Natural plant polyphenol composition with uric acid-lowering effect and application thereof

Abstract

This invention discloses a natural plant polyphenol composition with uric acid-lowering effects and its applications, belonging to the field of plant extract technology. Through a complete modern R&D chain of "in vitro quantitative screening → statistical ratio optimization → in vivo comprehensive efficacy verification," this invention successfully created a natural plant polyphenol composition with clearly defined components, scientifically proportioned formulations, comprehensive efficacy (uric acid lowering / anti-inflammatory / kidney protection), and superior safety. Its active ingredients consist of *Fomitopsis coarsenessi* polyphenol extract and plant polyphenol extracts, systematically solving problems in existing technologies such as vague active ingredients, empirically based formulation, single function, and potential kidney damage risk.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a natural plant polyphenol composition with uric acid-lowering effect and its application. Background Technology

[0002] Hyperuricemia is a metabolic disease caused by abnormal purine metabolism, characterized by elevated uric acid levels in the blood. Its pathogenesis is complex, influenced by multiple factors including genetics, diet, and lifestyle. Epidemiological surveys both domestically and internationally show that the global prevalence of hyperuricemia in adults is approximately 13% to 20%, while in some parts of China it is as high as 21.4%. Hyperuricemia is not only a major contributing factor to diseases such as gout and kidney stones, but it is also closely related to various chronic diseases such as cardiovascular disease, diabetes, and chronic kidney disease, seriously threatening patients' health and quality of life. Currently, commonly used uric acid-lowering drugs in clinical practice mainly include xanthine oxidase inhibitors and uricosuric agents. Xanthine oxidase inhibitors, such as allopurinol and febuxostat, effectively lower blood uric acid levels by inhibiting the activity of xanthine oxidase, a key enzyme in uric acid production; uricosuric agents, such as benzbromarone and probenecid, lower blood uric acid levels by promoting renal excretion of uric acid. While these drugs are highly effective in controlling hyperuricemia, long-term use can lead to adverse side effects such as liver and kidney damage and allergic reactions, limiting their widespread application. Therefore, finding safe, effective, and low-side-effect natural uric acid-lowering substances has become a key research focus.

[0003] In recent years, natural plants have gradually become an important research direction for the adjunctive treatment and prevention of hyperuricemia due to their diverse components, multi-target mechanisms of action, and low toxicity. However, the efficacy of single plant extracts is limited and cannot meet clinical needs. Multi-component compound formulation strategies, by integrating multiple plant active ingredients, can leverage their respective advantages and produce synergistic effects, thereby more effectively regulating uric acid metabolism, alleviating inflammatory responses, and improving related symptoms. Patent CN120131852A discloses a uric acid-lowering composition composed of corn silk, dried tangerine peel, and white kidney bean; Patent CN118416150A discloses a uric acid-lowering extract composition composed of wolfberry, hawthorn, mint, winter melon peel, and angelica dahurica, which is simple and safe; Patent CN116870110A discloses a uric acid-lowering uric acid-lowering edible and medicinal formula containing coix seed, poria cocos, plantain, yam, safflower, and kudzu root, which has both uric acid-lowering and kidney-protecting effects; Patent CN116019877A discloses a uric acid-lowering treatment formula containing dandelion, ginseng, sophora japonica flower, cherry, chrysanthemum, plantain seed, and other traditional Chinese herbs, using bio-enzymatic hydrolysis technology to enhance efficacy; Patent CN114366771A discloses a traditional Chinese medicine composition composed of kudzu flower, red peony root, white peony root, and jujube seed extract, which has a significant uric acid-lowering effect; Patent CN 120815142A discloses a formula based on celery seed, celery, mulberry fruit, mulberry leaf, sea buckthorn fruit powder, dandelion, polygonatum, poria cocos, and sea buckthorn, and includes auxiliary ingredients such as mulberry twig, black goji berry, kudzu root, yam, cat's whiskers, lysimachia christinae, eleutherococcus senticosus, goose muscle peptide, astragalus, purslane, small thistle, galangal, jujube fruit, astragalus, lutea, and luteolin. Patent CN120815142A discloses a food-based medicine for lowering uric acid and treating gout. Its basic formula consists of celery seed, celery, mulberry fruit, mulberry leaf, sea buckthorn fruit powder, dandelion, polygonatum, poria cocos, and sea buckthorn. It also includes auxiliary ingredients such as mulberry twigs, black goji berries, kudzu root, yam, cat's whiskers, lysimachia christinae, eleutherococcus senticosus, goose muscle peptide, astragalus, purslane, thistle, galangal, jujube fruit, astragalus, luteolin, and edible probiotics that lower uric acid, among others, in combination to treat hyperuricemia and gout.

