Imidazole dipeptide composition with kidney protection effect and application thereof

Abstract

The invention discloses an imidazole dipeptide composition with a kidney protecting effect and application thereof. The imidazole dipeptide composition with the kidney protection effect comprises goose carnosine and carnosine, and based on the total weight of the goose carnosine and the carnosine as 100%, the content of the goose carnosine is 10%-99%, and the content of the carnosine is 1%-90%. A mouse test proves that after a mouse with hyperuricemia renal injury continuously takes the imidazole dipeptide composition for a period of time, compared with a control group, kidney injury is obviously reduced, and the imidazole dipeptide composition has a very good kidney protection effect.

Description

Technical Field

[0001] The present invention relates to an imidazole dipeptide composition and its application, in particular, to an imidazole dipeptide composition with kidney-protecting effect and its application in preparing related products with kidney-protecting effect (such as medicines or special medical formula foods, etc.). Background Art

[0002] The kidney is an important organ in the human body. Its main function is to remove metabolic products, certain wastes and toxins from the body through the formation of urine, while retaining water and other useful substances through reabsorption. Bad eating habits can lead to the production of high uric acid, and long-term high uric acid levels can induce gout, diabetes, metabolic syndrome, oxidative stress, inflammation, hypertension, endothelial dysfunction and other complications. It can also put a serious burden on the kidneys and cause kidney damage.

[0003] Creatinine and urea nitrogen are commonly used biochemical indicators of renal function. Creatinine is a waste product produced by human muscles. Since creatinine is almost entirely excreted by the kidneys and is rarely affected by food, it reflects the function of the kidneys relatively objectively. If the creatinine concentration in the blood increases, it means that the kidneys' ability to remove waste has decreased. In addition, urea nitrogen is a metabolite produced by the digestion of protein, which is converted in the liver through the urea cycle. If renal function is impaired, the ability to eliminate urea naturally decreases, urea accumulates in the blood, and the level of blood urea nitrogen will increase.

[0004] CN113616688A discloses a composition for repairing kidney damage and its application, wherein the effective components of the composition are composed of anserine (β-alanyl-1-methyl-L-histidine, Ans) dry powder, astragalus extract, and sophora flavescens extract, and the mass ratio of the anserine dry powder, astragalus extract, and sophora flavescens extract in the composition is 80-90:3-10:5-15. The experiment shows that the composition composed of the anserine dry powder, astragalus extract, and sophora flavescens extract has a certain degree of repair of kidney damage, while the effect of anserine alone on repairing kidney damage is not ideal. In addition, the Chinese medicinal flavor of the astragalus extract and sophora flavescens extract used in the composition is usually unpleasant. Summary of the invention

[0005] An object of the present invention is to provide a composition having kidney-protecting effect.

[0006] Another object of the present invention is to provide application of the composition.

[0007] The present invention provides the following technical solutions:

[0008] Technical Solution 1: An imidazole dipeptide composition with kidney-protecting effect, the composition comprises anserine and carnosine, wherein, based on the total weight of anserine and carnosine as 100%, the content of anserine is 10%-99%, and the content of carnosine is 1%-90%.

[0009] Technical Solution 2: The imidazole dipeptide composition according to Technical Solution 1, wherein, based on the total weight of anserine and carnosine being 100%, the content of anserine is 91%, and the content of carnosine is 9%.

[0010] According to some specific embodiments of the present invention, in the imidazole dipeptide composition of the present invention, the sum of the weights of anserine and carnosine accounts for more than 50% of the total weight of the composition, preferably more than 60%, further preferably more than 70%, more than 80%, more than 85%, more than 90%, more than 95% or 100%.

[0011] Technical Solution 3: The imidazole dipeptide composition according to Technical Solution 1 or 2, which consists of anserine and carnosine.

[0012] Technical Solution 4: The imidazole dipeptide composition according to Technical Solution 1 or 2 further comprises other substances having kidney-protecting effects. According to some specific embodiments of the present invention, the amount of the other substances having kidney-protecting effects accounts for less than 50% of the total weight of the imidazole dipeptide composition of the present invention.

