Composition for assisting in protecting chemical liver injury and gastric mucosal injury as well as preparation method and product thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a composition for assisting in protecting chemical liver injury and gastric mucosal injury as well as a preparation method and a product of the composition. The composition is prepared from the following components in parts by weight: 35 to 45 parts of radix puerariae extract, 25 to 35 parts of semen hoveniae extract, 25 to 35 parts of radix codonopsis extract, 28 to 33 parts of radix salviae miltiorrhizae extract and 25 to 35 parts of rhizoma atractylodis macrocephalae extract. The composition has a comprehensive treatment effect on alcoholic liver injury and gastric mucosal injury by synergistically regulating lipid metabolism, oxidative stress, inflammatory response and cell signal pathways. According to the technical scheme provided by the invention, comprehensive protection on alcoholic liver injury and gastric mucosal injury is realized through multi-channel cooperative regulation and control, and the defects of single target spot and limited curative effect of the existing therapeutic drug are overcome. The technical scheme provides a safe and effective intervention measure for digestive system injury caused by alcohol, and has a wide application prospect in the field of health-care product and medicine development.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a composition for assisting in protecting chemical liver injury and gastric mucosal injury, a preparation method thereof and a product. BACKGROUND

[0002] Chemical liver injury is caused by chemical hepatotoxic substances, including alcohol, environmental chemical toxic substances and certain drugs. As an important detoxification organ of the human body, the liver has dual blood supply of the hepatic artery and the hepatic vein, and chemical substances can enter the liver for transformation through the gastrointestinal portal vein or the systemic circulation, so the liver is easily damaged by toxic substances in chemicals. There are some substances toxic to the liver in nature and the process of human industrial production, which are called "liver-loving poisons". These poisons are generally susceptible in the population, have a short incubation period, and the process of lesion is directly related to the dose of infection, which can cause liver cell necrosis, fatty degeneration, liver fibrosis, liver cirrhosis and liver cancer of different degrees.

[0003] Alcoholic liver injury is one of the common chemical liver injuries in clinical practice, which usually presents as alcoholic fatty liver in the early stage, and may develop into alcoholic hepatitis, liver fibrosis, cirrhosis and hepatocellular carcinoma without effective treatment. Long-term heavy drinking can also cause gastric mucosal injury. Ethanol can destroy the mucus layer of the gastric mucosa, damage the gastric mucosal barrier, and cause acute inflammation, bleeding, erosion and ulceration of the gastric mucosa.

[0004] There are some invention patents on the problem of solving the comprehensive treatment of alcoholic liver injury. For example, patent CN108066473A discloses a preparation for protecting chemical liver injury, which is made of pueraria extract, jujube seed extract, mulberry fruit extract and schisandra extract. The preparation can ensure that the health care function is fully and effectively exerted, and the safety of the product is ensured through the reasonable combination of each functional raw material. Patent CN117899145A discloses a traditional Chinese medicine composition for preventing and treating alcoholic liver injury, which is prepared from pueraria, jujube seed, bupleurum and red peony root as main raw materials. The composition has no toxic side effects and can be used for acute alcohol poisoning and chronic alcoholic liver injury.

[0005] In the prior art, there is still a significant gap in the treatment scheme that can simultaneously provide synergistic protection for alcoholic liver injury and gastric mucosal injury. First, from the perspective of treatment targets, the prior art mainly adopts single organ protection strategy. Clinically commonly used liver-protecting drugs (such as silymarin, bicyclol, etc.) mainly act on the liver through antioxidant or anti-inflammatory mechanisms, while gastric mucosal protective agents (such as bismuth agents, proton pump inhibitors) only target gastric acid secretion or mucosal repair mechanisms. This "headache medicine head, foot pain medicine foot" treatment mode cannot fundamentally block the multi-target damage process of alcohol in the digestive system.

[0006] Secondly, the existing patent technology generally lacks systematic and synergistic protection design. For example, although patent CN108066473A adopts a combination of various plant extracts, the component selection only considers liver protection function and does not involve gastric mucosa protection mechanism. Similarly, although patent CN117899145A expands the application range of traditional Chinese medicine composition, the mechanism research is still limited to liver pathological improvement and fails to reflect the design concept of overall protection of the digestive system.

