CN111773238A

CN111773238A - Traditional Chinese medicine preparation for treating insulin resistance syndrome and type 2 diabetes

Info

Publication number: CN111773238A
Application number: CN202010758028.7A
Authority: CN
Inventors: 丁赛丹; 王剑; 于贺; 刘乐平; 卢小爱; 游瑞敏
Original assignee: First Affiliated Hospital of Wenzhou Medical University
Current assignee: First Affiliated Hospital of Wenzhou Medical University
Priority date: 2020-07-31
Filing date: 2020-07-31
Publication date: 2020-10-16

Abstract

The invention discloses a traditional Chinese medicine preparation for treating insulin resistance syndrome and type 2 diabetes, which comprises a mixed preparation, wherein the mixed preparation comprises naringin, liquiritin, lycium barbarum polysaccharide, mangiferin and oleuropein. The composition mainly becomes a fruit component, has no side effect, and really achieves the effect of homology of medicine and food. The components of the composition of the invention have a synergistic effect with each other, and the insulin resistance syndrome and the type 2 diabetes mellitus are obviously improved.

Description

Traditional Chinese medicine preparation for treating insulin resistance syndrome and type 2 diabetes

Technical Field

The invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine preparation for treating insulin resistance syndrome and type 2 diabetes.

Background

The insulin resistance syndrome is also called "syndrome X" or "metabolic syndrome", and is mainly manifested as hyperinsulinemia, hyperglycemia, obesity, and the like. The insulin resistance syndrome is associated with the onset of a variety of cardiovascular diseases, the causes of which are complex, but most of which consider insulin resistance to be one of the major causes of the disease progression. Insulin resistance refers primarily to a decrease in the sensitivity of the target tissue to insulin, and generally to a decrease in the availability of insulin-mediated glucose to the tissue. Insulin resistance is a leading element of many diseases, and type 2 diabetes occurs when the body is unable to produce enough insulin to meet the needs of glucose metabolism in the body when insulin resistance is present.

Type 2 diabetes is the type of diabetes with the highest incidence at present, and the mortality rate among patients is always high, and the number of type 2 diabetes patients accounts for more than 90% of the total number of diabetes patients at present. Diabetes mellitus, one of the most common chronic diseases in the world, has a high incidence in all age groups. The current pathogenesis trend is younger, and the incidence rate of diabetes of the young population is obviously higher than that of the old population. It is reported that diabetics in our country reach hundreds of millions and continue to grow each year.

The etiology of diabetes is mainly the imbalance of carbohydrate metabolism in vivo, and insulin resistance is closely related to the occurrence of type 2 diabetes and metabolic diseases. Insulin resistance is considered to be the basis of the onset of type 2 diabetes, and the degree of insulin resistance is closely related to the level of glucose metabolism disorder in the patient. In normal humans, insulin inhibits hepatic glucose output and promotes glucose uptake by tissues, so that plasma glucose levels stabilize at normal values. In diabetic patients, insulin resistance causes a decrease in the sensitivity of the liver and peripheral tissues to insulin and a decrease in glucose uptake, resulting in an increase in plasma glucose levels. Therefore, the therapeutic results of insulin resistance are closely related to the degree of cure of the above diseases.

Disclosure of Invention

In order to solve the above problems, the present invention provides a Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes.

The purpose of the invention is realized by the following technical scheme: a Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes comprises mixed preparation comprising naringin, liquiritin, lycium barbarum polysaccharide, mangiferin, and oleuropein.

Further, the content of the mixed preparation is 12.5-50 mg/kg.

Further, the components of the mixed preparation comprise 10 parts of naringin, 2 parts of liquiritin, 33.4 parts of lycium barbarum polysaccharide, 40 parts of mangiferin and 1 part of oleuropein.

Further, the mixed preparation also comprises 150 parts of polygala tenuifolia sapogenin.

Further, the mixed preparation also comprises 20 parts of far alpha asarone.

Further, the mixed preparation also comprises 60 parts of ginkgolide B.

Further, the mixed preparation also comprises 0.15 part of huperzine A.

