Imidazole dipeptide composition with renal protective effect and use thereof

Abstract

Disclosed are an imidazole dipeptide composition with a renal protective effect and use thereof. The imidazole dipeptide composition with a renal protective effect comprises anserine and carnosine, wherein, on the basis of the total weight of anserine and carnosine being 100%, the content of anserine is 10%-99% and the content of carnosine is 1%-90%. Mouse experiments confirm that mice with hyperuricemic renal injury, after continuously receiving the imidazole dipeptide composition for a period of time, show significantly less renal injury compared to the control group, which indicates that the imidazole dipeptide composition has an excellent renal protective effect.

Description

Imidazole dipeptide composition with kidney-protecting effect and its application Technical Field

[0001] The present invention relates to an imidazole dipeptide composition and its application, specifically, 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 kidneys are vital organs in the human body. Their primary function is to eliminate metabolic products, certain waste products, and toxins from the body through urine production, while also retaining water and other useful substances through reabsorption. Poor dietary habits can lead to high uric acid levels. Long-term high uric acid levels can induce complications such as gout, diabetes, metabolic syndrome, oxidative stress, inflammation, hypertension, and endothelial dysfunction. It can also severely burden the kidneys and cause renal damage.

[0003] Creatinine and urea nitrogen are commonly used biochemical indicators of renal function. Creatinine is a waste product produced by human muscle. Since creatinine is almost entirely excreted by the kidneys and is rarely affected by food, it provides a relatively objective reflection of kidney function. Elevated creatinine levels in the blood indicate a decrease in the kidneys' ability to eliminate waste products. Urea nitrogen, on the other hand, is a metabolic product produced by the digestive breakdown of protein and converted in the liver through the urea cycle. If renal function is impaired, the ability to excrete urea naturally decreases, leading to urea accumulation in the blood and elevated blood urea nitrogen levels.

[0004] CN113616688A discloses a composition for repairing kidney damage and its use. The composition comprises anserine (β-alanyl-1-methyl-L-histidine, Ans) dry powder, astragalus extract, and sophora flavescens extract in a mass ratio of 80-90:3-10:5-15. Experiments have shown that the composition, comprising anserine dry powder, astragalus extract, and sophora flavescens extract, has a certain degree of renal repair efficacy, whereas anserine alone is not ideal for this purpose. Furthermore, the astragalus extract and sophora flavescens extract used in the composition often have an unpleasant herbal flavor.

[0005] Summary of the Invention

[0006] An object of the present invention is to provide a composition having kidney-protecting efficacy.

[0007] Another object of the present invention is to provide applications of the composition.

[0008] The present invention provides the following technical solutions:

[0009] Technical Solution 1: An imidazole dipeptide composition with kidney-protecting effect, comprising anserine and carnosine, wherein, based on the total weight of anserine and carnosine being 100%, the anserine content is 10%-99%, and the carnosine content is 1%-90%.

[0010] 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%.

[0011] According to some specific embodiments of the present invention, in the imidazole dipeptide composition of the present invention, the sum of the weight 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%.

[0012] Technical Solution 3: The imidazole dipeptide composition according to Technical Solution 1 or 2, which consists of anserine and carnosine.

[0013] Technical Solution 4: The imidazole dipeptide composition according to Technical Solution 1 or 2, further comprising 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.

[0014] Technical Solution 5: The imidazole dipeptide composition according to Technical Solution 4, wherein the other substance having kidney-protecting effects comprises histidine and / or histidine derivatives. The histidine derivatives include, but are not limited to, oligopeptides containing histidine residues, i.e., oligopeptides composed of multiple histidine residues or composed of histidine and other amino acids, specifically dipeptides, tripeptides, etc., preferably dipeptides. The histidine and histidine derivatives may be of animal and / or plant origin, for example, from chicken, fish, or other animal muscle.

[0015] 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 efficacy.

[0016] In the present invention, the "kidney protection" means having a protective effect on the kidneys, including assisting in protecting the kidneys and being beneficial to kidney health.

[0017] According to some specific embodiments of the present invention, the kidney-protecting effect includes alleviating kidney damage caused by high uric acid.

[0018] According to some specific embodiments of the present invention, the renal protective effect includes reducing the uric acid level, serum creatinine and / or urea nitrogen level in individuals with hyperuricemia and renal damage.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] 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.

