KR101127454B1 - Pharmaceutical composition comprising processed Aloe vera gel for preventing or treating type II diabetes - Google Patents

Abstract

The present invention is processed Aloe vera gel (processed aloe The present invention relates to a pharmaceutical composition for preventing or treating type 2 diabetes or a health functional food for improving type 2 diabetes, comprising vera gel, PAG) as an active ingredient.

Aloe vera gel, antidiabetic activity, type 2 diabetes

Description

Pharmaceutical composition comprising processed Aloe vera gel for preventing or treating type II diabetes}

Diabetes is largely divided into insulin-dependent diabetes (type 1 diabetes) and insulin-independent diabetes (type 2 diabetes), depending on the secretion and action of insulin. Of these, about 90% or more of all diabetics belong to insulin-independent diabetes (type 2 diabetes). In Western society, the number of type 2 diabetics is rapidly increasing, which is thought to be triggered by the increase in obese population and less active lifestyle. In addition, recent statistics show that by 2010, there will be about 220 million patients worldwide.

Type 2 diabetes is characterized by both increased peripheral insulin resistance and abnormal insulin secretion, with two or more abnormal insulin secretions observed. In addition, type 2 diabetes is a progressive disease and causes complications such as retinopathy, cataract, nephropathy, neuropathy and atherosclerosis. In order to reduce the incidence of these complications, patients with type 2 diabetes need to maintain blood glucose levels near normal levels, while those with type 2 diabetes have a focus on optimizing and potentially normalizing glycemic control. Lost

However, currently available oral formulations are not suitable for attempting such treatments with occasional side effects or other problems in some patient populations.

 Diabetes animal models used to confirm the efficacy as a diabetes treatment agent are very different from humans, so it is difficult to predict the efficacy as a therapeutic agent for treating diabetes in humans based on the results of animal experiments, especially in human type 2 The single model that can represent the essential characteristics of diabetes has had no problems.

Alloxan and streptozotocin are known as insulin-dependent diabetes (type 1 diabetes) models because they can selectively destroy pancreatic β cells and cause diabetes, and in the case of experimental animal models of type 2 diabetes, the formulation and timing of administration of these drugs It is known that it can be made by manipulating. However, since human type 2 diabetes often has a pattern caused by obesity, this animal model conceptually differs significantly from the pattern of type 2 diabetes in humans. In addition, commonly used as genetic models, such as ob / ob mice and db / db mice, have different aspects from type 2 diabetes in humans, which are leptin structural, which is rare in human type 2 diabetes. This is because there is a mutation in the gene (ob) or leptin receptor gene (db).

The present invention newly revealed that the aloe vera gel (PAG) processed on DIO mice, which is very similar to the human type 2 diabetes model, has an antidiabetic effect such as improving blood glucose and fat homeostasis. In particular, it aims at providing the pharmaceutical composition or health functional food which is effective in the treatment or prevention of type 2 diabetes or a diabetes-related disease or symptom.

The present invention is processed Aloe vera gel (processed aloe The present invention relates to a pharmaceutical composition for preventing or treating type 2 diabetes or a health functional food for improving type 2 diabetes, comprising vera gel (PAG) as an active ingredient, wherein oral administration of a specially processed aloe vera gel (PAG) is performed in humans. Newly discovered to exhibit anti-diabetic effects, such as the effect of improving blood glucose and fat homeostasis, in DIO mice, very similar to the Type 2 diabetes model of the drug, which contains processed aloe vera gel (PAG) as an active ingredient. The present invention relates to a pharmaceutical composition for preventing or treating type 2 diabetes.

Here, DIO mice are very similar to human type 2 diabetes models in terms of metabolic disorders such as hyperglycemia, obesity and insulin resistance, and therefore the present invention shows that processed aloe vera gel (PAG) is particularly effective for type 2 diabetes. It is significant that the model shows excellent antidiabetic effects.

In the circulatory system, insulin resistance can be caused by high-fat intake and by increasing levels of free fatty acids. When orally administered processed aloe vera gel (PAG) of the present invention to DIO mice, plasma fat levels and triacylglyceride concentrations in the liver have been shown to decrease. As a result, it was found that the reduction of plasma fat level and triacylglyceride concentration in the liver by the processed aloe vera gel (PAG) improved insulin resistance. It has also been shown that insulin resistance may be improved by reducing the toxicity of fat in the liver. When aloe vera gel (PAG) of the present invention was orally administered to DIO mice, plasma fat levels and triacylglyceride concentrations in the liver were shown to be reduced.