[0004] The aforementioned patented technologies all revolve around the combination and compatibility of various traditional Chinese medicines and plants that are both food and medicine. These combinations are largely based on traditional Chinese medicine theories or experience, emphasizing the synergistic effect of rational formulation in lowering uric acid, while also focusing on safety and optimizing the preparation process. However, the main active ingredients in these existing technologies are unclear, and there is a lack of systematic research on the compatibility ratios of specific plant extracts, which is detrimental to the quality control of the final product. Summary of the Invention

[0005] Given that existing technologies suffer from unclear main active ingredients and a lack of systematic research and in vivo activity verification on the compatibility ratio of specific plant extracts, the first objective of this invention is to provide a method for extracting and compatibility of active substances based on natural plants, for the purpose of creating a natural uric acid-lowering product that effectively regulates uric acid metabolism and reduces inflammatory responses.

[0006] To achieve the above-mentioned technical objectives, the inventors have successfully created a natural plant polyphenol composition with clearly defined components, scientifically formulated ratios, comprehensive efficacy (lowering uric acid / anti-inflammatory / kidney protection), and superior safety by adopting a complete modern R&D chain of "in vitro quantitative screening → statistical ratio optimization → in vivo comprehensive efficacy verification". This systematically solves the problems of vague active ingredients, empirical compatibility, single function, and potential kidney damage risk in the prior art.

[0007] Specifically, the objective of this invention is achieved as follows: a natural polyphenol composition with uric acid-lowering effect, the active ingredients of which consist of polyphenol extracts from *Polyporus cirrhosa* and plant polyphenol extracts, wherein the plant polyphenol extracts are one or more of the following: *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum*, *Tetrapanax papyriferus*, *Forsythia suspensa*, *Tetrapanax papyriferus*, lotus leaf, *Prunella vulgaris*, *Ganoderma lucidum*, *Elsholtzia ciliata*, *Phyllanthus emblica*, *Perilla frutescens*, *Eucommia ulmoides*, *Gnaphalium affine*, and buckwheat.

[0008] More preferably, the composition of the active ingredient is selected from any one of the following: (1) a polyphenol extract containing *Polyporus cirrhosa*, *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum* and *Tea japonica*; (2) a polyphenol extract containing *Polyporus cirrhosa*, *Tea japonica*, *Forsythia suspensa*, lotus leaf and *Prunella vulgaris*.

[0009] More preferably, the active ingredient is composed of polyphenol extracts of *Polyporus cirrhosa*, *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum*, and *Tea japonica* in the following mass ratio: *Polyporus cirrhosa* polyphenol extract: *Alpinia galanga* polyphenol extract: *Oroxylum indicum* polyphenol extract: *Oroxylum indicum* polyphenol extract: *Tea japonica* polyphenol extract = 33~40: 20~31: 17~30: 5~10: 5~10.

[0010] More preferably, the active ingredient is composed of polyphenol extracts of *Polyporus cirrhosa*, *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum*, and *Tea japonica* in the following mass ratio: *Polyporus cirrhosa* polyphenol extract: *Alpinia galanga* polyphenol extract: *Oroxylum indicum* polyphenol extract: *Oroxylum indicum* polyphenol extract: *Tea japonica* polyphenol extract = 35~40: 20~25: 17~21: 7~10: 7~10.

[0011] More preferably, the active ingredient is composed of polyphenol extracts of *Polyporus cirrhosa*, large-leaf green tea, *Forsythia suspensa*, lotus leaf, and *Prunella vulgaris* in the following mass ratio: *Polyporus cirrhosa* polyphenol extract: large-leaf green tea polyphenol extract: *Forsythia suspensa* polyphenol extract: lotus leaf polyphenol extract: *Prunella vulgaris* polyphenol extract = 20~30: 15~25: 15~25: 10~15: 10~15.

