Application of eryngium foetidum extract in preparation of medicine for preventing, relieving and / or treating hyperuricemia

Abstract

The invention provides an application of a eryngium foetidum extract in preparation of a medicine for preventing, relieving and / or treating hyperuricemia, and belongs to the technical field of application of natural product extracts. It is found for the first time that the eryngium foetidum extract can inhibit xanthine oxidase, the xanthine oxidase inhibition rate can reach 94.16% when the eryngium foetidum extract is 500 [mu] g / mL, and the eryngium foetidum extract can significantly reduce the uric acid value of hyperuricemia patients and improve liver and kidney injuries caused by hyperuricemia. The invention also provides an application of the eryngium foetidum extract as an active ingredient in preparation of a medicine, and the medicine can effectively prevent, relieve and / or treat hyperuricemia, is safe and free of side effects, and has a good application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of application of natural product extracts, and particularly relates to application of a spiny coriander extract in preparing a medicine for preventing, alleviating and / or treating hyperuricemia. Background Art

[0002] Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder, which can be divided into primary and secondary types. Primary hyperuricemia is mainly caused by reduced uric acid excretion or increased production, while secondary hyperuricemia is caused by certain systemic diseases or taking certain drugs to inhibit uric acid excretion. In addition, eating too much food with high purine content may also induce the onset of hyperuricemia. Long-term hyperuricemia can cause renal endothelial dysfunction, activate the renin-angiotensin system (RAS), inflammatory response, oxidative stress, etc. Clinically, its main features are acute uric acid nephropathy, chronic uric acid nephropathy and uric acid kidney stones. Accompanying symptoms are often obesity, type 2 diabetes, dyslipidemia, hypertension and arteriosclerosis.

[0003] Depending on the way hyperuricemia is formed, it is divided into excessive uric acid production type, poor uric acid excretion type and mixed type. From the perspective of uric acid production, xanthine oxidase (Xanthine Oxidase, Xanthine oxidase is the key enzyme in the reaction of purine metabolism to produce uric acid. It is mainly present in the liver and can catalyze xanthine and hypoxanthine to produce uric acid and oxygen anions. When xanthine oxidase increases abnormally, the uric acid content will surge, causing hyperuricemia. In view of the pathogenesis of hyperuricemia, the drugs that are currently widely used in the clinic to treat hyperuricemia mainly include two categories: drugs that inhibit uric acid production and drugs that promote uric acid excretion. Drugs that inhibit uric acid production are mainly xanthine oxidase inhibitors. The xanthine oxidase inhibitors currently used in the clinic include allopurinol and the new xanthine oxidase inhibitor febuxostat (also known as febuxostat). Allopurinol can reduce the activity of xanthine oxidase by 90%, effectively preventing the production of uric acid. However, the most serious side effect of allopurinol is severe drug rash witheosinophilia and systemic At the same time, studies have shown that Febuxostat increases cardiovascular mortality in patients with gout. Therefore, it is necessary to provide drugs that can safely and effectively lower uric acid levels. Summary of the invention

[0004] In order to solve the problems existing in the prior art, the purpose of the present invention is to provide the use of a spiny coriander extract in the preparation of a drug for preventing, alleviating and / or treating hyperuricemia, wherein the spiny coriander extract can significantly inhibit the activity of xanthine oxidase, reduce the uric acid level of hyperuricemia patients, and improve liver and kidney damage caused by hyperuricemia.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The invention provides application of a spiny coriander extract in preparing a medicine for preventing, alleviating and / or treating hyperuricemia.

[0007] Preferably, the spiny coriander extract inhibits xanthine oxidase.

[0008] Preferably, the spiny coriander extract reduces the uric acid level of patients with hyperuricemia and improves liver and kidney damage caused by hyperuricemia.

[0009] Preferably, the preparation method of the spiny coriander extract comprises: ultrasonic extraction and reflux extraction.