The invention has the following beneficial effects:

1. the composition mainly comprises fruit components, has no side effect, and really achieves the effect of homology of medicine and food.

2. The components of the composition of the invention have a synergistic effect with each other, and the insulin resistance syndrome and the type 2 diabetes mellitus are obviously improved.

Drawings

FIG. 1 shows the effect of the mixed preparation on fasting plasma glucose (FPG (mmol/L)) in insulin resistant rats.

FIG. 2 shows the effect of the mixed formulation on insulin resistance syndrome rat fasting insulin (FINS (mU/L)).

FIG. 3 is a graph showing the effect of the mixed formulation on insulin resistance syndrome the insulin resistance index (Homa-IR) of rats.

FIG. 4 is a graph showing the effect of the mixed formulation on fasting plasma glucose (FPG (mmol/L)) in diabetic rats.

FIG. 5 is a graph showing the effect of the mixed formulation on fasting insulin (FINS (mU/L)) in diabetic rats.

FIG. 6 is a graph showing the effect of the mixed formulation on insulin resistance index (Homa-IR) in diabetic rats.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to fig. 1 to 6 in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. The experimental procedures used in the following examples are all conventional procedures unless otherwise specified. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Polygala tenuifolia sapogenin is an active ingredient in traditional Chinese medicine Polygala tenuifolia and has the effects of protecting nerves, resisting oxidation and the like. In rat hippocampal neurons, the damage caused by acute cerebral hemorrhage can be relieved, and senegenin has good healing effect on cell damage induced by oxygen deprivation/reoxygenation in newborn rat hippocampal neural stem cells. Huperzine A is alkaloid extracted from Chinese medicinal herb Huperzia serrata, is a reversible high-efficiency and high-selectivity AChE inhibitor, easily penetrates blood brain barrier, and can improve cognitive impairment caused by Alzheimer disease. In foreign countries, huperzine a has been formulated as a nutraceutical to prevent cognitive impairment related disorders. The bilobalide is an active ingredient in ginkgo, is a commonly used platelet activating factor receptor antagonist, and has certain protection effect on the central nervous system and the cardiovascular system. The alpha asarone is the extract of the traditional Chinese medicine grassleaf sweelflag rhizome, and the grassleaf sweelflag rhizome is the traditional Chinese medicine in China and has the function of treating mental and cardiovascular and cerebrovascular diseases. Alpha-asarone is reported to inhibit HMG-COA reductase and treat hyperlipidemia. Based on the reported pharmacological actions of the medicines, a compatible formula is formed by the medicines and the five selected fruit glycosides, and the proportion of the medicines for optimally treating the insulin resistance syndrome and the type 2 diabetes is found.

1. Design of compatibility of medicines

According to L₁₂(2¹¹) The orthogonal design table design group randomly combines 12 groups, and respectively prepares mixture solutions of polygala tenuifolia sapogenin, α asarone, ginkgolide B, huperzine A, liquiritin, naringin, lycium barbarum polysaccharide, mangiferin and oleuropein with different proportions, determines the dosage levels of 9 effective components, performs an orthogonal experiment of comprehensive analysis by actual errors, determines the optimal curative effect proportion of 9 patients for preventing and treating insulin resistance syndrome and hypomnesis of diabetic mice, is an optimal drug compatibility group according to the experimental result, performs index detection after 4 weeks of administration, the dosage levels of 9 effective components are shown in table 1, and the dosage groups of 9 effective components are shown in table 2.

Table 1. drug compatibility: concentration level (mg/kg/d)

Medicine	Low dose	High dose
			Polygala tenuifolia sapogenin	60	150
α Fine octyl Ether	20	80
			Ginkgolide B	15	60
Huperzine A	0.1	0.15
			Naringin	10	40
Liquiritin	2	8
			Lycium barbarum polysaccharides	8.3	33.4
Mangiferin	10	40
			Oleuropein	1	4

TABLE 29 grouping of the effective component dosages (mg/kg/d)