[0012] More preferably, the active ingredient is composed of polyphenol extracts of *Polyporus cirrhosa*, large-leaf green tea, *Forsythia suspensa*, lotus leaf, and *Prunella vulgaris* in the following mass ratio: *Polyporus cirrhosa* polyphenol extract: large-leaf green tea polyphenol extract: *Forsythia suspensa* polyphenol extract: lotus leaf polyphenol extract: *Prunella vulgaris* polyphenol extract = 26~30: 20~24: 20~24: 11~14: 12~15.

[0013] In addition, the present invention also provides a method for preparing the above-mentioned natural polyphenol composition, the method comprising the following steps:

[0014] (1) Each raw material is dried and pulverized to obtain raw material dry powder, and then subjected to γ-ray irradiation treatment with an irradiation dose of 6~10kGy;

[0015] (2) Extract each raw material dry powder with ethanol solution with a volume fraction of 70%~95% respectively to obtain the extract of each raw material;

[0016] (3) The extracts of each raw material are concentrated and dried to obtain polyphenol extracts of each raw material;

[0017] (4) The various polyphenol extracts obtained in step (3) are compounded in a predetermined ratio to obtain the composition.

[0018] More preferably, the extraction step in step (2) is as follows: first, soak each raw material powder in an ethanol solution, stir at room temperature for 30 to 90 minutes, and then perform ultrasonic-assisted extraction with an ultrasonic power of 300 to 500W and an extraction time of 15 to 25 minutes.

[0019] The inventors verified by constructing a mouse model of hyperuricemia that the polyphenol extract of the present invention can significantly inhibit the activity of xanthine oxidase (XOD) in serum and liver, significantly reduce serum uric acid (UA), creatinine and urea nitrogen levels, and promote the excretion of related metabolites (such as uric acid) in urine. At the same time, the compound extract of the present invention significantly reduces the content of inflammatory factors such as IL-6 and TNF-α in mouse serum and alleviates inflammatory infiltration in liver and kidney tissues. Therefore, the present invention also provides the following technical solutions for product use: (1) the use of the above-mentioned natural polyphenol composition in the preparation of products for reducing serum uric acid, promoting uric acid excretion and / or inhibiting xanthine oxidase activity; (2) the use of the above-mentioned natural polyphenol composition in the preparation of products for relieving kidney inflammation or kidney function damage caused by hyperuricemia.

[0020] Compared with the prior art, the natural polyphenol composition provided by the present invention has the following advantages and significant progress:

[0021] (1) The active ingredients are clearly identified, and the screening process is scientific and systematic, breaking through the experience-based reliance on the traditional compound formula of "principal, assistant, adjuvant, and guide". This invention first conducted high-throughput in vitro screening of hundreds of plants (Example 1), using the inhibition rate of xanthine oxidase (a key enzyme in uric acid production) as an objective indicator, and quantitatively screened 16 effective plant extracts with an inhibition rate >50% (see Example 1). Figure 1 ), and its half-maximal inhibitory concentration (IC50) was determined. 50 (See Table 1). This makes it possible for core active ingredients (such as F. coarse-textured cilia, IC50) to be added. 50 The choice of concentration (as low as 1.17 mg / mL) is supported by clear experimental data, rather than based solely on experience.

[0022] (2) The compatibility ratio has been precisely optimized to maximize the synergistic effect, rather than simply piling it up. Based on the screening, this invention innovatively uses the mixing design method to optimize the ratio of the screened plant extracts (Examples 2 and 3). Multiple ratios are generated and tested through the model, and finally the predicted optimal ratio is obtained through variance analysis (Tables 3 and 5) (e.g., Formula 1: 40.00%: 22.58%: 20.00%: 8.62%: 8.80%), with a predicted inhibition rate as high as 81.07% (Formula 1) and 83.79% (Formula 2) (see Table 2, Group 23; Table 4, Group 11). This ensures that the compound is a scientifically verified "optimal solution", rather than an arbitrary combination.

[0023] (3) It has comprehensive effects, combining the triple functions of "lowering uric acid, anti-inflammation, and kidney protection," and the mechanism has been partially elucidated. The inventors verified by constructing a mouse model of hyperuricemia that the polyphenol extract of this invention can significantly inhibit the activity of xanthine oxidase (XOD) in serum and liver, significantly reduce serum uric acid (UA), creatinine, and urea nitrogen levels, and promote the excretion of related metabolites (such as uric acid) in urine. Simultaneously, the compound extract of this invention significantly reduces the levels of inflammatory factors such as IL-6 and TNF-α in mouse serum, and alleviates inflammatory infiltration in liver and kidney tissues.

