CN112089725A - Application of aster polysaccharide in preparation of medicine for treating and/or preventing liver diseases - Google Patents
Application of aster polysaccharide in preparation of medicine for treating and/or preventing liver diseases Download PDFInfo
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Abstract
The invention belongs to the field of traditional Chinese medicines, and relates to application of aster tataricus (Ligularia hodgsonii Hook.) polysaccharide in preparation of a medicine for treating and/or preventing liver diseases. The invention adopts a rat liver injury model induced by carbon tetrachloride and clivorine (an endogenous liver poison pyrrolizidine alkaloid), and examines the liver protection effect of the rat liver injury model, and the result shows that the aster tataricus polysaccharide can obviously reduce the liver function index and the oxidative stress index of a liver injury rat, and can be used for researching and developing safe and effective liver protection medicaments, in particular Chinese medicinal herb source liver injury medicaments for preventing and treating the pyrrolizidine alkaloid. The method has important significance for reasonable development and utilization of the Sichuan radix asteris which is a traditional Chinese medicine from Sichuan province.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to application of aster tataricus polysaccharide in preparation of a treatment and/or prevention medicine.
Background
Drug-induced liver injury (DILI) is one of the liver diseases which are clinically common at present, is a common cause of liver injury, has wide expression forms, and can cause acute liver failure in severe cases. In recent years, with the increase of the variety and demand of clinical medicines, the development of new medicines and the wide application of traditional Chinese medicines, the incidence rate of DILI (especially Chinese herbal medicine induced liver injury) is also increased.
Radix Asteris is derived from root and rhizome of ligularia purdomii (ligularia longissiHook.) of ligularia of Compositae, and has been used as national drug or herb for long time. The aster tataricus is recorded in the standards of traditional Chinese medicinal materials in Sichuan province, Guizhou province and Yunnan province. The aster tataricus medicinal material has rich resources, is often used for replacing aster tataricus recorded in Chinese pharmacopoeia in southwest regions, and has the effects of eliminating phlegm, relieving cough and the like.
Polysaccharides, also known as polysaccharides, are polymeric compounds with glycosidic bonds formed by dehydration condensation of 10 or more monosaccharides, which play a vital role in the life activities of living organisms. A large number of researches show that many traditional Chinese medicine polysaccharides show stronger biological activity and have the effects of resisting tumors, regulating immunity, resisting oxidation, protecting liver, reducing blood sugar and the like. Because the polysaccharide belongs to non-cytotoxic substances and has the characteristic of small toxic and side effects, the polysaccharide becomes a hot spot for research and development of medicines, food additives, cosmetics, health-care products and the like.
Pyrrolizidine Alkaloids (PAs), also known as hepatotoxic pyrrolizidine alkaloids, are common natural plant toxins and exist in more than 6,000 plants (including many Chinese medicinal materials such as aster tataricus) all over the world. Research shows that chronic toxicity is caused by long-term intake of hepatotoxic PAs, and the chronic toxicity is manifested by hepatic giant cell disease and hepatic fibrosis; exposure to high doses of PAs can lead to acute toxicity, inducing the Syndrome of Hepatic Sinus Obstruction (HSOS). HSOS is characterized by the main pathological features of hepatic sinus obstruction with or without hepatic venule obstruction, and has the main clinical manifestations of abdominal distension, abdominal pain, jaundice, hepatomegaly, ascites and the like. At present, the disease has some clinical supportive therapies (such as hormone shock, anticoagulation therapy and the like), but no effective preventive and therapeutic drugs exist.
The invention adopts a rat acute liver injury model induced by carbon tetrachloride and clivorine (a traditional Chinese medicine endogenous hepatotoxin pyrrolizidine alkaloid), and evaluates the liver protection efficacy of the polysaccharide by using rat liver function index and oxidative stress index of aster tataricus polysaccharide stem prognosis. The invention not only finds that the polysaccharide is an important bioactive component and endogenous detoxifying substance in the aster tataricus, but also can promote the clinical reasonable and safe medication of the aster tataricus, and provides a valuable clue for utilizing the polysaccharide to intervene and antagonize PAs hepatotoxicity.
Disclosure of Invention
The invention aims to solve the problems of the research and the insufficient utilization of the aster tataricus in the prior art and provides the application of aster tataricus polysaccharide in preparing low-toxicity and high-efficiency liver-protecting medicaments.
