Traditional Chinese medicine composition capable of protecting acute alcoholic liver injury as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition capable of protecting acute alcoholic liver injury and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine compositions. The composition consists of rhizoma polygonati and semen hoveniae, wherein the weight ratio of the rhizoma polygonati to the semen hoveniae is (1: 2)-(2: 1). Two acute alcoholic liver injury models show that the composition can significantly improve AST, ALT, TG, CHO, TP and ALB indexes in serum of mice after drinking through preventive administration or therapeutic administration. In addition, pathological results show that each administration group can obviously reverse liver tissue pathological injury caused by excessive drinking. The traditional Chinese medicine composition disclosed by the invention has a good effect of protecting the acute alcoholic liver injury, and the rhizoma polygonati and the semen hoveniae are used as medicines with homology of medicine and food, have the characteristics of low toxicity, low price and easiness in obtaining, and have a good application prospect in the aspect of protecting the alcoholic liver injury.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a traditional Chinese medicine composition with the function of protecting acute alcoholic liver injury, and its preparation method and application. Background Art

[0002] Alcoholic liver disease (ALD) is a disease caused by long-term excessive drinking, which can further develop into alcoholic hepatitis and alcoholic liver fibrosis, and finally even develop into alcoholic cirrhosis and liver cancer. In recent years, with the acceleration of people's living rhythm and social needs, the number of alcohol consumers has increased significantly, resulting in an annual increase in the incidence of alcoholic liver injury. At present, the research on alcoholic liver injury mainly focuses on chronic alcoholic liver injury, and relatively less attention is paid to acute alcoholic liver injury. Acute alcoholic liver injury is caused by a large amount of alcohol consumption in a short period of time, leading to liver inflammation and dysfunction. Its pathogenesis mainly involves the direct toxic effects of alcohol and its metabolites, oxidative stress, and immune-inflammatory responses. These mechanisms work together to cause hepatocyte damage, necrosis, and inflammatory edema, and then trigger a series of clinical symptoms. In severe cases, jaundice and liver failure may even occur. Currently, the therapeutic drugs for acute alcoholic liver injury, such as anti-inflammatory and hepatoprotective drugs, vitamin and mineral supplements, enzyme-lowering drugs, etc., although they can reduce liver injury to a certain extent, the curative effect is often limited and it is difficult to completely reverse the condition.

[0003] The treatment method of alcoholic liver injury is related to the severity of the disease. The main treatment methods include: ① Abstinence from alcohol; ② Nutritional therapy; ③ Corticosteroid therapy; ④ Anti-cytokine therapy; ⑤ Other therapies, including antioxidants (silibinin), anti-fibrotic substances (colchicine), anti-thyroid drugs (propylthiouracil), liver regeneration promoters (insulin, glucagon); ⑥ Liver transplantation. Abstinence from alcohol is currently the most basic and commonly used method. However, it is very difficult for people who are psychologically dependent on alcohol to completely abstain from it, and relapse is extremely easy to occur. Therefore, nutritional therapy is often used as an adjuvant treatment. The existing anti-alcohol and liver-protecting drugs are used alone, and the curative effect is limited. There is a lack of a drug composition with both the effects of relieving alcohol and protecting the liver, and it is impossible to fundamentally prevent or treat alcoholic liver injury.

[0004] Traditional Chinese medicine has a history of thousands of years in preventing and treating liver injury or relieving alcohol intoxication. Seeds of Hovenia dulcis Thunnb., Hovenia acerba Lindl., and Hovenia trichocarpa Chun et Tsiang of the genus Hovenia in the family Rhamnaceae are the mature seeds of Hovenia dulcis Thunnb., Hovenia acerba Lindl., and Hovenia trichocarpa Chun et Tsiang. It has the effects of relieving alcohol toxicity, quenching thirst and relieving vexation, stopping vomiting, promoting urination and defecation, and protecting the liver. Regarding its effect of relieving alcohol intoxication, it is recorded in many ancient books. For example, "Illustrated Classic of Materia Medica" written by Su Song in the Song Dynasty states: "The branches of Hovenia are not straight. Eating them is as sweet as maltose. They ripen in August and September and are called wood honey. It comes from the south and can weaken alcohol. If used as a house column, the alcohol in the whole house will become weak." Polygonatum sibiricum Red. is the dried rhizome of Polygonatum kingianum Coll. et Hemsl., Polygonatum sibiricum Red., or Polygonatum cyrtonema Hua of the family Liliaceae. It tastes sweet and is neutral in nature, and has the effects of replenishing qi and nourishing yin, strengthening the spleen, tonifying the kidney, and moistening the lungs. Due to its effects of prolonging life and being non-toxic, it was listed as a superior traditional Chinese medicine in "Shennong's Classic of Materia Medica". Research shows that Polygonatum sibiricum Red. has pharmacological effects of enhancing immunity, anti-inflammation, and anti-tumor. There are many reports on the prevention and treatment of liver fibrosis by its extracts, but whether its water extract has the effect of preventing and treating acute alcoholic liver injury, or whether it has a synergistic effect when combined with Hovenia seeds has not been reported yet. Summary of the Invention

