Application of asperuloside in preparation of medicine for treating diabetic nephropathy

Abstract

The invention provides application of asperuloside in preparation of a medicine for treating diabetic nephropathy, the structural formula of the asperuloside is as shown in the specification, and imgabs0 #. Experiments find that the asperuloside has the effect of delaying the diabetic nephropathy of db / db mice, and a new method is provided for treating the diabetic nephropathy.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine and relates to the use of calendula officinalis in preparing medicines for treating diabetic nephropathy. Background Art

[0002] Diabetic nephropathy (DKD) is a chronic kidney disease caused by diabetes, characterized by abnormally high levels of protein in the urine, i.e., urine protein / creatinine ratio (UACR) reaches or exceeds 30 mg / g, or glomerular filtration rate (GFR) drops below 60 ml per minute, and these symptoms persist for more than three months. In the early stages, patients may experience microalbuminuria, and as the disease progresses, symptoms such as persistent massive proteinuria and hypertension may occur, which may eventually lead to end-stage renal disease (ESRD).

[0003] Traditional Chinese medicine monomers are an important source of clinical drugs, and their safety and effectiveness have been widely recognized. Studies have shown that traditional Chinese medicine monomers have significant pharmacological effects. For example, flavonoids have antioxidant, anti-inflammatory, cardiovascular and cerebrovascular protection, neuroprotection and immunomodulatory functions, while alkaloids exhibit multiple effects such as anti-pathogenic microorganisms, hypoglycemic and hypolipidemic effects. Although many traditional Chinese medicines play an important role in the treatment of kidney disease, their molecular targets and mechanisms of action are still unclear. Screening out drugs with clear efficacy and clear mechanisms of action from hundreds of traditional Chinese medicine prescriptions has become a major challenge in the development of monomer drugs.

[0004] Therefore, in order to improve renal function, delay the development of kidney disease and treat kidney disease, it is particularly important to find and simplify the screening and verification process of Chinese medicine monomers, and identify the most promising monomer drugs. In-depth exploration of the role of Chinese medicine monomers in the treatment of diabetic nephropathy and elucidation of their mechanism of action and molecular targets will lay a more solid scientific foundation for the development of Chinese medicine monomer drugs for the treatment of kidney disease.

[0005] Iridoids are a class of natural products widely distributed in nature that contain a special acetal structure. These compounds are found in a variety of plants and have been extensively studied for their diverse biological activities. They show significant pharmacological effects in terms of hepatoprotection, choleresis, anti-inflammatory and neuroprotection. Of particular note, iridoids have shown good potential for the treatment of cerebral ischemic injury, Parkinson's disease and other diseases associated with aging.

[0006] Calendula glycoside is a specific iridoid compound, which is mainly extracted from plants such as Rubiaceae and Eucommiaceae. Modern pharmacological studies have shown that Calendula glycoside has a wide range of pharmacological effects such as anti-inflammatory, analgesic, and hypotensive, and has shown positive therapeutic effects on diseases such as cerebral ischemic injury, Alzheimer's disease, and Parkinson's disease. These studies provide a scientific basis for the application of Calendula glycoside in the treatment of kidney disease and other aspects, and point out the direction of further research, that is, to explore its specific mechanism of action and pathway targets in the treatment of diabetic nephropathy. Summary of the invention

[0007] In view of the above problems, the present invention provides the use of calendula glycoside in the preparation of a drug for treating diabetic nephropathy. The use of calendula glycoside in the preparation of a drug for treating diabetic nephropathy is intended to solve the technical problem that the drugs in the prior art are not effective in treating diabetic nephropathy.

[0008] The present invention provides the use of calendula glycoside in preparing a drug for treating diabetic nephropathy. The structural formula of the calendula glycoside is shown below:

[0009]

[0010] The molecular formula of the monomer compound of phytosinoside: C 18 H 22 O 11 , CAS: 14259-45-1.