In order to achieve the above purpose, the invention provides the following technical scheme: application of radix Asteris polysaccharide in preparing medicine for treating and/or preventing liver disease is provided.
According to the technical scheme of the invention, the molecular weight of the aster tataricus polysaccharide is 10-150 kDa.
According to the technical scheme of the invention, the aster tataricus polysaccharide comprises low-molecular aster tataricus polysaccharide, high-molecular aster tataricus polysaccharide and medium-molecular aster tataricus polysaccharide;
wherein the molecular weight of the low molecular radix Asteris polysaccharide is 10kDa-50kDa, the molecular weight of the high molecular radix Asteris polysaccharide is 100kDa-150kDa, and the molecular weight of the medium molecular radix Asteris polysaccharide is 50kDa-100 kDa.
According to the technical scheme of the invention, the aster tataricus polysaccharide comprises, by weight, 85-95% of low-molecular aster tataricus polysaccharide, 5-10% of high-molecular aster tataricus polysaccharide and 1-5% of medium-molecular aster tataricus polysaccharide.
According to the technical scheme of the invention, the low-molecular radix asteris polysaccharide at least comprises radix asteris polysaccharide LHP1a, and the weight-average molecular weight of the radix asteris polysaccharide LHP1a is 21290 Da;
the polymer radix Asteris polysaccharide at least contains radix Asteris polysaccharide LHP1b, and the weight average molecular weight of radix Asteris polysaccharide LHP1b is 131100 Da;
the medium molecular radix Asteris polysaccharide at least contains radix Asteris polysaccharide LHP2, and the weight average molecular weight of radix Asteris polysaccharide LHP2 is 76510 Da.
According to the technical scheme of the invention, the preparation method of the aster tataricus polysaccharide comprises the steps of drying, crushing and water extraction and alcohol precipitation of aster tataricus medicinal materials to obtain the aster tataricus crude polysaccharide, and deproteinizing the crude polysaccharide by a Sevag method and dialyzing the crude polysaccharide with deionized water to obtain the refined aster tataricus polysaccharide.
According to the technical scheme of the invention, the aster tataricus polysaccharide is separated by a CellufineA-500 cellulose chromatographic column and a toyopearlHW-55F gel chromatographic column, and the weight percentages of the aster tataricus polysaccharide LHP1a, the aster tataricus polysaccharide LHP1a and the aster tataricus polysaccharide LHP2 are 89.8%, 7.0% and 3.2%, respectively.
According to the technical scheme of the invention, the liver disease has an increase in aspartate aminotransferase.
According to the technical scheme of the invention, the aster tataricus polysaccharide achieves the effect of treating and/or preventing liver diseases by reducing serum aspartate Aminotransferase (AST) value.
According to the technical scheme of the invention, the aster tataricus polysaccharide can obviously improve the activities of antioxidant stress indexes SOD and CAT in the liver and the GSH/GSSG ratio by reducing the MDA level of the liver tissue so as to achieve the effect of treating and/or preventing liver diseases.
According to the technical scheme of the invention, the aster tataricus polysaccharide achieves the effect of treating and/or preventing liver diseases by reducing the increase of MPO activity in liver tissues.
According to the technical scheme of the invention, the dose of the aster tataricus polysaccharide for treating and/or preventing liver diseases is 1 time per day, and each time is 0.1-0.4g/kg of body weight.
According to the technical scheme of the invention, the liver disease is a liver disease induced by drug-induced liver injury, preferably, the liver disease is one or more of hepatic giant cell disease, hepatic fibrosis and hepatic sinus obstruction syndrome.
According to the technical scheme of the invention, the preparation of the medicine is one or more of tablets, hard capsules, soft capsules, powder, pills or granules.
The radix Asteris polysaccharide can be added with pharmaceutically acceptable adjuvants to make into tablet, hard capsule, soft capsule, powder, pill, and granule.
Radix Asteris polysaccharide can be used as active ingredient or pharmaceutical carrier.
The invention has the beneficial effects that:
animal test research provided by the applicant shows that the aster tataricus polysaccharide separated from the aster tataricus medicinal material can reduce serum AST value and liver tissue MDA level, remarkably improve SOD and CAT activities in liver antioxidant stress indexes, improve GSH/GSSG ratio, has the effect of antagonizing liver injury induced by carbon tetrachloride and clivorine, belongs to a potential drug for treating drug-induced liver injury diseases, can be applied to the research and development of low-toxicity high-efficiency liver protection drugs, and is beneficial to the safe and reasonable traditional Chinese medicine clinical application of aster tataricus and further development and utilization of the aster tataricus polysaccharide.