[0010] Preferably, the ultrasonic extraction comprises the following steps: mixing the spiny coriander powder and the ethanol solution, performing ultrasonic extraction, filtering the extract to obtain a filtrate; concentrating the filtrate by rotary evaporation, and drying under reduced pressure to a water content of ≤10% to obtain a spiny coriander extract.

[0011] Preferably, the reflux extraction comprises the following steps: mixing the spiny coriander powder with an ethanol solution, performing reflux extraction, filtering the extract to obtain a filtrate; concentrating the filtrate by rotary evaporation, and drying under reduced pressure to a water content of ≤10% to obtain a spiny coriander extract.

[0012] Preferably, the method for preparing the spiny coriander extract further comprises: purifying the spiny coriander extract, and the purification method comprises macroporous resin adsorption or organic solvent extraction.

[0013] Preferably, the macroporous resin adsorption comprises the following steps: adding ethanol solution to dissolve the spiny coriander extract, then adding macroporous resin for stirring and adsorption, loading the macroporous resin onto a column after adsorption, gradient eluting with ethanol solution, collecting the eluate of 30% to 50% ethanol solution, rotary evaporating and drying to obtain the purified spiny coriander extract.

[0014] Preferably, the organic solvent extraction comprises the following steps: dissolving the spiny coriander extract in an ethanol solution, extracting with dichloromethane and chloroform in sequence, discarding the extract, extracting with ethyl acetate, collecting the ethyl acetate extract, rotary evaporating, and drying to obtain a purified spiny coriander extract.

[0015] Preferably, the active ingredient of the drug is Coriander leaf extract.

[0016] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0017] The present invention firstly finds that the spiny coriander extract can effectively inhibit xanthine oxidase, and when the spiny coriander extract is 500 μg / mL, the inhibition rate of xanthine oxidase can reach 94.16%. The present invention finds that the spiny coriander extract can significantly reduce the uric acid level of hyperuricemia patients, improve liver and kidney damage caused by hyperuricemia, is safe and has no side effects, and helps to solve the current situation that Western medicine has high liver and kidney toxicity and poor patient compliance. DETAILED DESCRIPTION

[0018] Eryngium foetidum L., also known as eryngium and cilantro, is a plant of the genus Eryngium in the family Apiaceae. The present invention provides the use of an extract of eryngium foetidum in the preparation of a drug for preventing, alleviating and / or treating hyperuricemia. The eryngium foetidum extract of the present invention can inhibit xanthine oxidase. When the eryngium foetidum extract is 500 μg / mL, the inhibition rate of xanthine oxidase can reach 94.16%. The eryngium foetidum extract can significantly reduce the uric acid level of hyperuricemia patients and improve liver and kidney damage caused by hyperuricemia. And because eryngium foetidum is a traditional edible spice, the raw materials for the preparation of the eryngium foetidum extract are easily available and safe without side effects, and can safely and effectively reduce uric acid levels, and has more application prospects.

[0019] The spiny coriander extract of the present invention is preferably extracted from the above-ground part of spiny coriander (all parts of spiny coriander except the underground root system) as raw material. The above-ground part of spiny coriander is preferably fresh leaves of the above-ground part of spiny coriander in the vigorous growth period.

[0020] The preparation method of the spiny coriander extract of the invention comprises: ultrasonic extraction and reflux extraction.

[0021] The spiny coriander powder of the present invention is preferably obtained by grinding dried spiny coriander and passing through a 50-80 mesh sieve, more preferably through a 60 mesh sieve. The present invention does not limit the specific grinding method.