[0005] Aiming at the current technical situation that the curative effect of existing traditional Chinese medicine compositions in preventing or treating acute alcoholic liver injury is not clear enough, and the components are complex and cannot take into account the effects of relieving alcohol intoxication and protecting the liver, and whether the water extract of Polygonatum sibiricum Red. has the effect of protecting acute alcoholic liver injury, or whether it has a synergistic effect when combined with Hovenia seeds has not been reported yet, the present invention aims to provide a traditional Chinese medicine composition with the effect of protecting acute alcoholic liver injury, its preparation method and application. This traditional Chinese medicine composition has the effect of protecting acute alcoholic liver injury, simultaneously improves serum liver function indexes (AST, ALT), corrects lipid metabolism disorders (TG, CHO), restores protein metabolism balance (TP, ALB), and significantly reduces pathological damage of liver tissue.

[0006] To achieve the above object, the technical solution adopted by the present invention is as follows: The present invention provides a traditional Chinese medicine composition with the effect of protecting acute alcoholic liver injury. Calculated by weight, this traditional Chinese medicine composition is made from the following raw medicinal materials: 1 - 2 parts of Polygonatum sibiricum Red., 1 - 2 parts of Hovenia seeds. The traditional Chinese medicine composition is the concentrated traditional Chinese medicine granules and / or traditional Chinese medicine extracts of the above raw medicinal materials.

[0007] Furthermore, the traditional Chinese medicine composition is the water extract of the above raw medicinal materials.

[0008] Furthermore, the traditional Chinese medicine composition is obtained by mixing polygonatum water extract and hovenia dulcis water extract in a mass ratio of 1-2:1-2.

[0009] The polygonatum water extract contains 1.3 g / mL of crude drug, and the hovenia dulcis water extract contains 1.3 g / mL of crude drug.

[0010] The present invention provides a preparation method of the above-mentioned traditional Chinese medicine composition with the function of protecting acute alcoholic liver injury, including: (1) Decocting and extracting polygonatum with 5-15 times its weight of water, and concentrating to obtain polygonatum water extract; (2) Decocting and extracting hovenia dulcis with 5-15 times its weight of water, and concentrating to obtain hovenia dulcis water extract; (3) Mixing the polygonatum water extract and the hovenia dulcis water extract to obtain.

[0011] In step (1), the decocting and extracting time is 1-3 h, and the extraction times are 1-3 times.

[0012] In step (2), the decocting and extracting time is 1-3 h, and the extraction times are 1-3 times.

[0013] Application of the above-mentioned traditional Chinese medicine composition with the function of protecting acute alcoholic liver injury in the preparation of drugs for protecting acute alcoholic liver injury.

[0014] The present invention provides a drug for protecting acute alcoholic liver injury, and the drug contains the above-mentioned traditional Chinese medicine composition with the function of protecting acute alcoholic liver injury.

[0015] The drug further includes one or more pharmaceutically acceptable excipients optionally.

[0016] The dosage form of the drug is tablet, pill, powder, capsule, granule, injection or oral liquid.

[0017] Compared with the prior art, the beneficial effects of the present invention are: The traditional Chinese medicine composition of polygonatum and hovenia dulcis provided by the present invention has simple components, is only composed of two traditional Chinese medicine materials, polygonatum and hovenia dulcis, with a moderate compatibility ratio, definite curative effect, and can effectively prevent or treat alcoholic liver injury; this traditional Chinese medicine composition has both the dual effects of relieving alcohol and protecting the liver. Hovenia dulcis has the effects of relieving alcohol and sobering up, and polygonatum has the effects of nourishing the liver and kidney, and moistening dryness. The combination of the two can synergistically improve the levels of biochemical indexes such as AST, ALT, TG, CHO, TP and ALB in the serum of mice after drinking, and improve the pathological damage of the liver tissue of mice after drinking, so as to achieve the purpose of preventing or treating acute alcoholic liver injury.