The applicant finds that the aster tataricus polysaccharide consists of three polysaccharide components with different molecular weights through research and separation, determines the aster tataricus polysaccharide with specific molecular weight and content capable of treating liver diseases, and lays a foundation for accurate medication of Chinese medicine clinical in future and clinical application of single-component polysaccharide in the aster tataricus polysaccharide in future.
The research of the application is funded by the following fund: national science foundation project (number: 31970349); the health and health committee of Hubei province adopts the scientific research project of traditional Chinese medicine (number: ZY2019M 025).
Drawings
In all the figures, NC is a normal control group, MC is a model control group, PC is a positive control group, LC is a polysaccharide control group of radix Asteris, LL is 100mg/kg of polysaccharide low-dose group of radix Asteris, LM is 200mg/kg of polysaccharide middle-dose group of radix Asteris, and LH is 400mg/kg of polysaccharide high-dose group of radix Asteris; compared with the NC group, "+" indicates P <0.05, "+" indicates P < 0.01; in comparison to the MC group, "#" indicates P <0.05 and "##" indicates P < 0.01.
FIG. 1 shows the intervention effect of Aster tataricus polysaccharide on carbon tetrachloride-induced liver injury model liver function index (a: ALT; b: AST) of rats;
FIG. 2 shows the intervention effect of Aster tataricus polysaccharide on oxidative stress index (a: MDA; b: SOD; c: GSH) of carbon tetrachloride-induced rat acute liver injury model;
FIG. 3 shows the effect of Aster tataricus polysaccharide in the intervention of high-dose clivorine-induced oxidative stress index (a: MDA; b: SOD; c: CAT; d: GST; e: GSH/GSSG) in rat liver injury model;
FIG. 4 shows the effect of Aster tataricus polysaccharide on the intervention of high dose clivorine-induced liver injury model liver tissue inflammation response index (myeloperoxidase, MPO);
FIG. 5 shows the effect of Aster tataricus polysaccharide on the low dose of crivorine-induced oxidative stress injury index (a: MDA; b: SOD; c: CAT; d: GSH/GSSG) of rat liver tissue;
FIG. 6 shows the effect of Aster tataricus polysaccharide on the low dose of clivorine-induced inflammatory response index (myeloperoxidase, MPO) of rat liver tissue.
Detailed Description
The following examples further illustrate the present invention but are not to be construed as limiting the invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention.
The animal, reagent or instrument adopted by the invention is a common product sold on the market, and can be purchased on the market.
Example 1 extraction Process of Aster tataricus polysaccharide
The crude polysaccharide of the aster tataricus is obtained by drying, crushing and water extraction and alcohol precipitation, and the refined aster tataricus polysaccharide is obtained by deproteinizing the crude polysaccharide by a Sevag method and dialyzing the crude polysaccharide by deionized water.
The preparation method of the aster tataricus polysaccharide comprises the following steps: drying and crushing the aster tataricus medicinal material, performing reflux and degreasing by 95% ethanol, performing water extraction at 85 ℃ for 3h according to the material-liquid ratio of 1:36, precipitating by 80% ethanol, standing overnight at 4 ℃, centrifuging (7669g, 10min), collecting precipitates, washing by absolute ethyl alcohol and absolute ethyl ether respectively, and performing vacuum drying under reduced pressure to obtain crude polysaccharide; removing protein by Sevag method, dialyzing with deionized water for 3 days (dialysis bag MWCO: 8000Da-14000Da), precipitating with ethanol, washing, and drying to obtain refined radix Asteris polysaccharide.