It has been reported that the aloe component has an effective effect on human diabetes and diabetes in animals induced with streptozotocin or alloxan.

In addition, aborane A and arborane B, which are hypoglycemic polysaccharides, are used in Aloe arborescens , and a component called a "bitter ingredient" is derived from the aloe vera exudate, and the dried sap of aloe vera, molecular weight Two different antidiabetic components,> 3,500 Daltons, had isolated phytosterols from the leaf pulp and skin of aloe arborescens and from the gel of aloe vera, which showed antidiabetic activity. On the other hand, conflicting results were also reported. For example, oral administration of aloe vera gel, although clinical studies have shown that chronic administration of aloe vera gel reduces fasting blood glucose and hemoglobin A1c (HbA1c) levels (Bunyapraphatsara N, Yongchaiyudha S, Rungpitarangsi V, Chokechaijaroenporn O. Antidiabetic activity of Aloe vera L. juice. II. Clinical trial in diabetes mellitus patients in combination with glibenclamide. Phytomedicine 1996; 3: 245-8; Yongchaiyudha S, Rungpitarangsi V, Bunyapraphat sara N, Chokechaijaroenporn O. Antidiabetic activity of Aloe vera L. juice. I. Clinical trial in new cases of diabetes mellitus. Phytomedicine 1996; 3: 0.241 to 3), alloxan - were reported to have increased plasma glucose levels in diabetes-induced rats (Koo MWL Aloe vera : Antiulcer and antidiabetic effects. Phytother Res 1994; 8: 461-4). The opposite effect on this hypoglycemic activity of the aloe preparations appears to be due to the differences between the specific plant parts used and the animals to be tested.

The processed aloe vera gel (PAG) of the present invention has an antidiabetic effect, such as improving blood glucose and fat homeostasis, in DIO mice very similar to the type 2 diabetes model. A pharmaceutical composition or a dietary supplement can be provided that is effective for the treatment or prevention of type diabetes or diabetes-related diseases or symptoms.

Processed Aloe Vera Gel for Use in the Invention vera gel (PAG) is preferably a gel obtained after removing the shell of aloe vera leaves and 0.5-2.5 g of cellulase are reacted together at room temperature for 2-2.5 hours, and then anthraqui using an activated carbon column. The non-based compound and other pigments are removed and an activated carbon column is removed using a filter and then dried.

The processed aloe vera gel (PAG) is currently not commercially available, and the content of polysaccharides in the processed aloe vera gel (PAG) is the amount of dry fraction of residual fractions in the dialysis network upon extensive dialysis against distilled water. From about 5% to 40%, preferably from 20% to 30%, more preferably from 23% to 25% based on (weight cut-off, 3500 Daltons). In addition, mannose and glucose are contained in the average molar ratio of 5-40: 1.

One embodiment of the present invention is a pharmaceutical composition for the treatment or prevention of type 2 diabetes or diabetes-related diseases or symptoms containing processed aloe vera gel (PAG) as an active ingredient.

Another embodiment of the present invention is a health functional food for improving type 2 diabetes or diabetes-related diseases or symptoms containing processed aloe vera gel (PAG) as an active ingredient.

In another embodiment of the present invention, the processed aloe vera gel (PAG) has a polysaccharide content of about 5% to 40%, preferably 20% to 30%, more preferably 23% to 25% (measured based on the amount of dry fraction (weight cut-off, 3500 Daltons) of the residual fractions in the dialysis network upon extensive dialysis against distilled water).

In another embodiment of the present invention, the average molar ratio of mannose and glucose in the processed aloe vera gel (PAG) is 5-40: 1.

"Diabetes-related diseases or symptoms" as defined herein include hyperglycemia, hyperinsulinemia, hyperlipidemia, insulin resistance, glucose metabolism, obesity, diabetic retinopathy, macular degeneration, cataracts, diabetic nephropathy, glomerulosclerosis, diabetic Neurological disorders, impotence, premenstrual syndrome, vascular restenosis, ulcerative colitis, coronary artery disease, hypertension, angina pectoris, myocardial infarction, stroke, skin or connective tissue disease, foot ulcers, metabolic acidosis, arthritis, osteoporosis and impaired glucose tolerance Symptoms caused by, but not limited to.

