Application of nutgall or nutgall extract in preparation of antidiabetic drugs

Abstract

The invention belongs to the technical field of medicine research, and particularly relates to application of nutgall or nutgall extract in preparation of antidiabetic medicine. Tests prove that the nutgall extract can remarkably reduce the blood glucose level of a diabetic animal model, and it is prompted that the nutgall extract can be used as a potential anti-diabetic medicine.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical research technology, specifically relating to the application of gallnut or its extract in the preparation of antidiabetic drugs. Background Technology

[0002] Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. In recent years, the rapid increase in the global prevalence of diabetes has seriously impacted people's health and quality of life. Simultaneously, with the accelerating aging of the global population and changes in lifestyle, the number of elderly people with prediabetes is increasing significantly and rapidly. Prediabetes is a transitional stage from normal glucose metabolism to diabetes, and patients in this stage have an increasingly higher risk of developing diabetes than the general population. Type 2 diabetes has become a global concern, significantly impacting social development. Sustained hyperglycemia can lead to serious complications, such as cardiovascular complications and diabetic nephropathy, which not only severely reduces patients' quality of life but also places enormous pressure on society.

[0003] Galla ( Quercus infectoria Oliv. Galla (or gallnut) is the dried gall on the young branches of the *Galium affine* tree, a plant in the Fagaceae family, formed by the parasitic gallnut. Galla has a long history of medicinal use, dating back to ancient times when it was called "moza" in Uyghur. Its chemical components mainly include polyphenols, flavonoids, terpenes, sterols, trace elements, volatile oils, and sugars, with tannins and gallic acid being the main active ingredients. Galla is cold in nature, astringent and bitter, and warm in properties, entering the lung, spleen, and kidney meridians. It possesses the effects of drying and cooling, astringing and consolidating, clearing heat and reducing inflammation, and stopping diarrhea and dysentery. Traditional Chinese medicine believes that galla has astringent, sperm-strengthening, cough-suppressing, and wound-healing effects, and is clinically used for damp-heat diseases such as sore throat, festering sores, slow-healing wounds, and persistent diarrhea. While galla has a long history of medicinal use, there are relatively few research reports on it both domestically and internationally, and further exploration is needed to determine its potential applications. Summary of the Invention

[0004] To address the above-mentioned technical problems, this invention provides the application of gallnut or its extract in the preparation of antidiabetic drugs. Experiments have demonstrated that gallnut extract can significantly reduce blood glucose levels in diabetic animal models, suggesting its potential as an antidiabetic drug.

[0005] The specific technical solution provided by this invention is as follows: In a first aspect, the present invention provides the use of gallnut or its extract in the preparation of an antidiabetic drug, wherein the extract is an ethanol extract of gallnut.

[0006] In a preferred embodiment of the present invention, the extract is prepared according to the following steps: Gallnut seeds are used as raw material. An ethanol solution with a mass fraction of 0-95% is added for extraction, and the extract is collected. A 0% mass fraction ethanol solution is water.

[0007] More preferably, the ethanol solution has a mass fraction of 25%.

[0008] More preferably, the extraction is performed by ultrasonic extraction at 30~70℃ and 80~640W for 15~60 minutes.

[0009] More preferably, the extraction is performed by ultrasonic extraction at 30°C and 320W for 45 minutes.

[0010] More preferably, the extract is collected and the solvent is removed to obtain gallnut extract.

[0011] In a second aspect, the present invention provides an α-glucosidase inhibitor, wherein the active ingredient is the gallnut or the gallnut extract or any combination thereof.

[0012] In a third aspect, the present invention provides an antidiabetic drug, wherein the gallnut or the gallnut extract or any combination thereof is the sole active ingredient.

[0013] In a preferred embodiment of the present invention, the medicament includes pharmaceutically acceptable excipients.

[0014] More preferably, the drug is an oral or injectable formulation. Excipients that can be added during the preparation of oral formulations include binders, fillers, disintegrants, lubricants, solubilizers, colorants, flavoring agents, coating materials, etc. Excipients that can be added during the preparation of injectable formulations include solubilizers, antioxidants, pH adjusters, osmotic pressure adjusters, preservatives, etc.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides the application of gallnut or its extract in the preparation of antidiabetic drugs. The invention demonstrated that the ethanol extract of gallnut administered by gavage to SD rats fed sucrose or starch significantly reduced blood glucose levels in the animal model, suggesting that gallnut may be a potential candidate drug for the treatment of diabetes. Attached Figure Description

[0016] Figure 1 The effect of gallnut extract on postprandial blood glucose in rats fed sucrose; Figure 2 The effect of gallnut extract on postprandial blood glucose in starch-fed rats; Figure 3 The study involved measuring blood glucose changes within 120 minutes after gavage administration of starch and different drug concentrations. Figure 4This is a comparison of blood glucose AUC in rats after administration to each group. Detailed Implementation

[0017] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0018] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0019] Galla ( Quercus infectoria Oliv. Gallnut (Galium affine) is the dried gall of the young branches of the *Galium affine* tree, a plant in the Fagaceae family. Its chemical composition mainly includes polyphenols, flavonoids, terpenes, sterols, trace elements, volatile oils, and sugars, with tannins and gallic acid being the main active ingredients. Clinically, gallnut is commonly used for damp-heat diseases such as sore throat, festering sores, slow-healing wounds, and persistent diarrhea. However, whether gallnut has other potential applications requires further exploration.