[0013] Technical Solution 5: According to the imidazole dipeptide composition described in Technical Solution 4, the other substances having kidney-protecting effects include histidine and / or histidine derivatives. The histidine derivatives include, but are not limited to: oligopeptides containing histidine residues, that is, oligopeptides composed of multiple histidines or composed of histidine and other amino acids, which can be dipeptides, tripeptides, etc., preferably dipeptides. The histidine and histidine derivatives can be of animal and / or plant origin, for example, can be derived from chicken, fish or other animal muscles.

[0014] Technical Solution 6: Use of the imidazole dipeptide composition described in any one of Technical Solutions 1-5 in the preparation of a composition with kidney-protecting effect.

[0015] In the present invention, "kidney protection" means having a protective effect on the kidneys, including assisting in protecting the kidneys and being beneficial to kidney health.

[0016] According to some specific embodiments of the present invention, the kidney-protecting effect includes alleviating kidney damage caused by high uric acid.

[0017] According to some specific embodiments of the present invention, the kidney-protecting effect includes reducing the uric acid level, serum creatinine and / or urea nitrogen level in individuals with hyperuricemia and renal damage.

[0018] According to some specific embodiments of the present invention, the kidney-protecting effect includes improving kidney tissue damage caused by hyperuricemia and slowing down inflammatory cell infiltration in kidney tissue.

[0019] According to some specific embodiments of the present invention, the kidney-protecting effect includes reducing the levels of pro-inflammatory factors such as TNF-α, IL-1β, IL-6, etc. in individuals with renal damage.

[0020] According to some specific embodiments of the present invention, the kidney-protecting effect includes increasing the glutathione level in the serum and / or kidney tissue of individuals with hyperuricemia.

[0021] According to some specific embodiments of the present invention, the kidney-protecting effect includes increasing the SOD level in the serum and / or kidney tissue of individuals with hyperuricemia and slowing down oxidative damage.

[0022] According to some specific embodiments of the present invention, the kidney-protecting effect includes reducing the level of malondialdehyde in the serum and / or kidney tissue of individuals with hyperuricemia.

[0023] The present invention also provides a method for protecting the kidney, which comprises administering an effective amount of the imidazole dipeptide composition described in any one of technical solutions 1-5 of the present invention to an individual in need.

[0024] According to some specific embodiments of the present invention, the individual is a mammal or a human.

[0025] Technical Solution 7: The application according to Technical Solution 6, wherein the composition is used to prepare medicines.

[0026] Technical Solution 8: According to the application described in Technical Solution 7, the medicine contains an effective amount of the imidazole dipeptide composition.

[0027] Technical Solution 9: According to the application described in Technical Solution 7 or 8, the dosage of the imidazole dipeptide composition in the medicine is 1 mg-200 mg / day, preferably 1 mg-100 mg / day, and more preferably 5 mg-50 mg / day.

[0028] Technical Solution 10: The application according to any one of Technical Solutions 7-9, wherein the medicine further contains excipients, preferably, the excipients include one or a combination of two or more of sorbitol, maltodextrin, and magnesium stearate.

[0029] Technical Solution 11: The application according to any one of Technical Solutions 7-10, wherein the medicine is a tablet, capsule, powder or granule.

[0030] Technical Solution 12: The use according to Technical Solution 6, wherein the composition is used to prepare food. The food may be, for example, a functional food, a dietary supplement, etc. The functional food may be, for example, a health food, a food for special medical purposes, a therapeutic diet, etc.

[0031] Technical Solution 13: According to the application described in Technical Solution 12, the amount of the imidazole dipeptide composition in the food can be 1 mg-200 mg / day according to the adult consumption, preferably 1 mg-100 mg / day, and more preferably 5 mg-50 mg / day.

[0032] The present invention has been verified through experiments that the imidazole dipeptide composition of the present invention has a good protective effect on mouse kidneys and effectively alleviates kidney damage caused by high uric acid.