"Prevention" is a term that means prophylactically administering an agent, such as a pharmaceutical composition, to a healthy patient to prevent the onset of the diseases and symptoms referred to herein. "Prevention" also means prophylactically administering such an agent to a patient to be treated, especially a patient in the pre-stage of diabetes.

The term "treatment" as used herein not only treats the diseases referred to herein, but also prophylactically administers a combination formulation, such as a combination or pharmaceutical composition, to healthy patients, thereby preventing the development of the diseases and symptoms referred to herein. To prevent.

Oral compositions according to the invention may further comprise inert ingredients, including pharmaceutically acceptable carriers, diluents, fillers, solubilizers or emulsifiers and salts well known in the art. For example, tablets used in combination therapy may be formulated according to conventional methods using solid carriers well known in the art. Capsules used in the combination therapy of the present invention can be prepared from any pharmaceutically acceptable substance, such as gelatin or cellulose derivatives.

In practical use, a pharmaceutical composition comprising the processed aloe vera gel (PAG) of the present invention as an active ingredient may be combined with pharmaceutical carriers according to conventional pharmaceutical preparation techniques. The carrier can take a wide variety of forms depending on the preparation desired, for example, for oral or parenteral administration (including intravenous administration).

Pharmaceutical compositions comprising the aloe vera gel (PAG) of the present invention as an active ingredient are useful for the treatment of diabetes mellitus, and for these purposes, the combination formulations of the present invention are conventional non-toxic pharmaceutically acceptable carriers, adjuvants and carriers ( oral parenteral (subcutaneous injection, intravenous injection, intramuscular injection, intrasternal injection or infusion, etc.), or rectally, in the form of a dosage unit formulation comprising a vehicle).

Each oral composition according to the present invention further comprises an inert ingredient, including a pharmaceutically acceptable carrier. As used herein, a “pharmaceutically acceptable carrier” is a term that refers to a composition, specifically an ingredient except for the active substance of the pharmaceutical composition. Examples of pharmaceutically acceptable carriers include binders, disintegrants, diluents, fillers, glidants, solubilizers or emulsifiers and salts.

In addition, the processed aloe vera gel (PAG) of the present invention can be added to foods to produce health functional foods for alleviating type 2 diabetes or diabetes-related diseases or symptoms. In this case, the health functional food refers to foods that can be manufactured in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients having useful functions for the human body.

Acronym Definition

PAG (processed Aloe vera gel); Processed Aloe Vera Gel

Type 2 diabetes (T2DM); Type 2 diabetes

Die-induced obesity (DIO); Dietary-induced obesity

Pioglitazone (PGZ); Pioglitazone

Regular diet (RD); Usually dietary

High-fat diet (HFD); High fat diet

Indexes of insulin resistance (IRI); Insulin resistance index

Intraperitoneal glucose tolerance testing (IPGTT); Intraperitoneal Glucose Resistance Test

Hereinafter, the present invention for hypoglycemic and hypolipidemic efficacy of Type 2 diabetes of a pharmaceutical composition containing processed aloe vera gel (PAG) will be described in more detail based on the following examples. I would like to.

However, these examples are provided to illustrate and specifically describe the present invention and should not be construed as limiting the scope thereof.

Example  1.Processed Aloe Vera Gel ( Processed Aloe vera gel , PAG Manufacturing

The processed aloe vera gel of the present invention (provided by Aloecorp, Harlingen, TX, USA) is prepared by first removing the aloe vera leaf's bark and then using 0.5-2.5 g of cellulase and room temperature. The reaction was terminated by heating together for 2 to 2.5 hours at 88-90 ° C. for 30-50 minutes, after which the anthraquinones and other pigments were removed using an activated carbon column, Qiu Z, et and prepared according to the method described in al . (Qiu Z, Jones K, Wylie M, Jia Q, Orndorff S. Modified Aloe barbadensis polysaccharide with immunoregulatory activity.Planta Med 2000; 66: 152-6.).