[0024] (4) It provides a safer solution for hyperuricemia, making up for the side effects of existing drugs. The natural plant polyphenol extract of the present invention has shown better renal safety than allopurinol in animal experiments, avoiding the problem of "long-term use of traditional chemical drugs may cause adverse side effects such as liver and kidney damage and allergic reactions", and providing a potentially safer alternative or auxiliary option for people who need long-term uric acid management.

[0025] (5) The product quality is controllable, laying the foundation for industrialization. Because the active ingredients are clearly defined, the ratio has been quantitatively optimized, and the extraction process is simple, the quality stability and repeatability of the final product are greatly improved, which is conducive to achieving standardized production and quality control.

[0026] (6) The application prospects are clear, providing a direct basis for the development of functional foods or drugs. Based on solid in vitro screening, formulation optimization and in vivo efficacy verification data, the natural plant polyphenol composition of this invention has clear data support for the application in "the preparation of products for lowering serum uric acid, promoting uric acid excretion, inhibiting XOD activity, reducing inflammatory factors and relieving kidney inflammation", providing a strong research and development basis for its transformation into functional foods, health foods or drugs with claims of lowering uric acid, anti-inflammation and kidney protection. Attached Figure Description

[0027] Figure 1 Xanthine oxidase (XOD) inhibition rate of polyphenol extracts from different raw materials.

[0028] Figure 2 Comparison of uric acid-lowering related indicators in mice from different experimental groups.

[0029] Figure 3 Comparison of serum inflammatory factor levels in mice from different experimental groups.

[0030] Figure 4 Changes in renal function indicators in mice from different experimental groups.

[0031] Figure 5 Analysis of HE staining results of mouse kidneys in different experimental groups. Detailed Implementation

[0032] The present invention is further described below through preferred embodiments; however, the scope of the invention is not limited to these embodiments. All changes or equivalent substitutions that do not depart from the concept of the invention are included within the scope of protection of the present invention.

[0033] Example 1: Preparation and Screening of Polyphenol Extracts from Various Raw Materials

[0034] Different raw materials were successively dried in a 50 °C oven to constant weight, then pulverized and filtered through a 40-mesh sieve to obtain dry powder. The dry powder was irradiated with 8 kGy and stored at 4 °C. The dry powders of each raw material were immersed in a 70% (v / v) ethanol solution at a material-to-liquid ratio of 1:40 (m / v) and magnetically stirred at room temperature for 60 min to ensure complete extraction. Then, ultrasonic-assisted extraction was performed at 400 W for 20 min, followed by centrifugation to separate the supernatant. The residue was extracted twice more, and the supernatants were combined. The supernatants were then concentrated to a certain volume by rotary evaporation and freeze-dried to obtain a 70% ethanol extract (the extract prepared by this method was used as the test substance in Examples 1-4). The xanthine oxidase inhibition rate of different extracts was then determined. The specific steps were as follows: 0.65 mL of phosphate buffer (0.10 mol / L, pH=8.50), 0.20 mL of xanthine solution (2.00 mmol / L), and 0.05 mL of sample solution were vortexed in a 1.50 mL centrifuge tube; then 0.20 mL of xanthine oxidase solution (0.10 U / mL) was added and the mixture was reacted in a water bath at 25℃ for 30 min; after completion, 0.20 mL of HCl solution (1.00 mol / L) was added to terminate the reaction. The absorbance was measured at a wavelength of 290 nm. Each experiment was repeated three times, and the average value was taken. The xanthine oxidase inhibition rate of different medicinal materials was calculated. The formula for calculating the xanthine oxidase inhibition rate is as follows:

[0035] (1)

[0036] In the formula:

[0037] Y – Inhibition rate, %

[0038] A – Absorbance value of the enzyme reaction group;

[0039] B – Absorbance value of the blank group;

[0040] C – Absorbance value of the inhibitor group;

[0041] D – Absorbance value of the control group.

