Uses of a combination of tart cherry powder and celery seed powder, and complexes containing this combination.

Abstract

This invention belongs to the field of pharmaceutical technology, and relates to the use of a combination of sour cherry powder and celery seed powder, and complexes containing this composition. Specifically, the sour cherry powder and celery seed powder composition is used in the preparation of drugs for treating or regulating intestinal flora imbalance caused by hyperuricemia. The preparation method of this composition is as follows: pitting sour cherries, freezing them separately with liquid nitrogen, grinding them into powder using a pulverizer, and sieving them separately to obtain sour cherry powder and celery seed powder; mixing the obtained sour cherry powder and celery seed powder at a ratio of (0.5~3):1. This invention discusses the diversity, richness, and evenness of intestinal flora through diversity analysis, community bar chart analysis, and Venn diagram analysis. The results show that this composition can increase beneficial bacteria (Prevotella, Mulliez, Lactobacillus, etc.), reduce harmful bacteria (Alternaria), improve the structure of intestinal flora, and maintain the balance of intestinal flora.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the use of a composition of sour cherry powder and celery seed powder and a complex containing the composition. Background Technology

[0002] Hyperuricemia (HUA) is an abnormal physiological state in which, under normal dietary conditions and fasting, serum uric acid (SUA) levels exceed 420 μmol / L in men and 360 μmol / L in women. The abnormally elevated uric acid (UA) is due to purine metabolism disorders, often manifesting in two ways: increased production and decreased excretion. HUA can be primary or secondary to other diseases. Currently, commonly used drugs for treating HUA include allopurinol, febuxostat, and benzbromarone, which primarily promote uric acid excretion and inhibit uric acid production. However, long-term use may cause common adverse reactions including nausea, vomiting, decreased appetite, dizziness, headache, and allergies. Compared to Western medicine, traditional Chinese medicine (TCM) has advantages such as safety and fewer side effects. For example, Chinese patent CN108498783A discloses a composition for treating hyperuricemia, whose active ingredients include: sunflower disc extract, corn silk extract, sour cherry extract, cactus fruit extract, plantain seed extract, carrot extract, anserine peptide, and minerals. This composition has the effect of lowering hyperuricemia, has a protective effect on the kidneys, and can synergistically enhance the efficacy and reduce the toxicity of clinical uric acid-lowering drugs. Chinese patent CN115299602A discloses a uric acid-lowering composition, which includes sour cherry extract, sophora japonica flower extract, celery seed extract, and potassium citrate. This composition can not only inhibit the formation of uric acid but also promote the excretion of uric acid, enabling rapid control of uric acid levels in patients with hyperuricemia and reducing the side effect of lowering blood pressure. Although existing traditional Chinese medicine (TCM) compositions can alleviate hyperuricemia (HUA) by reducing SUA concentration and promoting UA excretion, clinical studies have shown that patients with hyperuricemia generally have gut microbiota dysbiosis. This means that hyperuricemia further induces gut microecological imbalance, leading to a decrease in the abundance of beneficial bacteria and an overgrowth of harmful bacteria. This dysbiosis, in turn, exacerbates abnormal uric acid metabolism through metabolic disorders and intestinal barrier damage, creating a vicious cycle. Because existing TCM compositions cannot block this vicious cycle of hyperuricemia, rebound in indicators and relapse of the condition often occur within 3-6 months after discontinuation of the medication.

[0003] Currently, there are many types of microbial agents used to regulate gut microbiota, such as live bacteria preparations like Bifidobacterium and Lactobacillus. However, gut microbiota dysbiosis caused by different metabolic diseases exhibits significant heterogeneity. Influenced by differences in disease etiology, the structural characteristics of gut microbiota imbalance vary considerably, making existing microbial agents unsuitable for gut microbiota dysbiosis caused by hyperuricemia. Existing literature reports that the active ingredients of traditional Chinese medicine can promote the growth of beneficial bacteria and inhibit the proliferation of harmful bacteria, thus serving to regulate gut microbiota structure. However, to date, no research has been reported on the effects of sour cherry powder and celery seed powder on gut microbiota regulation. Summary of the Invention

[0004] In view of the shortcomings and deficiencies of the existing technology, the purpose of the present invention is to provide a use of a composition of tart cherry powder and celery seed powder and a complex containing the composition, specifically, the use of the composition of tart cherry powder and celery seed powder in the preparation of a drug for treating or regulating intestinal flora disorder caused by hyperuricemia.