[0020] Based on this, the present invention provides the application of gallnut or its extract in the preparation of antidiabetic drugs.

[0021] The following description is based on specific embodiments.

[0022] Example 1 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution with a mass concentration of 30% (10 times their total weight). Extract the extract by ultrasonication at 70°C for 60 minutes with an ultrasonic power of 640 W. Collect the extract, evaporate it by rotary evaporation, and then dry it to obtain the gallnut extract.

[0023] Example 2 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 50 times their total weight (95% by mass). Extract the extract by ultrasonication at 30°C for 15 minutes with an ultrasonic power of 80W. Collect the extract, evaporate by rotary evaporation, and then dry to obtain the gallnut extract.

[0024] Example 3 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 20 times their total weight (30% by mass). Extract the extract by ultrasonication at 70°C for 60 minutes with an ultrasonic power of 640 W. Collect the extract, evaporate by rotary evaporation, and then dry to obtain the gallnut extract.

[0025] Example 4 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 30 times their total weight (30% by mass). Extract the extract by ultrasonication at 70°C for 60 minutes with an ultrasonic power of 640 W. Collect the extract, evaporate by rotary evaporation, and then dry to obtain the gallnut extract.

[0026] Example 5 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 40 times their total weight (30% by mass). Extract the extract by ultrasonication at 70°C for 60 minutes with an ultrasonic power of 640 W. Collect the extract, evaporate by rotary evaporation, and then dry to obtain the gallnut extract.

[0027] Example 6 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 50 times their total weight (50% by mass). Extract the extract by ultrasonication at 40°C for 30 minutes with an ultrasonic power of 160W. Collect the extract, evaporate by rotary evaporation, and then dry to obtain the gallnut extract.

[0028] Example 7 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 50 times their total weight (70% by mass). Extract the extract by ultrasonication at 50°C for 45 minutes with an ultrasonic power of 320 W. Collect the extract, evaporate by rotary evaporation, and then dry to obtain the gallnut extract.

[0029] Example 8 An extract of gallnut, prepared according to the following steps: Take gallnut seeds, add water equivalent to 50 times their total weight, and extract by ultrasonication at 60℃ for 45 minutes with ultrasonic power set to 480w. Collect the extract, evaporate by rotary evaporation, and dry to obtain gallnut extract.

[0030] Example 9 An extract of gallnut, prepared according to the following steps: Take gallnut seeds and add an ethanol solution of 50 times their total weight (25% by mass). Extract the gallnut seeds by ultrasonication at 30°C for 45 minutes with an ultrasonic power of 320 W. Collect the extract, evaporate it by rotary evaporation, and then dry it to obtain the gallnut extract.

[0031] Since the gallnut extracts and gallnuts provided in Examples 1-9 all have significant inhibitory effects on α-glucosidase and have good anti-diabetic effects, the following description of the effects of the gallnut extract provided in Example 9 will only be based on this invention.

[0032] In vivo rat postprandial blood glucose detection To further demonstrate the inhibitory effect of the hypoglycemic active fraction of gallnut on α-glucosidase and to explore its effect on lowering postprandial blood glucose, this invention conducted an in vivo hypoglycemic activity evaluation experiment. SD rats were used in this experiment, and sucrose and starch were administered respectively to investigate the effect of the hypoglycemic active fraction of gallnut on postprandial blood glucose.

[0033] SD rats (SPF grade) were purchased from the Experimental Animal Center of Xinjiang Medical University. The rats were housed in an environment with a temperature of 23 ± 2℃ and humidity of 50 ± 5%, with alternating day and night lighting, and free access to food and water. Before the experiment, the rats were acclimatized for one week to adapt to the experimental environment.

[0034] After the adaptation period, the rats were randomly divided into two main groups: a starch gavage group and a sucrose gavage group. Each main group was further divided into four subgroups (n=5 rats per subgroup): a blank control group (BC), a low-dose group (LD) of the active hypoglycemic component of gallnut (LD), a middle-dose group (MD) of the active hypoglycemic component of gallnut (MD), a high-dose group (HD) of the active hypoglycemic component of gallnut (HD), and a positive control group (PC) of acarbose.

[0035] Before the experiment, rats were fasted for 18 hours and then gavaged with corn starch or sucrose at a dose of 2 g / kg. The blank control group was given drinking water. The low, medium and high dose groups were given gallnut extract at doses of 70 mg / kg, 150 mg / kg and 300 mg / kg, respectively. The positive control group was given acarbose at a dose of 20 mg / kg.