[0042] like Figure 1As shown, 16 polyphenol extracts exhibited xanthine oxidase (XOD) inhibition rates >50%, namely Ganoderma lucidum, *Trichophyton rubrum*, *Elsholtzia ciliata*, *Phyllanthus emblica*, *Perilla frutescens* leaf, lotus leaf, *Alpinia galanga*, *Eucommia ulmoides*, *Gnaphalium affine*, buckwheat, *Prunella vulgaris*, *Forsythia suspensa*, *Orthosiphon aristatus*, *Oroxylum indicum*, *Tetrapanax papyriferus*, and *Tetrapanax papyriferus*. Among them, *Trichophyton rubrum*, *Tetrapanax papyriferus*, and *Tetrapanax papyriferus* showed better inhibitory effects.

[0043] To further evaluate its inhibitory efficacy, the IC50 of 16 polyphenol extracts with inhibition rates >50% on XOD was determined. 50 Value. Ultimately determined by IC. 50 The results were used to determine the compatibility of the 16 medicinal polyphenol extracts. 50 The values ​​and fitting formulas are shown in Table 1.

[0044] Table 1. IC50 values ​​of 16 polyphenol extracts inhibiting xanthine oxidase 50 value

[0045]

[0046] Example 2 Optimization of Extract Formulation 1

[0047] Based on the mixing design optimization: According to the previous orthogonal results, the inhibitory effects of *Polyporus dauricum* and *Alpinia galanga* were found to be extremely significant. The minimum addition amount of *Polyporus dauricum* polyphenol extract was set at 30%, and the minimum addition amount of *Alpinia galanga* polyphenol extract was set at 20%. *Orthosiphon aristatus* polyphenol extract showed significant inhibitory effects, and its addition amount was set at a minimum of 20%. In addition, the minimum addition amounts of *Oroxylum indicum* polyphenol extract and *Tea vine* polyphenol extract were set at 5%. Based on this premise, 25 sets of experiments were generated according to the Mixture-Optimal mode in Design-Expert 13 to investigate the effects of mixtures of five medicinal materials (A: *Polyporus dauricum*, B: *Alpinia galanga*, C: *Oroxylum indicum*, D: *Oroxylum indicum*, E: *Tea vine*) under different ratios on the xanthine oxidase inhibition rate. The predicted results are shown in Table 2.

[0048] Table 2. Mixing design scheme and results for Formula 1

[0049]

[0050] The optimal mixing design model was established using the xanthine oxidase inhibition rate as the response value, and the results are shown in Table 3.

[0051] Table 3. Results of ANOVA for Formula 1

[0052]

[0053] Based on the model, under the constraints, the predicted ratio for maximizing the inhibition rate (Formula 1) is 40.00% for *Polyporus umbellatus* polyphenol extract, 22.58% for *Alpinia galanga* polyphenol extract, 20.00% for *Orthosiphon aristatus* polyphenol extract, 8.62% for *Oroxylum indicum* polyphenol extract, and 8.80% for *Tea vine* polyphenol extract.

[0054] Example 3 Optimization of Extract Formulation 2

[0055] Preliminary experimental results showed that *Polyporus dauricum* had a highly significant inhibitory effect, so the minimum addition amount of *Polyporus dauricum* polyphenol extract was set at 20%. The inhibitory effects of *Tetracentron sinense* polyphenol extract and *Forsythia suspensa* polyphenol extract were also significant, so their minimum addition amount was set at 15%. In addition, the minimum addition amounts of *Nelumbo nucifera* leaf polyphenol extract and *Prunella vulgaris* polyphenol extract were set at 10%. Based on these findings, 25 sets of experiments were generated using the Mixture-Optimal mode in Design-Expert 13 to investigate the effects of mixtures of five medicinal materials (A: *Polyporus dauricum*, B: *Tetracentron sinense*, C: *Forsythia suspensa*, D: *Nelumbo nucifera* leaf, E: *Prunella vulgaris*) under different ratios on the xanthine oxidase inhibition rate. The predicted results are shown in Table 4.

[0056] Table 4. Mixing design scheme and results for Formula 2

[0057]

[0058] The optimal mixing design model was established using the xanthine oxidase inhibition rate as the response value, and the results are shown in Table 5.

