CN110946849A

CN110946849A - Application of piceatannol in preparing medicine for preventing and treating diabetes

Info

Publication number: CN110946849A
Application number: CN201911382408.9A
Authority: CN
Inventors: 翁丹; 赵梦姝; 张建法
Original assignee: Nanjing University of Science and Technology
Current assignee: Nanjing University of Science and Technology
Priority date: 2019-12-28
Filing date: 2019-12-28
Publication date: 2020-04-03

Abstract

The invention discloses an application of piceatannol in preparing a medicament for preventing and treating diabetes. Experiments show that the piceatannol has good effect of preventing and treating diabetes, has good treatment effect on diabetes, and particularly has good treatment effect on type 1 diabetes. When the piceatannol and a pharmaceutically acceptable carrier are prepared into the drugs for preventing and treating diabetes, such as capsules, tablets or ointments, the piceatannol does not generate toxic or side effect, and is expected to be developed into safe and effective drugs for preventing and treating diabetes and complications thereof.

Description

Application of piceatannol in preparing medicine for preventing and treating diabetes

Technical Field

The invention belongs to the technical field of diabetes prevention and treatment, and relates to application of piceatannol in preparation of a medicament for preventing and treating diabetes.

Background

The diabetes is a metabolic disease characterized by hyperglycemia, and is one of the most common metabolic diseases, the hyperglycemia existing in a diabetic patient for a long time can cause chronic damage and dysfunction of various tissues, particularly eyes, kidneys, hearts, blood vessels and nerves, the diabetes is mainly divided into two types, namely type 1 diabetes (T1DM) and type 2 diabetes (T2DM), the most common type is type 2 diabetes, accounting for 85% -90% of the total number of the diabetic patients, and insulin resistance is the main characteristic of the type 2 diabetes, the type 1 diabetes is mainly characterized in that damage of islet β cells causes insufficient insulin secretion, the total number of the diabetic patients accounts for 5% -10%, most of the diabetic patients are adolescents, the pathogenesis of the diabetes is very complex, no unified theory exists for the specific pathogenesis of each type of diabetes at present, but research shows that the diabetes is the result of combined action of genetic factors, autoimmune system factors and environmental factors.

Among these different factors, oxidative stress and inflammation are two key mediators of the pathogenesis of diabetes and its secondary complications, suggesting that compounds or natural products with antioxidant and anti-inflammatory properties may have a potential role in the treatment of diabetes. The research shows that the natural product resveratrol has certain relieving effect on type 2 diabetes of rats, about two weeks after administration, and the blood sugar of rats in a treatment group is reduced to about 60 percent of that of a model group, but is still twice of that of the rats in a normal value. There was also some recovery of serum insulin levels and glucose tolerance in Rats treated with Resveratrol (Yang and Kang, Anti-diabetes Effect of treatment with Quercetin and Resveratrol in streptozocin-induced diabetes rates, biomol. Ther. (2018), https:// doi. org/10.4062/biomollther. 2017.254).

The molecular formula of piceatannol is C₁₄H₁₂O₄The chemical name is 3, 3, 4, 5-tetrahydroxy-trans-stilbene, and the structural formula is

Piceatannol is mainly present in grapes, rhubarb moss, rhubarb and sugarcane, is a polyhydroxy phenolic compound, is used as a strong antioxidant, and has the potential of preventing and treating human diseases. It has been found that piceatannol has biological activities such as anti-tumor, anti-oxidation, anti-inflammation, etc. At present, researches on piceatannol mostly focus on cardiovascular protection action mechanism researches, and piceatannol is not reported for preparing medicaments for preventing and treating type 1 diabetes.

Disclosure of Invention

The invention aims to provide application of piceatannol in preparing a medicament for preventing and treating diabetes. The experimental result shows that the piceatannol has good effect of preventing and treating diabetes and has no adverse reaction.

The inventor shows through a large number of experimental studies that piceatannol has a good effect of treating diabetes and can be used for preparing a medicament for preventing and treating diabetes.

Preferably, the medicament for preventing and treating diabetes mellitus is a medicament for preventing and treating type 1 diabetes mellitus.

The piceatannol provided by the invention can be used for preparing medicines in dosage forms of capsules, tablets, ointments and the like by mixing piceatannol and a pharmaceutically acceptable carrier.

When the piceatannol is prepared into capsules, the piceatannol and a medicament carrier, such as lactose or corn starch, can be uniformly mixed, granulated and then encapsulated to prepare the capsules.

When the piceatannol is prepared into tablets, piceatannol and drug carrier lactose or corn starch and the like can be uniformly mixed and then tableted to prepare the tablets.

When the piceatannol is prepared into granules, piceatannol and drug carrier lactose or corn starch can be uniformly mixed, sized, dried and prepared into granules.

The invention discovers for the first time that the piceatannol has good effect of preventing and treating diabetes, has good biocompatibility, does not show adverse reactions such as side effect and the like in the experimental process, and is expected to be developed into a new generation of safe and effective medicine for preventing and treating diabetes.

Drawings

FIG. 1 is a graph showing the change in body weight and the drinking and eating intake of mice in each experimental group, wherein A, B is a graph showing the change in body weight of mice with time, C is the daily drinking intake of mice, and D is the daily drinking intake of mice.

In FIG. 2, A is a fasting plasma glucose value of mice in each experimental group, B is a serum insulin level of the mice, C is a glucose tolerance of the mice, and D is an area under the curve of the C.

