CN114767803B - Dendrobium officinale traditional Chinese medicine composition for down-regulating kidney PDZK1 protein to prevent hyperuricemia, and preparation method and application thereof - Google Patents
Dendrobium officinale traditional Chinese medicine composition for down-regulating kidney PDZK1 protein to prevent hyperuricemia, and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a dendrobium candidum traditional Chinese medicine composition for preventing and treating hyperuricemia by downregulating kidney PDZK1 protein, and a preparation method and application thereof, wherein the dendrobium candidum traditional Chinese medicine composition is prepared by mixing and crushing medicinal components according to the weight ratio of 5-80 parts of dendrobium candidum, 5-30 parts of rhizoma atractylodis, 5-30 parts of rhizoma smilacis glabrae, 5-30 parts of semen plantaginis, 2.5-50 parts of radix cyathulae and 2.5-50 parts of semen coicis, adding a certain amount of water, soaking for a period of time, reflux extracting, filtering an extracting solution, and concentrating filtrate under reduced pressure to obtain a traditional Chinese medicine composition extract. The composition has better prevention and treatment effect on hyperuricemia, can obviously reduce the serum uric acid level of hyperuricemia model animals, plays a role in reducing uric acid, and further proves that the uric acid reducing mechanism of the traditional Chinese medicine composition is related to down-regulating the expression of kidney PDZK1 protein. The traditional Chinese medicine composition disclosed by the invention is simple to prepare, good in safety and obviously better in uric acid reducing effect than the modified pill of the classical prescription.
Description
Technical field:
the invention belongs to the technical field of medicines, and particularly relates to a dendrobium candidum traditional Chinese medicine composition for preventing and treating hyperuricemia by downregulating kidney PDZK1 protein and application thereof.
The background technology is as follows:
hyperuricemia (HUA) is a metabolic disease mainly represented by abnormal rise of blood uric acid level of a human body, is closely related to gout, hypertension, hyperlipidemia, diabetes mellitus, cardiovascular diseases and the like, and seriously endangers life health of human beings. At present, no medicine suitable for asymptomatic hyperuricemia exists clinically. Commonly used drugs such as febuxostat, benzbromarone and the like are only suitable for gout; there is also a risk of adverse drug reactions such as impairment of renal function and allergic reactions, etc. in the case of long-term use of such drugs. Therefore, the medicine for safely and effectively improving hyperuricemia with mild medicine effect is found to have important research significance and clinical value.
PDZ structural domain protein 1 (PDZK 1) belongs to a transport protein family containing PDZ structural domain, is a scaffold protein of various transport proteins and regulatory proteins, and is mainly expressed in tissues such as kidneys, small intestines and the like. There are studies reporting that PDZK1 site mutations are associated with serum Uric Acid (UA) levels; in the chinese han group of men, PDZK1 genetic diversity is associated with an increased risk of developing HUA/gout. PDZK1 can interact with uric acid reabsorption proteinuria transporter 1 (URAT 1), increase URAT1 transport activity, promote uric acid absorption, and cause an increase in blood uric acid. Inhibition of PDZK1 expression is thus a potential target for reducing the risk of hyperuricemia.
The traditional Chinese medicine has a long history in treating hyperuricemia, and the traditional Chinese medicine compound has the advantages of safety, multiple targets and multiple ways of regulation. For example, the classic formula of two wonderful pills, wuling powder and the like, and the modern proved formula of turbid discharge and arthralgia removal and the like. However, the prescription is mainly aimed at gout patients, and has a certain effect of relieving gout symptoms, but is not suitable for asymptomatic hyperuricemia. The compound drug effect of the traditional Chinese medicine which can be reported at the present stage and can be used for asymptomatic hyperuricemia also has certain limitation, for example, the search number is DOI:10.13748/j.cnki.issn1007-7693.2019.02.006 shows the uric acid reducing effect and mechanism of the classical four-component pill addition and subtraction on hyperuricemia model rats, wherein the dosage in the four-component pill addition and subtraction respectively reduces the uric acid level by 23.06% and 32.46% in the 2 nd and 3 rd weeks of administration, but the uric acid reducing amplitude is not large. The invention can reduce the blood uric acid level by more than 50% by up-regulating the PDZK1 expression.
The invention comprises the following steps:
aiming at the technical problems, the invention aims to provide a dendrobium candidum traditional Chinese medicine composition for preventing and treating hyperuricemia by downregulating kidney PDZK1 protein, and a preparation method and application thereof.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a dendrobium candidum traditional Chinese medicine composition for down regulating kidney PDZK1 protein to prevent hyperuricemia comprises the following medicine components in parts by weight: 5 to 80 parts of dendrobium candidum, 5 to 30 parts of rhizoma atractylodis, 5 to 30 parts of rhizoma smilacis glabrae, 5 to 30 parts of semen plantaginis, 2.5 to 50 parts of medicinal cyathula root and 2.5 to 50 parts of coix seed.