[0022] Preferably, the ultrasonic extraction comprises the following steps: mixing the spiny coriander powder and the ethanol solution, performing ultrasonic extraction, filtering the extract to obtain a filtrate; the filtrate is concentrated by rotary evaporation and dried under reduced pressure to a water content of ≤10% to obtain a spiny coriander extract. In the present invention, an ethanol solution is added to the spiny coriander powder for ultrasonic extraction, and the ethanol solution is a 30% to 90% ethanol solution, preferably a 50 to 60% ethanol solution; the amount of the ethanol solution added is 8 to 12 times the mass of the spiny coriander powder, preferably 10 times. The power of the ultrasonic extraction of the present invention is 450 to 500W, the frequency is 30 to 50kHz, the temperature is 40 to 60°C, and the time is 20 to 40min; the power is preferably 480W; the frequency is preferably 40kHz; the temperature is preferably 50°C; the time is preferably 30min. The number of ultrasonic extractions of the present invention is 2 times, and the 2 extracts are combined for filtration. As an optional embodiment, the present invention adds ethanol solution to the filter residue after the first ultrasonic extraction for a second ultrasonic extraction, and combines the filtrate obtained from the two extractions as an extract. The parameter setting of the second ultrasonic extraction of the present invention is the same as that of the first one.

[0023] Preferably, the reflux extraction comprises the following steps: mixing the spiny coriander powder with an ethanol solution, performing reflux extraction, filtering the reflux extract to obtain a filtrate; concentrating the filtrate by rotary evaporation, and drying under reduced pressure to a water content of ≤10% to obtain a spiny coriander extract. In the present invention, an ethanol solution is added to the spiny coriander powder for reflux extraction (boiling reflux), and the ethanol solution is a 30% to 90% ethanol solution, preferably a 50 to 60% ethanol solution; the amount of the ethanol solution added is 8 to 12 times the mass of the spiny coriander powder, preferably 10 times. The time for the reflux extraction of the present invention is 50 to 70 minutes, preferably 60 minutes. The number of reflux extractions of the present invention is 2 times, and the 2 extracts are combined for filtration. As an optional embodiment, the present invention adds ethanol solution to the filter residue after the first reflux extraction for a second reflux extraction, and the filtrate obtained by combining the two extractions is the extract. The amount of ethanol solution added in the second reflux extraction of the present invention is half of the amount of ethanol solution added in the first reflux extraction, and the reflux time is the same as the first time.

[0024] The present invention filters the extract obtained by ultrasonic extraction or reflux extraction, and the vacuum degree of the filtration is preferably 0.1MPa. The filtrate obtained by filtration is subjected to rotary evaporation, and the temperature of the rotary evaporation is 40 to 60°C, preferably 50°C; the speed of the rotary evaporation is 20 to 30r / min. The rotary evaporation of the present invention is stopped when the wall hanging phenomenon occurs. The present invention pours the solution after rotary evaporation into an evaporating dish for reduced pressure drying, and the reduced pressure drying temperature is 55 to 65°C, preferably 60°C, and the vacuum degree is 0.1MPa, and the water content is ≤10% to obtain a spiny coriander extract.

[0025] The present invention preferably purifies the spiny coriander extract obtained by ultrasonic extraction or reflux extraction, and the purification method includes macroporous resin adsorption or organic solvent extraction.

[0026] Preferably, the macroporous resin adsorption comprises the following steps: adding ethanol solution to dissolve the spiny coriander extract, then adding macroporous resin for stirring and adsorption, loading the macroporous resin after adsorption, using ethanol solution gradient elution, collecting the eluate of 30% to 50% ethanol solution, rotary evaporation and drying to obtain a purified extract. The ethanol solution of the present invention is a 30% to 90% ethanol solution, preferably a 50% to 60% ethanol solution; the amount of the ethanol solution added is 8 to 12 times the mass of the spiny coriander powder, preferably 10 times. The macroporous resin is preferably a D101 type macroporous resin, and the macroporous resin is pretreated before use; the stirring adsorption speed is 8 to 12 r / min, and the time is 20 to 40 min. The elution flow rate is 3 to 7 mL / min, and the concentration of the gradient elution ethanol solution is 0%, 30%, 40%, and 50%, and each gradient concentration uses 8 to 12 times (volume) of ethanol solution for elution. The present invention collects the eluates of the three parts of ethanol solution of 30%, 40% and 50%, and performs rotary evaporation after the collection. The rotary evaporation of the present invention is preferably 20-30r / min, and the rotary evaporation is stopped when the wall hanging phenomenon occurs under the condition of temperature of 40-60°C. The present invention pours the solution after rotary evaporation into an evaporating dish for reduced pressure drying, the reduced pressure drying temperature is 55-65°C, preferably 60°C, the vacuum degree is 0.1MPa, and the water content is ≤10%, so as to obtain the purified spiny coriander extract.