[0005] As a preferred embodiment of the present invention, the preparation method of the sour cherry powder and celery seed powder composition is as follows: Step 1. Remove the pits from the sour cherries and freeze them separately with liquid nitrogen along with the celery seeds. After freezing, grind them into powder using a grinder and sieve them separately to make sour cherry powder and celery seed powder. Step 2. Mix the obtained sour cherry powder and celery seed powder, wherein the weight ratio of sour cherry powder to celery seed powder is (0.5~3):1.

[0006] As a preferred embodiment of the present invention, the combination of sour cherry powder and celery seed powder is used to improve the diversity, richness and uniformity of intestinal flora, increase the abundance of beneficial bacteria and reduce the abundance of harmful bacteria.

[0007] As a preferred embodiment of the present invention, the pitted sour cherries are frozen in liquid nitrogen for 5-10 minutes, then ground into powder using a pulverizer and passed through an 80-mesh sieve; the celery seeds are frozen in liquid nitrogen for 5-8 minutes, then ground into powder using a pulverizer and passed through a 100-mesh sieve.

[0008] As a preferred embodiment of the present invention, dihydroquercetin (DHQ) is also added to the composition of sour cherry powder and celery seed powder. The specific preparation method is as follows: first, mix sour cherry powder and celery seed powder, and then add dihydroquercetin and mix evenly a second time.

[0009] As a preferred embodiment of the present invention, the beneficial bacteria are Prevotella, Mullieb, and Lactobacillus; the harmful bacteria are Alternaria.

[0010] As a further preferred embodiment of the present invention, the weight ratio of the sour cherry powder, celery seed powder and dihydroquercetin is 1:1:(0.5~2).

[0011] As a further preferred embodiment of the present invention, the weight ratio of the sour cherry powder, celery seed powder and dihydroquercetin (DHQ) is 1:1:(1.3~2).

[0012] The present invention also provides a complex containing a composition of tart cherry powder and celery seed powder, the complex being composed of tart cherry powder, celery seed powder, and dihydroquercetin, wherein the weight ratio of tart cherry powder, celery seed powder, and dihydroquercetin (DHQ) is 1:1:(1.3~2). The complex is used to regulate intestinal flora imbalance caused by hyperuricemia, lower UA (uric acid), and protect the liver and kidneys.

[0013] Advantages and beneficial effects of the present invention: (1) The present invention demonstrates through experiments that the combination of sour cherry powder and celery seed powder prepared in this application can improve the intestinal flora disorder caused by hyperuricemia, improve the diversity, richness and uniformity of intestinal flora, increase the abundance of beneficial bacteria (Prevotella, Mullieb, Lactobacillus), reduce the abundance of harmful bacteria (Alternaria), make the intestinal flora tend to be normal, and maintain the balance of intestinal flora. Therefore, it can be used in the preparation of drugs for treating or regulating intestinal flora disorder caused by hyperuricemia.

[0014] (2) Through comparative experiments, this invention has determined that when sour cherry powder and celery seed powder are mixed in a 1:1 ratio, it not only regulates the intestinal flora but also has the best effect in treating hyperuricemia. The uric acid-lowering effect is significantly better than other groups, with a significant difference (p<0.01), achieving unexpected technical results.

[0015] (3) The combination of sour cherry powder and celery seed powder provided by the present invention can alleviate hyperuricemia by reducing the concentration of SUA and promoting the excretion of UA. At the same time, it can also improve the intestinal flora disorder caused by hyperuricemia and block the vicious cycle of hyperuricemia. The discovery of this new use not only provides a new method and favorable basis for the treatment of intestinal flora disorder, but also provides a new multi-target treatment plan for the treatment of hyperuricemia, which is conducive to reducing the recurrence rate of hyperuricemia.

