Uric acid-reducing food composition containing food-borne melanin

Abstract

The invention relates to a food-borne melanin-containing uric acid-reducing food composition which is prepared by mixing 2-10 parts by weight of celery seed extract, 1-6 parts by weight of food-borne melanin and 0-5 parts by weight of astragalus extract, plays a role in reducing uric acid by inhibiting the activity of xanthine oxidase, and has a better effect of treating hyperuricemia and / or gout. The liver and kidney injury caused by hyperuricemia can be improved, the toxic and side effects are low, and the food can be eaten for a long time.

Description

Technical Field

[0001] The present invention belongs to the technical field of health foods, and relates to a functional food with the function of reducing uric acid, in particular to a food composition for reducing uric acid containing food-derived melanin and a preparation method thereof. Background Art

[0002] The prevalence of hyperuricemia has been increasing year by year and shows a trend of getting younger. According to statistics, hyperuricemia has become the second largest metabolic disease after diabetes. Due to dietary habits, lifestyle and biological differences, etc., the incidence of hyperuricemia in men is higher than that in women. With the younger age of onset of hyperuricemia, young men are more likely to suffer from the risk of hyperuricemia than other groups.

[0003] Hyperuricemia is a metabolic disease caused by purine metabolism disorder, which leads to an increase in the content of uric acid in the blood and thus causes tissue damage. The pre-disease stage is hyperuricemia, and in the later stage, some develop into gout. When a gout attack occurs, the patient suffers severe pain, seriously affecting the quality of life. An increase in blood uric acid level can not only cause gout, but is also closely related to the occurrence and development of diseases in systems such as the kidney, endocrine metabolism, cardiovascular and cerebrovascular systems.

[0004] Uric acid is the end product of purine metabolism in the human body. 80% of the purines in the human body are produced by cell metabolism, and 20% are obtained from food. The main reasons for the increase in uric acid in the human blood are excessive uric acid production and reduced uric acid excretion. In the process of excessive uric acid production, xanthine oxidase and adenosine deaminase are two key enzymes. Xanthine oxidase can convert hypoxanthine into xanthine and further oxidize it into uric acid; adenosine deaminase promotes the conversion of adenosine into creatinine, and creatinine is then converted into hypoxanthine through the action of nucleoside phosphatase, and finally converted into uric acid through the action of xanthine oxidase. The uric acid in the blood mainly enters the urine through kidney filtration and is excreted out of the body with the urine. Any situation that leads to a decrease in glomerular filtration rate, a weakening of proximal renal tubular secretion function or an enhancement of reabsorption function may cause hyperuricemia.

[0005] Currently, the drugs used for the treatment of hyperuricemia mainly include:

[0006] 1) Drugs that inhibit uric acid production, which reduce uric acid production by inhibiting xanthine oxidase, such as allopurinol and febuxostat;

[0007] 2) Drugs that promote uric acid excretion, which reduce the blood uric acid level by increasing the excretion of uric acid from the kidney, such as benzbromarone, etc.;

[0008] 3) Anti-inflammatory and antioxidant drugs, such as colchicine and diclofenac sodium.

[0009] These chemical drugs can all effectively reduce the level of blood uric acid, but may be accompanied by some side effects, such as rashes, abnormal liver function, gastrointestinal diseases, etc. Therefore, further research and development of new health substances with excellent safety and effectiveness for reducing uric acid are the urgent needs of patients with hyperuricemia and gout in clinical practice.

[0010] Celery seeds ( Apium graveolens L.) are the seeds of celery, and the main active ingredient is apigenin, which is often used to manufacture functional foods for reducing uric acid. Research has shown that apigenin, as a xanthine oxidase inhibitor, can promote uric acid excretion, down-regulate the expression of mURAT1 protein levels in the kidneys, reduce the urate reabsorption capacity of the kidneys, and has an obvious effect on reducing uric acid.

[0011] However, it has been reported that intragastric administration of apigenin can cause changes in the cell number and cell cycle of mouse testicular tissues at each time phase, mainly manifested in a significant decrease in the number of spermatogonia in the G0 phase, secondary spermatocytes, Sertoli cells, and interstitial cells (Liu Shuyu et al. Experimental study on the effect of apigenin on the spermatogenic cell cycle of mice [J]. Journal of Environment and Health, 2010, 27(1): 33-35.), suggesting that apigenin inhibits the differentiation process of primary spermatocytes into secondary spermatocytes to a certain extent or promotes the differentiation process of secondary spermatocytes into spermatid cells, that is, it has a certain inhibitory effect on the spermatogenesis process. This may be caused by subacute oxidative damage to mouse testes induced by a higher dose of apigenin (Zheng Xin et al. Effect of apigenin on antioxidant levels in mouse testicular tissues [J]. Chinese Journal of Birth Health & Heredity, 2013, 21(9): 103-105.).