[0027] Preferably, the organic solvent extraction comprises the following steps: adding ethanol solution to dissolve the spiny coriander extract, extracting with dichloromethane and chloroform in sequence, discarding the extract, extracting with ethyl acetate, collecting the ethyl acetate extract, rotary evaporation, and drying to obtain a purified extract. The ethanol solution of the present invention is a 30% to 90% ethanol solution, preferably a 50 to 60% ethanol solution; the amount of the ethanol solution added is 16 to 24 times the mass of the spiny coriander powder, preferably 20 times. The amount of dichloromethane used in the present invention is 8 to 12 times the amount (volume) of the spiny coriander crude extract solution, preferably 10 times the amount. After the extraction of the present invention, the dichloromethane phase is discarded and the next step of extraction is carried out. The amount of chloroform used in the present invention is 8 to 12 times the amount (volume) of the extract to be extracted, preferably 10 times the amount. After the extraction of the present invention, the chloroform phase is discarded and the next step of extraction is carried out. The amount of ethyl acetate used in the present invention is 8 to 12 times the amount (volume) of the liquid to be extracted, preferably 10 times. After the extraction, the ethyl acetate phase is collected, and the purified extract is obtained by rotary evaporation and drying. The rotary evaporation speed of the present invention is preferably 20 to 30 r / min, and the temperature is preferably 40 to 60° C. The rotary evaporation of the present invention is stopped when the wall hanging phenomenon occurs. The solution after rotary evaporation is poured into an evaporating dish for reduced pressure drying, and the reduced pressure drying temperature is 55 to 65° C., preferably 60° C., and the vacuum degree is 0.1 MPa, and the water content is ≤10% to obtain the purified spiny coriander extract.

[0028] The active ingredient of the drug for preventing, alleviating and / or treating hyperuricemia of the present invention is coriander extract. The present invention can use coriander extract as the only active ingredient, or coriander extract can be used in combination with other active ingredients. In the drug of the present invention, the content of coriander extract is preferably 50-99wt%. The drug of the present invention also includes a pharmaceutically acceptable carrier, that is, a pharmaceutically acceptable pharmaceutical excipient is added to the drug for preventing, alleviating and / or treating hyperuricemia to ensure the convenient preparation and clinical application of the prepared pharmaceutical preparation. Further preferably, the pharmaceutical excipient of the present invention includes but is not limited to at least one of a diluent, a wetting agent, an adhesive, a lubricant, a colorant, and a coating agent. The dosage form of the drug for preventing, alleviating and / or treating hyperuricemia of the present invention is selected from at least one of tablets, capsules, granules, pills, injections, suspensions, dispersants, and syrups. However, the dosage form of the drug for preventing, alleviating and / or treating hyperuricemia described in the present invention is not limited thereto, and other achievable dosage forms are within the protection scope of the present invention.

[0029] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] In the specific embodiment of the present invention, the spiny coriander used is collected from wild species in Xishuangbanna area, and fresh leaves of the above-ground part of the spiny coriander in the vigorous growth period are selected for the experiment.

[0031] In the following embodiments, unless otherwise specified, all of them are conventional methods.

[0032] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0033] Example 1

[0034] 1. Preparation of Coriander Extract:

[0035] Take fresh leaves of the aerial part of spiny coriander, cut them into sections and dry them naturally until the moisture content is ≤13%. The dried spiny coriander is crushed and passed through a 60-mesh sieve to obtain spiny coriander powder, which is used for the subsequent preparation of the extract:

[0036] Method 1: Ultrasonic extraction + column chromatography enrichment

[0037] Add 10 times the mass of ethanol solution (50% ethanol solution) to the prickly coriander powder and perform the first ultrasonic extraction. Ultrasonic extraction was performed for 30 minutes at an ultrasonic power of 480W, 40kHz and 50°C. The extract was filtered, and the first extraction filtrate and filter residue were collected. 10 times the mass of ethanol solution (50% ethanol solution) was added to the filter residue again, and the second ultrasonic extraction was performed. Ultrasonic extraction was performed for 30 minutes at an ultrasonic power of 480W, 40kHz and 50°C, and the second extraction filtrate was collected. The two extraction filtrates were combined and filtered (vacuum degree was 0.1MPa), and the filtrate obtained by filtration was subjected to rotary evaporation (speed 30r / min, temperature 50°C), and the evaporation was stopped when the wall hanging phenomenon appeared (30min). The solution after rotary evaporation was poured into an evaporating dish, and vacuum dried at 60°C and 0.1MPa to a water content of 9%, thereby obtaining a crude prickly coriander extract.

[0038] The crude extract of cilantro is dissolved with 10 times the mass of ethanol (50% ethanol solution), and adsorbed with 10 times the mass of D101 macroporous resin in a beaker at a stirring speed of 10r / min for 30min. After adsorption, the macroporous resin is loaded on the column, and gradient elution is performed at a flow rate of 5mL / min: first eluted with 10 times the amount of pure water, then eluted with 10 times the amount of 10% ethanol solution, and then eluted with 30%, 40%, and 50% ethanol solutions respectively, and the eluents of 30%, 40%, and 50% ethanol solutions are collected, and concentrated by rotary evaporation (speed 30r / min, temperature 50°C), and stopped when wall hanging phenomenon appears (30min). The solution after rotary evaporation is poured into an evaporating dish, and vacuum dried at 60°C and 0.1MPa to a water content of 10%, thereby obtaining a purified cilantro extract.

[0039] Method 2: Ultrasonic extraction + extraction enrichment

[0040] Add 8 times the mass of ethanol solution (60% ethanol solution) to the prickly coriander powder and perform the first ultrasonic extraction. Ultrasonic extraction was performed for 20 minutes at an ultrasonic power of 500W, 30kHz, and 60°C. The extract was filtered, and the first extraction filtrate and filter residue were collected. 8 times the mass of ethanol solution (60% ethanol solution) was added to the filter residue again, and the second ultrasonic extraction was performed. Ultrasonic extraction was performed for 20 minutes at an ultrasonic power of 00W, 30kHz, and 60°C, and the second extraction filtrate was collected. The two extraction filtrates were combined and filtered (vacuum degree was 0.1MPa), and the filtrate obtained by filtration was subjected to rotary evaporation (speed 20r / min, temperature 55°C), and the evaporation was stopped when the wall hanging phenomenon appeared (29min). The solution after rotary evaporation was poured into an evaporating dish, and vacuum dried at 60°C and 0.1MPa to a water content of 9%, thereby obtaining a crude extract of prickly coriander.

[0041] The crude extract of cilantro is dissolved with 20 times of water, extracted with 10 times of dichloromethane and chloroform in turn, and the extract is discarded. Then, 10 times of ethyl acetate is used for extraction, and the ethyl acetate extract is collected and concentrated by rotary evaporation (speed 30r / min, temperature 50°C), and the solution is stopped when wall hanging phenomenon appears (30min). The rotary evaporated solution is poured into an evaporating dish, and vacuum dried under the conditions of 60°C and 0.1MPa to a water content of ≤10%, thereby obtaining a purified cilantro extract.

[0042] Method 3: Reflux Extraction + Column Chromatography Enrichment

[0043] Add 10 times the mass of ethanol solution (50% ethanol solution) to the spiny coriander powder and boil and reflux for extraction for 1 hour, then filter. Add 5 times the mass of ethanol solution (50% ethanol solution) to the medicinal residue and boil and reflux for extraction for 1 hour, filter, combine the filtrate and filter (vacuum degree is 0.1MPa), and perform rotary evaporation (speed 25r / min, temperature 40°C) on the filtrate obtained by filtration, and stop when the wall hanging phenomenon appears (31min). Pour the solution after rotary evaporation into an evaporating dish, vacuum dry at 55°C and 0.1MPa to a water content of 9%, and obtain a crude spiny coriander extract.