[0059] Table 5. Results of ANOVA for Formula 2

[0060]

[0061] Based on the model, under the constraints, the predicted ratio for maximizing the inhibition rate (Formula 2) is 27.79% for *Polyporus cirrhosa* polyphenol extract, 22.81% for *Tetracentron sinense* polyphenol extract, 22.11% for *Forsythia suspensa* polyphenol extract, 12.37% for *Lotus ternata* polyphenol extract, and 14.92% for *Prunella vulgaris* polyphenol extract.

[0062] Example 4: Animal experiments to verify product efficacy

[0063] 1. Experimental Design and Methods

[0064] 1.1 Establishment of animal models and feeding experiments

[0065] Fifty SPF-grade male Kunming mice (8 weeks old, 20±2 g) were purchased from the Hubei Provincial Center for Disease Control and Prevention. Experimental conditions: temperature 25±2 ℃, humidity 50±20%, 12-hour light-dark cycle, free access to water, and no food restrictions. After 7 days of acclimatization, the mice were randomly divided into 5 groups, as shown in Table 6. Except for the control group, each group was administered 200 mg / kg·d of potassium oxonate + hypoxanthine daily by gavage to establish a hyperuricemia model. After 7 days, one hour after administering the modeling drugs, different experimental samples were administered by gavage. The control and model groups were administered the same dose of 0.5% CMC-Na, the allopurinol group was administered 30 mg / kg·d of allopurinol, the OL group was administered Formula 1 prepared in Example 2, and the CF group was administered Formula 2 prepared in Example 3. During the experiment, the mice were weighed daily along with their feed to observe their daily weight and diet. After 30 days of continuous feeding, the mice were fasted for 12 hours. All mice were anesthetized with ether, and blood was collected from their eyeballs. They were then euthanized, dissected, and organ, tissue, and gut microbiota samples were collected. These samples were fixed in 4% paraformaldehyde or cryopreserved at -20 °C until use. Fresh blood samples were allowed to stand at room temperature for 30 min, then centrifuged at 3000 × g for 10 min at 4 °C. The supernatant was collected to obtain serum, which was aliquoted and stored at -20 °C for later use.

[0066] Table 6. Modeling and experimental protocols for different groups of mice

[0067]

[0068] 1.2 Determination of biochemical index content

[0069] Serum uric acid (UA), blood urea nitrogen (BUN), and creatinine (CRE) levels, serum and liver xanthine oxidase activity, and serum inflammatory factors IL-6 and TNF-α levels were detected using biochemical reagent kits from Nanjing Jiancheng Bioengineering Institute.

[0070] 1.3 Observation of mouse kidney tissue sections

[0071] After being removed, the kidney tissue was immediately fixed by soaking in 4% paraformaldehyde for 24 h, then embedded in paraffin, and 5 μm thick sections were taken, stained with hematoxylin and eosin (HE). Finally, the pathological condition of the kidney was observed under a microscope at 10× magnification.

[0072] 2. Analysis of Experimental Results

[0073] 2.1 Comparison of uric acid-lowering related indicators in mice from different experimental groups

[0074] Figure 2 The effects of different experimental groups on uric acid-lowering indicators in mice were shown. Figure 2 A and Figure 2Results B showed that, compared with the normal control group (NC), the model control group (MC) had significantly higher serum uric acid (UA) levels and significantly lower urinary UA levels (P<0.05), indicating that the hyperuricemia (HUA) model was successfully established. Among the treatment groups, the serum UA level in the positive control group (AP) was significantly lower than that in the MC group (P<0.01), and that of formula 2 (CF) was significantly lower (P<0.05), while formula 1 (OL) showed a decrease, but this was not statistically significant. Regarding urinary UA, both OL and CF significantly increased urinary UA levels (P<0.01). In summary, CF has a clear dual effect of reducing serum UA and promoting uric acid excretion; although OL did not significantly affect serum UA, it could exert a uric acid-lowering effect by promoting uric acid excretion.

[0075] Xanthine oxidase (XOD) is a key rate-limiting enzyme in the purine metabolism pathway, and its activity directly affects uric acid production, playing an important role in the development and progression of hyperuricemia. Figure 2 As shown in Figure C, compared with the NC group, the serum XOD activity in the MC group was significantly increased (P<0.05), indicating enhanced purine catabolism and accelerated uric acid synthesis after modeling. Among the intervention groups, the serum XOD activity in the AP group was significantly lower than that in the MC group (P<0.01), showing a strong XOD inhibitory effect; the CF group showed a significant inhibitory effect (P<0.05), while the LC group showed a decrease, but not a significant one. Changes in liver XOD activity are shown in Figure C. Figure 2 As shown in D, liver XOD activity in the MC group was significantly higher than that in the NC group (P<0.05), further confirming that the endogenous uric acid synthesis pathway was activated in the model group. Liver XOD activity in the AP, OL, and XF groups all showed a decreasing trend, but none of them reached statistical significance compared with the MC group.