[0012] Therefore, in view of the characteristics of the younger age of the high-incidence population of hyperuricemia and the higher incidence rate in men, it is urgent to explore a health food with synergistic anti-hyperuricemia and no toxic side effects.

[0013] Melanin is a natural pigment widely present in organisms such as animals and plants, and its main function is to protect organisms from oxidative stress damage such as ultraviolet rays. Due to the strong free radical scavenging ability of melanin, it can effectively reduce the damage of oxidative stress to cells. Melanin derived from food usually has high nutritional value and certain medicinal value. However, there is currently no drug or health food that combines celery seed extract and food-derived melanin for patients with hyperuricemia or gout. Summary of the Invention

[0014] The purpose of the present invention is to provide a food composition for reducing uric acid containing food-derived melanin, so as to be able to achieve the function of reducing uric acid while being non-toxic and harmless for long-term consumption.

[0015] The food composition containing food-derived melanin for reducing uric acid according to the present invention is obtained by mixing the following raw materials in parts by weight: 2-10 parts of celery seed extract, 1-6 parts of food-derived melanin, and 0-5 parts of astragalus extract.

[0016] Furthermore, the parts by weight of each raw material in the food composition containing food-derived melanin for reducing uric acid according to the present invention are: 4-8 parts of celery seed extract, 1-5 parts of food-derived melanin, and 0.5-3 parts of astragalus extract.

[0017] Even further, the parts by weight of each raw material in the food composition containing food-derived melanin for reducing uric acid are: 5-7 parts of celery seed extract, 2-4 parts of food-derived melanin, and 0.5-2 parts of astragalus extract.

[0018] More specifically, in the food composition containing food-derived melanin for reducing uric acid, the parts by weight of each raw material are preferably 6 parts of celery seed extract, 3 parts of food-derived melanin, and 1 part of astragalus extract.

[0019] The selection and dosage of the above various raw materials are obtained by the inventor through a large amount of exploration and summary. Practice has proved that when various raw materials are within the above weight part ranges, they all have good effects in reducing uric acid.

[0020] Among them, the food-derived melanin is melanin extracted from any natural black food, including but not limited to natural animals and plants containing melanin such as black radish, black sesame, black rice, black bean, black corn, cuttlefish, black-bone chicken, rye, black fungus, mulberry, dark plum, black wolfberry, black peanut, black potato, and black date.

[0021] The celery seed extract is an extract obtained by extracting and separating celery seeds with ethanol as the extraction solution and drying.

[0022] The astragalus extract is the product after drying the aqueous extract of astragalus medicinal materials.

[0023] More specifically, the food composition containing food-derived melanin according to the present invention can be obtained by the following method: After accurately weighing the celery seed extract, food-derived melanin, and astragalus extract according to the above parts by weight, mix them evenly according to the method of equal increment to obtain the food composition.

[0024] Furthermore, the present invention also provides the application of the food composition in the preparation of drugs or functional foods for treating hyperuricemia and / or gout.

[0025] Even further, the present invention also provides the application of the food composition in the preparation of drugs for reducing uric acid levels.

[0026] Specifically, the food composition of the present invention exerts the effect of reducing uric acid by inhibiting the activity of xanthine oxidase. Therefore, the present invention also provides the application of the food composition in the preparation of drugs or functional foods of xanthine oxidase inhibitors.

[0027] More specifically, the present invention also provides the application of the food composition in the preparation of drugs or functional foods for improving liver and kidney injuries caused by hyperuricemia.

[0028] The food composition of the present invention has the following beneficial effects:

[0029] 1. Verified by pharmacological experiments, it shows that the food composition of the present invention has a significant effect in treating hyperuricemia and has good application prospects in the development of hyperuricemia drugs.

[0030] 2. The food composition of the present invention is composed of celery seeds, food-derived melanin and astragalus membranaceus which is both food and medicine. It aims to ensure that while the composition inhibits hyperuricemia, it avoids the testicular damage in males that may be caused by high-concentration celery seeds. Celery seeds have the effect of inhibiting xanthine oxidase and can significantly reduce the uric acid level in patients with hyperuricemia. It is a natural substance for treating gout. However, high-concentration apigenin has a certain inhibitory effect on the spermatogenesis process in mice. In the experimental process of the present invention, it was also observed that testicular oxidative damage occurred during the treatment of hyperuricemic mice with celery seed extract, which may be caused by subacute oxidative damage of the testis in mice caused by relatively high-concentration apigenin. After the food composition of the present invention combines with food-derived melanin with strong antioxidant capacity, it can effectively avoid testicular oxidative damage in mice during the process of reducing uric acid and has a synergistic effect on reducing uric acid. It can be used as a health food, medicinal health product and drug for treating hyperuricemia and / or gout.