[0044] The crude extract of cilantro is dissolved with 10 times the mass of ethanol (50% ethanol solution), and adsorbed with 10 times the mass of D101 macroporous resin in a beaker at a stirring speed of 10r / min for 30min. After adsorption, the macroporous resin is loaded on the column, and gradient elution is performed at a flow rate of 5mL / min: first eluted with 10 times the amount of pure water, then eluted with 10 times the amount of 10% ethanol solution, and then eluted with 30%, 40%, and 50% ethanol solutions respectively, and the eluents of 30%, 40%, and 50% ethanol solutions are collected, and concentrated by rotary evaporation (speed 30r / min, temperature 50°C), and stopped when wall hanging phenomenon appears (30min). The solution after rotary evaporation is poured into an evaporating dish, and vacuum dried at 60°C and 0.1MPa to a water content of 10%, thereby obtaining a purified cilantro extract.

[0045] Method 4: Reflux Extraction and Enrichment

[0046] Add 12 times the mass of ethanol solution (50% ethanol solution) to the spiny coriander powder, boil and reflux extract for 65 minutes, and filter. Add 6 times the mass of ethanol solution (50% ethanol solution) to the medicinal residue, boil and reflux extract for 65 minutes, filter, combine the filtrate and filter (vacuum degree is 0.1MPa), and perform rotary evaporation (speed 30r / min, temperature 50°C) on the filtrate obtained by filtration, and stop when the wall hanging phenomenon appears (30min). Pour the solution after rotary evaporation into an evaporating dish, vacuum dry at 60°C and 0.1MPa to a water content of 9%, and obtain a crude spiny coriander extract.

[0047] The crude extract of cilantro is dissolved with 20 times of water, extracted with 10 times of dichloromethane and chloroform respectively, and the extract is discarded. Then, 10 times of ethyl acetate is used for extraction, and the ethyl acetate extract is collected, and concentrated by rotary evaporation (speed 30r / min, temperature 50°C), and the solution is stopped when wall hanging phenomenon appears (30min). The rotary evaporated solution is poured into an evaporating dish, and vacuum dried under the conditions of 60°C and 0.1MPa to a water content of ≤10%, thereby obtaining a purified cilantro extract.

[0048] 2. Efficacy verification of Coriander extract

[0049] (1) Xanthine oxidase inhibition assay: Using xanthine as substrate, the xanthine oxidase inhibition activity was detected by an ELISA instrument.

[0050] The reaction settings are shown in Table 1: blank group, enzyme reaction group, drug administration group, and control group, and the total volume of each group is 250 μL. The drug administration groups were given the spiny coriander extracts obtained by method one, method two, method three, and method four, respectively.

[0051] Table 1 Dosage and grouping

[0052]

[0053] Blank group: 50 μL water, 50 μL phosphate buffer and 50 μL xanthine (3 mmol / L) were incubated for 15 min, then 50 μL water was added and incubated at 37°C for 15 min before adding 50 μL HCL solution (1 mol / L) to terminate the reaction.

[0054] Enzyme reaction group: 50 μL phosphate buffer, 50 μL water and 50 μL xanthine (3 mmol / L) were incubated for 15 min, then 50 μL xanthine oxidase was added (xanthine oxidase needs to be pre-incubated at 37°C for 30 min to stabilize the enzyme activity, and the enzyme activity concentration is 0.4 U / mL) and mixed evenly. After 15 min at 37°C, 50 μL HCL solution (1 mol / L) was added to terminate the reaction.

[0055] Administration group: 50 μL of 50% ethanol solution of the extract (500 μg / mL, extracts from method one, method two, method three, and method four, respectively), 50 μL of phosphate buffer and 50 μL of xanthine (3 mmol / L) were incubated for 15 min, and then 50 μL of xanthine oxidase (xanthine oxidase needs to be pre-incubated at 37°C for 30 min to stabilize the enzyme activity, and the enzyme activity concentration is 0.4 U / mL) was added and mixed evenly. After 15 min at 37°C, 50 μL of HCL solution (1 mol / L) was added to terminate the reaction.