Group of	Polygala tenuifolia sapogenin	α Fine octyl Ether	Ginkgolide B	Huperzine A	Naringin	Liquiritin	Lycium barbarum polysaccharides	Mangiferin	Oleuropein
										1	60	20	15	0.1	10	2	8.3	10	1
2	60	20	15	0.1	10	8	33.4	40	4
										3	60	20	60	0.15	40	2	8.3	10	4
4	60	80	15	0.15	40	2	33.4	40	1
										5	60	80	60	0.1	40	8	8.3	40	1
6	60	80	60	0.15	10	8	33.4	10	4
										7	150	20	60	0.15	10	2	33.4	40	1
8	150	20	60	0.1	40	8	33.4	10	1
										9	150	20	15	0.15	40	8	8.3	40	4
10	150	80	60	0.1	10	2	8.3	40	4
										11	150	80	15	0.15	10	8	8.3	10	1
12	150	80	15	0.1	40	2	33.4	10	4

2. Moulding and grouping

2.1 model of insulin resistance syndrome

48 male Wistar rats (from experimental animal center, university of medical, Wenzhou) of SPF grade 8 weeks old, body mass (180- "200") g, care and use in all experiments the mouse program was in accordance with the Provisions of the ethical Committee of the first Hospital, affiliated with the university of medical, Wenzhou. After one week of basal diet feeding, the group was divided into normal group, model group, positive control group (metformin), low-medium dose treatment group (mixed preparation), and 8 each group according to the randomized block design. The normal group is fed with basal feed, and the rest groups are fed with high-sugar, high-fat and high-salt feed for 6 weeks to establish an insulin resistance syndrome model. After the model is established, the injection is performed, captopril (0.1 g/kg) is administered to a positive control group, 12.5 mg/kg of mixed preparation is administered to a low-dose treatment group, 20 mg/kg of mixed preparation is administered to a medium-dose treatment group, and 50mg/kg of mixed preparation is administered to a high-dose treatment group, and the administration is performed once a day for 4 weeks. The normal group and the model group are respectively detected by using physiological saline with equal volume for 4 weeks.

2.22 type diabetic rat model

48 male Wistar rats (from experimental animal center, university of medical, Wenzhou) of SPF grade 8 weeks old, body mass (180- "200") g, care and use in all experiments the mouse program was in accordance with the Provisions of the ethical Committee of the first Hospital, affiliated with the university of medical, Wenzhou. After one week of basal diet feeding, the group was divided into normal group, model group, positive control group (metformin), low-medium dose treatment group (mixed preparation), and 8 each group according to the randomized block design. After feeding high-fat high-sugar feed for 4 weeks, fasting is carried out for 12h, STZ 30mg/kg is injected into the abdominal cavity, and an equal volume of citric acid buffer solution is injected into a blank group. The fasting blood sugar is more than or equal to 11.1mmol/L, and the random blood sugar is more than or equal to 16.7mmol/L, which is taken as the model forming standard of type 2 diabetes. After 1 week, the administration was started, metformin (85 mg/kg) was administered to the positive control group, 12.5 mg/kg of the mixed preparation was administered to the low-dose treatment group, 20 mg/kg of the mixed preparation was administered to the medium-dose treatment group, 50mg/kg of the mixed preparation was administered to the high-dose treatment group, and the normal group and the model group were administered once a day with an equal volume of physiological saline, respectively. A total of 28 days, fasting plasma insulin, fasting glucose measurements were taken every 7 days, and the insulin resistance index (Homa-IR) was calculated.

2.3 detection of indicators

Recording the weight change of the rats before and after administration; the tail sleeve method is adopted to measure the tail artery systolic pressure (SBP) of the rat in a waking state. The average of 3 consecutive readings was taken. After the last gastric lavage is finished, the rats are fasted for 12 hours, the weight is weighed, and after being anesthetized by the abdominal cavity with phenobarbital (50 mg/kg), the rats are respectively subjected to blood sampling by a common carotid artery intubation tube to detect various indexes; measuring Triglyceride (TG) by adopting a glycerol phosphate oxidase method; measuring Total Cholesterol (TC) and high density lipoprotein (HDL-C) by cholesterol oxidase method; fasting plasma insulin (FINS) by radioimmunoassay; the method comprises the following steps of (1) adopting an oxidase method for fasting blood glucose (FPG); insulin resistance index (Homa-IR) = fasting plasma glucose (mmol/L) × fasting plasma insulin (mU/L)/22.5.