[0031] 3. The components selected for the food composition of the present invention are all foods or both food and medicine. It is prepared by water extraction or alcohol extraction and has high safety. Compared with commonly used clinical western medicines, the food composition of the present invention will not cause adverse reactions such as liver and kidney injuries and rashes. It has the advantage of high safety and can be eaten in sufficient amounts for a long time without producing adverse reactions.

[0032] 4. The raw materials used in the food composition of the present invention are inexpensive and easy to prepare. It can be made into various forms of foods for use and has the advantages of low economic cost, flexible and convenient use, and has good application prospects in the daily diet of patients with hyperuricemia. Description of the Drawings

[0033] Figure 1 It is the condition of the mouse kidney tissue turning white observed during the animal experiment in the celery seed extract group.

[0034] Figure 2It is the condition of testicular swelling and injury observed in mice in the celery seed extract group during animal experiments.

[0035] Figure 3 It is the HE staining results of the livers of mice in each group.

[0036] Figure 4 It is the HE staining results of the kidneys of mice in each group. Embodiment

[0037] The following further describes in detail the specific embodiments of the present invention in conjunction with the accompanying drawings and embodiments. The following embodiments are only used to more clearly illustrate the technical solutions of the present invention, so that those skilled in the art can fully understand and utilize the present invention well.

[0038] However, the present invention can be implemented in many other ways different from those described in the following embodiments, and those skilled in the art can also make similar improvements without departing from the connotation of the present invention. Therefore, the protection scope of the present invention is not limited by the specific embodiments disclosed below.

[0039] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the art. The terms used in the specification of the present invention are only for describing specific embodiments and are not used to limit the present invention.

[0040] The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0041] The terms "multiple", "diverse", "multiple times", "multiple groups", etc. used in the present invention, unless otherwise specified, refer to a quantity greater than or equal to 2; "above" includes the number itself, such as "two or more" includes two, three or more.

[0042] The term "preferred" used in the present invention only describes embodiments or examples with better effects and does not constitute a limitation on the protection scope of the present invention.

[0043] The production processes, experimental methods or detection methods involved in the embodiments of the present invention, unless otherwise specified, are all conventional methods in the prior art, and their names and / or abbreviations are all conventional names in the field. They are very clear and definite in the relevant application fields, and those skilled in the art can understand the conventional process steps according to the name and apply the corresponding equipment, according to the conventional conditions or the conditions recommended by the manufacturer, or refer to the experimental methods known in the art for implementation.

[0044] There are no special restrictions on the sources of various instruments, equipment, raw materials or reagents used in the embodiments of the present invention. They are all conventional products that can be obtained through regular commercial channels, and can also be prepared according to the conventional methods well-known to those skilled in the art.

[0045] The food composition containing food-derived melanin for reducing uric acid involved in the following specific embodiments is obtained by mixing the raw materials in the following parts by weight: 2-10 parts of celery seed extract, 1-6 parts of black radish melanin, and 0-5 parts of astragalus extract.

[0046] Further, the parts by weight of each raw material in the food composition are 4-8 parts of celery seed extract, 1-5 parts of black radish melanin, and 0.5-3 parts of astragalus extract.

[0047] Still further, the parts by weight of each raw material in the food composition are 5-7 parts of celery seed extract, 2-4 parts of black radish melanin, and 0.5-2 parts of astragalus extract.

[0048] Preferably, the parts by weight of each raw material in the food composition are 6 parts of celery seed extract and 4 parts of black radish melanin.

[0049] More preferably, the parts by weight of each raw material in the food composition are 6 parts of celery seed extract, 3 parts of black radish melanin, and 1 part of astragalus extract.

[0050] In the specific embodiments of the present invention, the celery seed extract is obtained by crushing celery seeds, soaking them in 10 times the volume of 95% ethanol for 24 hours, filtering, separating the extract, rotary evaporation, freeze-drying, and then crushing.

[0051] In the specific embodiments of the present invention, the food-derived melanin is melanin extracted from any natural black food, including but not limited to natural animals and plants containing melanin such as black radish, black sesame, black rice, black beans, black corn, cuttlefish, black-boned chicken, rye, black fungus, mulberry, dark plum, black wolfberry, black peanut, black potato, and black date.