[0016] (4) The present invention has demonstrated through experiments that adding an appropriate amount of DHQ to the combination of sour cherry powder and celery seed powder can better regulate the intestinal flora and further improve the effect of reducing SUA.

[0017] (5) Through experiments, the present invention also found that the combination of sour cherry powder and celery seed powder with added high concentration of DHQ can effectively alleviate liver and kidney damage caused by hyperuricemia and protect the liver and kidneys. Attached Figure Description

[0018] Figure 1 The change in body weight of mice in each group at the end of the modeling process; Figure 2 The SUA levels in each group of mice were determined at the end of the modeling process. Figure 3 The effect of different proportions of the composition in Example 1 on the SUA content in mice; Figure 4 This illustrates the effect of different drug treatment groups on SUA levels in mice in Example 2. Figure 5 The values ​​represent the levels of xanthine oxidase (XOD), blood urea nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the blood of mice in different drug treatment groups in Example 2; where (a) is the XOD content; (b) is the BUN content; (c) is the AST content; and (d) is the ALT content. Figure 6 Alpha diversity analysis (Chao index bar chart) for Example 2; Figure 7 Alpha diversity analysis (Simpson index bar chart) for Example 2. Figure 8 Alpha diversity analysis (Shannon index bar chart) for Example 2. Figure 9 Venn diagram analysis of species in Example 2; Figure 10 This is a community heatmap analysis at the genus level for Example 2; Figure 11 This is a community histogram analysis at the genus level for Example 2; Figure 12 PCA analysis for Example 2; Figure 13 This is an HE staining image of liver and kidney tissues from hyperuricemic mice in Example 2. Detailed Implementation

[0019] To more clearly illustrate the technical solution of the present invention, the present invention will be further described below through specific embodiments. However, these embodiments are only for illustration and not for limiting the present invention.

[0020] Example 1:

[0021] 1. Experimental Procedure 1.1 Experimental Materials Sour cherry (scientific name: Prunus cerasus L., belonging to the genus Prunus of the family Rosaceae (Rosa genus). Prunus Celery seed (scientific name: *Celtis sinensis*) is a cultivated species. Apium graveolens L., belonging to the genus Celery of the family Apiaceae (L.). ApiumThe plant was used. Yeast extract and allopurinol were purchased from Shanghai Bioengineering Co., Ltd., which also provided detection kits for SUA, xanthine oxidase (XOD), blood urea nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Several SPF-grade male ICR mice, weighing 20-22g, were purchased from Liaoning Changsheng Biotechnology Co., Ltd., Animal Qualification Certificate No. SCXK(Liaoning) 2025-0001. The mice were housed in an environment with a relative humidity of 55%-60%, a temperature of 20-22℃, and a 12-hour dark / 12-hour light cycle. During the housing period, the mice had free access to water and food, and the experiment was conducted after one week of acclimatization.

[0022] 1.2. Experimental Methods 1.2.1. Modeling of hyperuricemia and grouping for drug administration A mouse model of hyperuricemia induced by yeast extract was established. Mice were administered yeast extract (15 g / kg) by gavage for 14 consecutive days, followed by a 10-hour fast before the experiment. The mice were divided into three groups: a blank control group (CK), a model control group (AC), and an administration group (0.46 mg / g) (n=8). The CK and AC groups were given distilled water, while the administration group was given a mixture of tart cherry powder and celery seed powder. Five groups were established according to the ratio of tart cherry powder to celery seed powder: 7:3, 3:2, 5:4, 1:1, and 3:4. During the experiment, the mice's mental state, diet and water intake, hair growth, and color changes were observed. The weight of the mice in each group was also measured and recorded.