[0024] The present invention also provides a method for protecting the kidneys, which comprises administering an effective amount of the imidazole dipeptide composition described in any one of technical solutions 1 to 5 of the present invention to an individual in need.

[0025] According to some specific embodiments of the present invention, the individual is a mammal or a human.

[0026] Technical Solution 7: The application according to Technical Solution 6, wherein the composition is used to prepare medicines.

[0027] Technical Solution 8: The application according to Technical Solution 7, wherein the medicine contains an effective amount of the imidazole dipeptide composition.

[0028] Technical Solution 9: The use according to Technical Solution 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.

[0029] 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.

[0030] Technical Solution 11: The application according to any one of Technical Solutions 7-10, wherein the medicine is a tablet, capsule, powder or granule.

[0031] Technical Solution 12: The use according to Technical Solution 6, wherein the composition is used to prepare a food. The food may be, for example, a functional food, a dietary supplement, or the like. The functional food may be, for example, a health food, a food for special medical purposes, a therapeutic diet, or the like.

[0032] 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 amount, preferably 1 mg-100 mg / day, and more preferably 5 mg-50 mg / day.

[0033] The present invention has confirmed through experiments that the imidazole dipeptide composition of the present invention has a good protective effect on the kidneys of mice and effectively alleviates kidney damage caused by high uric acid.

[0034] According to a specific embodiment of the present invention, the imidazole dipeptide composition has a good uric acid-lowering effect on mice with hyperuricemia and renal damage, and the serum creatinine and urea nitrogen levels of the intervention group dropped significantly to normal levels, indicating that the intervention of imidazole dipeptide can alleviate the renal damage caused by hyperuricemia. 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 infiltration of inflammatory cells in the renal tissue. Furthermore, the levels of three pro-inflammatory 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 fragments showed that the imidazole dipeptide composition treatment was able to 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 fragments showed that the imidazole dipeptide composition treatment method was able to 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. Glutathione peroxidase assays in serum and renal tissue fragments showed that the imidazole dipeptide combination treatment increased glutathione peroxidase levels in the serum and renal tissue of hyperuricemia model mice, slowing down oxidative damage caused by uric acid production. Malondialdehyde assays in serum and renal tissue fragments showed that the imidazole dipeptide combination treatment significantly reduced malondialdehyde levels in the serum and renal tissue of hyperuricemia model mice. There were no significant differences in malondialdehyde levels between all intervention groups and the normal group, indicating that all treatments were able to slow down oxidative damage caused by uric acid production.

[0035] The imidazole dipeptide composition provided by the present invention has a kidney-protecting effect. Mouse experiments have confirmed that after mice with hyperuricemia kidney damage continuously took the imidazole dipeptide composition of the present invention for a period of time, the kidney damage was significantly less than that of the control group, showing a good kidney-protecting effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 is a schematic diagram of the animal experiment process.

[0037] Figure 2 shows the effects of different interventions on serum uric acid in mice.

[0038] Figure 3 shows the effects of different interventions on serum creatinine levels in mice.

[0039] Figure 4 shows the effects of different interventions on serum urea nitrogen levels in mice.

[0040] Figure 5 shows the pathological analysis of the effects of different interventions on mouse kidneys.

[0041] FIG6 shows the levels of inflammatory factors (TNF-α) in mouse kidneys.

[0042] FIG7 shows the levels of inflammatory factors (IL-1β) in mouse kidneys.

[0043] FIG8 shows the levels of inflammatory factors (IL-6) in mouse kidneys.

[0044] FIG9 shows the levels of inflammatory factors (IL-10) in mouse kidneys.

[0045] FIG10 shows the serum lipopolysaccharide levels in mice.

[0046] FIG11 shows the serum lactate dehydrogenase level in mice.

[0047] FIG12 shows the serum glutathione levels in mice.

[0048] FIG13 shows the glutathione levels in mouse kidney tissue.

[0049] FIG14 shows the level of superoxide dismutase in mouse serum.

[0050] FIG15 shows the superoxide dismutase level in mouse kidney tissue.

[0051] FIG16 shows the serum glutathione peroxidase levels in mice.

[0052] FIG17 shows the glutathione peroxidase level in mouse kidney tissue.

[0053] FIG18 shows the serum malondialdehyde levels in mice.

[0054] FIG19 shows the malondialdehyde level in mouse kidney tissue.