[0011] The present invention predicts the therapeutic effect of calendula glycoside in diabetic nephropathy by detecting the fasting blood sugar, body weight and food intake of db / db mice, which is helpful to explore the mechanism of action for treating diabetic nephropathy and provides a new treatment scheme for treating diabetic nephropathy. The present invention finds through experiments that calendula glycoside has the effect of delaying diabetic nephropathy in db / db mice, and provides a new method for treating diabetic nephropathy.

[0012] Compared with the prior art, the technical effect of the present invention is positive and obvious. Compared with compound Chinese medicine, the calendula glycoside of the present invention has no obvious toxic side effects, and the single efficacy Chinese medicine treatment has better efficacy controllability and efficacy evaluation. The Chinese medicine monomer calendula glycoside is used to treat diabetic nephropathy, which has a wide source, low cost, good efficacy, and can be used for long-term treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It was shown that strychnosyl glycoside improved fasting blood glucose, body weight, and food intake in diabetic nephropathy mice.

[0014] Figure 2 It was shown that calendula officinalis reduced the 24-hour urine volume in diabetic nephropathy mice.

[0015] Figure 3showed that calendula officinalis reduced urine albumin and urine albumin / creatinine ratio in diabetic nephropathy mice.

[0016] Figure 4 It was shown that calendula officinalis reduced serum creatinine in diabetic nephropathy mice.

[0017] Figure 5 showed that calendula officinalis reduced urea nitrogen in diabetic nephropathy mice.

[0018] Figure 6 PAS staining of glomeruli and tubules of diabetic nephropathy mice is shown.

[0019] Figure 7 It was shown that calendula officinalis improved glomerular sclerosis in mice with diabetic nephropathy.

[0020] Figure 8 It was shown that calendula officinalis glycoside improved the thickening of renal tubular basement membrane and interstitial fibrosis in mice with diabetic nephropathy. DETAILED DESCRIPTION

[0021] The downstream of Example 1 was tested by animal model to verify its therapeutic effect on diabetic nephropathy.

[0022] The mice used in this experiment were purchased from Saiye Biotechnology Co., Ltd. The db / db diabetic mice were given oral administration for 12 consecutive weeks. Mice with fasting blood glucose>=16.7mmol / L were selected for inclusion in the study. When significant proteinuria occurred, the mice were randomly divided into a control group (NC), a model group (DN), and a treatment group (DN+ASP).

[0023] The safflower glycoside was dissolved in a sodium carboxymethylcellulose solution with a mass percentage concentration of 0.5%, and was gavage-administered at a dose of 80 mg / kg, once a day, for 12 weeks. The control group and the model group were given an equal amount of sodium carboxymethylcellulose (CMC-Na) with a mass percentage concentration of 0.5%. During the administration, the weight and blood sugar of the mice were tested every two weeks, and the random urine of the mice was collected once. After the administration, the mice were anesthetized with sodium pentobarbital with a mass percentage concentration of 0.1%, and blood and kidney tissue were collected.

[0024] The fasting blood glucose of mice was tested regularly by blood glucose meter. In order to evaluate the effect of scutellaria baicalensis on the renal function of diabetic nephropathy mice, the urine albumin and urine creatinine levels of each group of animals were detected by kits, and the urine albumin to urine creatinine ratio (UACR), as well as the blood creatinine (sCr) and blood urea nitrogen (BUN) levels were calculated. Pathological changes in the structure of renal tissue are the direct cause of decreased renal function. In order to detect the effect of scutellaria baicalensis on renal pathological changes, the pathological changes of mouse renal tissue were observed by PAS staining and transmission electron microscopy.

[0025] Experimental Results

[0026] 1. Cherifoliin had no significant effect on improving blood sugar, body weight, food intake and water intake of diabetic nephropathy mice

[0027] In this study, the blood glucose level of diabetic mice treated for 12 weeks (W0-W12) was Figure 1 -a), weight ( Figure 1 -b) Food intake ( Figure 1 -c) Water intake ( Figure 1 -d) decreased compared with the model group, but there was no significant difference and it was not statistically significant.