[0033] According to a specific embodiment of the present invention, the intervention of the imidazole dipeptide composition in hyperuricemia renal injury mice has a good uric acid-lowering effect, and the serum creatinine and urea nitrogen levels of the intervention group significantly decreased to normal levels, indicating that the intervention of imidazole dipeptide can reduce the renal damage caused by hyperuricemia. The histopathological sections of the mouse kidneys showed that the imidazole dipeptide composition intervention group was able to significantly improve the renal tissue damage caused by hyperuricemia and slow down the inflammatory cell infiltration of renal tissue. Further, the levels of three proinflammatory factors, TNF-α, IL-1β, and IL-6, in the imidazole dipeptide composition intervention group were significantly reduced. Furthermore, the results of glutathione detection in serum and renal tissue crushing fluid showed that the treatment of the imidazole dipeptide composition can increase the glutathione levels in the serum and renal tissue of hyperuricemia model mice, and slow down the oxidative damage caused by uric acid production. The results of superoxide dismutase detection in serum and renal tissue crushing fluid showed that the imidazole dipeptide composition treatment method can increase the SOD levels in the serum and renal tissue of hyperuricemia model mice, and slow down the oxidative damage caused by uric acid production. The results of glutathione peroxidase detection in serum and kidney tissue fragments showed that the imidazole dipeptide combination treatment method can increase the glutathione peroxidase level in the serum and kidney tissue of hyperuric acid model mice and slow down the oxidative damage caused by uric acid production. The results of malondialdehyde detection in serum and kidney tissue fragments showed that the imidazole dipeptide combination treatment method can significantly reduce the malondialdehyde level in the serum and kidney tissue of hyperuric acid model mice. There was no significant difference in the malondialdehyde level of all intervention groups compared with the normal group, indicating that all treatment methods can slow down the oxidative damage caused by uric acid production.

[0034] The imidazole dipeptide composition provided by the present invention has the function of protecting kidneys. Mouse experiments have confirmed that after mice with high uric acid kidney damage continuously take the imidazole dipeptide composition of the present invention for a period of time, kidney damage is significantly less than that of the control group, and it has a good kidney protection effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 Schematic diagram of the animal experiment process.

[0036] Figure 2 Showing the effects of different interventions on serum uric acid in mice.

[0037] Figure 3 Shown are the effects of different interventions on serum creatinine levels in mice.

[0038] Figure 4 Showing the effects of different interventions on serum urea nitrogen levels in mice.

[0039] Figure 5 Pathological analysis showing the effects of different interventions on mouse kidneys.

[0040] Figure 6 Shows the level of inflammatory factor (TNF-α) in mouse kidney.

[0041] Figure 7 The levels of inflammatory factors (IL-1β) in mouse kidneys are shown.

[0042] Figure 8 Shows the levels of inflammatory factors (IL-6) in mouse kidneys.

[0043] Fig. 9 Shows the levels of inflammatory factors (IL-10) in mouse kidneys.

[0044] Fig.10 Shown are the levels of serum lipopolysaccharide in mice.

[0045] Fig.11 Shown are the serum lactate dehydrogenase levels of mice.

[0046] Fig.12 Shown are the serum glutathione levels of mice.

[0047] Fig.13 Shows the glutathione level in mouse kidney tissue.

[0048] Fig.14 Shown are the levels of serum superoxide dismutase in mice.

[0049] Fig.15 Shows the level of superoxide dismutase in mouse kidney tissue.

[0050] Fig.16 Shown are the levels of serum glutathione peroxidase in mice.

[0051] Fig.17 Shows the level of glutathione peroxidase in mouse kidney tissue.

[0052] Fig.18Shown are the serum malondialdehyde levels of mice.

[0053] Fig.19 Shows the level of malondialdehyde in mouse kidney tissue.

[0054] In the attached figures, the data represent the mean ± standard deviation. Letters such as a, b, and c represent the results of significance analysis of the same column of data (p < 0.05). If the letters are the same, there is no significant difference between the marked values. DETAILED DESCRIPTION

[0055] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the technical solution of the present invention is now described in detail below, but it should not be construed as limiting the applicable scope of the present invention.

[0056] Example 1

[0057] This embodiment provides an imidazole dipeptide composition, which comprises, by weight:

[0058] Anserine 91 parts

[0059] Carnosine 9 parts.

[0060] Take anserine and carnosine according to the above ratio and mix them evenly to obtain the bioactive peptide of this embodiment, which is an imidazole dipeptide composition.

[0061] Example 2

[0062] This embodiment provides a medicine, which comprises the composition provided in Example 1.

[0063] Example 3

[0064] This embodiment provides a food, which comprises the composition provided in Example 1.

[0065] Experimental study on the kidney protection effect of imidazole dipeptide

[0066] The present invention verifies the kidney-protecting effect of the imidazole dipeptide of the present invention through animal experiments.