[0055] In the accompanying figures, data are expressed as mean ± standard deviation. Letters such as a, b, and c represent the results of significance analysis (p < 0.05) for the same column of data. If the letters are the same, there is no significant difference between the values ​​marked. DETAILED DESCRIPTION

[0056] In order to have a clearer understanding of the technical features, objectives 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 understood as limiting the scope of implementation of the present invention.

[0057] Example 1

[0058] This embodiment provides an imidazole dipeptide composition, which comprises, in parts by weight:

[0059] 91 servings of anserine

[0060] 9 parts of carnosine.

[0061] Anserine and carnosine are taken in the above ratio and mixed evenly to obtain the bioactive peptide of this embodiment, which is an imidazole dipeptide composition.

[0062] Example 2

[0063] This embodiment provides a medicine comprising the composition provided in Example 1.

[0064] Example 3

[0065] This embodiment provides a food comprising the composition provided in Example 1.

[0066] Experimental study on the kidney protection effect of imidazole dipeptide

[0067] The present invention verifies the kidney-protecting effect of the imidazole dipeptide of the present invention through animal experiments.

[0068] 1. Test samples and test animals

[0069] Test sample: the bioactive peptide of Example 1 (i.e., an imidazole dipeptide composed of 91 parts of anserine and 9 parts of carnosine).

[0070] Experimental animals: 5-week-old male ICR mice were purchased from Shanghai JSJ Laboratory Animal Co., Ltd., SPF grade.

[0071] 2. Grouping and Treatment of Experimental Animals

[0072] All mice were adaptively housed at a temperature of 24±2°C, with 12h light and 12h dark alternation, and free access to food and water. After one week of environmental adaptation, the mice were randomly divided into groups of 7 each, 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 four weeks. During the modeling period, except for the normal control group, the other groups were gavaged with 300 mg / kg of potassium oxonate and hypoxanthine (prepared as a suspension with 0.5% CMC-Na solution) every day to establish a high uric acid model. During the intervention period, except for the normal control group, the other groups were first gavaged with 300 mg / kg of potassium oxonate and hypoxanthine every day for continuous modeling. After 2 hours of modeling, the mice in each group were administered according to the doses shown in 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.

[0073] 3. Sampling and processing of test samples

[0074] During the modeling period, blood was collected by tail cutting once a week to detect changes in serum uric acid. Fresh feces were collected from each group of mice 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.

[0075] 4. Detection method

[0076] 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 methods specified in the kit instructions; the weight of mice was measured by direct weighing twice a week; the pH of mouse urine was measured once a week using pH test paper; renal histopathological analysis was performed in collaboration with Wuhan Savier Biotechnology Co., Ltd.; and renal uric acid transporter immunoblot analysis was performed according to routine laboratory procedures.

[0077] 5. Data processing method data

[0078] Statistical analysis was performed using SPSS 22.0 software using the Tukey method, and differences were considered statistically significant when p < 0.05. GraphPad Prism 8 and R studio were used for graphing, correlation analysis, and bioinformatics analysis.

[0079] 6. Experimental results and conclusions

[0080] 6.1 Modeling results

[0081] One week after modeling with potassium oxonate and hypoxanthine, blood was taken from the tail 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 was continued for another week). Two weeks after modeling, blood was taken from the tail 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 in the normal group, and the increase was about twice that of the mice in the normal group, indicating that the hyperuric acid modeling was very successful. Therefore, from the third week, imidazole dipeptide or probiotic intervention was performed while modeling.

[0082] 6.2 Changes in mouse body weight and urine pH during oral administration

[0083] During the six-week oral gavage intervention, although some groups experienced weight fluctuations, most groups showed minimal or no significant changes. Urine pH fluctuated between groups over the same period, and within the same group over time, but the fluctuations were small and irregular.