[0018] The preparation method provided by the present invention can ensure the maximum retention of the active pharmaceutical ingredients compared with other chemical preparation methods. The main core components of Polygonatum sibiricum and Hovenia dulcis are polysaccharides and saponins, which have good water solubility and higher water extraction yields. Decoction extraction with water conforms to the traditional medication theory and the requirements of industrial production. Thereby, it can improve the prevention and treatment effects of the traditional Chinese medicine composition on acute alcoholic liver injury; without using organic solvents and other chemical reagents, it avoids the potential hazards caused by solvent residues and by-products generated by chemical reactions to the human body, and improves the safety of the extract; the required equipment is simple and the cost is low.

[0019] The application provided by the present invention. The traditional Chinese medicine composition of Polygonatum sibiricum and Hovenia dulcis provided by the present invention has a synergistic effect compared with single Polygonatum sibiricum or Hovenia dulcis. Through two administration methods of preventive administration and therapeutic administration in two acute alcoholic liver injury models [Model I (acute alcoholic liver injury model induced by single large-dose intragastric administration of white liquor: 56% (V / V) Red Star Erguotou liquor was given at a dose of 0.12 mL / 10 g once); Model II (acute alcoholic liver injury model induced by continuous multiple intragastric administrations of white liquor): 56% (V / V) Red Star Erguotou liquor was given at a dose of 0.12 mL / 10 g by intragastric administration for 3 consecutive days], it can improve the levels of biochemical indexes such as AST, ALT, TG, CHO, TP, and ALB in the serum of mice after drinking, and improve the pathological damage of the liver tissue of mice after drinking, so as to achieve the purpose of preventing or treating acute alcoholic liver injury. The traditional Chinese medicine composition provided by the present invention can be used to prepare foods or drugs for protecting acute alcoholic liver injury, and has the characteristics of significant efficacy, safety and non-toxicity, easy absorption, wide application range, etc., and has broad clinical application value. Description of the Drawings

[0020] Figure 1 Effects of different treatment groups of the present invention on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury 10 h after drinking. Among them, A is AST, B is ALT, C is ALP, D is TG, E is CHO, F is TP, and G is ALB; Figure 2 Improvement effects of different treatment groups of the present invention on liver tissue injury of mice with acute alcoholic liver injury 10 h after drinking. Scale bar: 200 μm; Figure 3 Effects of different treatment groups of the present invention on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury 16 h after drinking. Among them, A is AST, B is ALT, C is ALP, D is TG, E is CHO, F is TP, and G is ALB; Figure 4 Improvement effects of different treatment groups of the present invention on liver tissue injury of mice with acute liver injury 16 h after drinking. Scale bar: 200 μm.

[0021] Figure 5 For the effects of post - drinking therapeutic administration of different treatment groups of the present invention on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury after drinking, where A is AST, B is ALT, C is ALP, D is TG, E is CHO, F is TP, and G is ALB; Figure 6 For the improvement effect of post - drinking therapeutic administration of different treatment groups of the present invention on liver tissue injury in mice with acute liver injury after drinking. Scale bar: 200 μm. Detailed implementation manners

[0022] In order to enable those skilled in the art of the present technology to better understand the solution of the present invention, the following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0023] The following further describes the present invention in detail: The materials and reagents involved in the following embodiments are: Male ICR mice, 4 weeks old, weighing 16 - 18 g, provided by Jicui Pharmaceutical. This experimental study was approved by the Biomedical Ethics Committee of the School of Medicine, Xi'an Jiaotong University (XJTUAE2025 - 2595). Silybin capsules (batch number: H20040299) were purchased from Tianjin Tasly Pharmaceutical Co., Ltd. Red Star Erguotou (batch number: GB / T10781.2) was purchased from Beijing Red Star Co., Ltd. Hovenia dulcis (batch number: 2024126) was purchased from Bozhou Fushuotang Biotechnology Co., Ltd. Polygonatum sibiricum was purchased from Wuyangtang Health Industry Co., Ltd. in Taishan Scenic Area, Tai'an City. I. Specific embodiments Example 1 This example provides a traditional Chinese medicine composition with the function of protecting acute alcoholic liver injury. The preparation method is as follows: Extraction of Polygonatum sibiricum: Weigh an appropriate amount of Polygonatum sibiricum, add 10 times the amount of water and decoct for extraction twice, each time for 2 h. After combining the two filtrates, concentrate to a concentration of 1.3 g / mL of crude drug content to obtain the water extract of Polygonatum sibiricum. The extracted drug is stored at - 20 °C for later use.