[0056] Control group: 50 μL of 50% ethanol solution of the extract (500 μg / mL), 50 μL of phosphate buffer and 50 μL of xanthine (3 mmol / L) were incubated for 15 min, then 50 μL of water was added and incubated at 37°C for 15 min before adding 50 μL of HCL solution (1 mol / L) to terminate the reaction.

[0057] The absorbance of each group was measured at 294 nm, and the inhibition rate of the spiny coriander extract on xanthine oxidase was calculated. The calculation formula was: All determinations were repeated three times. The results showed that when the extract of Coriander leaf was 500 μg / mL, the xanthine oxidase inhibition rate of the extract of method 1 was 94.16±4.12%, the xanthine oxidase inhibition rate of the extract of method 2 was 90.24±3.58%, the xanthine oxidase inhibition rate of the extract of method 3 was 87.63±3.59%, and the xanthine oxidase inhibition rate of the extract of method 4 was 85.44±3.63%, indicating that the Coriander leaf extracts obtained by the four extraction methods can inhibit the activity of xanthine oxidase, proving that the Coriander leaf extract can effectively inhibit the activity of xanthine oxidase.

[0058] (2) Animal experiments:

[0059] Modeling and drug administration: 48 SPF male KM mice were randomly divided into 6 groups after the feeding adaptation period: blank group (CON), model group (MOD), positive control group (allopurinol group), method 1 extract, method 2 extract, method 3 extract, and method 4 extract. Each group had free diet, and the environmental temperature and light exposure time were controlled according to routine procedures without special requirements.

[0060] The experimental period was 2 weeks. Except for the blank group, the other 5 groups were intraperitoneally injected with potassium oxonate (300 mg / kg·d) and hypoxanthine (500 mg / kg·d) every day to establish the model. One hour later, the positive control group was given allopurinol 10 mg / kg·d (allopurinol was dissolved in 0.5% sodium carboxymethyl cellulose solution), method 1, method 2, method 3, and method 4 were given 300 mg / kg·d of spiny coriander extract (the extract was dissolved in 0.5% sodium carboxymethyl cellulose solution), and the model group was gavaged with the corresponding volume of 0.5% sodium carboxymethyl cellulose solution. During the entire experimental process, the blank group was gavaged with the corresponding volume of 0.5% sodium carboxymethyl cellulose solution every day.

[0061] After fasting for 12 hours from the night before to the day of execution, the last oral gavage was performed according to the above dose, and water was not allowed. Blood was collected from the eyeballs 1 hour after oral gavage, and then the animals were killed by dislocation of the neck. The whole organs were weighed and the organ coefficients were calculated. The kit was used to determine uric acid (UA), creatinine (CRE) and urea nitrogen (BUN) in the serum. The results are shown in Tables 2 and 3.

[0062] Table 2 Organ index of each group

[0063] Group Dosage (mg / kg) Liver coefficient (%) Kidney coefficient (%) CON - 5.11±0.24 1.37±0.06 MOD - 5.97±0.17## 1.98±0.08## Allopurinol group 10 5.46±0.29 1.49±0.19 Method 1: Coriander extract 300 5.32±0.13* 1.41±0.11* Method 2: Coriander extract 300 5.38±0.21* 1.45±0.08* Methods Cilantro trispinata extract 300 5.4±0.28* 1.5±0.14* Method 4 Coriander extract 300 5.41±0.19* 1.52±0.07*

[0064] Table 3 Organ index of each group

[0065] Grouping Serum uric acid (μmol / L) Creatinine (μmol / L) Urea nitrogen (mmol / L) CON 112.4±4.81 19.62±2.52 7.1±0.87 MOD 197.6±12.08## 29.63±2.48# 16.62±3.01## Allopurinol group 141±17.83* 26.34±4.2 13.52±1.12* Method 1: Coriander extract 136.6±6.86** 18.28±3.63* 9.76±0.96*** Method 2: Coriander extract 131±4.62*** 20.93±3.47* 10.58±1.32** Methods Cilantro trispinata extract 150±4.94* 22.62±2.16* 11.72±1.27* Method 4 Coriander extract 154±3.75* 23.46±1.79* 12.41±1.29*

[0066] Note: Compared with the blank group##P<0.01; compared with the model group***P<0.001, **P<0.01, *P<0.05.