Example 2 composition analysis of Aster tataricus polysaccharide
The Aster tataricus polysaccharide obtained in example 1 was further separated by CellufineA-500 cellulose column and toyopearlHW-55F gel column. The specific method comprises the following steps: dissolving Aster tataricus refined polysaccharide in appropriate amount of water, loading, performing CellufineA-500 column chromatography (2.0cm × 50cm), eluting with water, performing gradient elution with 0.1mol/L, 0.5mol/L NaCl solution and 2.0mol/L sodium chloride-Tris-HCl (0.05M, pH8.0) at flow rate of 1mL/min, collecting 1 tube every 10min, tracking and detecting sugar content of each tube by phenol-sulfuric acid method, and drawing elution curve. Separating by CellufineA-500 column chromatography to obtain two main components, namely 0.1M NaCl elution component LHP1, with a yield of 68.8%; 0.5M NaCl eluted fraction LHP2, yield 2.27%. LHP1 is purified by a Toyopearl HW-55F gel column (2.2cm multiplied by 50cm) to obtain two purified components LHP1a and LHP1b, wherein the yield of LHP1a is 4.47 percent, and the yield of LHP1b is 57.5 percent. The mass percentages of LHP1b, LHP1a and LHP2 are 89.8%, 7.0% and 3.2%, respectively.
The molecular weight was determined by gel permeation chromatography, 18-angle laser light scattering (between 14 and 163 ℃) in combination with a differential refractometer (SEC-MALLS-RI). Respectively weighing certain amount of LHP1a, LHP1b and LHP2, adding mobile phase, stirring with magnetic cyclone to dissolve to obtain 1.0mg/mL test solution, filtering with 0.45 μm microporous membrane, and introducing sample. The samples were tested for relative molecular mass using Astrasoftware (v.6.1.1) software, which resulted in a molecular weight of 2.129 x 10 for the major polysaccharide component LHP1b4Da (+ -3.666%), LHP1a is 1.311X 105Da (+ -2.090%), LHP2 7.651 × 104Da(±2.577％)。MW/MnThe ratio is called the dispersion coefficient (d) or molecular weight dispersity of the polysaccharide, and is used for representing the distribution width of the molecular weight of the polysaccharide, and the closer the value of d is to 1, the narrower the distribution is; m of LHP1a, LHP1b and LHP2W/MnRespectively 1.487 (+ -2.776%), 1.503 (+ -5.112%), and 1.323 (+ -4.167%), indicating a narrow distribution of the three components.
Example 3 study of hepatoprotective effect of Aster tataricus polysaccharide
1. Animal grouping, modeling and administration method
(1) Carbon tetrachloride moulding
After the SD rats are adaptively fed for 1 week, the SD rats are randomly divided into 6 groups (6 per group), namely a normal control group, a model group, a high-, medium-and low-dose group of Aster tataricus polysaccharide and a positive control group (bifendate), and are both administered by intragastric administration. The rats in the high, medium and low dose administration groups of polysaccharide are respectively administered with 400mg/kg, 200mg/kg and 100mg/kg of aster polysaccharide per day, the rats in the positive control group are respectively administered with 100mg/kg of bifendate per day, and the rats in the normal control group and the model control group are respectively administered with 1mL/100g of distilled water per day, and the rats are fed with water and water as usual and continuously for 7 days. After 1h of last gastric lavage administration, the model group, the administration group and the positive control group are administered with sesame oil solution containing 50% carbon tetrachloride according to 1 mL/kg; the normal control group is given with the same dose of sesame oil solution, the rats are fasted without water prohibition, pentobarbital (35mg/mL, 0.2mL/100g, intraperitoneal injection) anesthetized 24h after the last administration, the abdominal aorta is subjected to blood sampling, serum is separated for measuring serum transaminase and biochemical indexes, and livers are picked up for biochemical index analysis and pathological examination.
(2) Clivorine molding (high dose)
Ciivorine solution: weighing an appropriate amount of clivorine, adding distilled water to dissolve, and preparing into a solution with the concentration of 15mg/mL for later use.
After the SD rats were adaptively fed for 1 week, the SD rats were randomly divided into 6 groups (6 per group), namely, a normal control group, a model group, a high Sichuan aster polysaccharide dose group (400mg/kg), a medium Sichuan aster polysaccharide dose group (200mg/kg), a Sichuan aster polysaccharide control group and a positive control group (reduced glutathione, GSH), and both of them were subjected to intragastric administration. The polysaccharide of the aster tataricus is given to rats in the control group of aster tataricus polysaccharide at 400mg/kg per day, the polysaccharide of the aster tataricus is given to rats in the positive control group at 150mg/kg per day, and the normal control group and the model control group are given 1mL/100g of distilled water per day respectively, and the food and the water are kept as normal for 7 days. After the last gavage administration for 1h on the 7 th day, the clivorine solution is administered to the model group, the polysaccharide administration group and the positive control group according to the ratio of 150 mg/kg; feeding 1mL/100g of distilled water into the stomach of both the normal control group and the Aster tataricus polysaccharide control group, fasting without water, anesthetizing the rat by pentobarbital (35mg/mL, 0.2mL/100g of intraperitoneal injection) after 48h, collecting blood from abdominal aorta, and separating serum for serum biochemical index analysis; the liver is picked up for the determination of tissue biochemical index and pathological examination.