[0067] 1. Test samples and test animals

[0068] Test sample: the bioactive peptide of Example 1 (i.e., anserine 91 parts and carnosine 9 parts of imidazole dipeptide).

[0069] Experimental animals: 5-week-old male ICR mice were purchased from Shanghai JSJ Experimental Animal Co., Ltd., SPF grade.

[0070] 2. Grouping and treatment of experimental animals

[0071] All mice were adaptively raised at a temperature of 24±2℃, with 12h light and 12h dark alternation, and free access to food and water. After 1 week of environmental adaptation, the mice were randomly divided into 7 groups, namely normal control group, model group, positive control group, low-dose imidazole dipeptide group (IDP-L), and high-dose imidazole dipeptide group (IDP-H). The modeling period was two weeks, and the intervention period was 4 weeks. During the modeling period, except for the normal control group, the other groups were gavaged with 300mg / kg of potassium oxonate and hypoxanthine (prepared into a suspension with 0.5% CMC-Na solution) every day to carry out hyperuric acid modeling. During the intervention period, except for the normal control group, the other groups were first gavaged with 300mg / kg of potassium oxonate and hypoxanthine every day for continuous modeling. After 2h of modeling, the mice in each group were treated according to Figure 1 The samples in each group were dissolved in normal saline, and the normal group and the model group were gavaged with the same dose of normal saline.

[0072] 3. Sampling and processing of test samples

[0073] During the modeling period, the tails were cut off and blood was collected once a week to detect changes in serum uric acid. Fresh feces of each group of mice were collected on the last two days of the experiment and stored in a -20°C refrigerator. Before the mice were killed, they were fasted for 12 hours and the last modeling was performed. Blood was collected 1 hour after the modeling, and then they were killed and dissected. The whole blood of the mice was placed at 4°C for 2 hours, then centrifuged at 3000rpm for 10 minutes, and the serum was divided and stored in a -80°C refrigerator. After the liver and kidneys of the mice were removed, one of the kidneys was preserved with 4% paraformaldehyde for pathological analysis, and the other tissue samples were immediately quick-frozen in liquid nitrogen and stored in separate devices at -80°C.

[0074] 4. Detection method

[0075] Uric acid, creatinine, urea nitrogen, lactate dehydrogenase, xanthine oxidase (XOD), lipopolysaccharide (LPS); oxidative stress levels (glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)), inflammatory factors (TNF-alpha, IL-1β, IL-6, IL-10) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) were detected according to the method in the kit instructions; the weight of mice was directly weighed twice a week; the pH of mouse urine was tested once a week with pH test paper; renal tissue pathology analysis was completed in cooperation with Wuhan Saiweier Biotechnology Co., Ltd.; renal uric acid transporter immunoblot analysis was performed according to routine laboratory operating procedures.

[0076] 5. Data processing method data

[0077] SPSS 22.0 software was used for statistical analysis using the Tukey method, and p < 0.05 was considered statistically significant. GraphPad Prism 8 and R studio were used for drawing, correlation analysis, and bioinformatics analysis.

[0078] 6. Experimental results and conclusions

[0079] 6.1 Modeling results

[0080] After one week of modeling with potassium oxonate and hypoxanthine, blood was collected by tail cutting to detect serum uric acid levels. One week after modeling, although the serum uric acid levels of some mice increased significantly, the serum uric acid levels of most mice did not increase significantly, so the mice were modeled a second time (modeling continued for another week). Two weeks after modeling, blood was collected by tail cutting to detect the serum uric acid levels of the mice. The results showed that two weeks after modeling, except for the mice in the normal group, the serum uric acid levels of all other mice increased significantly compared with those of the normal group mice, and the degree of increase was about twice, indicating that the hyperuric acid modeling was very successful. Therefore, from the third week, imidazole dipeptide or probiotic intervention was performed while modeling.

[0081] 6.2 Changes in mouse body weight and urine pH during oral administration

[0082] During the 6-week oral gavage intervention, although the weight of mice in some groups fluctuated, the weight of most groups did not change significantly or changed very little. During the 6-week period, the urine pH of different groups at the same time and the urine pH of the same group at different times fluctuated, but the fluctuation was not large and irregular.