[0025] Extraction of Hovenia dulcis: Weigh an appropriate amount of Hovenia dulcis, add 10 times the amount of water and decoct for extraction twice, each time for 2 h. After combining the two filtrates, concentrate to a concentration of 1.3 g / mL of crude drug content to obtain the water extract of Hovenia dulcis. The extracted drug is stored at - 20 °C for later use.

[0026] Weigh the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. according to a mass ratio of 2:1, and mix them evenly to obtain a traditional Chinese medicine composition with the function of protecting against acute alcoholic liver injury.

[0027] Example 2 On the basis of Example 1, weigh the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. according to a mass ratio of 1:1, and mix them evenly to obtain a traditional Chinese medicine composition with the function of protecting against acute alcoholic liver injury.

[0028] Example 3 On the basis of Example 1, weigh the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. according to a mass ratio of 1:2, and mix them evenly to obtain a traditional Chinese medicine composition with the function of protecting against acute alcoholic liver injury.

[0029] II. Performance verification On the basis of Examples 1 to 3, a performance verification test was carried out on the traditional Chinese medicine composition of the present invention with the function of protecting against acute alcoholic liver injury.

[0030] Administration Group I: Weigh the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. according to a mass ratio of 1:1, and mix them evenly to obtain a traditional Chinese medicine composition with the function of protecting against acute alcoholic liver injury (the same as Example 2) Administration Group II: Weigh 50 g each of Polygonatum sibiricum Red. and Hovenia dulcis Thunb., mix them, add 10 times the amount of water and decoct for extraction twice, each time for 2 h. After combining the two filtrates, concentrate them to a concentration of 1.3 g / mL of the crude drug content to obtain a mixed aqueous extract of Polygonatum sibiricum Red. and Hovenia dulcis Thunb., and store the extracted drug at -20 °C for later use.

[0031] Preparation of silybin solution (positive drug): Dissolve 140 mg of silybin powder in water to 10 mL to prepare a 14 mg / mL solution, and administer it by gavage at 0.1 mL / 10 g.

[0032] (1) Effects on AST, ALT, ALP, TG, CHO, TP and ALB in the serum of mice with acute alcoholic liver injury 10 h after drinking Forty-eight male ICR mice, weighing 18 - 20 g, were adaptively fed for one week. After that, all the mice were divided into 8 groups according to body weight by randomized block design, namely: blank group, model group, Hovenia dulcis + white liquor group, group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 2:1 (Example 1) + white liquor group, group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 1:1 (Example 2) + white liquor group, group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 1:2 (Example 3) + white liquor group, Polygonatum sibiricum + white liquor group, and positive drug + white liquor group. Mice were prophylactically administered three days in advance. The model group was intragastrically administered distilled water at 0.1 mL / 10 g, and the other groups were intragastrically administered different medicinal liquids at 0.1 mL / 10 g. One hour after the fourth administration at the same dose, except for the blank group, the other mice were intragastrically administered Erguotou white liquor (alcohol concentration 56%) at 0.12 mL / 10 g once to induce an acute alcoholic liver injury model. Ten hours after alcohol gavage, the mice were anesthetized, blood was collected by enucleating the eyeballs, and serum was collected and separated. The indexes of ALT, AST, ALP, TG, CHO, TP, and ALB in the serum were detected by Wuhan Sevier Biotechnology Co., Ltd. GraphPad (6.0) was used to analyze the experimental data, and all experimental results were expressed as mean ± S.E.M. One-way ANOVN was used to analyze the differences between groups. P <0.05 indicates statistical significance, indicates compared with the normal control group P <0.001, *** indicates compared with the model group P <0.001, ** indicates compared with the model group P <0.01, * indicates compared with the model group P <0.05, ns indicates P >0.05 indicates no statistical significance; the results are as Figure 1 shown.