[0052] In the specific embodiments of the present invention, the black radish melanin extract is obtained by washing, drying, and crushing fresh black radishes, adding 2 times the volume of 95% ethanol, refluxing and extracting at 70°C for 3 hours, filtering, separating the extract, rotary evaporation, freeze-drying, and then crushing.

[0053] In the specific embodiments of the present invention, the black sesame melanin extract is obtained by crushing black sesame seeds, adding 50 times the volume of 50% ethanol, extracting at 65°C for 1 hour, filtering, separating the extract, rotary evaporation, and drying.

[0054] In the specific embodiments of the present invention, the black rice melanin extract is obtained by washing, drying, and crushing black rice, adding 10 times the volume of 50% ethanol, extracting at 80°C for 30 minutes, filtering, separating the extract, rotary evaporation, and drying.

[0055] In a specific embodiment of the present invention, for the black bean melanin extract, the black beans are dehulled by dry method. After the black bean skins are crushed, 60 times the volume of 60% ethanol is added, and extraction is carried out at 60 °C for 60 min. The extract is separated, rotary evaporated, and dried to obtain the melanin extract derived from black beans.

[0056] In a specific embodiment of the present invention, for the black corn melanin extract, the black corns are washed, dried, crushed, and then 5 times the volume of 80% ethanol is added. Reflux extraction is carried out at 80 °C for 1 h, filtered, the extract is separated, rotary evaporated, and dried to obtain the melanin extract derived from black corns.

[0057] In a specific embodiment of the present invention, for the cuttlefish melanin extract, the ink is taken out from fresh cuttlefish, 20 times the volume of water is added, stirred overnight, the precipitate is collected by centrifugation, and the precipitate is washed 6 times with distilled water and then vacuum freeze-dried to obtain the melanin extract derived from cuttlefish.

[0058] In a specific embodiment of the present invention, for the black-bone chicken melanin extract, after the black-bone chicken is slaughtered, its head, claws, and internal organs are removed, washed, ground into minced meat with a meat grinder, 5 times the volume of absolute ethanol is added, reflux extraction is carried out at 90 °C for 1 h and filtered while it is hot. The filter residue is hydrolyzed with protease A-E, filtered, then hydrolyzed with hydrochloric acid, filtered, and dried to obtain the melanin extract derived from black-bone chicken.

[0059] In a specific embodiment of the present invention, for the rye melanin extract, the rye is shelled and then crushed. Before extraction, 2 freeze-thaw cycles (-20 °C / 25 °C) are carried out to break the cells. 10 times the volume of 80% ethanol is added, and extraction is carried out at a constant temperature of 55 °C with shaking for 4 h. Filter while it is hot, and after reduced pressure distillation, vacuum drying is carried out to obtain the melanin extract derived from rye.

[0060] In a specific embodiment of the present invention, for the black fungus melanin extract, after the black fungus is sterilized by high-pressure steam, the slice thickness is ≤1 mm, 12 times the volume of water is added, ultrasonic-assisted extraction is carried out at 70 °C for 3 h, 0.5% papain (pH 6.0) is added to hydrolyze polysaccharides for 3 h, the precipitate is collected by centrifugation, and after drying, the melanin extract derived from black fungus is obtained.

[0061] In a specific embodiment of the present invention, for the mulberry melanin extract, the freshly picked mulberries are frozen quickly, 60% ethanol added with 0.1% ascorbic acid and 0.05% citric acid is used as a color protection agent, the solid-liquid ratio is 1:5, reflux extraction is carried out at 65 °C in the dark for 2 h, nitrogen is introduced at intervals to prevent oxidation, and after reduced pressure distillation, freeze-drying is carried out to obtain the melanin extract derived from mulberries.

[0062] In a specific embodiment of the present invention, for the smoked plum melanin extract, after the smoked plums are mechanically pitted and sterilized by steam, 6 times the volume of water is added, water bath extraction is carried out at 80 °C for 4 h, ceramic membrane is used to separate small molecule pigments and pectin, and after reduced pressure distillation, freeze-drying is carried out to obtain the melanin extract derived from smoked plums.

[0063] In a specific embodiment of the present invention, the black wolfberry melanin extract is prepared by washing and drying black wolfberries, using 70% ethanol containing 0.02% BHT antioxidant as the extraction agent, with a solid-liquid ratio of 1:4, extracting in a water bath at 80°C for 3 h under nitrogen protection during the extraction process, collecting the extract, concentrating and drying to obtain the black wolfberry-derived melanin extract.

[0064] In a specific embodiment of the present invention, the black peanut melanin extract is obtained by using the friction screening method to obtain the black peanut seed coat, which is pulverized and then added with 10 times the volume of 50% ethanol, refluxed and extracted at 60°C for 5 h, collecting the extract, concentrating and drying to obtain the black peanut-derived melanin extract.