Further, the medicinal components of the composition are glycoside substances, and the maximum content of the glycoside substances is acteoside and astilbin. The medicinal components of the Chinese medicinal composition extract comprise acteoside, astilbin and the like.
A preparation method of a dendrobium candidum traditional Chinese medicine composition for down-regulating kidney PDZK1 protein to prevent hyperuricemia comprises the following steps: mixing the medicinal components, pulverizing, adding water 5-100 times of the total mass of the medicinal components, soaking for 2-30 h, reflux-extracting for 1-10 times at 30-100 ℃ for 1-10 h, filtering the extracting solution, concentrating the filtrate under reduced pressure at 35-80 ℃ to obtain the traditional Chinese medicine composition extract.
An application of dendrobium candidum traditional Chinese medicine composition for preventing and treating hyperuricemia by downregulating kidney PDZK1 protein is disclosed, wherein the application is the application in preparing a medicine for preventing and treating hyperuricemia, and the composition achieves the purpose of preventing and treating hyperuricemia by downregulating kidney PDZK1 protein.
The dendrobium candidum traditional Chinese medicine composition takes dendrobium candidum and rhizoma atractylodis as monarch drugs, wherein the dendrobium candidum is sweet and enters stomach and kidney channels, functions of benefiting stomach and promoting fluid production, nourishing yin and tonifying kidney; rhizoma Atractylodis is added into spleen and stomach channel, has the functions of eliminating dampness and strengthening spleen, is used for treating damp obstruction of middle energizer, edema and rheumatalgia, and combines the two medicines as monarch medicines, thereby playing the roles of tonifying stomach and spleen, tonifying kidney and promoting diuresis. Rhizoma smilacis glabrae enters stomach meridian, has the effects of detoxification, dehumidification and joint promotion, and is used for treating arthralgia and myalgia and damp-heat stranguria with turbid urine; semen plantaginis enters kidney and small intestine channels, clears heat and excretes dampness, and promotes urination and relieves stranguria, is used for treating common cold caused by heat stranguria and edema distention, and the two medicines are combined as ministerial medicines, so that the efficacy of the monarch medicine of tonifying stomach and spleen and tonifying kidney and promoting diuresis is enhanced. The radix achyranthis bidentatae enters liver and kidney meridians, and is used as an adjuvant drug and also as a guiding drug for inducing diuresis for treating stranguria and guiding blood downward. Coix seed enters spleen and stomach meridian, has the functions of promoting diuresis, removing dampness, strengthening spleen, detoxifying and resolving masses, and is commonly used for edema, dysuria, spleen deficiency and dampness arthralgia, and is an adjuvant drug.
According to the guidance of the traditional Chinese medicine theory, the dendrobium candidum composition is matched with six wonderful medicines for tonifying stomach and spleen to eliminate dampness, nourishing yin and tonifying kidney to promote turbid, so that the traditional Chinese medicine composition not only can strengthen spleen and kidney to treat disease, but also can release turbid and remove dampness to treat disease, and both principal and secondary aspects of the disease are applied, thereby playing roles in tonifying stomach and spleen, tonifying kidney and promoting diuresis, and playing roles in reducing uric acid. The dendrobium candidum traditional Chinese medicine composition can play a more obvious uric acid reducing role by downregulating kidney PDZK1 protein.
The application of the traditional Chinese medicine composition in preparing medicines or foods for preventing and treating hyperuricemia: the Chinese medicinal composition can be combined with pharmaceutically acceptable auxiliary materials to prepare tablets, capsules, pills, granules or oral liquid, and the Chinese medicinal composition can be added into various health-care foods with allowable addition in small dosage.
Compared with the prior art, the invention has the following beneficial effects:
1. the Chinese medicinal composition can obviously reduce the serum UA level of model animals by more than 50%.
2. The main way of taking effect of preventing and treating hyperuricemia is to reduce uric acid reabsorption by reducing kidney PDZK1 protein expression, thereby achieving the effect of reducing uric acid level.