[0023] In this embodiment, the preparation method of the sour cherry powder and celery seed powder composition is as follows: Step 1. Remove the pits from the sour cherries and freeze them separately with liquid nitrogen along with the celery seeds. After freezing, grind them into powder using a grinder and sieve them separately to make sour cherry powder and celery seed powder. Specifically, the sour cherries are frozen with liquid nitrogen for about 8 minutes after being pitted, and then ground into powder using a grinder and passed through an 80-mesh sieve. The celery seeds are frozen with liquid nitrogen for about 6 minutes, and then ground into powder using a grinder and passed through a 100-mesh sieve. Step 2. Mix the obtained sour cherry powder and celery seed powder according to the preset ratio.

[0024] 1.2.2. Mouse Blood Collection Blood was collected from mice before the start of the experiment and on day 7. The blood was centrifuged at 3000 r / min for 15 min at 4°C, and the supernatant was collected and stored at -80°C for later use. The SUA content was then determined using a SUA detection kit. The mice were euthanized on day 8 of the experiment.

[0025] 1.2.3. Mouse fecal collection Fresh feces were collected from mice prior to dissection. Fresh feces were collected directly from mice using 1.5 mL sterile EP tubes, with sterile gloves worn throughout the process to avoid sample contamination. At least 3 g of fresh feces were collected from each sample and stored in a sterile feces container.

[0026] The collected fecal samples were sent to Shanghai Meiji Biomedical Technology Co., Ltd. for 16S rRNA gene sequencing.

[0027] 2. Experimental Results 2.1. Blood analysis results The modeling and experimental results are shown below. Figure 1 and Figure 2 .like Figure 1 As shown, during the modeling period, the body weight of mice in the CK group increased normally, while the body weight of mice in the AC group increased significantly. After randomization, SUA levels were measured, and the results are as follows: Figure 2 As shown, compared with the CK group, the SUA levels in the AC group and the five groups were significantly increased after the modeling was completed (p<0.001). Both results indicate that the yeast extract-induced hyperuricemia mouse model was successfully established.

[0028] The results of treating the combination of tart cherry powder and celery seed powder are as follows: Figure 3 As shown. (Through) Figure 3 As can be seen, compared with the AC group, the SUA levels in all five drug administration groups with different ratios were significantly reduced (p<0.001): 7:3 group (32.5%), 3:2 group (32.8%), 5:4 group (31.8%), 1:1 group (36.8%), and 4:5 group (32.6%). This demonstrates that each drug administration group has a significant therapeutic effect on hyperuricemia. Furthermore, by comparing the SUA-lowering effects of the five ratios of tart cherry powder and celery seed powder combinations, the results showed that the 1:1 ratio drug administration group had a significantly better SUA-lowering effect than the other drug administration groups (p<0.01), a result that completely exceeded experimental expectations.

[0029] 2.2 Results of fecal analysis In this embodiment, alpha diversity analysis, PCA analysis, community heatmap analysis, and community bar chart analysis were performed on fecal samples. The results showed that the combination of tart cherry powder and celery seed powder had a good regulatory effect on intestinal flora imbalance caused by hyperuricemia, significantly improving the diversity, richness, and evenness of intestinal flora, while increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria.

[0030] Note: In this embodiment, in order to further improve the therapeutic effect, it is further optimized based on Example 1, and the 1:1 ratio of the drug administration group is compared with the optimized regimen. For details of the fecal analysis results, please refer to Example 2.

[0031] Example 2:

[0032] This invention, through Example 1, determined that the 1:1 ratio of drug administration group significantly reduced SUA levels compared to other ratios. It also showed significant effects in reducing XOD, BUN, AST, and ALT, as well as regulating intestinal flora imbalance caused by hyperuricemia. To further improve the therapeutic effect, this example further added different doses of DHQ. The specific experimental process is as follows: In this embodiment, the same modeling method as in Example 1 was used to obtain hyperuricemic mice, which were randomly divided into 7 groups of 8 mice each. The groups included: blank control group (CK), model control group (AC), positive control group (MG), 1:1 administration group (i), 1:1 + low concentration DHQ administration group (iL), 1:1 + medium concentration DHQ administration group (iM), and 1:1 + high concentration DHQ administration group (iH). Among them, the blank control group (CK) and model control group (AC) were given distilled water, the positive control group (MG) was given allopurinol (10 mg / kg), the 1:1 administration group (i) was given a combination of sour cherry powder and celery seed powder, and the 1:1 + low concentration DHQ administration group (iL), 1:1 + medium concentration DHQ administration group (iM), and 1:1 + high concentration DHQ administration group (iH) were given different doses of DHQ in addition to the 1:1 administration group.