[0065] In a specific embodiment of the present invention, the black potato melanin extract is prepared by washing and drying black potatoes, pulverizing them, enzymatically degrading the starch with 0.5% α-amylase at 50°C for 2 h, subjecting them to high-pressure homogenization at 60 MPa for 3 times to break the cell walls, then adding 8 times the volume of water, stirring and extracting at 75°C for 3 h, collecting the extract, concentrating and drying to obtain the black potato-derived melanin extract.

[0066] In a specific embodiment of the present invention, the black date melanin extract is prepared by washing and drying black dates, pulverizing them and then adding 15 times the volume of 70% ethanol, refluxing and extracting at 60°C for 2 h, collecting the extract, concentrating and drying to obtain the black date-derived melanin extract.

[0067] In a specific embodiment of the present invention, the astragalus extract is prepared by pulverizing the medicinal material astragalus, adding 10 times the volume of water, refluxing and extracting for 1 h, filtering, separating the extract, rotary evaporating, freeze-drying, and pulverizing to obtain the astragalus extract.

[0068] In a specific embodiment of the present invention, more specifically, after accurately weighing the celery seed extract, black radish melanin, and astragalus extract according to parts by weight, they are mixed evenly according to the method of equal increment to prepare the food composition.

[0069] Unless otherwise specified, the amounts of raw material components, temperature, time, and other measurement parameters involved in the embodiments of the present invention may have slight deviations within the weighing or measurement accuracy range, and acceptable deviations caused by instrument test accuracy or operation accuracy are allowed. Example

[0070] Example 1

[0071] The pulverized celery seeds are soaked in 10 times the volume of 95% ethanol for 24 h, filtered, the extract is separated, rotary evaporated, freeze-dried, and pulverized to obtain the celery seed extract.

[0072] Example 2

[0073] Take fresh black radish, wash, dry, and pulverize it. Add 2 times the volume of 95% ethanol, and reflux extract at 70 °C for 3 h. Filter, separate the extract, perform rotary evaporation, freeze-dry, and pulverize to obtain food-derived melanin from black radish.

[0074] Example 3

[0075] Pulverize the astragalus membranaceus medicinal material, add 10 times the volume of water, reflux extract for 1 h, filter, separate the extract, perform rotary evaporation, freeze-dry, and pulverize to obtain astragalus membranaceus extract.

[0076] Example 4

[0077] Weigh 6 parts by weight of celery seed extract and 4 parts by weight of food-derived melanin from black radish, and mix them evenly according to the equal increment method to prepare a food composition for reducing uric acid.

[0078] Example 5

[0079] Weigh 6 parts by weight of celery seed extract, 3 parts by weight of food-derived melanin from black radish, and 1 part by weight of astragalus membranaceus extract, and mix them evenly according to the equal increment method to prepare a food composition for reducing uric acid.

[0080] Example 6

[0081] Take out the ink from fresh cuttlefish, add 20 times the volume of water, stir overnight, centrifuge to collect the precipitate, and continue to wash the precipitate with distilled water 6 times. After vacuum freeze-drying, obtain food-derived melanin from cuttlefish.

[0082] Weigh 6 parts by weight of celery seed extract, 3 parts by weight of food-derived melanin from cuttlefish, and 1 part by weight of astragalus membranaceus extract, and mix them evenly according to the equal increment method to prepare a food composition for reducing uric acid.

[0083] Example 7

[0084] Wash, dry, and pulverize black corn, add 5 times the volume of 80% ethanol, reflux extract at 80 °C for 1 h, filter, separate the extract, perform rotary evaporation and drying to obtain food-derived melanin from black corn.

[0085] Weigh 6 parts by weight of celery seed extract, 3 parts by weight of food-derived melanin from black corn, and 1 part by weight of astragalus membranaceus extract, and mix them evenly according to the equal increment method to prepare a food composition for reducing uric acid.

[0086] Application Example

[0087] Use a hyperuricemia model mouse induced by a combination of potassium oxonate and hypoxanthine for animal experiments, observe the efficacy of the food composition of the present invention in treating hyperuricemia, and verify its role in preventing and treating hyperuricemia.

[0088] The experimental animals were SPF-grade Kunming mice, 6 weeks old, male, weighing 18-20 g, provided by Spf (Beijing) Biotechnology Co., Ltd. The license number for experimental animal breeding was: SYXK (Jin) 2019-007.