[0028] 2. Cherimoside can reduce urine volume in diabetic nephropathy mice

[0029] Polydipsia and polyuria are complications of hyperglycemia. When blood sugar concentration exceeds a certain level, that is, exceeds the renal glucose threshold, the glucose filtered through the glomerulus exceeds the reabsorption capacity of the renal tubules, causing osmotic diuresis. Synechoside can alleviate the symptoms of osmotic diuresis to a certain extent, such as Figure 2 .

[0030] 3. Cherimoside improves the renal function and renal pathological changes in diabetic nephropathy mice.

[0031] Persistent microalbuminuria is one of the characteristics of diabetic nephropathy and is closely related to progressive kidney damage. Therefore, effectively reducing urinary albumin levels in the early and middle stages is one of the goals of traditional Chinese medicine in the development of new drugs for diabetic nephropathy. This study observed that compared with the control group (NC), the blood glucose and body weight of diabetic nephropathy mice were significantly increased, accompanied by a significant increase in UACR, indicating that diabetic nephropathy mice had obvious proteinuria.

[0032] After 12 weeks of treatment with calendula officinalis, the urinary albumin ( Figure 3 -a) and UACR( Figure 3 -b) were significantly reduced.

[0033] In addition, this study also found that the decrease in serum creatinine and urine albumin content in diabetic nephropathy mice was correlated with the increase in urine creatinine (Cr) and urea nitrogen (BUN). Therefore, it can be inferred that calendula glycosides can promote the excretion of urea nitrogen and creatinine, thereby reducing blood sugar in diabetic mice and improving symptoms caused by albuminuria and high serum creatinine, such as Figure 4 , 5.

[0034] 4. Ceropegol reduces glomerular inflammation in mice

[0035] Inflammation and glomerular sclerosis are key pathological features in the development of diabetic nephropathy. Sustained inflammatory response is a key factor in causing various types of kidney damage. In recent years, studies have found that calendula glycosides have anti-inflammatory effects. In the study of diabetic nephropathy, calendula glycosides have shown the potential to reduce inflammatory responses, which may be related to its inhibition of the production and release of inflammatory mediators, such as Figure 6 Compared with the model group, the interstitial thickening in the glycoside-treated group was alleviated, and the inflammatory response of endothelial cells and renal tubular epithelial cells was reduced, indicating that glycoside has an anti-glomerulonephritis effect.

[0036] 5. Cherifoliin improves glomerular sclerosis symptoms in diabetic nephropathy mice

[0037] Glomerular sclerosis in the renal tissue of diabetic nephropathy mice, the replacement of glomerular cells by fibrous tissue is one of the glomerular pathological characteristics of diabetic nephropathy, and is an important cause of impaired renal filtration function. Compared with the model group (DKD), the glomerular sclerosis characteristics of the ASP group were significantly alleviated, indicating that ASP can delay the development of diabetic nephropathy by alleviating glomerular sclerosis in diabetic nephropathy mice. Figure 7 .

[0038] 6. Cherifoliin can improve the symptoms of renal interstitial fibrosis in diabetic nephropathy mice

[0039] The tubular basement membrane thickening, interstitial area widening, and tubular atrophy in the renal tissue of diabetic nephropathy mice are typical characteristics of diabetic nephropathy tubules. These changes can lead to tubular dysfunction and affect the filtration and excretion function of the kidney. Compared with the model group (DKD), the thickening characteristics of the tubular basement membrane in the phytosterol-treated group (ASP) were significantly reduced, indicating that phytosterol can alleviate the progression of the mouse kidney disease after being administered to diabetic nephropathy mice. Figure 8 .

Claims

1. Use of calendula glycoside in the preparation of a drug for treating diabetic nephropathy. The structural formula of calendula glycoside is shown below:

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