[0033] Following the experimental method described in Example 1, mouse blood and feces were collected and tested. The results are as follows: like Figure 4 As shown, after drug treatment, compared with the AC group, the serum SUA levels in all four drug-treated groups were significantly reduced (p<0.001): group i decreased by 30.8%, group iL by 30.9%, group iM by 31.1%, and group iH by 35.9%. This indicates that, compared with the model group AC, the serum uric acid levels in all drug-treated groups were significantly reduced. In terms of the magnitude of the reduction, group iH showed a stronger SUA-lowering ability (p<0.001); it also showed a stronger SUA-lowering ability compared to allopurinol.

[0034] like Figure 5As shown, compared with the CK group, the levels of XOD, BUN, AST, and ALT in the AC group mice were significantly increased (p<0.001), indicating that the model mice had obvious abnormal uric acid metabolism and liver and kidney function damage. Compared with the AC group, the above indicators were significantly reduced in all drug-treated groups after drug treatment (p<0.001). The specific reductions are as follows: Group i: XOD level decreased by 0.818 U / L, BUN level decreased by 9.11 mg / dL, AST level decreased by 1.83 U / dL, and ALT level decreased by 4.72 U / dL; Group iL: XOD level decreased by 0.842 U / L, BUN level decreased by 8.97 mg / dL, AST level decreased by 1.81 U / dL, and ALT level decreased by 5.01 U / dL; Group iM: XOD level decreased by 0.875 U / L, BUN level decreased by 9.21 mg / dL, AST level decreased by 1.804 U / dL, and ALT level decreased by 4.97 U / dL; Group iH: XOD level decreased by 0.928 U / L, BUN level decreased by 10.6 mg / dL, AST level decreased by 1.967 U / dL, and ALT level decreased by 5.23 U / dL; Group MG: XOD level decreased by 0.785 U / L, and BUN level decreased by 6.09 U / dL. mg / dL, AST content decreased by 1.9 U / dL, and ALT content decreased by 2.33 U / dL (see Table 1 for details).

[0035] The above results indicate that this composition can reduce uric acid production by inhibiting XOD activity, while simultaneously improving liver function by lowering AST and ALT levels and improving kidney function by lowering BUN levels. Compared with allopurinol, the combination of tart cherry powder and celery seed powder with added DHQ is more effective, and the 1:1 + high-concentration DHQ administration group shows a more significant effect.

[0036] Table 1. Serum levels of various indicators in different drug administration groups Group SUA (mg / L) XOD (U / L) BUN (mg / dL) AST (U / dL) ALT (U / dL) CK 0.397±0.02 0.15±0.01 27.86±1.13 2.991±0.52 2.414±0.18 AC 0.901±0.11 1.49±0.02 40.55±1.86 5.678±0.64 12.567±0.43 MG 0.583±0.09 0.74±0.01 34.31±1.15 2.871±0.56 7.852±0.64 i 0.598±0.10 0.66±0.03 31.90±0.58 2.895±1.01 7.976±0.15 iL 0.597±0.04 0.64±0.02 31.78±1.17 2.881±0.75 7.931±0.25 iM 0.585±0.15 0.61±0.04 31.16±1.57 2.881±0.43 7.918±0.27 iH 0.569±0.22 0.57±0.02 30.15±1.38 2.857±0.47 7.841±0.29 In this embodiment, fecal samples from mice in the CK, AC, i, and iH groups were sent to Shanghai Meiji Biomedical Technology Co., Ltd. for 16S rRNA gene sequencing, and Alpha diversity analysis (including Chao, Simpson, and Shannon indices) was conducted to assess the richness, diversity, and evenness of the gut microbiota in each group of mice.