[0089] After one week of adaptive feeding, the mice were randomly divided into a normal group, a model group, an allopurinol group, a benzbromarone group, a celery seed group (extract of Example 1), a black radish group (extract of Example 2), an astragalus group (extract of Example 3), a composition group 1 (composition of Example 4), and a composition group 2 (composition of Example 5), with 6 mice in each group.

[0090] Except for the normal group, the mice in the other groups were intraperitoneally injected with potassium oxonate at 100 mg / kg / d at 9:00 every morning and gavaged with hypoxanthine at 500 mg / kg / d to establish a hyperuricemia model; the mice in the normal group were intraperitoneally injected and gavaged with an equal volume of normal saline.

[0091] On the 3rd day of the experiment, 1 hour after modeling, the corresponding drugs were gavaged to each administration group: the allopurinol group and the benzbromarone group were respectively given allopurinol tablet solution and benzbromarone tablet solution at 10 mg / kg / d; the celery seed group, the black radish group, the astragalus group, the composition group 1, and the composition group 2 were respectively given the corresponding extract or composition at 150 mg / kg / d; the normal group and the model group were given an equal volume of 0.5% CMC-Na solution.

[0092] The drugs were administered once a day for 8 consecutive days. Before the last administration, the mice were fasted for 12 hours without water restriction.

[0093] On the last day, the corresponding therapeutic drugs were not given. One hour after giving the modeling drugs, blood was collected by eye socket puncture. Plasma was collected by centrifuging at 2500 rpm for 20 minutes at 4°C. The levels of plasma UA, CRE, BUN, and XOD were measured using a kit; the mice were sacrificed, and the liver and kidneys were weighed; liver homogenate was prepared and the XOD level was measured; the kidney and liver tissues were fixed, paraffin-embedded, and stained with H&E to observe the pathological changes of the liver and kidney tissues of mice in each group.

[0094] 1. Effect of the anti-hyperuricemia food composition on the liver / kidney coefficients of hyperuricemic mice

[0095] The liver / kidney coefficients of the mice in each group were calculated according to the formula: liver / kidney coefficient (mg / g) = liver / kidney mass (mg) / mouse body mass (g), and the specific results are listed in Table 1.

[0096]

[0097] The change in the liver / kidney coefficient can reflect the damage of the corresponding organs. A decrease in the coefficient indicates organ atrophy, while an increase indicates that the organ may have inflammation, edema, and hyperplasia.

[0098] In Table 1, the liver coefficient and kidney coefficient of the model group were higher than those of the normal group, indicating that potassium oxonate and hypoxanthine used in the process of establishing the hyperuricemia model damaged the animal organs and could cause hepatomegaly and nephromegaly.

[0099] The liver coefficient and kidney coefficient of the allopurinol group were significantly higher than those of the model group, indicating that allopurinol further exacerbated hepatomegaly and nephromegaly in the hyperuricemia mouse model, showing that it had damaging effects on the liver and kidney of hyperuricemic mice.

[0100] Both the celery seed extract and the astragalus extract could reverse the liver coefficient to the level of the normal group, indicating that these two extracts had protective effects on the livers of hyperuricemic mice.

[0101] When the black radish extract was used alone, the liver coefficient did not change significantly compared with the model group. However, when it was combined with the celery seed extract and the astragalus extract, it could resist the hepatomegaly caused by hyperuricemia.

[0102] Except for the allopurinol group, the other medicated groups could reverse nephromegaly in hyperuricemic mice. Among them, the astragalus extract and Composition II containing the astragalus extract could reverse the kidney coefficient to the level of the normal group, indicating that the addition of the astragalus extract had a protective effect on the kidneys of hyperuricemic mice.

[0103] 2. Effects of the anti-hyperuricemia food composition on the levels of uric acid, creatinine, and blood urea nitrogen in the plasma of hyperuricemic mice

[0104] Uric acid (UA) is the final product of purine metabolism in the human body. Under normal circumstances, the production and excretion of uric acid are balanced. However, if uric acid production is excessive or excretion is poor, it will lead to an increase in blood uric acid levels, resulting in hyperuricemia.

[0105] Plasma creatinine (CRE) and blood urea nitrogen (BUN) are important evaluation indicators of renal function. CRE is mainly filtered and excreted by the glomerulus. When the glomerular filtration rate decreases, plasma CRE rises rapidly. Therefore, when plasma CRE is significantly higher than normal, renal function is damaged; BUN is the product of amino acid catabolism in the body and is freely filtered by the glomerulus and excreted in the urine. An increase in plasma BUN concentration indicates damaged renal function.

[0106]

[0107] In Table 2, the uric acid level of the model group was significantly higher than that of the normal group. After treatment with the positive drug, the uric acid levels in the allopurinol group and the benzbromarone group decreased significantly, proving that the hyperuricemia model was successfully established.