[0084] 6.3 Effects of different interventions on three parameters of renal function in mice

[0085] Serum uric acid levels are the most important indicator for directly assessing hyperuricemia. Creatinine is formed in muscle through spontaneous and irreversible conversion from creatine phosphate. Unless there are significant changes in muscle mass, the amount of creatinine formed is generally quite constant. The amount of free creatinine circulating is entirely dependent on its excretion rate. Therefore, measuring creatinine in serum or plasma can be used to assess glomerular filtration efficiency and thus determine renal function. Blood urea nitrogen, on the other hand, originates from the liver and is excreted in the urine via the kidneys. Renal failure, nephritis, and urinary obstruction can increase blood urea nitrogen levels. Therefore, serum creatinine and urea nitrogen are two indicators for assessing renal function. The results of the three renal function tests are shown in Figures 2, 3, and 4. Regarding uric acid levels, the model group had significantly higher uric acid levels than all other groups. After a four-week intervention, uric acid levels in all intervention groups decreased significantly, demonstrating that all intervention formulas had a significant uric acid-lowering effect. Among them, the uric acid levels of the positive control group and the high and low dose groups of imidazole dipeptide dropped to the level of the normal group (no significant difference from the normal group). Although the uric acid levels of the other intervention groups were slightly higher than that of the normal group, they were significantly lower than those of 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 of all other intervention groups dropped 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 the 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.

[0086] 6.4 Protective effects of different interventions on mouse kidneys

[0087] Clinically, changes in renal tissue structure and inflammatory cell infiltration are significant pathological features of hyperuricemia. Figure 5 shows histopathological sections of the kidneys of each group of mice. Among them, in the sections of the normal group, the glomerular matrix is ​​uniform, the renal tubular epithelial cells are round and plump, and the connective tissue between the urinary tubules is the renal interstitium, and there is no obvious proliferation of the interstitium, and no obvious inflammatory changes are seen. In the model group, a small amount of lymphocyte infiltration (black arrows) can be seen around the blood vessels in the field of view, granulocytes (red arrows) are found in the glomeruli, and more renal tubular epithelial cells are watery degeneration, cell swelling, and loose cytoplasm (green arrows) can be seen; the renal tubules are dilated, the renal tubular epithelial cells are flattened, the lumen is enlarged (blue arrows), the lumen is filled with eosinophilic flocs (purple arrows), and there are epithelial cells (yellow arrows) that have fallen off in the rare renal tubules. In the positive group, tubular atrophy, decreased eosinophilia of epithelial cells, narrow tubular lumen, and unclear structure (white arrows) were observed in the visual field. A small amount of surrounding connective tissue proliferation (orange arrows) was accompanied by a small amount of lymphocytes (black arrows) and granulocyte infiltration (red arrows). A large number of tubular epithelial cells showed hydropic degeneration, cell swelling, and loose and lightly stained cytoplasm (green arrows). A small number of tubular dilatation, flattened tubular epithelial cells, enlarged tubular lumen, and few granulocytes in the tubular lumen were observed (blue arrows). Eosinophilic substances were rarely found in the tubular lumen (purple arrows). The renal tissue damage of mice in the other groups was significantly improved compared with the model group. A small amount of tubular epithelial cells showed hydropic degeneration, cell swelling, and loose and lightly stained cytoplasm (green arrows) in the visual field. Eosinophilic substances were rarely found in the tubular lumen (purple arrows). Hyperuricemia was modeled by potassium oxonate and hypoxanthine, and the mice showed obvious inflammation and tissue structural damage in the kidneys. Tubular reabsorption and glomerular filtration have an important influence on uric acid levels. Tubular damage and glomerular filtration dysfunction will further increase uric acid concentrations, leading to uric acid crystal deposition. Although allopurinol treatment can reduce the uric acid level in hyperuricemia mice, it can cause severe renal damage. Except for the positive control group, the other intervention groups can significantly improve the renal tissue damage caused by hyperuricemia and slow down the infiltration of inflammatory cells in the renal tissue. Pathological scores were performed according to the diagnostic criteria for pathological changes (Table 1), and the results are shown in Table 2.

[0088] Table 1. Pathology scoring criteria

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

[0090] 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 tissue of mice. As shown in Figures 6-9, 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 were significantly increased compared with the normal group, while the level of the anti-inflammatory factor IL-10 was significantly decreased, indicating that modeling can cause a significant inflammatory response 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 from the normal group in terms of TNF-α.

[0091] Lipopolysaccharide is a component of the outer wall of the 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 exhibit 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, and serum lipopolysaccharide will increase with systemic inflammation. There was no significant difference in serum lipopolysaccharide levels among all experimental groups in this experiment (Figure 10), indicating that kidney inflammation was not to the extent of causing enteritis.