[0037] like Figure 6 As shown (the Chao index is a species richness index calculated based on OTUs; a higher value indicates a greater number of species (richness) in the community), the Chao indices of groups i and iH are both higher than those of group AC, and the Chao index of group iH is higher than that of group i. Figure 7As shown (a higher Simpson value indicates higher community diversity, reflecting both species richness and species evenness), the Simpson indices of groups i and iH are both higher than those of group AC, and the Simpson index of group iH is higher than that of group i. Figure 8 As shown (the Shannon index is a classic indicator for measuring alpha diversity in microbial communities, integrating species richness and evenness; a higher index value indicates stronger community diversity, richer species, and more evenly distributed species), the Shannon indices of groups i and iH were higher than those of group AC, and the Shannon index of group iH was higher than that of group i. These results indicate that the combination of tart cherry powder and celery seed powder can enrich the gut microbiota, increase microbiota diversity, and make the microbiota distribution more even, with the effect being more pronounced after adding a high concentration of DHQ.

[0038] like Figure 9 As shown, Venn diagrams were used to analyze the operational taxonomic units (OTUs) of the gut microbiota in each experimental group to reveal the abundance of species unique to and shared among the groups, and to assess the overlap and similarity of the microbial communities. Experimental data showed that the total number of OTUs in the CK, AC, i, and iH groups were 276, 226, 254, and 276, respectively. Further analysis of the number of shared OTUs revealed that there were 135 shared OTUs across the four groups; specifically, the AC group shared 154 OTUs with the CK group; the AC group shared 181 OTUs with the i group and 207 with the iH group; and the CK group shared 174 OTUs with the i group and 175 with the iH group. Based on these data, the community similarity among the experimental groups was calculated. The results showed that the iH group and the CK group had a total of 175 OTUs, and the i group and the CK group had a total of 174 OTUs. The total number of OTUs in the iH group recovered to be equal to that in the CK group (both had 276). Furthermore, statistical analysis indicated that the total number of OTUs in both the i and iH groups was higher than that in the AC group, with the iH group having a higher total number of OTUs than the i group. This suggests that both the i and iH groups can improve gut microbiota diversity, with the iH group having a more significant effect on improving microbiota richness.

[0039] In conclusion, tart cherry powder combined with celery seed powder and high-concentration DHQ is more effective than a combination of tart cherry powder and celery seed powder in enhancing the richness and diversity of gut microbiota and optimizing gut microbiota structure.

[0040] This embodiment performed community heatmap analysis and relative abundance bar chart analysis on mouse fecal samples at the genus level (selecting the top 10 genera in terms of relative abundance). Due to the taxonomic resolution limitations of 16S rRNA gene sequencing, some sequences could only be annotated to the family level (e.g., ...). Prevotellaceae UCG-001 Muribaculaceae, Prevotellaceae In subsequent analysis, this invention retained these family-level taxonomic units and incorporated them into the genus-level statistical chart to ensure the integrity of the data. The results are as follows: Figure 10 and Figure 11 As shown.

[0041] 1. The impact of model construction on gut microbiota like Figure 10 and Figure 11 As shown, the gut microbiota structure of the AC group was altered compared to the CK group. Specifically, the relative abundance of beneficial bacteria genera was significantly reduced, including Prevotaceae_UCG-001 (… Prevotellaceae _UCG-001), Mulliebaceae ( Muribaculaceae Lactobacillus ( ) Lactobacillus ) and Prevotaceae ( Prevotellaceae At the same time, the relative abundance of harmful bacteria genera increased significantly, including Bacteroides ( Bacteroides ) and other fungi ( Alistipes The above results indicate that the hyperuricemia model successfully induced an imbalance in the intestinal microecology of mice, manifested as the inhibition of beneficial bacteria and the abnormal proliferation of harmful bacteria.

