasons for diabetic nephropathy, including hemodynamic changes in renal tissue caused by diabetes (including the imbalance of blood flow regulation of renal vessels by renin-angiotensin and kinin-prostaglandin-thromboxane), diabetes-induced renal Biochemical metabolic disorders of tissues (including increased polyol pathway, increased protein non-enzymatic glycosylation, lipid metabolism disorders, etc.) and some diabetic patients also have symptoms of hypertension, etc. About 20-30% of diabetic patients suffer from nephropathy, which manifests as ex...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61P3/10A61P13/12A61K31/56
Inventor 郑凌周翼黄昆
Owner WUHAN UNIV
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