[0083] 6.3 Effects of different interventions on three parameters of renal function in mice

[0084] Serum uric acid level is the most important indicator that can directly determine hyperuricemia. Creatinine is formed in the muscle from creatine phosphate through spontaneous and irreversible conversion. Unless there is a large change in muscle mass, the amount of creatinine formed is usually quite constant. The amount of free creatinine in circulation depends entirely on its excretion rate. Therefore, measuring the amount of creatinine in serum or plasma can be used to evaluate the glomerular filtration efficiency to determine the state of renal function. The urea nitrogen in the blood comes from the liver and is excreted from the body with urine through the kidneys. Renal failure, nephritis, urethral obstruction, etc. can increase the blood urea nitrogen content. It can be seen that serum creatinine and urea nitrogen are two indicators for evaluating renal function. The results of the three renal function tests are as follows: Figure 2 , Figure 3 , Figure 4As shown. In terms of uric acid levels, the uric acid level in the model group was significantly higher than that in all other groups. After a 4-week intervention, the uric acid levels in all intervention groups decreased significantly, indicating that all formula interventions have a good uric acid-lowering effect. Among them, the uric acid levels in the positive control group and the high and low dose groups of imidazole dipeptide decreased to the level of the normal group (no significant difference from the normal group), and the uric acid levels in other intervention groups were slightly higher than the normal group, but significantly lower than the model group. While the uric acid concentration in the model group increased, the serum creatinine and urea nitrogen levels also increased significantly compared with the normal group mice, which is consistent with the results reported in the literature, that is, hyperuricemia is associated with renal damage in mice. Except for the positive control group, the serum creatinine and urea nitrogen levels in all other intervention groups decreased significantly to normal levels (no significant difference from the normal group, and significant difference from the model group), indicating that the intervention of imidazole dipeptide can alleviate the renal damage caused by hyperuricemia. The creatinine and urea nitrogen levels of mice in the positive control group increased, indicating that although allopurinol can reduce the uric acid level of hyperuricemia mice, it has strong nephrotoxicity to mice.

[0085] 6.4 Protective effects of different interventions on mouse kidneys

[0086] Clinically, changes in renal tissue structure and inflammatory cell infiltration are significant pathological features of hyperuricemia. Figure 5The histopathological sections of the kidneys of mice in each group are shown. In the sections of the normal group, the glomerular matrix is ​​uniform, the renal tubular epithelial cells are round and plump, the connective tissue between the urinary tubules is the renal interstitium, there is no obvious hyperplasia of the interstitium, and no obvious inflammatory changes are observed. In the model group, a small amount of lymphocyte infiltration around the blood vessels can be seen in the field of view (black arrows), granulocytes in the glomeruli (red arrows), and more renal tubular epithelial cells are watery degeneration, cell swelling, and loose and lightly stained cytoplasm (green arrows); the renal tubules are dilated, the renal tubular epithelial cells are flattened, the tubular lumen is enlarged (blue arrows), the tubular lumen is filled with eosinophilic flocs (purple arrows), and there are few exfoliated epithelial cells in the renal tubules (yellow arrows). In the positive group, tubular atrophy, decreased eosinophilia of epithelial cells, narrow tubular lumen, unclear structure (white arrow), a small amount of connective tissue hyperplasia around (orange arrow), accompanied by a small amount of lymphocytes (black arrow) and granulocyte infiltration (red arrow); a large number of tubular epithelial cells with watery degeneration, cell swelling, loose and lightly stained cytoplasm (green arrow); a small number of tubular dilatation, flattened tubular epithelial cells, enlarged tubular lumen, and few granulocytes in the lumen (blue arrow). Eosinophilic substances are rarely found in the lumen of renal tubules (purple arrow). The renal tissue damage of mice in other groups was significantly improved compared with that in the model group. A small number of tubular epithelial cells with watery degeneration, cell swelling, loose and lightly stained cytoplasm (green arrow) were seen in the field of view; eosinophilic substances are rarely found in the renal tubules (purple arrow). The hyperuricemia model was established by potassium oxonate and hypoxanthine, and the kidneys of mice showed obvious inflammation and tissue structural damage. The reabsorption of renal tubules and the filtration effect of glomeruli have an important influence on the uric acid level. Tubular damage and glomerular filtration dysfunction will further increase the uric acid concentration, leading to the deposition of uric acid crystals. Although allopurinol treatment can reduce the uric acid level of hyperuricemia mice, it can cause severe renal damage. Except for the positive control group, other intervention groups can significantly improve the renal tissue damage caused by hyperuricemia and slow down the infiltration of inflammatory cells in renal tissue. Pathological scoring was performed according to the diagnostic criteria for pathological changes (Table 1), and the results are shown in Table 2.