Analysis was performed using SPSS.22 software, data in order

S, and comparisons between groups were analyzed by t-test, using p<The 0.05 bit disparity is statistically significant.

3. Results

3.1 insulin resistance syndrome and 2 type diabetes rats before and after treatment of systolic pressure, blood lipid changes comparison.

Compared with a normal group after treatment, the rat tail arterial systolic pressure of the model group is increased, and the comparative difference between the two groups has significance (P < 0.05), compared with the model group after treatment, the rat arterial systolic pressure of each dose group and the rat arterial systolic pressure of the captopril group of the mixed preparation are reduced after treatment, and the comparative difference between the groups has significance (P < 0.05). Compared with the normal group, the TC, TG and HDL-C of the model group rats are obviously increased, and the significant difference (P < 0.05) is obtained in comparison between the two groups; the TC, TG and HDL-C of each dose group of the mixed preparation are reduced, and the mixed preparation has significant difference (P < 0.05) compared with a model group, and is shown in a table 3.

TABLE 3 Effect of the Mixed preparation on systolic arterial pressure and blood fat before and after the treatment of rats with insulin resistance syndrome

（n=8，

±s）

Compared with a normal group after treatment, the tail arterial systolic pressure of the rats in the model group is increased, and the comparative difference between the two groups has significance (P < 0.05), and compared with the model group after treatment, the arterial systolic pressure of the rats in each dose group and the metformin group of the mixed preparation is reduced, and the comparative difference between the groups has significance (P < 0.05). Compared with the normal group, the model group rats have increased TC and TG and reduced HDL-C, and have significant difference (P < 0.05) compared between the two groups; the TC and TG of each dose group of the mixed preparation are reduced, the HDL-C is increased, and the mixed preparation has significant difference (P < 0.05) compared with a model group, and the Table 4 shows.

TABLE 4 Effect of the Mixed preparation on the systolic arterial pressure and blood fat before and after the treatment of type 2 diabetic rats

（n=8，

±s）

3.2 insulin resistance syndrome and type 2 diabetes rats varied in body weight, food intake and water intake.

Before administration, the body weights of rats in all groups have no obvious difference; after feeding for 4 weeks, the body weight of the model group is reduced compared with that of the normal group, and the two groups have significant difference (p is less than 0.05); after 8 weeks of feeding, the model groups lost significantly and there was a significant difference in comparison between the two groups (p < 0.05). Compared with the model group, the captopril group and the low, medium and high dose group have the effect of obviously improving the symptoms of diabetic rats, and have significant difference (p is less than 0.05) in comparison among the groups, as shown in table 5.

TABLE 5 Mixed preparation for pancreasIslets resist the effects of the body weight of the syndrome (n =8,

±s）

before administration, the body weights of rats in all groups have no obvious difference; after feeding for 4 weeks, the body weight of the model group is reduced compared with that of the normal group, and the two groups have significant difference (p is less than 0.05); after 8 weeks of feeding, the model groups lost significantly and there was a significant difference in comparison between the two groups (p < 0.05). Compared with the model group, the metformin group and the low, medium and high dose group have the effect of obviously improving the symptoms of diabetic rats, and have significant difference (p is less than 0.05) among the groups, as shown in table 6.

Table 6 effect of the mixed formulation on body weight of type 2 diabetic rats (n =8,

±s）

3.3 insulin resistance syndrome and type 2 diabetes mellitus rats in each group of fasting blood glucose, insulin resistance index results comparison.

In the rats with the insulin resistance syndrome, after 4 weeks of treatment, compared with a normal group, the fasting blood glucose, the fasting insulin level and the Homa-IR index of the rats in the model group are all increased, and the rats have significant difference (P < 0.05) compared with the normal group; compared with the model group, rats in each treatment group have reduced fasting blood glucose, fasting insulin level and Homa-IR index, rats in captopril have reduced fasting insulin level and Homa-IR index, and the rats in each treatment group have significant difference (P < 0.05) compared with the rats in each group, and the differences are shown in Table 7.