(3) Clivorine molding (Low dose)
Ciivorine solution: weighing an appropriate amount of clivorine, adding distilled water for dissolving, and preparing into a solution with the concentration of 0.5mg/mL for later use.
After the SD rats are adaptively fed for one week, the SD rats are randomly divided into 4 groups (6 per group), namely a normal control group, a model group, a radix asteris polysaccharide administration group and a positive control Group (GSH), and the groups are subjected to intragastric administration. The polysaccharide of the aster tataricus is administrated to rats in the aster tataricus polysaccharide administration group at 100mg/kg daily, the polysaccharide of the aster tataricus is administrated to rats in the positive control group at 150mg/kg daily, and the normal control group and the model control group of rats are perfused with 1mL/100g of stomach distilled water daily; after the stomach is irrigated for 1h every day, the model group, the polysaccharide administration group and the positive control group are all administered clivorine according to 5mg/kg, the normal control group is administered distilled water according to 1mL/100g, and the patient continuously takes 3d after eating and drinking water; before animals are treated for 16h, the animals are fasted without water prohibition, the rats are anesthetized with pentobarbital (35mg/mL, 0.2mL/100g and intraperitoneal injection) 24h after the last administration, the abdominal aorta is subjected to blood collection, and serum is separated for serum biochemical index analysis; the livers were harvested for tissue biochemical index analysis and pathology examination.
2. Liver function index detection
(1) Serum index detection: each rat was weighed, anesthetized with 35mg/mL pentobarbital sodium solution at 0.2mL/100g, blood was taken from the abdominal aorta, the vessel was incubated for 1h at 37 ℃ in an incubator, and then centrifuged (955 Xg, 10min, 4 ℃), and the supernatant was collected and assayed for alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) using a fully automatic biochemical analyzer.
The experimental results are shown in figure 1, compared with the normal group, the AST and ALT values of the model group are obviously increased, compared with the model group, the AST values of the administration group and the positive medicine group with different dosages are obviously reduced, and simultaneously, the ALT values are also reduced to different degrees. The result shows that the aster tataricus polysaccharide has a protective effect on rat acute liver injury caused by carbon tetrachloride. In addition, histopathological observation shows that the polysaccharide administration obviously relieves the fatty vacuole degeneration and the liver cell necrosis lesion of the liver tissues of rats.
(2) Liver tissue: accurately weighing 1g of rat liver tissue, adding 9 times of physiological saline for homogenizing to prepare liver tissue homogenate with the mass fraction of 10%, and taking out a part for MPO (determination uses 5% homogenate) determination; the remaining homogenate was centrifuged at 4 ℃ and 955 Xg for 15min, the supernatant was stored at-80 ℃ for further use, and the activities of MDA (using 10% homogenate), SOD (using 0.2% homogenate), CAT (using 0.25% homogenate), and GST (using 10% homogenate) were determined, and the other operations were performed strictly according to the kit instructions.
Accurately weighing 0.2g of liver tissue according to the weight-volume ratio of 1:4, adding 0.8mL of newly-prepared reagent IV (reference GSH/GSSG determination kit) for tissue homogenization, 1300 Xg, and centrifuging for 10 minutes; the supernatant was taken as a 20% liver homogenate. And (3) adding 950 microliter of reagent into 50 microliter of supernatant for four dilution during determination to obtain 1% liver homogenate for later use, wherein the liver homogenate is used for determination of GSH and GSH/GSSG, and other operations are strictly performed according to a kit instruction method.
The experimental results are shown in fig. 2, compared with the normal group, the liver lipid peroxidation induced by the common carbon tetrachloride (model group) can obviously increase the MDA content, and simultaneously the SOD activity and the GSH content are also obviously reduced. Compared with the model group, the liver MDA level of the rat with high dose (200mg/kg and 400mg/kg) in the previously-administered aster tataricus polysaccharide is obviously reduced, while the SOD activity and the GSH content of the liver tissue are obviously increased and are dose-dependent. The adoption of bifendate pretreatment (positive group, 100mg/kg) can also obviously inhibit the MDA content of the liver and improve the GSH content, but the influence on the SOD is not obvious. These results suggest that aster tataricus polysaccharide can improve the antioxidant capacity of rat liver and promote the improvement of rat liver pathological changes.