[0076] 2.2 Comparison of serum inflammatory factor levels in mice from different experimental groups

[0077] TNF-α and IL-6 are important pro-inflammatory factors associated with hyperuricemia. Elevated levels of these factors can reflect a systemic inflammatory state in the body and play a key role in tissue damage, metabolic disorders, and related complications caused by hyperuricemia. Figure 3 As shown in Figure A, serum TNF-α levels in the MC group were also significantly higher than those in the NC group (P < 0.01), further indicating that hyperuricemia can induce systemic inflammation. After intervention, TNF-α levels in the CF group decreased significantly (P < 0.01), approaching the levels in the NC group, showing a strong anti-inflammatory effect; although the AP and OL groups showed a decreasing trend, they did not reach significant levels, suggesting that their inhibitory ability on TNF-α was limited. Figure 3As shown in Figure B, serum IL-6 levels in the MC group were significantly higher than those in the NC group (P < 0.01), indicating a significant inflammatory activation state in the hyperuricemia model animals. After intervention, IL-6 levels in the OL group decreased significantly (P < 0.05), indicating that it has a certain effect in alleviating hyperuricemia-related inflammation.

[0078] 2.3 Changes in renal function indicators in mice from different experimental groups

[0079] Serum BUN and CRE levels are important indicators for evaluating renal function. Changes in serum urea nitrogen (BUN) and creatinine (CRE) levels are as follows: Figure 4 A and Figure 4 As shown in Figure B, compared with the NC group, the MC group showed significantly higher levels of BUN and CRE (P<0.05), indicating renal impairment in the model group. Notably, although the AP group exhibited excellent uric acid-lowering effects, its BUN and CRE levels were further elevated (P<0.05), significantly higher than other groups, suggesting that AP may exacerbate the burden on the kidneys. In contrast, the BUN and CRE levels in the OL and CF groups were lower than those in the MC and AP groups, and approached the levels of the NC group, indicating that both products effectively lowered uric acid without causing significant renal impairment, demonstrating better safety.

[0080] 2.4 Analysis of HE staining results of kidneys in mice from different experimental groups

[0081] like Figure 5 As shown, HE staining of the kidneys of mice in different treatment groups revealed significant differences. Compared with the NC group, the MC group showed significant interstitial inflammatory cell infiltration in its kidney tissue, suggesting that hyperuricemia caused inflammatory damage to the kidneys. The AP group showed a large accumulation of inflammatory cells in its kidney sections, further indicating a significant inflammatory response in this group. In contrast, the OL and CF groups showed significantly reduced inflammatory cell infiltration in their kidney tissues, suggesting that the experimental treatments effectively alleviated kidney inflammation caused by hyperuricemia. This histological result, coupled with the aforementioned decrease in serum pro-inflammatory factor levels, further validates the protective effect of the experimental samples against kidney inflammation.

[0082] The results of this invention show that the hyperuricemia model mice exhibited elevated serum uric acid (UA), increased renal function indicators (BUN, CRE), elevated serum pro-inflammatory factors (IL-6, TNF-α), and significant renal inflammatory cell infiltration, indicating successful model establishment. After treatment as described in this invention, the AP group showed a significant decrease in serum UA and inhibition of serum XOD activity, but renal functional burden increased; the OL and CF groups not only reduced serum UA levels but also alleviated the elevation of serum pro-inflammatory factors and renal inflammatory infiltration, demonstrating good safety and renal protective effects. This invention can achieve a dual effect of lowering uric acid and alleviating hyperuricemia-related inflammation, and has potential application value.