[0087] Table 1. Pathological scoring criteria

[0088]

[0089] Table 2. Pathological scores (average scores of each group)

[0090]

[0091] After pathological analysis of the kidneys, the present invention further studied the effects of hypoxanthine and potassium oxonate-induced hyperuricemia on the levels of various cytokines in the renal tissues of mice. Figure 6-Figure 9As shown in the figure, after six weeks of modeling, the levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) in the kidneys of the model group mice increased significantly compared with the normal group, while the level of the anti-inflammatory factor IL-10 decreased significantly, indicating that modeling causes significant inflammatory reactions in the kidneys of mice. After various interventions, the levels of the three pro-inflammatory factors in all intervention groups decreased significantly, among which the high-dose imidazole dipeptide group had no significant difference in TNF-α from the normal group.

[0092] Lipopolysaccharide is a component of the outer cell wall of Gram-negative bacteria. It is a substance composed of lipids and polysaccharides (glycolipids). Lipopolysaccharide is an endotoxin. When it acts on other biological cells such as humans or animals, it will show a variety of biological activities. Lipopolysaccharide is toxic to the host. Endotoxins are only released when the bacteria die and dissolve or when the bacterial cells are destroyed by artificial methods, so they are called endotoxins. Literature reports that high uric acid can affect intestinal permeability, accompanied by systemic inflammation, and serum lipopolysaccharide will increase. There was no significant difference in serum lipopolysaccharide levels among all experimental groups in this experiment ( Fig.10 ), indicating that kidney inflammation has not reached the extent of causing enteritis.

[0093] Lactate dehydrogenase is a glycolytic enzyme (LDH) whose main function is to catalyze the oxidation of lactate to pyruvate. It is an important enzyme in the body's energy metabolism. Lactate dehydrogenase is mainly used to evaluate myocardial damage and hepatocyte damage. When the body's tissues and organs are diseased, the LDH of the tissues and organs themselves will change, and cause changes in LDH in the blood. The LDH in the urine of patients with chronic glomerulonephritis, diabetic nephrosis, and renal malignant tumors is generally 3 to 6 times higher than that of normal people, but urea and small molecule peptides in the urine can inhibit enzyme activity. The serum LDH of chronic kidney disease patients with uremia is generally normal. There was no significant difference in the lactate dehydrogenase levels among all experimental groups in this experiment ( Fig.11 ).

[0094] 6.5 Improvement of oxidative stress in mice by different interventions

[0095] When xanthine oxidase catalyzes the production of uric acid from purine, it produces a large amount of superoxide anions and H 2 O 2, which triggers an increase in the body's systemic oxidative stress level. Glutathione is an important endogenous antioxidant substance in the body that can neutralize reactive oxygen in the body. Superoxide dismutase is the most important antioxidant enzyme in the body, which can catalyze the dismutation of superoxide anions to produce hydrogen peroxide and oxygen. Glutathione peroxidase can use reduced glutathione to catalyze hydrogen peroxide and many organic peroxides to produce water or organic alcohols. It can remove peroxides in living cells and plays a key role in protecting cells from free radical damage. Lipids in cells easily react with free radicals to produce lipid peroxides. Glutathione peroxidase can use reduced glutathione to reduce lipid peroxides, thereby eliminating the toxic effects of free radicals. Glutathione peroxidase is distributed in almost all tissues. In some pathological conditions, the activity of glutathione peroxidase will be significantly upregulated or downregulated. Malondialdehyde is a natural product of lipid oxidation in organisms. When animal or plant cells experience oxidative stress, lipid oxidation occurs, and the level of malondialdehyde can reflect the level of oxidative stress in the body.