3. Compared with the traditional four-ingredient pill, the uric acid reducing drug effect is improved by 63.67-84.12%.
4. The composition has better prevention and treatment effect on hyperuricemia, can obviously reduce the serum uric acid level of hyperuricemia model animals, plays a role in reducing uric acid, reduces uric acid by more than 50 percent, and further proves that the uric acid reducing mechanism of the traditional Chinese medicine composition is related to down-regulating the expression of kidney PDZK1 protein. The traditional Chinese medicine composition disclosed by the invention is simple to prepare, good in safety, and obviously better in uric acid reducing effect than the addition and subtraction of the traditional four-ingredient pill, and has a good development prospect in the field of new traditional Chinese medicines or health-care foods for preventing and treating hyperuricemia.
Drawings
Fig. 1 shows characteristic peaks of a high performance liquid spectrum of the Chinese medicinal composition (A is astilbin; B is acteoside).
The specific embodiment is as follows:
the invention will be further described with reference to specific examples and figures of the accompanying drawings, to which the scope of protection of the invention is not limited. The following examples are given in parts by weight unless otherwise specified.
Example 1
Weighing 5 parts of dendrobium candidum, 30 parts of rhizoma atractylodis, 20 parts of glabrous greenbrier rhizome, 25 parts of plantain seed, 20 parts of medicinal cyathula root and 10 parts of coix seed, mixing and crushing the six medicinal materials, adding water which is 5 times of the total weight of the medicinal materials, soaking for 30 hours, carrying out reflux extraction for 8 times, wherein the extraction temperature is 100 ℃, the extraction time is 2 hours, filtering the extracting solution, concentrating the filtrate under reduced pressure, and concentrating the filtrate at the concentration temperature of 80 ℃ to obtain the traditional Chinese medicine composition extract.
The characteristic peak of the high performance liquid spectrum of the Chinese medicinal composition extract is shown in figure 1, the maximum peak area of HPLC is astilbin, and B is acteoside. The medicinal components of the Chinese medicinal composition extract comprise acteoside, astilbin and the like.
Example 2
70 parts of dendrobium candidum, 5 parts of rhizoma atractylodis, 10 parts of glabrous greenbrier rhizome, 5 parts of plantain seed, 7.5 parts of medicinal cyathula root and 2.5 parts of coix seed are weighed, the six medicinal materials are mixed and crushed, water which is 100 times of the total weight of the medicinal materials is added, the mixture is soaked for 30 hours, the reflux extraction is carried out for 1 time, the extraction temperature is 60 ℃ and the extraction time is 1 hour, the filtrate is concentrated under reduced pressure after the filtering of the extracting solution, and the concentration temperature is 55 ℃ to obtain the traditional Chinese medicine composition extract.
Example 3
Weighing 20 parts of dendrobium candidum, 30 parts of rhizoma atractylodis, 15 parts of glabrous greenbrier rhizome, 15 parts of plantain seed, 10 parts of medicinal cyathula root and 10 parts of coix seed, mixing and crushing the six medicinal materials, adding water which is 30 times of the total weight of the medicinal materials, soaking for 12 hours, carrying out reflux extraction for 3 times, wherein the extraction temperature is 90 ℃, the extraction time is 3 hours, filtering the extracting solution, concentrating the filtrate under reduced pressure, and concentrating the filtrate at the concentration temperature of 70 ℃ to obtain the traditional Chinese medicine composition extract.
Comparative example
Modified Simiao pills of classical formula: mixing and pulverizing herba Dendrobii, rhizoma Atractylodis, achyranthis radix and Coicis semen, adding water 30 times of the total weight of the materials, soaking for 12 hr, reflux-extracting for 3 times at 90deg.C for 3 hr, filtering the extractive solution, concentrating the filtrate under reduced pressure at 70deg.C to obtain the comparative example.
Pharmacodynamic test
The extract can be prepared into tablets, capsules, pills, granules or oral liquid with various pharmaceutically acceptable auxiliary materials, and the daily dosage of the extract is selected to be 0.01-10 g/kg of rat body weight.
Grouping animals: healthy SPF grade SD rats, male, 80, were randomly divided into 7 groups by body mass and haematuria: normal control group (NG), model control group (MG), febuxostat group (FBST, 6 MG/kg), benzbromarone group (BXML, 8 MG/kg), example (1) group (13.2 g/kg), example (2) group (6.6 g/kg), example (3) group (3.3 g/kg), comparative example group (13.2 g/kg). Each group of 10.
Pathological model: except for the normal control group, the rats of each group are infused with the hyperuricemia rat model prepared by the fat emulsion for molding, and are administered simultaneously with molding for 3 weeks.
The administration mode is as follows: each group of animals is irrigated once daily, the volume of the irrigated stomach is 1mL/100g, and the period is 3 weeks continuously; the normal control group and the model control group were given corresponding volumes of water, and the other groups were given medicinal solutions.