[0108] The celery seed extract has the ability to reduce uric acid equivalent to allopurinol, while the black radish extract and astragalus extract have relatively poor uric acid-lowering ability when used alone. After the black radish extract and astragalus extract are combined with the celery seed extract, the uric acid-lowering ability of Composition 1 and Composition 2 obtained is significantly improved, and there is no significant difference from the allopurinol group.

[0109] Compared with the normal group, the CRE in the model group was significantly increased. After treatment with allopurinol, benzbromarone, celery seed extract and Composition 2, the CRE level was significantly decreased. At the same time, the black radish extract, astragalus extract and Composition 1 could also reverse the increase in plasma CRE content caused by hyperuricemia, but the effect was not as good as that of the positive drugs, celery seed extract and Composition 2.

[0110] Compared with the normal group, the BUN in the model group was significantly increased, but the serum BUN in the allopurinol group was significantly higher than that in the model group, indicating that allopurinol significantly damaged renal function while reducing blood uric acid and creatinine levels.

[0111] The remaining drugs could significantly improve the plasma BUN level in hyperuricemia model mice. However, only Composition 1 and Composition 2 reduced the BUN to the normal group plasma BUN level, and the effect of Composition 2 in reducing BUN was better than that of Composition 1.

[0112] The BUN of the mice in the celery seed extract group was relatively high, indicating that the celery seed extract has limited protective effect on kidney injury caused by hyperuricemia. At the same time, as Figure 1 shown, during the experiment, it was also observed that the kidneys of the mice in the celery seed group turned white similar to those in the allopurinol group, further confirming that the celery seed extract has an unsatisfactory protective effect on the kidneys of hyperuricemia mice.

[0113] In addition, as Figure 2 shown, obvious testicular oxidative damage was also observed in the celery seed extract group, which is consistent with the literature reports.

[0114] Although the celery seed extract has the medicinal value of reducing uric acid, its potential risk of oxidative damage to the testis cannot be ignored, and this risk has become a key factor restricting the application of celery seeds.

[0115] The above test results show that Composition 1 and Composition 2 can protect renal function while reducing uric acid. The composition strategy proposed in the present invention not only has good anti-hyperuricemic activity, but also can significantly reduce the toxicity of celery seed extract to the testis, providing a new way for the development of safe and effective uric acid-lowering functional foods.

[0116] 3. Effects of Uric Acid-Lowering Food Compositions on Xanthine Oxidase Levels in Hyperuricemia Mice

[0117] Xanthine is oxidized to uric acid under the action of xanthine oxidase (XOD), which is the main source of uric acid in the body. Inhibiting the activity of XOD is an effective means to reduce the content of uric acid in the body, which is of great significance for the treatment of hyperuricemia and even gout.

[0118] The XOD levels in the plasma and liver tissues of mice in each group were measured respectively, and the specific results are listed in Table 3.

[0119]

[0120] The content of XOD in the plasma of the model group increased significantly. Allopurinol and probenecid could significantly reduce the XOD level in the plasma. The inhibitory effect of celery seed extract on plasma XOD was equivalent to that of the positive drug, and black radish extract, astragalus extract, Composition 1 and Composition 2 could also inhibit the plasma XOD level of hyperuricemic mice.

[0121] Among them, Composition 2 composed of celery seed extract, black radish extract and astragalus extract had the best inhibitory level on plasma XOD, and its average plasma XOD value could be as low as 3.5±0.5 U / L.

[0122] At the same time, modeling caused a significant increase in the XOD level in the liver of mice in the model group, while the positive drug could significantly reverse this change, and the effect of allopurinol was better than that of probenecid. Allopurinol belongs to an XOD inhibitor and can reduce uric acid by inhibiting the activity of XOD.

[0123] Celery seed extract, black radish extract, astragalus extract, Composition 1 and Composition 2 could reverse the liver XOD level of hyperuricemic mice to varying degrees, and Composition 2 had the best inhibitory effect, and its ability to reduce the liver XOD content was significantly higher than that of each extract used alone.

[0124] 4. Effects of the anti-hyperuricemia food composition on HE staining of the liver and kidney of hyperuricemic mice

[0125] Figure 3 In the normal group, the hepatic tissue structure was intact, the cells were arranged neatly, and the sinusoidal vessels had clear running patterns. In celery seed extract, black radish extract, astragalus extract and Composition 1, vacuolar edema of hepatocytes and cytoplasmic loosening were observed, while there were no obvious pathological changes in the liver tissue of Composition 2, indicating that Composition 2 could improve the liver pathological changes caused by hyperuricemia and had the activity to treat liver lesions caused by hyperuricemia.