[0033] From the attached Figure 1 data, it can be seen that compared with the normal group, the levels of ALT, AST, and TG in the model group were significantly increased, and the level of ALB was significantly decreased. Among them, ALT and AST are the most sensitive indicators for evaluating the liver injury model, indicating that the acute liver injury model was successfully induced. Compared with the model group, each administration group could significantly improve the levels of ALT, AST, and TG in the serum of mice. In addition, the Hovenia dulcis group, the group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 2:1, and the group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 1:1 could significantly reduce the expression level of CHO in the serum. The group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 1:1 and the Polygonatum sibiricum group could significantly improve the expression level of ALB. Based on the comprehensive evaluation of the above indexes, the group with the mixture of aqueous extract of Hovenia dulcis and aqueous extract of Polygonatum sibiricum at a mass ratio of 1:1 was superior to other treatment groups in improving each index.

[0034] (2) Effects on the pathological injury of liver tissue in mice with acute alcoholic liver injury 10 h after drinking This experiment investigated the effects of different ratios of aqueous extracts of Hovenia dulcis Thunb. and Polygonatum sibiricum Red. on the pathological injury of liver tissue in mice with acute alcoholic liver injury 10 h after drinking.

[0035] Forty-eight ICR male mice were used, and the method of modeling and administration was the same as described in (1) of the performance test in Example 3. Ten hours after the last alcohol gavage, the mice were anesthetized, blood was taken by enucleating the eyeballs, and large lobes of liver tissue were dissected and fixed in 4% PFA fixative. The degree of liver injury was detected by hematoxylin-eosin (HE) staining. The specific operation steps were as follows: (A) Dewaxing paraffin sections to water: The sections were successively placed in environment-friendly dewaxing solution I for 20 min - environment-friendly dewaxing solution II for 20 min - absolute ethanol I for 5 min - absolute ethanol II for 5 min - 75% alcohol for 5 min, and then washed with tap water.

[0036] (B) Rewarming and fixing frozen sections: The frozen sections were taken out from the -20°C refrigerator and restored to room temperature, fixed with tissue fixative for 15 min, and then rinsed with running water. (C) Pretreatment: The sections were treated with a high-definition constant staining pretreatment solution for 1 min. (D) Hematoxylin staining: The sections were stained with hematoxylin solution for 3 - 5 min, washed with tap water, differentiated with a differentiating solution, washed with tap water, blued with a bluing solution, and rinsed with running water. (E) Eosin staining: The sections were dehydrated in 95% alcohol for 1 min and stained with eosin solution for 15 s. (F) Dehydration and mounting: The sections were successively placed in absolute ethanol I for 2 min - absolute ethanol II for 2 min - absolute ethanol III for 2 min - n-butanol I for 2 min - n-butanol II for 2 min - xylene I for 2 min - xylene II for 2 min for clearing, and then mounted with neutral balsam. (G) Microscopic examination and image acquisition and analysis.

[0037] The results were as Figure 2 shown. In the normal control group, the liver lobule structure was intact, irregular in shape, and was the normal liver tissue structure. The staining results of the model group showed that alcohol could cause obvious liver injury, including hepatocyte necrosis, infiltration of inflammatory cells, and unclear structure of liver lobules and portal areas, with vacuoles appearing. Compared with the model group, each administration group could significantly reverse the liver injury caused by alcohol. Among them, in the Hovenia dulcis Thunb. group, the degree of hepatocyte injury was significantly reduced. In the groups with the mass ratio of aqueous extract of Hovenia dulcis Thunb. to aqueous extract of Polygonatum sibiricum Red. being 2:1, 1:1, and 1:2, as well as the Polygonatum sibiricum Red. group and the positive drug group, no obvious liver tissue injury was observed.

[0038] (3) Effects on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury 16 h after drinking On the basis of Examples 1-3, the effects of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. and different ratios on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury 16 h after drinking were investigated.