[0042] 2. Analysis of Intervention Effects 2.1 The intervention effect of the combination of sour cherry powder and celery seed powder Intervention with a combination of tart cherry powder and celery seed powder significantly improved intestinal flora imbalance. Figure 10 As shown, beneficial bacteria genera such as Prevotaceae ( Prevotellaceae ), Muribacteriumceae and Lactobacillus genus ( Lactobacillus The abundance of all genera showed an upward trend; at the same time, the abundance of harmful bacteria—Alternaria ( Alistipes The abundance of ) decreased significantly. Combined with Figure 11 The bar chart data shows that the relative abundance of each bacterial genera gradually approaches that of the CK group, indicating that the composition can effectively regulate the intestinal flora structure, alleviate flora imbalance, and promote microecological balance.

[0043] 2.2 Intervention Effects of Tart Cherry Powder and Celery Seed Powder + High Concentration DHQ The regulatory effect was more significant after intervention with tart cherry powder and celery seed powder plus high concentration of DHQ. Figure 10 As shown, compared to group i, the abundance of beneficial bacteria genera in group iH was further increased, specifically Prevotaceae (… Prevotellaceae ), Muribacteraceae, Lactobacillus ( Lactobacillus ) and Prevotaceae_UCG-001 ( PrevotellaceaeSignificant enrichment of _UCG-001); simultaneously, harmful bacteria—Bacteroides spp. ( Bacteroides The abundance of ) was more significantly suppressed.

[0044] like Figure 11 As shown, the beneficial bacteria in group iH belong to the Mulliebaceae family ( Muribaculaceae ) and Prevotaceae ( Prevotellaceae The relative abundance of ) was significantly higher in group i than in group i, while the harmful genus Bacteroides ( Bacteroides The relative abundance of group I was lower than that of group II. The bacterial community structure of this group was closer to that of group CK, showing stronger resilience and stability.

[0045] 3. Conclusion The experimental results above indicate that the combination of tart cherry powder and celery seed powder can effectively increase the abundance of beneficial bacteria in the gut and inhibit the proliferation of harmful bacteria, thereby improving gut microbiota imbalance caused by hyperuricemia. Furthermore, the addition of a high concentration of DHQ produced a significant synergistic effect: it not only further promoted the growth of beneficial bacteria but also more effectively inhibited the proliferation of harmful bacteria, allowing the gut microbiota structure to more stably return to a normal physiological state. Therefore, the complex of tart cherry powder and celery seed powder + high concentration of DHQ has outstanding technical effects in improving the stability of the gut microbiota.

[0046] like Figure 12 As shown, principal component analysis (PCA) was performed at the genus level. The results showed that the cumulative contribution rates of principal components PC1 and PC2 were as high as 96.71% (65.68% and 31.03%, respectively), indicating that the model could explain most of the gut microbiota variation information. In the PCA score plot, group AC showed a clear separation trend from groups i and iH along the PC1 axis, and there was a significant spatial distance between the groups, indicating that the combination of sour cherry powder and celery seed powder, along with the addition of DHQ, could significantly alter the gut microbiota structure. Specifically, although group i and group CK showed some aggregation, spatial distance still existed, indicating that while simple administration had a regulatory effect, it failed to completely reverse the microbiota structure to a normal physiological state. In contrast, group iH was closer to group CK on the PC1 axis and was clearly distinguishable from group i. This result suggests that adding a high concentration of DHQ can produce a synergistic effect, more efficiently reshaping the gut microbiota structure and causing it to regress towards the normal group. This conclusion is consistent with the aforementioned analysis results of the Alpha diversity index.

[0047] Furthermore, considering that high concentrations of SUA can deposit and damage renal tubules and liver parenchyma, inducing oxidative stress, inflammation, and metabolic disorders in liver and kidney tissues, long-term continuous exposure can gradually weaken liver and kidney function and further aggravate organ pathological damage. To further investigate the effects of the DHQ-added sour cherry powder and celery seed powder composition provided in this embodiment on mouse liver and kidney tissues, mice were euthanized on day 8 of the experiment. Intact liver and kidney tissues were collected, rinsed with physiological saline, blotted dry with filter paper to remove surface moisture and impurities, and then weighed. Subsequently, the tissues were fixed in 4% paraformaldehyde tissue fixative for subsequent HE staining. The staining results are shown below. Figure 13 As shown.