Table 7 effect of the combined preparation on fasting plasma glucose, fasting insulin, insulin resistance index in insulin resistance syndrome rats (n =8,

±s）

group of	FPG（mmol/L）	FINS（mU/L）	Homa-IR
				Normal group	5.45±1.46	15.35±4.21	3.05±.0.56
Model set	9.87±2.71	30.17±3.18	14.53±1.22
				Captopril group	6.51±1.09	20.58±6.09	6.33±1.06
Low dose group	8.12±1.27	24.77±5.26	8.62±0.92
				Middle dose group	7.09±0.61	21.19±6.01	7.02±1.33
High dose group	6.54±0.92	19.54±5.31	6.22±0.98

After 28 days of total administration, fasting plasma insulin and fasting plasma glucose are detected every 7 days, and an insulin resistance index (Homa-IR) is calculated, wherein the fasting plasma glucose detection result is shown in table 8, the fasting insulin detection result is shown in table 9, the insulin resistance index calculation result is shown in table 10, and the statistical results are shown in tables 1-3.

TABLE 8 Effect of the combination preparation on insulin resistance rat fasting plasma glucose (FPG (mmol/L))

（n=8，

±s）

Group of	7 days	14 days	21 days	28 days
					Normal group	4.89±0.67	5.37±0.55	4.89±1.01	5.45±1.46
Model set	11.34±0.15	12.52±0.56	10.02±1.33	9.87±2.71
					Captopril	12.47±0.6	10.08±1.26	7.91±0.87	6.51±1.09
Low dose group	10.94±0.45	9.88±0.02	9±1.32	8.12±1.27
					Middle dose group	11.53±0.45	10.5±0.14	8.39±1.31	7.09±0.61
High dose group	12.84±1.15	11.3±1.76	8.25±0.52	6.54±0.92

TABLE 9 Effect of the combination preparation on insulin resistance syndrome in rats fasting insulin (FINS (mU/L))

（n=8，

±s）

Group of	7 days	14 days	21 days	28 days
					Normal group	13.93±0.95	14.36±1.18	12.97±1.83	15.35±4.21
Model set	30.89±0.1	29.03±0.52	28.94±1.57	30.17±3.18
					Captopril	31.33±0.51	27.71±0.23	22.94±1.12	20.58±6.09
Low dose group	30.45±1.24	27.39±0.95	24.68±0.45	24.77±5.26
					Middle dose group	29.72±0.69	26.83±0.8	23.62±0.93	21.19±6.01
High dose group	31.03±0.35	27.73±0.73	22.54±1.32	19.54±5.31

TABLE 10 Effect of the Mixed formulations on insulin resistance syndrome the insulin resistance index (Homa-IR) of rats

（n=8，

±s）

Group of	7 days	14 days	21 days	28 days
					Normal group	3.25±0.03	3.24±0.05	3.01±0.12	3.05±0.56
Model set	15.97±0.02	16.13±0.09	13.11±0.29	14.53±1.22
					Captopril	16.89±0.03	12.37±0.22	7.93±0.08	6.33±1.06
Low dose group	15.03±0.05	11.99±0.12	10.03±0.13	8.62±0.92
					Middle dose group	15.09±0.11	11.83±0.03	9.09±0.25	7.02±1.33
High dose group	17.81±0.08	12.91±0.07	8.82±0.33	6.22±0.98

Table 11 effect of the combined preparation on fasting plasma glucose, fasting insulin, insulin resistance index in diabetic rats (n =8,

±s）

group of	FPG（mmol/L）	FINS（mU/L）	Homa-IR
				Normal group	5.01±0.26	15.52±0.11	3.88±1.23
Model set	19.08±2.48	28.78±1.78	25.41±0.99
				Metformin	8.17±1.27	19.56±3.34	7.68±1.33
Low dose group	12.11±2.45	21.15±0.71	12.97±2.44
				Middle dose group	10.25±1.19	20.63±3.65	9.40±0.88
High dose group	8.58±1.62	19.67±2.88	7.32±1.09

After 28 days of total administration, fasting plasma insulin and fasting plasma glucose were measured every 7 days, and insulin resistance index (Homa-IR) was calculated, the fasting plasma glucose measurement results are shown in Table 12, the fasting insulin measurement results are shown in Table 13, the insulin resistance index calculation results are shown in Table 14, and the statistical results are shown in FIGS. 4-6.