[0039] Forty-eight ICR male mice, weighing 18-20 g, were randomly divided into 8 groups according to body weight by randomized block design after one week of adaptive feeding. The groups were: blank group, model group, Hovenia dulcis Thunb. + white liquor group, aqueous extract of Hovenia dulcis Thunb. and aqueous extract of Polygonatum sibiricum Red. in a mass ratio of 2:1 + white liquor group, aqueous extract of Hovenia dulcis Thunb. and aqueous extract of Polygonatum sibiricum Red. in a mass ratio of 1:1 + white liquor group, aqueous extract of Hovenia dulcis Thunb. and aqueous extract of Polygonatum sibiricum Red. in a mass ratio of 1:2 + white liquor group, Polygonatum sibiricum Red. + white liquor group, and positive drug + white liquor group. Mice were prophylactically administered three days in advance. The model group was intragastrically administered distilled water at 0.1 mL / 10 g, and the other groups were intragastrically administered different medicinal liquids at 0.1 mL / 10 g. One hour after administration on the fourth day, except for the blank group, the other mice were intragastrically administered Erguotou white liquor (alcohol concentration 56%) at 0.12 mL / 10 g once to induce an acute alcoholic liver injury model. Sixteen hours after alcohol gavage, the mice were anesthetized, blood was collected by enucleation of the eyeballs, the serum was collected and separated, and the ALT, AST, ALP, TG, CHO, TP, and ALB indexes in the serum were detected. The specific operation steps were the same as in experiment (1). GraphPad (6.0) was used to analyze the experimental data, and all experimental results were expressed as mean±S.E.M. One-way ANOVN was used to analyze the differences between groups. P <0.05 indicates statistical significance. indicates compared with the normal control group P <0.001, *** indicates compared with the model group P <0.001, ** indicates compared with the model group P <0.01, * indicates compared with the model group P <0.05, ns indicates P >0.05 indicates no statistical significance.

[0040] The results are as Figure 3As shown, the levels of ALT, AST, and TG in the model group were significantly increased, while the levels of TP and ALB were significantly decreased. Among them, ALT and AST are the most sensitive indicators for evaluating the liver injury model, and TP and ALB are important indicators for evaluating liver function and nutritional status. The above results indicate that the acute liver injury model was successfully induced. Compared with the model group, each administration group could significantly improve the levels of ALT and AST in the serum of mice. Among them, in terms of improving ALT, the groups with the mass ratio of 2:1, 1:1, and 1:2 of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. showed significantly better curative effects than the groups administered with Hovenia dulcis Thunb. or Polygonatum sibiricum Red. alone. In terms of improving AST, the group with the mass ratio of 1:1 of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. had a more significant curative effect. In terms of improving the TG index, Hovenia dulcis Thunb. and the group with the mass ratio of 2:1 of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. did not significantly reduce the level of TG in the serum of mice. Therefore, in terms of improving the TG level, the groups with the mass ratio of 1:1 and 1:2 of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. showed more obvious advantages. In addition, in terms of improving the levels of CHO and TP, there was no statistical difference between each treatment group and the model group. However, in terms of improving the ALB index, the groups with the mass ratio of 2:1, 1:1 of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red., and the group administered with Polygonatum sibiricum Red. alone were superior to other treatment groups. Based on the comprehensive evaluation of the above indicators, the group with the mass ratio of 1:1 of the aqueous extract of Hovenia dulcis Thunb. and the aqueous extract of Polygonatum sibiricum Red. was superior to other treatment groups in improving each indicator.

[0041] (4)Effect on the pathological injury of liver tissue in acute alcoholic liver injury mice 16 h after drinking On the basis of experiment (1), the effect of Hovenia dulcis Thunb., Polygonatum sibiricum Red., and different ratios on the pathological injury of liver tissue in acute alcoholic liver injury mice 16 h after drinking was investigated.

[0042] Forty-eight male ICR mice were modeled and administered according to the method of experiment (3). Sixteen hours after the last alcohol gavage, the mice were anesthetized, blood was taken by enucleating the eyeballs, and the large lobes of liver tissue were dissected and fixed in 4% PFA fixative. HE staining was used to observe the degree of liver injury. The specific implementation steps of HE staining were the same as those in experiment (2).

[0043] The results were as Figure 4As shown, the hepatic lobule structure of the normal control group was intact, irregular in shape, and represented the normal hepatic tissue structure. The staining results of the model group indicated that alcohol could cause obvious liver damage, including hepatocyte necrosis, inflammatory cell infiltration, and unclear hepatic lobule and portal area structures, with vacuoles appearing. Compared with the model group, each drug administration group could significantly reverse alcohol-induced liver injury. Among them, no obvious pathological liver tissue damage was observed in the Hovenia dulcis group, the group of Hovenia dulcis aqueous extract and Polygonatum sibiricum aqueous extract in a mass ratio of 2:1, the group of Hovenia dulcis aqueous extract and Polygonatum sibiricum aqueous extract in a mass ratio of 1:1, the group of Hovenia dulcis aqueous extract and Polygonatum sibiricum aqueous extract in a mass ratio of 1:2, the Polygonatum sibiricum group, and the positive drug group.