[0036] The results are shown in Tables 1-2 and... Figures 1-2 As shown.

[0037] Table 1. Effects of gallnut extract on postprandial blood glucose levels in sucrose-fed rats. After rats in each group were treated with sucrose and different drug concentrations, blood glucose changes were measured within 120 minutes. Figure 1As shown in the figure, at 0 h, there was no significant difference in blood glucose levels among the animal models in each group, all being normal fasting blood glucose levels of 4.0 ± 0.44 mmol / L. After 15 min of gavage, the blood glucose levels of each group of rats reached their highest values ​​within the group, and then gradually decreased over time, returning to normal levels approximately 2 h after feeding. The curves show that, compared to the blank control group, the positive control drug acarbose reduced postprandial blood glucose, and blood glucose tended to normalize after 60 min. The high, medium, and low doses of the hypoglycemic active component of gallnut all reduced blood glucose levels in the three groups of rats, with the effect of improving blood glucose being more significant with increasing extract concentration. The high-dose group reduced blood glucose to a level close to that of the positive control drug acarbose at 15 min, but the subsequent decrease in blood glucose level tended to plateau, and blood glucose approached normal levels at 60 min. During the same time period, the low and medium dose groups also reduced postprandial blood glucose, which gradually decreased over time (from 15 min to 90 min) and tended to normalize after 90 min.

[0038] like Figure 2 As shown in the figure, the area under the curve indicates that, compared to the control group, rats treated with the hypoglycemic active fraction of gallnut showed a decrease in blood glucose levels. Furthermore, blood glucose levels improved significantly with increasing extract concentration, and the hypoglycemic effect of the positive control drug acarbose was even more pronounced. The results suggest that the hypoglycemic active fraction of gallnut can control postprandial blood glucose elevation, and the high-dose group can accelerate the recovery of postprandial blood glucose to normal levels. This effect is related to the inhibitory activity of gallnut on α-glucosidase.

[0039] Table 2. Effects of gallic acid extract on postprandial blood glucose levels in starch-fed mice. Blood glucose changes were measured within 120 minutes after gavage administration of starch and different drug concentrations. Figure 3 As shown in the figure, the changes in blood glucose levels were similar to those in the sucrose gavage group. However, it is noteworthy that the peak blood glucose level in this group of rats was delayed compared to the sucrose group. After 60 minutes of gavage, the blood glucose levels in each group reached their highest values. Since starch is a polysaccharide, it takes longer to be broken down and absorbed than sucrose, thus reducing the absorption of glucose into the bloodstream within the same timeframe and delaying the rise in postprandial blood glucose. The positive control drug acarbose significantly reduced postprandial blood glucose and effectively inhibited the rise in blood glucose during the peak period (30-90 minutes). The high-dose group of the hypoglycemic active component of gallium showed better blood glucose control, approaching that of the positive control drug group. The low- and medium-dose groups of the hypoglycemic active component of gallium showed slightly lower blood glucose levels than the control group from 30 to 60 minutes, subsequently returning to normal levels.

[0040] like Figure 4As shown in the curve, the area under the curve indicates that, compared to the control group, rats treated with the hypoglycemic active component of gallnut showed a significant reduction in blood glucose levels. Furthermore, blood glucose levels improved markedly with increasing extract concentration. The high-dose group of the hypoglycemic active component of gallnut exhibited a hypoglycemic effect similar to that of the positive control drug acarbose. These results demonstrate that the high-dose group of the hypoglycemic active component of gallnut can control postprandial blood glucose elevation and accelerate the recovery of postprandial blood glucose to normal levels.

[0041] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. The use of gallnut or its extract in the preparation of antidiabetic drugs, characterized in that, The extract is an ethanol extract of gallnut.

2. The application according to claim 1, characterized in that, The extract was prepared according to the following steps: Galla seeds are used as raw material. An ethanol solution with a mass fraction of 0-95% is added for extraction, and the extract is collected to obtain the product.

3. The application according to claim 2, characterized in that, The ethanol solution has a mass fraction of 25%.

4. The application according to claim 1, characterized in that, The extraction was performed by ultrasonic extraction at 30~70℃ and 80~640W for 15~60 minutes.

5. The application according to claim 4, characterized in that, The extraction was performed at 30℃ and 320W ultrasonic extraction for 45 minutes.

6. The application according to claim 1, characterized in that, Collect the extract, remove the solvent, and you will get the gallnut extract.

7. An α-glycosidase inhibitor, characterized in that, It uses the gallnut as described in claim 1, or the gallnut extract, or any combination of both as the active ingredient.

8. An antidiabetic drug, characterized in that, It uses the gallnut as described in claim 1, or the gallnut extract, or any combination of both as the sole active ingredient.

9. The antidiabetic drug according to claim 8, characterized in that, The drug includes pharmaceutically acceptable excipients.

10. The antidiabetic drug according to claim 9, characterized in that, The drug is an oral or injectable formulation.

Images