The processed aloe vera gel (PAG) is currently not commercially available, and the content of polysaccharides in the processed aloe vera gel (PAG) is the amount of dry fraction of residual fractions in the dialysis network upon extensive dialysis with distilled water. (Weight cut-off, 3500 daltons) based on approximately 23.85 ± 0.35%. After completion of the dialysis of polysaccharides with 2 M trifluoroacetic acid in GAG, the monosaccharide composition was analyzed and contained mannose, glucose, and galactose. The average molar ratio of mannose, galactose and glucose was 8.9: 0.3: 1. Processed aloe vera gel (PAG) was used after dissolving in phosphate buffer (PBS) just before administration.

Example  2

A pharmaceutical tablet for treating or preventing type 2 diabetes was produced by the following method with the following composition.

Processed Aloe Vera Gel 50 (wt%) prepared in Example 1

Lactose 25

Starch 6

Magnesium stearate 2

Crystalline 10

Methylcellulose calcium 7

Sterilized purified water was mixed with the mixture of processed aloe vera gel (PAG), lactose, starch, and methyl cellulose, appropriately and uniformly mixed, and dried at 45 ° C. for 3 hours to add magnesium stearate to the dried product. It was then compressed in a conventional manner to obtain a tablet.

Example  3

A health functional food for alleviation or improvement of type 2 diabetes or diabetes-related diseases or symptoms was prepared by the following method with the following composition.

Processed aloe vera gel prepared in Example 1 (PAG, 200: 1, solids 95% or more) 0.5 (% by weight)

Agamix 1

Potassium Sorbate 0.05

Citric Acid 0.05

Purified water 98.4

The processed aloe vega gel, agamix, potassium sorbate and citric acid were dissolved in purified water with uniform stirring, and warmed to 80 ° C. to obtain a liquid dietary supplement.

Experimental Example  1. Animal models and experimental methods

C57BL / 6NCrjBgi male mice fed a normal diet for one week of four weeks were used for the experiments (mouses were purchased from Charles River Laboratory of Animal Science, Orient Co., Seoul, Korea). Mice were housed in independent cages with free access to water and food, and were kept in an animal breeding space with a temperature of 22 ± 2 ° C. and a humidity of 55 ± 5%. Mice were also fed a high-fat diet (OpenSource diets # D12492; Research Diets Inc., New Brunswick, NJ) to induce obesity, or a normal diet (OpenSource diets # D12450B; Research Diets Inc.). The nutritional component of a high-fat diet is similar to that of a normal diet, except that it is low in carbohydrates and high in fat.

At 26 weeks of age, mice with blood glucose levels> 180 mg / dL were selected and classified as type 2 diabetic mice and divided into five groups of 18 animals per group.

One group received only PBS, which was used as a diabetic control group; The three groups received 25, 50 or 100 mg / kg of processed aloe vera gel (PAG) daily, respectively; The other group received pioglitazone (pioglitazone, PGZ, 2.5 mg / kg, Lilly, USA), which has recently been used clinically as a diabetes treatment.

Mice were weighed, fasted for 4 hours, and blood samples were taken from the tails using hairpin-coated tubes. After the experiment, mice were sacrificed and blood samples were taken from the inferior vena cava to measure plasma insulin and fat levels. After collecting blood, the liver, thymus, pancreas, kidneys, lungs, heart and spleens were removed, rinsed with physiological saline and immediately stored at -70 ° C. White adipose tissue was removed from the periepididymal and perirenal fats for morphological observation.

Experimental Example  2. Processed Aloe Vera for Diet-Induced Type 2 Diabetes Of gel (PAG)  Experiment on the effect

The effect of processed aloe vera gel (PAG) on the established dietary-induced type 2 diabetes (T2DM) process was confirmed by C57BL / 6J mouse experiments.

T2DM was induced by a high-fat diet in C57BL / 6J mice. Mice with blood glucose levels of 180 mg / dL or higher, indicating diet-induced obesity (DIO), were selected to test the antidiabetic efficacy of the processed aloe vera gel (PAG). The processed aloe vera gel (PAG) was orally administered to DIO mice for 8 weeks, resulting in a decrease in blood glucose levels to normal levels. In addition, plasma insulin was significantly reduced when processed aloe vera gel (PAG) was administered. Intraperitoneal glucose resistance tests also confirmed the antidiabetic efficacy of the processed aloe vera gel (PAG). Administration of processed aloe vera gel (PAG) lowered triglyceride levels in liver and plasma. Histological examination of periepididymal fat pad showed that the processed aloe vera gel (PAG) reduced the mean size of adipocytes. These results suggest that oral administration of processed aloe vera gel (PAG) can prevent the progression of type 2 diabetes (T2DM) -related symptoms in mice fed high fat-diet and processed aloe vera gel (PAG). Can be useful for treating type 2 diabetes (T2DM).