[0044] (5)Effects of different extraction methods of the 1:1 compatibility of Hovenia dulcis and Polygonatum sibiricum on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury after drinking To more comprehensively evaluate the effects of the combination of Hovenia dulcis and Polygonatum sibiricum on acute alcoholic liver injury, based on the preventive administration results of experiments (1) to (4) in this study, two drug extraction methods of the group of Hovenia dulcis aqueous extract and Polygonatum sibiricum aqueous extract in a mass ratio of 1:1 with the most significant comprehensive efficacy (see Administration Group I and Administration Group II in the performance test of Example 3) were selected to conduct a post-drinking treatment administration test on mice, and the effects of the 1:1 compatibility of Hovenia dulcis aqueous extract and Polygonatum sibiricum aqueous extract on AST, ALT, ALP, TG, CHO, TP, and ALB in the serum of mice with acute alcoholic liver injury after drinking were investigated.

[0045] For ICR male mice, weighing 18 - 20 g, after one week of adaptive feeding, all mice were divided into 8 groups according to body weight using a randomized block design, namely: blank group, model group, Administration Group I + white liquor group (2 h), Administration Group II + white liquor group (2 h), positive drug + white liquor group (2 h), Administration Group I + white liquor group (4 h), Administration Group II + white liquor group (4 h), positive drug + white liquor group (4 h). After the model group and the drug administration groups were intragastrically administered white liquor at 9 am every day, the drug administration groups were intragastrically administered different medicinal liquids at 2 h and 4 h after drinking, respectively. The blank group and the model group were given the same volume of distilled water. After 3 consecutive days, the mice were treated and various indicators were observed. The experimental data were analyzed using GraphPad (6.0), and all experimental results were expressed as mean ± S.E.M. One-way ANOVN was used to analyze the differences between groups. P <0.05 indicates statistical significance. indicates compared with the normal control group P <0.001, *** indicates compared with the model group P <0.001, ** indicates compared with the model group P <0.01, * indicates compared with the model group P <0.05, ns indicates P >0.05 indicates no statistical significance. The results are asFigure 5 as shown

[0046] From the attached Figure 5 data, it can be seen that the levels of ALT, AST, TG, and CHO in the model group were significantly increased, while the levels of TP and ALB were significantly decreased, indicating that the acute liver injury model was successfully induced. Compared with the model group, the levels of ALT and AST in the serum of mice in the drug administration group I and the drug administration group II were significantly improved when administered 2 hours after drinking, but the drug administration group II did not significantly improve the ALT index when administered 4 hours after drinking. None of the drug administration groups had an obvious improvement effect on the ALP index. In terms of improving the TG index, both the drug administration group I and the drug administration group II could significantly reduce the level of TG in the serum of mice when administered 2 hours or 4 hours after drinking. Among them, the effect of the drug administration group II when administered 4 hours after drinking was slightly weaker than that of the 2-hour administration group. Therefore, both drug administration groups showed obvious advantages in improving the TG level. In addition, there was no statistical difference in improving the CHO level among the treatment groups compared with the model group. At the same time, both the drug administration group I and the drug administration group II could significantly improve the abnormal indexes of TP and ALB in the serum of mice after drinking.

[0047] Based on the comprehensive evaluation of the above indexes, both the drug extraction methods of the drug administration group I and the drug administration group II can significantly improve the indexes of AST, ALT, TG, ALB, and TP, and the effects of improving AST and ALT are significantly stronger than those of the positive drug.

[0048] (6) Effects on the pathological injury of liver tissue in mice with acute alcoholic liver injury On the basis of experiment (5), this experiment investigated the effects of different drug extraction methods of 1:1 Hovenia dulcis and Polygonatum sibiricum on the pathological injury of liver tissue in mice with acute alcoholic liver injury when administered 2 hours or 4 hours after drinking.