The experimental results are shown in fig. 3 and 4, compared with the normal group, the serum AST and ALT activities of the rats in the high-dose clivorine (i.e. gavage for 1 day at a dose of 150mg/kg per day) model group are obviously improved, and the MDA content is further obviously improved, which indicates that the liver has a more serious lipid peroxidation phenomenon. Both the high dose polysaccharide and the positive drug group had significantly reduced MDA content (figure 3). Compared with the normal group, the levels of SOD, CAT and GST in the model group are all obviously reduced; compared with the model group, the activities of SOD, CAT and GST in the livers of the rats in the polysaccharide high-dose group are obviously improved, wherein GST is almost recovered to a normal level; the low dose polysaccharide also caused a significant increase in GST activity. The GSH and GSSG in the model group both increased significantly, and the GSH/GSSG ratio decreased significantly compared to the normal group. Compared with the model group, the GSH content of the aster tataricus polysaccharide administration group is in a descending trend according to the dosage, the GSSG content is more obviously reduced, and the GSH/GSSG ratio is obviously increased, wherein the GSH/GSSG ratio of the polysaccharide high-dosage group is basically equal to that of the normal group. The level of GSH in the liver tissue of the positive drug group is obviously increased, and the ratio of GSH/GSSG is also obviously increased (figure 3). MPO (myeloperoxidase), a heme-containing peroxidase, is expressed primarily in neutrophils, has been shown to be a local mediator of tissue injury and can cause inflammation in a variety of inflammatory diseases. Compared with the normal group, the MPO activity of the liver tissue of the model group rats is obviously increased, and the MPO activity of the Aster tataricus polysaccharide is obviously reduced and is dose-dependent (figure 4).
The results are shown in FIGS. 5 and 6, and compared with the normal group, the serum index (AST, ALT) and liver index of the rats in the low dose clivorine (i.e. continuous gavage for 3 days at 5mg/kg daily dose) model group are not statistically different, but the MDA content is obviously increased (FIG. 5). Compared with the model group, the MDA values of the polysaccharide administration group and the positive medicine group are reduced to different degrees. Meanwhile, the SOD and CAT activities of the rat liver tissues in the model group are obviously reduced, and the SOD and CAT activities of the rat in the aster tataricus polysaccharide group are obviously improved and restored to normal levels. The SOD activity of the liver tissue of the positive medicine group is obviously improved. In the model group, the GSH content of the liver tissue was significantly decreased, while the GSSG content was significantly increased, and as a result, the GSH/GSSG ratio was significantly decreased, the GSH of both aster tataricus polysaccharide and the masculin group rat was significantly increased, while GSSG was significantly decreased, and the GSH/GSSG ratio was increased to a normal level (fig. 5). In addition, the MPO activity of the model group is obviously increased, the MPO activity of the aster tataricus polysaccharide group is obviously reduced and is almost recovered to a normal level, and the positive drug has no obvious improvement effect (figure 6).
In conclusion, the aster tataricus polysaccharide has a remarkable protective effect on rat liver injury induced by carbon tetrachloride and a traditional Chinese medicine endogenous hepatotoxic pyrrolizidine alkaloid component clivorine, has the characteristic of small toxic and side effects, and has an important significance in the research and development of medicines for preventing or treating drug-induced liver injury (including Chinese herbal medicine drug-derived liver injury).
The foregoing is only a preferred embodiment of the present invention, and it should be noted that it is obvious to those skilled in the art that various modifications and improvements can be made without departing from the principle of the present invention, and these modifications and improvements should also be considered as the protection scope of the present invention.
Claims (10)
1. Application of radix Asteris polysaccharide in preparing medicine for treating and/or preventing liver disease is provided.
2. The use of claim 1, wherein the aster tataricus polysaccharide has a molecular weight of 10-150 kDa; preferably, the aster tataricus polysaccharide comprises low-molecular aster tataricus polysaccharide, high-molecular aster tataricus polysaccharide and medium-molecular aster tataricus polysaccharide.