[0096] The results of glutathione detection in serum and kidney tissue fragments showed that ( Fig.12 , Fig.13 ), the glutathione concentration in the model group mice was significantly lower than that in the normal group. All treatments were able to increase the glutathione levels in the serum and kidney tissue of the hyperuricemia model mice and slow down the oxidative damage caused by uric acid production. The trends of glutathione concentrations in serum and kidney tissue fragments in different experimental groups were basically the same. Among all intervention groups, the glutathione concentrations in serum and kidney tissue fragments in the allopurinol group and low-dose imidazole dipeptide group were significantly higher than those in the model group, and their levels were not significantly different from those in the normal group.

[0097] The results of superoxide dismutase detection in serum and kidney tissue fragments showed that ( Fig.14 , Fig.15 ), the superoxide dismutase activity of mice in the model group was significantly lower than that in the normal group. All treatment methods can increase the SOD levels in the serum and kidney tissues of hyperuricemia model mice and slow down the oxidative damage caused by uric acid production. The changing trends of SOD enzyme activity in serum and kidney tissue fragments of different experimental groups were basically the same. Among all intervention groups, the SOD enzyme activity in serum and kidney tissue fragments of the allopurinol group and high-dose imidazole dipeptide group was significantly higher than that of the model group. The results of glutathione peroxidase detection in serum and kidney tissue fragments showed that ( Fig.16 , Fig.17), the glutathione peroxidase activity of mice in the model group was significantly lower than that in the normal group. All treatment methods can increase the level of glutathione peroxidase in the serum and kidney tissue of hyperuricemia model mice, and slow down the oxidative damage caused by uric acid production. The changing trends of glutathione peroxidase activity in serum and kidney tissue fragments of different experimental groups were basically the same. Among all intervention groups, the glutathione peroxidase activity in serum and kidney tissue fragments of the allopurinol group and high and low doses of imidazole dipeptide groups was significantly higher than that of the model group. The results of malondialdehyde detection in serum and kidney tissue fragments showed that ( Fig.18 , Fig.19 ), the MDA concentration in the model group was significantly higher than that in the normal group. All treatments were able to significantly reduce the MDA levels in the serum and kidney tissues of the hyperuricemia model mice, and there was no significant difference between the MDA levels in all intervention groups and the normal group, indicating that all treatments were able to slow down the oxidative damage caused by uric acid production.

[0098] The above experiments show that the imidazole dipeptide composition of the present invention has kidney-protecting effect.

Claims

1. An imidazole dipeptide composition having kidney-protecting effect, the composition comprising anserine and carnosine, wherein: Taking the total weight of anserine and carnosine as 100%, the content of anserine is 10%-99%, and the content of carnosine is 1%-90%.

2. The imidazole dipeptide composition according to claim 1, wherein Taking the total weight of anserine and carnosine as 100%, the content of anserine is 91% and the content of carnosine is 9%.

3. The imidazole dipeptide composition according to claim 1 or 2, which consists of anserine and carnosine.

4. The imidazole dipeptide composition according to claim 1 or 2, further comprising other substances having kidney-protecting effects.

5. The imidazole dipeptide composition according to claim 4, wherein The other substances having kidney-protecting effects include histidine and / or histidine derivatives; preferably, the histidine derivatives include but are not limited to: oligopeptides containing histidine residues, more preferably dipeptides or tripeptides; Preferably, the histidine and histidine derivatives are of animal and / or plant origin, such as chicken, fish or other animal muscles.

6. Use of the imidazole dipeptide composition according to any one of claims 1 to 5 in the preparation of a composition having kidney-protecting effects.

7. The use according to claim 6, wherein: The composition is used for preparing medicine.

8. The use according to claim 7, wherein: The medicine contains an effective amount of the imidazole dipeptide composition.

9. The use according to claim 7 or 8, wherein: The dosage of the imidazole dipeptide composition in the medicine is 1 mg-200 mg / day, preferably 1 mg-100 mg / day, and more preferably 5 mg-50 mg / day.

10. The use according to any one of claims 7 to 9, wherein: The medicine further contains excipients. Preferably, the excipients include one or a combination of two or more of sorbitol, maltodextrin, and magnesium stearate.

11. The use according to any one of claims 7 to 10, wherein: The medicine is in the form of tablets, capsules, powders or granules.

12. The use according to claim 6, wherein: The composition is used for preparing food.

13. The use according to claim 12, wherein: The amount of the imidazole dipeptide composition in the food is 1 mg-200 mg / day, preferably 1 mg-100 mg / day, and more preferably 5 mg-50 mg / day.

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