[0049] The establishment of the acute alcoholic liver injury model and the administration method were the same as in experiment (5). After 16 hours of the last alcohol gavage, the mice were anesthetized, blood was taken by removing the eyeballs, and large lobes of liver tissue were dissected and fixed in 4% PFA fixative. HE staining was used to observe the degree of liver injury. The specific implementation steps of HE staining were the same as in experiment (1). The results are as Figure 6 shown

[0050] From the attached Figure 6 data, it can be seen that the hepatic lobule structure of the normal control group was complete, irregular in shape, and was the normal liver tissue structure. The staining results of the model group showed that alcohol could cause obvious liver damage, including hepatocyte necrosis, inflammatory cell infiltration, and unclear hepatic lobule and portal area structures, with vacuoles appearing. Compared with the model group, the drug administration group I, the drug administration group II, and the positive drug could all significantly reverse the liver damage caused by alcohol, and no obvious pathological damage to the liver tissue was seen, indicating that the traditional Chinese medicine compositions provided in Examples 1 to 3 of the present invention can significantly improve the liver damage in mice with acute alcoholic liver injury.

[0051] In summary, the present invention demonstrates that prophylactic or therapeutic administration of the combination of Hovenia dulcis Thunb. and Polygonatum sibiricum Redoute can significantly improve the levels of ALT, AST, TG, CHO, TP, and ALB, and the curative effect is superior to that of the group administered with Hovenia dulcis Thunb. or Polygonatum sibiricum Redoute alone, indicating that the combination of Hovenia dulcis Thunb. and Polygonatum sibiricum Redoute can play a synergistic effect in preventing and treating acute alcoholic liver injury. In addition, the HE staining results show that each administration group can improve the pathological damage of liver tissue in mice after drinking; it reveals the possibility of the Hovenia dulcis Thunb. and Polygonatum sibiricum Redoute composition in the preparation of drugs for protecting acute alcoholic liver injury, laying a foundation for further preventing and treating drugs for acute alcoholic liver injury, and having important development value and popularization significance.

[0052] The above content is only to illustrate the technical idea of the present invention and cannot be used to limit the protection scope of the present invention. Any modification made on the basis of the technical solution according to the technical idea proposed by the present invention falls within the protection scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for protecting acute alcoholic liver damage, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials by weight: 1-2 parts of polygonatum sibiricum and 1-2 parts of hovenia dulcis.

2. A Chinese medicine composition for protecting acute alcoholic liver damage according to claim 1, characterized in that: The Chinese medicine composition is concentrated Chinese medicine granules and / or Chinese medicine extracts of the raw material medicine.

3. A Chinese medicine composition for protecting acute alcoholic liver damage according to claim 2, characterized in that: The Chinese medicine composition is a water extract of the raw material drug.

4. A Chinese medicine composition for protecting acute alcoholic liver damage according to claim 3, characterized in that: The traditional Chinese medicine composition is obtained by mixing the water extract of polygonatum sibiricum and the water extract of hovenia dulcis in a mass ratio of 1-2:1-2.

5. A Chinese medicine composition for protecting acute alcoholic liver damage according to claim 4, characterized in that: The water extract of polygonatum contains 1.3 g / mL of crude drug, and the water extract of hovenia dulcis contains 1.3 g / mL of crude drug.

6. A method for preparing the Chinese medicine composition for protecting acute alcoholic liver damage according to any one of claims 1 to 5, characterized in that: include: (1) boiling and extracting Polygonatum sibiricum with 5 to 15 times the weight of water, and concentrating the water extract to obtain Polygonatum sibiricum; (2) decoct the Hovenia dulcis fruit with 5 to 15 times the weight of water, and concentrate to obtain a Hovenia dulcis fruit water extract; (3) The method is obtained by mixing the water extract of Polygonatum sibiricum and the water extract of Hovenia dulcis.

7. The method for preparing the Chinese medicine composition for protecting acute alcoholic liver damage according to claim 6, characterized in that: In step (1), the water decoction extraction time is 1 to 3 hours, and the number of extractions is 1 to 3 times; in step (2), the water decoction extraction time is 1 to 3 hours, and the number of extractions is 1 to 3 times.

8. Use of the Chinese medicinal composition for protecting acute alcoholic liver injury according to any one of claims 1 to 5 in the preparation of a medicine for protecting acute alcoholic liver injury.

9. A drug for protecting against acute alcoholic liver damage, characterized in that: The medicine comprises the Chinese medicinal composition for protecting acute alcoholic liver damage according to any one of claims 1 to 6.

10. A drug for protecting against acute alcoholic liver damage according to claim 9, characterized in that: The drug further comprises one or more pharmaceutically acceptable excipients, and the drug dosage form is tablets, pills, powders, capsules, granules, injections or oral liquids.

Images