Claims

1. A natural polyphenol composition with uric acid-lowering effect, characterized in that, Its active ingredients consist of polyphenol extracts from *Fomitopsis coccinea* and plant polyphenol extracts. The plant polyphenol extracts are one or more of the following: Alpinia galanga, Orchidonia suffruticosa, Oroxylum indicum, vine tea, Forsythia suspensa, large-leaf green tea, lotus leaf, Prunella vulgaris, Ganoderma lucidum, Elsholtzia ciliata, Phyllanthus emblica, Perilla frutescens leaf, Eucommia ulmoides, Gnaphalium affine, and buckwheat.

2. The natural polyphenol composition according to claim 1, characterized in that, The composition of the active ingredient is selected from any one of the following: (1) a polyphenol extract containing *Polyporus cirrhosa*, *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum* and *Tea japonica*; (2) a polyphenol extract containing *Polyporus cirrhosa*, *Tea japonica*, *Forsythia suspensa*, lotus leaf and *Prunella vulgaris*.

3. The natural polyphenol composition according to claim 2, characterized in that, The active ingredients are composed of polyphenol extracts from *Polyporus umbellatus*, *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum*, and *Tea japonica* in the following mass ratio: Polyphenol extracts of *Polyporus cirrhosa*: *Alpinia galanga*: *Orthosiphon aristatus*: *Oroxylum indicum*: *Oroxylum indicum*: *Oroxylum indicum* = 33~40: 20~31: 17~30: 5~10: 5~10.

4. The natural polyphenol composition according to claim 3, characterized in that, The active ingredients are composed of polyphenol extracts from *Polyporus umbellatus*, *Alpinia galanga*, *Orthosiphon aristatus*, *Oroxylum indicum*, and *Tea japonica* in the following mass ratio: Polyphenol extracts of *Polyporus cirrhosa*: Polyphenol extracts of Alpinia galanga: Polyphenol extracts of Orchidonia spp.: Polyphenol extracts of Oroxylum indicum: Polyphenol extracts of Chaenomeles speciosa = 35~40: 20~25: 17~21: 7~10: 7~10.

5. The natural polyphenol composition according to claim 2, characterized in that, The active ingredient is composed of polyphenol extracts from *Polyporus cirrhosa*, large-leaf green tea, *Forsythia suspensa*, lotus leaf, and *Prunella vulgaris* in the following mass ratio: Polyphenol extracts of *Polyporus cirrhosa*: polyphenol extracts of *Tetrapanax papyriferus*: polyphenol extracts of *Forsythia suspensa*: polyphenol extracts of lotus leaf: polyphenol extracts of *Prunella vulgaris* = 20~30: 15~25: 15~25: 10~15: 10~15.

6. The natural polyphenol composition according to claim 5, characterized in that, The active ingredient is composed of polyphenol extracts from *Polyporus cirrhosa*, large-leaf green tea, *Forsythia suspensa*, lotus leaf, and *Prunella vulgaris* in the following mass ratio: Polyphenol extracts of *Polyporus cirrhosa*: polyphenol extracts of *Tetrapanax papyriferus*: polyphenol extracts of *Forsythia suspensa*: polyphenol extracts of lotus leaf: polyphenol extracts of *Prunella vulgaris* = 26~30: 20~24: 20~24: 11~14: 12~15.

7. A method for preparing the natural polyphenol composition according to any one of claims 1-6, characterized in that, The method includes the following steps: (1) Each raw material is dried and pulverized to obtain raw material dry powder, and then subjected to γ-ray irradiation treatment with an irradiation dose of 6~10 kGy; (2) Extract each raw material dry powder with ethanol solution with a volume fraction of 70%~95% respectively to obtain the extract of each raw material; (3) The extracts of each raw material are concentrated and dried to obtain polyphenol extracts of each raw material; (4) The various polyphenol extracts obtained in step (3) are compounded in a predetermined ratio to obtain the composition.

8. The method according to claim 7, characterized in that, In step (2), the extraction step is as follows: first, soak each raw material powder in an ethanol solution, stir at room temperature for 30 to 90 minutes, and then perform ultrasonic-assisted extraction with an ultrasonic power of 300 to 500 W and an extraction time of 15 to 25 minutes.

9. The use of a natural polyphenol composition according to any one of claims 1-6 in the preparation of products for lowering serum uric acid, promoting uric acid excretion and / or inhibiting xanthine oxidase activity.

10. The use of a natural polyphenol composition as described in any one of claims 1-6 in the preparation of a product for relieving kidney inflammation or kidney dysfunction caused by hyperuricemia.

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