FIG. 3 is a graph showing the level of oxidative stress in liver tissues of mice in each experimental group, wherein A is the level of Malondialdehyde (MDA), B is the level of superoxide dismutase (SOD), C is the level of glutathione peroxidase (GSH-PX), and D is the level of expression of thioredoxin interacting protein (TXNIP) mRNA.

Detailed Description

The present invention will be described in further detail with reference to the following examples and the accompanying drawings. It will be understood by those skilled in the art that the specific material ratios, process conditions and results thereof described in the examples are illustrative only and should not be taken as limiting the invention as described in detail in the claims.

Example 1

Therapeutic effect of piceatannol on STZ-induced type 1 diabetes in mice

1. Animals: 32, 18-22g, clean grade C57BL/6 male mice at about 5 weeks of age.

Preparing a piceatannol solution: the piceatannol is dissolved by ethanol to prepare a mother solution with the concentration of 220mg/mL, and the mother solution is diluted to the concentration of 5mg/mL by using normal saline before each gastric lavage.

2. Grouping: after one week of pre-feeding all mice were randomized into three groups: 6 normal groups (Con), 6 piceatannol control groups (PIC) and 20 experimental groups. Mice in the experimental group of week 1 are injected with Streptozotocin (STZ) in the abdominal cavity for molding, fasting blood sugar measurement is carried out in week 2 and week 3, and the molding success is judged if the blood sugar stability is higher than 11.1mmol/L, and the stability is continued for one week. The successfully modeled 16 mice were randomly divided into two groups: model group (DM) and piceatannol treatment group (DM + PIC, 40 mg/kg).

3. The administration scheme is as follows: the piceatannol solution is administered to the piceatannol control group and piceatannol treatment group from the 5 th week, the gavage is carried out according to the dosage of 40mg/kg, the equal volume of physiological saline is gavage in the model group and the normal group, and the drug intervention is carried out for 4 weeks.

4. Experimental reagent: piceatannol, streptozotocin

Detection indexes are as follows: body weight, food and water intake, blood sugar, insulin

5. Statistical analysis: analysis was performed using GraphPad 7.01 software, expressed as mean + standard deviation, and comparisons between groups were performed using the t-test.

6. Results of the experiment

(1) The model group mice showed obvious symptoms of polyphagia, diuresis and weight loss, as shown in A, B in figure 1, the weight of the model group is obviously reduced compared with the normal group in the later period of the experiment, the result of the C, D graph shows that the food intake and the water intake of the model group mice are obviously higher than those of the normal group, which is the typical symptom of type 1 diabetes, and the water intake of the mice after the treatment of piceatannol is reduced to a certain extent. The detailed results are shown in FIG. 1.

(2) Compared with the normal group, the fasting blood glucose value of the model group mouse is obviously increased. The blood sugar value is reduced after the treatment of the piceatannol, and the statistical significance is achieved. The insulin level of the model group mice is obviously reduced, and the insulin level is recovered after the treatment of the piceatannol. It is shown that piceatannol can lower blood sugar level of diabetic mice and reduce insulin deficiency. According to the results of glucose tolerance test (OGTT), the area under the curve (AUC) of the piceatannol treatment group is obviously smaller than that of the model group, which shows that piceatannol can improve the glucose tolerance of diabetic mice, and no obvious side effect is seen in the single piceatannol treatment. The detailed results are shown in FIG. 2.

(3) Compared with the normal group, the liver tissue of the mouse in the model group has obviously increased Malondialdehyde (MDA). Malondialdehyde represents lipid peroxidation levels and is often used as a marker of oxidative stress in vivo. The superoxide dismutase (SOD) and the glutathione peroxidase (GSH-PX) of the mouse liver of the model group are obviously reduced compared with those of the control group. Piceatannol treatment not only significantly inhibited MDA levels, but also increased SOD and GSH-PX activities. Thioredoxin interacting protein (TXNIP) regulates the antioxidant function of thioredoxin (Trx), plays an important role in the redox homeostasis, and the expression of TXNIP is obviously increased in the liver tissue of a model group mouse, while the expression of TXNIP is inhibited by the treatment of piceatannol. It is suggested that piceatannol may exert anti-diabetic effects through its anti-oxidative effects. The detailed results are shown in FIG. 3.

Statistically significant differences were p < 0.05, p < 0.01, p < 0.001.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and improvements can be made without departing from the principle of the present invention, and these modifications and improvements should also be construed as the protection scope of the present invention.

Claims

1. Application of piceatannol in preparing medicine for preventing and treating diabetes is provided.

2. The use according to claim 1, wherein the diabetes-preventing drug is a diabetes-1 preventing drug.

3. The use according to claim 1, wherein the medicament for the prevention or treatment of diabetes is a capsule, tablet or ointment medicament prepared from piceatannol and a pharmaceutically acceptable carrier.

4. The use of claim 3, wherein when the diabetes prevention and treatment drug is a capsule, the drug is prepared by mixing piceatannol with the drug carrier lactose or corn starch, granulating, and encapsulating.

5. The use of claim 3, wherein the antidiabetic agent is a tablet, which is prepared by mixing piceatannol with lactose or corn starch as a pharmaceutical carrier, and tabletting.

6. The use of claim 3, wherein when the diabetes prevention and treatment drug is a granule, the drug is prepared by mixing paclitaxel and lactose or corn starch as drug carrier, granulating, drying, and making into granule.