[0126] Figure 4In the normal group, the renal unit structure was intact, the renal tubule structure was clear, and the cell morphology was normal and plump. In the model group, the cytoplasm was loose, and in some severe cases, it was vacuolated. The renal tubules were dilated and there was local inflammatory cell infiltration, and the edges of the glomeruli were blurred. In the celery seed extract group, the astragalus extract group, the black radish extract group, and Composition Group 1, dilation and edema of the collecting ducts and hyperemia of the glomeruli were observed. In the celery seed extract group, podocytes were not seen, and the renal capsule cavity was relatively large. At the same time, during the sampling process, the kidneys of the mice in this group were pale, suggesting that while the celery seed extract reversed the levels of plasma uric acid and others in the mice, it caused damage to the kidneys of the mice, possibly leading to edema and urinary retention in the kidneys of the model mice and further damaging the renal tissue. However, it is worth noting that the renal tissue structure of Composition Group 2 was intact, the cell morphology was normal and plump, and the renal tubule structure was clear.

[0127] Based on the above experimental results, both compositions of the present invention can significantly reduce the levels of UA, CRE, BUN, XOD in the plasma of hyperuricemia mice and XOD in the liver, and at the same time protect the liver and kidney functions, and the effect of Composition 2 is particularly better. In addition, it was found in the study that when only the celery seed extract was used to treat hyperuricemia model mice, testicular oxidative damage side effects occurred in the mice. However, when an appropriate amount of melanin with antioxidant effects was added to the extract, it could protect male mice from testicular damage while reducing the serum uric acid level. The experimental results prove that the compositions of the present invention have low toxicity and side effects, have a good ability to reverse the blood biochemistry and liver and kidney pathological changes in mice caused by hyperuricemia, and have the potential to be developed into drugs or functional foods for treating or assisting in the treatment of hyperuricemia.

[0128] The technical features of the above embodiments of the present invention can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as within the scope described in the specification of the present invention.

[0129] The above embodiments represent several relatively specific and detailed implementation manners of the present invention, but should not be construed as limiting the protection scope of the present invention. It should be noted that those of ordinary skill in the art can make several substitutions, deformations or improvements without departing from the principle and purpose of the present invention, and all of them should be included in the protection scope of the present invention.

Claims

1. A uric acid-lowering food composition containing food-derived melanin, which is prepared by mixing the following raw materials in parts by weight: 2 to 10 parts of celery seed extract, 1 to 6 parts of food-derived melanin, and 0 to 5 parts of astragalus extract.

2. The uric acid-lowering food composition containing food-derived melanin according to claim 1, characterized in that The weight proportions of the raw materials are: 4 to 8 parts of celery seed extract, 1 to 5 parts of food-derived melanin, and 0.5 to 3 parts of astragalus extract.

3. The uric acid-lowering food composition containing food-derived melanin according to claim 1, characterized in that The weight proportions of the raw materials are: 5 to 7 parts of celery seed extract, 2 to 4 parts of food-derived melanin, and 0.5 to 2 parts of astragalus extract.

4. The uric acid-lowering food composition containing food-derived melanin according to claim 1, characterized in that The weight proportions of the raw materials are: 6 parts of celery seed extract, 3 parts of food-derived melanin, and 1 part of astragalus extract.

5. The uric acid-lowering food composition containing food-derived melanin according to any one of claims 1 to 4, characterized in that The food-derived melanin is any melanin extracted from natural black foods such as black radish, black sesame, black rice, black beans, black corn, cuttlefish, black-bone chicken, rye, black fungus, mulberry, black plum, black wolfberry, black peanut, black potato and black date.

6. The method for preparing the uric acid lowering food composition containing food-derived melanin according to any one of claims 1 to 4 is to accurately weigh celery seed extract, food-derived melanin, and astragalus extract according to the stated weight proportions, and then mix them uniformly in equal and incremental amounts to prepare the food composition.

7. Use of the uric acid-lowering food composition containing food-derived melanin according to any one of claims 1 to 4 in the preparation of medicines or functional foods for treating hyperuricemia and / or gout.

8. Use of the uric acid lowering food composition containing food-derived melanin according to any one of claims 1 to 4 in the preparation of a medicament for lowering uric acid levels.

9. Use of the food composition for lowering uric acid containing food-derived melanin according to any one of claims 1 to 4 in the preparation of drugs or functional foods of xanthine oxidase inhibitors.

10. Use of the uric acid-lowering food composition containing food-derived melanin according to any one of claims 1 to 4 in the preparation of a medicine or functional food for improving liver and kidney damage caused by hyperuricemia.

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