[0092] Lactate dehydrogenase (LDH) 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. LDH is mainly used to assess myocardial damage and hepatocyte damage. When various tissues and organs in the body are diseased, the LDH content of the tissues and organs themselves will change, causing changes in LDH in the blood. The LDH content in the urine of patients with chronic glomerulonephritis, diabetic nephrosis, and renal malignancies is generally 3 to 6 times higher than that of normal people. However, urea and small molecule peptides in the urine can inhibit enzyme activity. Serum LDH in patients with chronic kidney disease and uremia is generally normal. In this experiment, there was no significant difference in lactate dehydrogenase levels among all experimental groups (Figure 11).

[0093] 6.5 Improvement of oxidative stress in mice by different interventions

[0094] When xanthine oxidase catalyzes the conversion of purine to uric acid, it produces large amounts of superoxide anions and H₂O₂, triggering an increase in systemic oxidative stress. Glutathione is an important endogenous antioxidant in the body that neutralizes reactive oxygen species. Superoxide dismutase is the most important antioxidant enzyme in the body, catalyzing the dismutation of superoxide anions to produce hydrogen peroxide and oxygen. Glutathione peroxidase, using reduced glutathione, catalyzes the conversion of hydrogen peroxide and many organic peroxides to water or organic alcohols. It scavenges peroxides within living cells and plays a key role in protecting cells from free radical damage. Intracellular lipids readily react with free radicals to produce lipid peroxides. Glutathione peroxidase uses reduced glutathione to reduce lipid peroxides, thereby eliminating the toxic effects of free radicals. Glutathione peroxidase is distributed in nearly all tissues. In some pathological conditions, glutathione peroxidase activity can be significantly upregulated or downregulated. Malondialdehyde (MDA) is a natural product of lipid oxidation in organisms. When animal or plant cells experience oxidative stress, lipid oxidation occurs, and MDA levels can reflect the level of oxidative stress in the body.

[0095] The results of glutathione detection in serum and renal tissue fragments showed (Figures 12 and 13) that 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 renal tissue of hyperuricemia model mice and slow down the oxidative damage caused by uric acid production. The trends of changes in glutathione concentrations in serum and renal tissue fragments of different experimental groups were basically the same. Among all intervention groups, the glutathione concentrations in serum and renal tissue fragments of 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.

[0096] Results from superoxide dismutase assays in serum and renal tissue fragments (Figures 14 and 15) showed that the superoxide dismutase activity in the model group was significantly lower than that in the normal group. All treatments were able to increase SOD levels in the serum and renal tissue of hyperuricemia model mice, mitigating the oxidative damage caused by uric acid production. The trends in SOD activity in serum and renal tissue fragments across the different experimental groups were generally consistent. Among all intervention groups, SOD activity in serum and renal tissue fragments in the allopurinol and high-dose imidazole dipeptide groups was significantly higher than that in the model group. Results from glutathione peroxidase assays in serum and renal tissue fragments (Figures 16 and 17) showed that the glutathione peroxidase activity in the model group was significantly lower than that in the normal group. All treatments were able to increase glutathione peroxidase levels in serum and renal tissue of hyperuricemia model mice, mitigating the oxidative damage caused by uric acid production. The trends in glutathione peroxidase activity in serum and renal tissue fragments across the different experimental groups were generally consistent. In all intervention groups, the glutathione peroxidase activity in the serum and renal tissue fragments of the allopurinol group and the high- and low-dose imidazole dipeptide groups was significantly higher than that of the model group. The results of malondialdehyde detection in serum and renal tissue fragments showed (Figures 18 and 19) that the malondialdehyde concentration in the model group mice was significantly higher than that in the normal group. All treatments were able to significantly reduce the malondialdehyde levels in the serum and renal tissue of hyperuricemia model mice. The malondialdehyde levels in all intervention groups were not significantly different from those in the normal group, indicating that all treatments were able to slow down the oxidative damage caused by uric acid production.

[0097] The above experiments show that the imidazole dipeptide composition of the present invention has kidney-protecting effects.

Claims

1. An imidazole dipeptide composition having kidney-protecting effect, the composition comprising anserine and carnosine, in, 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, in, 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, in, 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, in, The composition is used for preparing medicine.

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

9. The use according to claim 7 or 8, in, 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, in, 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, in, The medicine is in the form of tablets, capsules, powders or granules.

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

13. The use according to claim 12, in, 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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