Experimental Example  3.blood Glucose  And plasma insulin

Blood glucose concentration was measured using a glucometer (Glucometer, Optimum, Medisence), and plasma insulin concentration was measured using an insulin ELISA kit (Shibayagi Co., Japan).

Experimental Example  4.Insulin Resistance Index ( Indexes of insulin resistance , IRI )

The insulin resistance index was calculated using the following formula based on the relationship between blood glucose and plasma insulin levels at fasting:

IRI = insulin (μU / mL) X glucose (mM) /22.5.

Experimental Example  4. Intraperitoneal Glucose  Resistance test ( Intraperitoneal glucose  tolerance testing , IPGTT )

Blood glucose levels were measured by taking intraperitoneally administered 1.5 g / kg of glucose to the intraperitoneal overnight, and taking blood samples from the tail at 0 minutes (immediately before glucose) and at 30, 60, and 120 minutes post-dose. .

Experimental Example  5. Plasma and liver fat levels ( Plasma and hepatic lipid levels )

Plasma triglycerides and total cholesterol levels were measured using a blood chemistry analyzer (Express Plus, Bayer, USA). To measure the triglyceride level in the liver, 50 mg of liver tissue was collected from each mouse, placed in 1 mL of PBS, homogenized, and centrifuged at 3000 rpm for 10 minutes at 4 ° C. Supernatants were collected to determine triglyceride and cholesterol content.

Experimental Example  6.morphological test Histological examinations )

The epididymal fats isolated from representative mice in each group were fixed in overnight in 10% neutral buffered formalin, inserted in paraffin, thinly sliced (4 mm) and placed on slide glass. Hematoxylin and eosin were stained in a general manner to see the general morphology. Micrographs were taken at x100 (BX41, Olympus, Tokyo).

Statistical analysis ( Statistical analysis )

Data was collected using the SPSS program (version 15.0, SPSS Inc., Chicago, IL, USA). Among the mean values, cases with P <0.05 were considered statistically significant.

Experimental Example  7.Processed Aloe Vera Gel (PAG)  spandrel Glucose  Impact on numbers

To test the effects of processed aloe vera gel (PAG) on the progression of symptoms associated with type 2 diabetes, C57BL / 6 male mice were subjected to high-fat diet (HFD) for 21 weeks to type 2 diabetes. On the other hand, the general diet. The DIO phenotype was expressed in all mice fed the high fat diet, and the blood glucose level was much higher than the mice fed the normal diet. DIO mice with fasting glucose levels greater than 180 mg / dL were selected and randomly placed in five groups of 18 animals each, PBS, other doses of the processed aloe vera of the present invention in an environment with free access to a high-fat diet. Gels (PAG, 25, 50 and 100 mg / kg, respectively), and PGZ (2.5 mg / kg) were orally administered for 8 weeks. Mice fed the normal diet were used as normal controls. Blood samples were collected weekly from the tail after 4 hours of fasting and blood glucose levels were measured using a glucometer.

The mean fasting glucose level of DIO mice before PAG administration was 199.7 ± 21.7 mg / dL, and 131.5 ± 13.4 mg / dL for mice on a normal diet. In the untreated DIO mice during the 8 week treatment period, fasting blood glucose levels gradually increased to 266.5 ± 0.7 mg / dL. In contrast, fasting blood glucose levels were significantly reduced in mice administered orally with processed aloe vera gel (PAG) (FIG. 1). 1 shows the effect of processed aloe vera gel (PAG) on fasting glucose levels (results are mean ± SEM).

The anti-hyperglycemic effect of the processed aloe vera gel (PAG) was evident at 2 weeks of treatment and lasted for the duration of the experiment. The average fasting blood glucose level of DIO mice administered 100 mg / kg of processed aloe vera gel (PAG) for 8 weeks was 127.7 ± 11.4 mg / dL, which was not significantly different from that of the diet fed mice. The activity of reducing plasma glucose of processed aloe vera gel (PAG) was close to the activity seen when DIO mice were dosed daily with 2.5 mg / kg PGZ at a dose of 100 mg / kg. No differences were observed during the treatment period between PAG-treated and untreated DIO mice in food-intake or weight.