[0048] Depend on Figure 13 As can be seen, the hepatocytes of the CK group mice were neatly arranged, with oval or round nuclei, uniform staining depth, and regular chromatin arrangement. The hepatocytes of the AC group mice showed significant swelling and enlargement, and vacuoles of varying sizes were visible in the cytoplasm. While the hepatocytes of the iH group mice also showed slight swelling and enlargement, the degree of hepatocyte damage was significantly less than that of the AC group. These cytoplasmic vacuoles are caused by lipid metabolism disorders leading to fat accumulation in the hepatocytes, i.e., hepatocyte steatosis. Specifically, this manifests as spherical vacuoles in the cytoplasm; larger vacuoles are called macrovesicular steatosis, while smaller or denser vacuoles are called microvesicular steatosis.

[0049] In mouse kidney sections, the CK group showed a clear boundary between the renal cortex and medulla, with glomeruli exhibiting round or oval structures and pinkish inner capillary plexuses. Both the AC and iH groups showed white granular material in their kidney tissues, along with localized fibrosis caused by urate deposition in the renal interstitium; however, the degree of damage in the iH group was significantly less than that in the AC group, with urate deposition and interstitial fibrosis significantly alleviated. These results indicate that the combination of tart cherry powder and celery seed powder with added high concentrations of DHQ significantly alleviates liver and kidney damage caused by hyperuricemia.

[0050] Finally, it should be noted that the above examples are merely some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and many variations are possible. All variations that are directly derived or conceived by those skilled in the art from the disclosure of the present invention should be considered within the scope of protection of the present invention.

Claims

1. The combination of tart cherry powder and celery seed powder is used in the preparation of drugs for treating or regulating intestinal flora imbalance caused by hyperuricemia.

2. The application according to claim 1, characterized in that, The preparation method of the sour cherry powder and celery seed powder composition is as follows: Step 1. Remove the pits from the sour cherries and freeze them separately with liquid nitrogen along with the celery seeds. After freezing, grind them into powder using a grinder and sieve them separately to make sour cherry powder and celery seed powder. Step 2. Mix the obtained sour cherry powder and celery seed powder evenly, wherein the weight ratio of sour cherry powder to celery seed powder is (0.5~3):

1.

3. The application according to claim 1 or 2, characterized in that, The combination of sour cherry powder and celery seed powder is used to improve the diversity, richness and uniformity of intestinal flora, increase the abundance of beneficial bacteria and reduce the abundance of harmful bacteria.

4. The application according to claim 1 or 2, characterized in that, The sour cherry powder and celery seed powder composition also contains dihydroquercetin. The specific preparation method is as follows: first, mix the sour cherry powder and celery seed powder, then add dihydroquercetin and mix evenly a second time.

5. The application according to claim 2, characterized in that, The pitted sour cherries are frozen in liquid nitrogen for 5-10 minutes, then ground into powder using a grinder and passed through an 80-mesh sieve; the celery seeds are frozen in liquid nitrogen for 5-8 minutes, then ground into powder using a grinder and passed through a 100-mesh sieve.

6. The application according to claim 3, characterized in that, The beneficial bacteria are Prevotella, Mullieb, and Lactobacillus; the harmful bacteria are Alternaria.

7. The application according to claim 4, characterized in that, The weight ratio of the sour cherry powder, celery seed powder, and dihydroquercetin is 1:1:(0.5~2).

8. The application according to claim 7, characterized in that, The weight ratio of the sour cherry powder, celery seed powder, and dihydroquercetin is 1:1:(1.3~2).

9. A complex containing a composition of sour cherry powder and celery seed powder, characterized in that, The complex is composed of tart cherry powder, celery seed powder, and dihydroquercetin, with a weight ratio of tart cherry powder, celery seed powder, and dihydroquercetin of 1:1:(1.3~2). The complex is used to regulate intestinal flora imbalance caused by hyperuricemia, lower uric acid, and protect the liver and kidneys.

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