3. The use of claim 2, wherein the low molecular vladimiria polysaccharide has a molecular weight of 10kDa-50kDa, the high molecular vladimiria polysaccharide has a molecular weight of 100kDa-150kDa, and the medium molecular vladimiria polysaccharide has a molecular weight of 50kDa-100 kDa;
preferably, the aster tataricus polysaccharide comprises, by weight, 85-95% of low-molecular aster tataricus polysaccharide, 4-10% of high-molecular aster tataricus polysaccharide and 1-5% of medium-molecular aster tataricus polysaccharide.
4. The use of claims 2-3, wherein the low molecular Aster tataricus polysaccharide comprises at least Aster tataricus polysaccharide LHP1a, preferably the weight average molecular weight of the Aster tataricus polysaccharide LHP1a is 21290Da (+ 3.666%);
the polymer radix asteris polysaccharide at least contains radix asteris polysaccharide LHP1b, preferably, the weight average molecular weight of the radix asteris polysaccharide LHP1b is 131100Da (+ -2.090%);
the medium molecular radix Asteris polysaccharide at least contains radix Asteris polysaccharide LHP2, preferably, the weight average molecular weight of radix Asteris polysaccharide LHP2 is 76510Da (+ -2.577%).
5. The use of any one of claims 1 to 4, wherein the Aster tataricus polysaccharide is prepared by drying Aster tataricus, pulverizing, extracting with water and precipitating with ethanol to obtain crude Aster tataricus polysaccharide, deproteinizing the crude polysaccharide by Sevag method, and dialyzing with deionized water to obtain refined Aster tataricus polysaccharide.
6. The use of claim 5, wherein the Aster tataricus polysaccharide is separated by Cellufine A-500 cellulose column and Toyopearl HW-55F gel column, and the weight percentages of the Aster tataricus polysaccharide LHP1a, the Aster tataricus polysaccharide LHP1a and the Aster tataricus polysaccharide LHP2 are 89.8%, 7.0% and 3.2%, respectively.
7. The use according to any one of claims 1 to 6, wherein said liver disease is characterized by an elevated aspartate transaminase;
preferably, the aster tataricus polysaccharide achieves the effect of treating and/or preventing liver diseases by reducing serum aspartate Aminotransferase (AST) value;
preferably, the aster tataricus polysaccharide remarkably improves the activities of antioxidant stress indexes SOD and CAT in the liver and the GSH/GSSG ratio by reducing the MDA level of liver tissues so as to achieve the effect of treating and/or preventing liver diseases;
preferably, the aster polysaccharides have the effect of treating and/or preventing liver diseases by reducing the increase of MPO activity in liver tissues.
8. The use according to claims 1 to 7, wherein the dose of the aster tataricus polysaccharide for treating and/or preventing liver diseases is 1 time per day, and 0.1 to 0.4g/kg of body weight per time;
preferably, the liver disease is a liver disease induced by drug-induced liver injury, preferably, the liver disease is one or more of hepatic giant cell disease, hepatic fibrosis and hepatic sinus obstruction syndrome;
preferably, the preparation of the medicament is one or more of tablets, hard capsules, soft capsules, powder, pills or granules.
9. The preparation of the aster tataricus polysaccharide as claimed in any one of claims 1 to 8, wherein the aster tataricus polysaccharide is prepared into tablets, hard capsules, soft capsules, powder, pills and granules by adding pharmaceutically acceptable auxiliary materials.
10. A pharmaceutical composition characterized by comprising the aster tataricus polysaccharide as claimed in any one of claims 1 to 9 as an active ingredient or a pharmaceutically acceptable carrier.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110194754A (en) * | 2019-04-29 | 2019-09-03 | 首都医科大学 | A kind of ligularia fischeri fat-soluble extract and its preparation method and application |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110194754A (en) * | 2019-04-29 | 2019-09-03 | 首都医科大学 | A kind of ligularia fischeri fat-soluble extract and its preparation method and application |
Non-Patent Citations (4)
| Title |
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| XUEPING SONG 等: "Extraction Optimization, Preliminary Characterization and Bioactivities in Vitro of Ligularia hodgsonii Polysaccharides", 《INT. J. MOL. SCI.》 * |
| 刘春兰 等: "鹿蹄橐吾多糖LW21的分离纯化及其结构分析", 《食品科学》 * |
| 无: "国家自然科学基金委员会生命科学部2019年度面上项目", 《生命科学》 * |
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