Experimental Example  8.Processed Aloe Vera Gel (PAG) Glucose  Impact on resistance

To determine the effect of processed aloe vera gel (PAG) on glucose resistance, at the end of the eight-week experiment (3 days before sacrifice), glucose resistance was tested using the IPGTT method. Blood glucose levels of mice fasted overnight were previously measured, and blood samples were taken from the tail at specific time points after intraperitoneal injection of 1.5 g / kg of glucose (total blood glucose levels were measured. Mean ± SEM (n = 18)).

As shown in FIG. 2, DIO mice receiving 100 mg / kg of processed aloe vera gel (PAG) showed a significant improvement in the overall glucose response compared to untreated DIO mice. The effect of processed aloe vera gel (PAG) to reduce the was observed during the first hour after glucose administration.

Experimental Example  9. Plasma Insulin Levels and IRI Processed Aloe Vera for Of gel (PAG)  effect

To determine the effect of processed aloe vera gel (PAG) on plasma insulin levels, plasma insulin levels measured after various treatments were measured (FIG. 3). Blood samples were taken from the inferior vena cava at the end of the eight-week experiment, and plasma insulin concentrations were measured using the insulin ELISA kit (results were mean ± SEM (n = 18)).

Plasma insulin levels of untreated DIO mice were significantly higher (4.2 fold) than those of mice fed a normal diet. Plasma insulin levels were shown to be markedly reduced in DIO mice treated with aloe vera gel (PAG) processed for 8 weeks. The measured plasma glucose and insulin levels were used to calculate homeostatic model assessment values for insulin resistance (Table 1). The mean IRI index of the untreated DIO group was 8.2 times higher than that of the normal diet group. The IRI indices of the DIO group administered 25, 50 and 100 mg / kg doses of processed aloe vera gel (PAG) were 31.4, 32.1, and 31.1% of the IRI indices of the untreated DIO group, respectively.

Table 1. Insulin Resistance Index (IRI)

IRI values were calculated using the following formula:

IRI = insulin (μU / mL) X glucose (mM) /22.5.

Comparison with the mice fed the normal diet, ⁺ P <0.05

Comparison with untreated DIO mice, * P <0.05, ** P <0.01.

Experimental Example  10. Processed Aloe Vera Gel (PAG)  Effect on liver and plasma fat profile

At the end of the eight-week experimental period, triglyceride and cholesterol levels in the liver and plasma of each group were measured (Table 2). Triglyceride levels in the liver and plasma are untreated DIO mice were significantly higher than normal diet mice (respectively, 178.2 ± 7.1 vs . 52.0 ± 26.0 mg / dL, 128.9 ± 7.0vs . 83.7 ± 1.5 mg / dL).After eight weeks of processing aloe vera gel (PAG), triglyceride levels in liver and plasma were significantly reduced in dose-dependent manner. In the DIO group administered the 100 mg / kg dose of Aloe Vera Gel (PAG), triglyceride levels in the liver and plasma were 51.0 and 72.7% of the untreated DIO group, respectively.

Table 2. Effect of Processed Aloe Vera Gel (PAG) on Triacylglycerides and Cholesterol Content in Liver (A) and Plasma (B)

Experimental Example  11. Processed Aloe Vera Gel (PAG)  Fat mass ( fat mass ) And epididymal area ( periepididymal fat pad ) Effect on morphology

At the end of the experiment, epididymal fat bands were isolated from representative mice of each experimental group, cut and stained with hematoxylin and eosin, and micrographs of tissues isolated from normal dietary mice (Fig. 4 (A) (a)), Tissues of untreated DIO mice (Figure 4 (A) (b)), tissues of mice administered 25 mg / kg of processed Aloe Veragel (PAG) (Figure 4 (A) (c)), PAG 50 mg / kg Tissue of mice administered (FIG. 4 (A) (d)), tissue of mice administered PAG 100 mg / kg (FIG. 4 (A) (e)), of 2.5 mg / kg of PGZ Micrographs of tissues (FIG. 4 (A) (f)) were taken respectively (100 × magnification). In addition, the average size of adipocytes was measured (Fig. 4 (B)).