And (3) measuring indexes: the UA (SUA) levels in rat serum were measured at weeks 2 and 3 of dosing. After the last administration, the rats of each group were dissected and examined for the expression of the PDZK1 protein in the kidney tissue after 12 hours of fasting.
TABLE 1 Effect of Dendrobium officinale traditional Chinese medicine composition on serum UA level of hyperuricemia rats
Note that: in comparison with the normal control group, ## P<0.01， # P<0.05; in comparison with the model control group, ** P<0.01， * P<0.05。
the experimental results are shown in table 1, and compared with the normal control group, the SUA level of the model group rats after molding for 2 weeks is obviously increased by 71.16%; the SUA level of the model group rats after 3 weeks of molding is obviously increased, and the average value is increased by 146.1%. Indicating that hyperuricemia model is successfully established and SUA level can be stably maintained.
Compared with a model control group, SUA level mean of rats in three example groups is obviously reduced by 19.30-34.12% after 2 weeks of administration; three examples all significantly reduced the SUA level in HUP model rats by 50.59-56.91% after 3 weeks of dosing. The continuous administration of the dendrobium candidum traditional Chinese medicine composition is suggested to obviously reduce serum UA of a model rat, and compared with the comparative example, the uric acid reducing amplitude is increased by 63.67-84.12%, and the uric acid reducing effect of the example (13.2 g/kg) and the example (3.3 g/kg) is superior to that of two positive medicines after 3 weeks of administration.
Table 2 protein Effect of Dendrobium officinale traditional Chinese medicine composition on transfer of kidney UA of hyperuricemia rat
Note that: in comparison with the normal control group, ## P<0.01， # P<0.05; in comparison with the model control group, ** P<0.01， * P<0.05。
compared with the normal control group, the kidney PDZK1 protein expression level of the model control group is increased, which suggests that the gastric lavage fat emulsion can inhibit the function of the kidney excretion UA of the model rat, thereby leading to the increase of the SUA level in vivo. Compared with the model control group, the expression level of the rat kidney PDZK1 protein in each example group is reduced, and the expression level of the rat kidney PDZK1 protein in the comparative example group is not obvious. The continuous administration of the dendrobium candidum traditional Chinese medicine composition can promote UA excretion by reducing UA reabsorption, thereby reducing UA level in vivo. The results are shown in Table 2.
In conclusion, the traditional Chinese medicine composition provided by the embodiment of the invention has the advantages that the raw materials are green and natural, the safety is high, the kidney PDZK1 protein expression can be quickly and efficiently regulated down, and the serum uric acid is reduced. The preparation method of the traditional Chinese medicine composition is simple and controllable in operation, can be quantitatively produced and has good curative effect. The Chinese medicinal composition can obviously reduce the serum UA level of model animals by more than 50%, and compared with the traditional four wonderful pills, the uric acid reducing medicinal effect is improved by 63.67-84.12%. Enriches the clinical application variety of asymptomatic hyperuricemia.
The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the invention is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Claims (7)
1. A dendrobium candidum traditional Chinese medicine composition for preventing and treating hyperuricemia by downregulating kidney PDZK1 protein is characterized by being prepared from the following medicine components in parts by weight: 5-80 parts of dendrobium candidum, 5-30 parts of rhizoma atractylodis, 5-30 parts of rhizoma smilacis glabrae, 5-30 parts of semen plantaginis, 2.5-50 parts of radix cyathulae and 2.5-50 parts of semen coicis.
2. A preparation method of a traditional Chinese medicine composition for down-regulating kidney PDZK1 protein to prevent hyperuricemia comprises the following steps:
the following medicine components in parts by weight are taken: mixing and crushing 5-80 parts of dendrobium candidum, 5-30 parts of rhizoma atractylodis, 5-30 parts of rhizoma smilacis glabrae, 5-30 parts of semen plantaginis, 2.5-50 parts of radix cyathulae and 2.5-50 parts of coix seed into fine powder, adding water, soaking, reflux extracting and reflux extracting: the extraction temperature is 30-100 ℃, the extraction time is 1-10 hours, the filtrate is concentrated under reduced pressure after the filtering of the extracting solution, and the traditional Chinese medicine composition extract is obtained.
3. The preparation method of claim 2, wherein the water is added in an amount of 5 to 100 times the total mass of the pharmaceutical components.
4. The method of claim 2, wherein the soaking is performed for 2-30 hours.
5. The method of claim 2, wherein the reflux extraction is performed 1 to 10 times.
6. The method of claim 2, wherein the concentration temperature is 30-90 ℃.
7. Use of the dendrobium candidum traditional Chinese medicine composition according to claim 1 in preparing medicines for preventing and treating hyperuricemia.
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