TABLE 12 Effect of the Mixed preparation on fasting plasma glucose (FPG (mmol/L)) in diabetic rats

（n=8，

±s）

Group of	7 days	14 days	21 days	28 days
					Normal group	5.21±0.55	5.13±0.64	4.99±0.99	5.01±0.26
Model set	23.44±0.12	20.53±1.54	18.97±2.56	19.08±2.48
					Metformin	20.33±1.59	18.45±2.01	12.77±1.94	8.17±1.27
Low dose group	22.45±0.33	20.54±0.78	18.36±1.66	12.11±2.45
					Middle dose group	25.67±1.23	19.49±0.03	13.11±3.1	10.25±1.19
High dose group	24.13±2.1	20.12±0.13	11.24±2.52	8.58±1.62

TABLE 13 Effect of the combination preparation on fasting insulin (FINS (mU/L)) in diabetic rats

（n=8，

±s）

Group of	7 days	14 days	21 days	28 days
					Normal group	14.23±1.22	15.56±0.18	13.24±2.23	15.52±0.11
Model set	30.3±2.1	28.79±1.02	27.34±0.57	28.78±1.78
					Metformin	31.22±0.23	26.56±1.33	23.78±0.57	19.56±3.34
Low dose group	28.44±0.57	25.34±2.2	23.46±1.7	21.15±0.71
					Middle dose group	29.56±0.59	26.24±0.11	24.78±1.32	20.63±3.65
High dose group	33.1±1.29	24.29±1.02	21.33±0.27	19.67±2.88

TABLE 14 Effect of the Mixed formulation on the insulin resistance index (Homa-IR) of diabetic rats

（n=8，

±s）

Group of	7 days	14 days	21 days	28 days
					Normal group	3.52±0.15	3.55±0.05	3.10±0.18	3.88±1.23
Model set	33.73±0.07	25.94±0.12	22.95±1.02	25.41±0.99
					Metformin	29.94±0.22	21.59±0.34	13.70±0.09	7.68±1.33
Low dose group	28.38±0.33	23.98±0.13	18.87±0.65	12.97±2.44
					Middle dose group	32.44±0.03	23.01±0.07	14.89±0.18	9.40±0.88
High dose group	36.70±0.84	21.22±0.02	11.12±0.13	7.32±1.09

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it is therefore intended that the present embodiments be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims

1. The traditional Chinese medicine preparation for treating insulin resistance syndrome and type 2 diabetes is characterized by comprising a mixed preparation, wherein the mixed preparation comprises naringin, liquiritin, lycium barbarum polysaccharide, mangiferin and oleuropein.

2. The Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes according to claim 1, wherein the content of the mixed preparation is 12.5-50 mg/kg.

3. The traditional Chinese medicine preparation for treating insulin resistance syndrome and type 2 diabetes as claimed in claim 2, wherein the mixed preparation comprises naringin 10 parts, liquiritin 2 parts, lycium barbarum polysaccharide 33.4 parts, mangiferin 40 parts, and oleuropein 1 part.

4. The Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes according to claim 3, characterized in that the mixed preparation further comprises 150 parts of tenuigenin.

5. The Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes as claimed in claim 4, wherein the mixed preparation further comprises 20 parts of alpha asarone.

6. The Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes as claimed in claim 5, wherein the mixed preparation further comprises bilobalide B60 parts.

7. The Chinese medicinal preparation for treating insulin resistance syndrome and type 2 diabetes as claimed in claim 6, wherein the mixed preparation further comprises huperzine A0.15 parts.