The mean weight of the untreated DIO group animals was approximately 29.7% higher than that of the normal diet group, and the untreated DIO group showed a 1.3-fold increase in the epididymal fat zone mass compared to the normal diet mice. This result was confirmed through morphological analysis of the epididymal fat band, which indicates that the untreated DIO mice increase the fat cell size of the epididymal fat band mainly due to fat accumulation (FIG. 4). On the other hand, mice treated with 25, 50 and 100 mg / kg doses of processed aloe vera gel (PAG) showed a decrease in the average size of adipocytes around the epididymal fat zone 1.8, 2.8 and 30%, respectively (Fig. 4).

It has been established that dietary induced obesity (DIO) and hyperglycemia develop in C57BL / 6J mice fed a high-fat diet, which is a human type 2 diabetes model. As occurs in humans, this mouse model has a genetic base, is associated with obesity that can be induced by a high-fat diet, and exhibits a number of type 2 diabetes symptoms. The processed aloe vera gel (PAG) of the present invention affected the progression of type 2 diabetes in C57BL / 6J mice fed a high-fat diet. Processed aloe vera gel (PAG) was orally administered to DIO mice that had already developed moderate type 2 diabetes (blood glucose: 180-220 mg / dL). In particular, when the processed aloe vera gel (PAG) was administered to this mouse model, the effect of preventing the development of type 2 diabetes-related symptoms was shown.

The administration of processed aloe vera gel (PAG) to DIO mice resulted in fasting blood glucose concentrations to normal levels despite a sustained high fat diet. The anti-hyperglycemic effect of the processed aloe vera gel (PAG) was evident two weeks after treatment, and then continued for eight weeks of treatment. Recent studies of disease progression in type 2 diabetes have been shown to cause insulin resistance in peripheral tissues to cause compensatory hyperinsulinemia and to cause β cell failure.

The inventors of the present invention have found that processed aloe vera gel (PAG) significantly reduces plasma insulin concentrations in the fasting state. These results indicate that processed aloe vera gel (PAG) increases insulin sensitivity by decreasing blood glucose and insulin levels. Improved blood glucose homeostasis was also observed in the intraperitoneal glucose tolerance test in PAG-treated DIO mice.

1 shows the effect of processed aloe vera gel (PAG) on fasting glucose levels.

Results are mean ± SEM.

Relative value for mice in the normal diet ⁺ P <0.05, ⁺⁺ P <0.01.

Relative value for untreated DIO mice * P <0.05, ** P <0.01.

2 shows the effect of processed aloe vera gel (PAG) on glucose resistance.

Results were mean ± SEM (n = 18).

Relative value for untreated DIO mice * P <0.05, ** P <0.01.

3 shows the effect of processed aloe vera gel (PAG) on plasma insulin levels.

Results were mean ± SEM (n = 18).

Relative value for mice in normal diet ⁺⁺ P <0.01.

Relative value for untreated DIO mice * P <0.05, ** P <0.01.

Figure 4 (A) shows the micrograph of the form of the epididymal fat band, (B) shows the average size of the fat cells measured from the results of (A).

Claims (7)

Contains processed aloe vera gel (PAG) as an active ingredient, The polysaccharide content in the processed aloe vera gel (PAG) is 20% to 30% based on the amount of dry fraction (weight cut-off, 3500 Daltons) in the dialysis network, upon extensive dialysis with distilled water. It is characterized by Pharmaceutical composition for the prevention or treatment of type 2 diabetes. The pharmaceutical composition according to claim 1, wherein the average molar ratio of mannose and glucose in the processed aloe vera gel (PAG) is 5-40: 1. Contains processed aloe vera gel (PAG) as an active ingredient, The polysaccharide content in the processed aloe vera gel (PAG) is 20% to 30% based on the amount of dry fraction (weight cut-off, 3500 Daltons) in the dialysis network, upon extensive dialysis with distilled water. It is characterized by Health functional foods for the relief or improvement of type 2 diabetes. The dietary supplement of claim 3 wherein the average molar ratio of mannose and glucose in the processed Aloe Vera Gel (PAG) is 5-40: 1. delete delete delete

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