[0067] The results showed that the liver and kidney coefficients of the model group mice were significantly increased compared with those of the blank group (P<0.01), indicating that intraperitoneal injection of potassium oxonate and oral gavage of hypoxanthine can cause liver and kidney enlargement in mice, and the model was successfully established. The liver and kidney coefficients of the hyperuricemia mice after oral gavage of coriander extract by method 1, method 2, method 3, and method 4 were all reduced compared with those in the model group (P<0.05), indicating that the coriander extract obtained by the above methods can alleviate the hepatomegaly and kidney enlargement of hyperuricemia mice induced by the modeling agent. Compared with the blank group, the serum uric acid in the model group increased significantly by 58.0% (P<0.01), indicating that the hyperuricemia model was successfully established. Method 1, Method 2, Method 3, and Method 4 all showed that the extracts of Coriander leaf significantly reduced the uric acid levels of hyperuricemia mice (P<0.05). Method 1, Method 2, Method 3, and Method 4 all showed that the extracts of Coriander leaf significantly reduced the creatinine levels of hyperuricemia mice (P<0.05).

[0068] The above results show that the coriander extracts obtained by method 1, method 2, method 3, and method 4 can not only effectively reduce uric acid but also improve liver and kidney damage caused by modeling drugs (P<0.05), and its mechanism of action may be related to the inhibition of xanthine oxidase.

[0069] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Use of a spiny coriander extract in the preparation of a medicament for preventing, alleviating and / or treating hyperuricemia.

2. The use according to claim 1, characterized in that: The spiny coriander extract inhibits xanthine oxidase.

3. The use according to claim 1, characterized in that: The spiny coriander extract reduces the uric acid level of patients with hyperuricemia and improves liver and kidney damage caused by hyperuricemia.

4. The use according to claim 1, characterized in that: The preparation method of the spiny coriander extract comprises: ultrasonic extraction and reflux extraction.

5. The use according to claim 4, characterized in that: The ultrasonic extraction comprises the following steps: mixing coriander powder and ethanol solution, performing ultrasonic extraction, filtering the extract to obtain filtrate; concentrating the filtrate by rotary evaporation, and drying under reduced pressure to a water content of ≤10% to obtain coriander extract.

6. The use according to claim 4, characterized in that: The reflux extraction comprises the following steps: mixing the spiny coriander powder with an ethanol solution, performing reflux extraction, filtering the extract to obtain a filtrate; and concentrating the filtrate by rotary evaporation and drying under reduced pressure until the water content is less than or equal to 10% to obtain the spiny coriander extract.

7. The use according to any one of claims 4 to 6, characterized in that: The preparation method of the spiny coriander extract further comprises: purifying the spiny coriander extract, and the purification method comprises macroporous resin adsorption or organic solvent extraction.

8. The use according to claim 7, characterized in that: The macroporous resin adsorption comprises the following steps: adding ethanol solution to dissolve the spiny coriander extract, adding macroporous resin for stirring and adsorption, loading the macroporous resin onto a column after adsorption, gradient eluting with ethanol solution, collecting eluate with 30% to 50% ethanol solution, rotary evaporation and drying to obtain purified spiny coriander extract.

9. The use according to claim 7, characterized in that: The organic solvent extraction comprises the following steps: adding ethanol solution to dissolve the spiny coriander extract, extracting with dichloromethane and chloroform in sequence, discarding the extract, extracting with ethyl acetate, collecting the ethyl acetate extract, rotary evaporating and drying to obtain the purified spiny coriander extract.

10. The use according to claim 1, characterized in that: The active ingredient of the medicine is coriander extract.

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