[0007] Therefore, it has important theoretical and application value to develop a product capable of realizing comprehensive protection of alcoholic liver injury and gastric mucosa injury through multi-channel synergistic regulation. SUMMARY

[0008] In view of the above deficiencies, the present application provides a composition for auxiliary protection of chemical liver injury and gastric mucosa, as well as a preparation method and product thereof. The composition is composed of five traditional Chinese medicine extracts in a specific ratio, including pueraria extract, jujube seed extract, radix ginseng extract, atractylodes extract and salvia miltiorrhiza extract. The compound preparation plays a comprehensive protection role of multi-target and multi-channel through the synergistic effect of multiple active ingredients, aiming at the damage of the digestive system caused by alcohol. It provides a safe and multi-effect intervention scheme for alcohol-induced damage of the digestive system, and provides a new idea and means for the prevention and treatment of alcoholic diseases.

[0009] The technical scheme of the present application is as follows: On the one hand, the present application provides a composition for auxiliary protection of chemical liver injury and gastric mucosa, which is composed of the following ingredients by weight fraction: pueraria extract 35-45 parts, jujube seed extract 25-35 parts, radix ginseng extract 25-35 parts, atractylodes extract 25-35 parts and salvia miltiorrhiza extract 28-33 parts.

[0010] Specifically, the puerarin in the pueraria extract is ≥10.5%; The total flavonoids in the jujube seed extract are ≥10%; The polysaccharide in the radix ginseng extract is ≥10%; The crude polysaccharide in the atractylodes extract is ≥15%; The salvianolic acid B in the salvia miltiorrhiza extract is ≥5%.

[0011] Specifically, the composition consists of one of the following (1)-(3) combinations by weight fraction: (1) pueraria extract 35 parts, jujube seed extract 35 parts, radix ginseng extract 35 parts, salvia miltiorrhiza extract 28 parts and atractylodes extract 25 parts; (2) pueraria extract 40 parts, jujube seed extract 30 parts, radix ginseng extract 30 parts, salvia miltiorrhiza extract 30 parts and atractylodes extract 30 parts; (3) 45 parts of Pueraria extract, 32 parts of Hovenia extract, 25 parts of Codonopsis extract, 33 parts of Salvia extract and 35 parts of Atractylodes extract.

[0012] In another aspect, the present application provides use of the aforementioned composition in the preparation of a product for assisting in the protection of chemical-induced liver injury and gastric mucosa.

[0013] Specifically, the product is a medicine or a health product.

[0014] Specifically, the medicine or health product further comprises a pharmaceutical excipient.

[0015] Preferably, the pharmaceutical excipient is one or more of dextrin, starch, microcrystalline cellulose, talc, magnesium stearate.

[0016] Specifically, the dosage form of the medicine or health product is a capsule, a tablet, a powder, a granule, an oral liquid, a liquor, a pill, a mixture or a tincture.

[0017] In another aspect, the present application provides a preparation method of the aforementioned composition, comprising weighing Pueraria extract, Hovenia extract, Codonopsis extract, Atractylodes extract and Salvia extract in parts by weight and mixing them.

[0018] In another aspect, the present application provides a health product comprising the aforementioned composition.

[0019] Specifically, the health product further comprises a pharmaceutical excipient.

[0020] Preferably, the pharmaceutical excipient is one or more of dextrin, starch, microcrystalline cellulose, talc, magnesium stearate.

[0021] Specifically, the dosage form of the health product is a capsule, a tablet, a powder, a granule, an oral liquid, a liquor, a pill, a mixture or a tincture.

[0022] In another aspect, the present application provides a medicine comprising the aforementioned composition.

[0023] Specifically, the medicine further comprises a pharmaceutically acceptable excipient.

[0024] Preferably, the pharmaceutically acceptable excipient is selected from one or more of a wetting agent, an emulsifying agent, a preservative, an antioxidant, a buffering agent, an excipient, a diluent, a lubricant, a bacteriostatic agent, a suspending agent, a suspending aid, a solubilizing agent, a thickening agent, a stabilizing agent, a sweetener and a flavoring agent.

[0025] Preferably, the pharmaceutically acceptable adjuvant is selected from at least one of lactose, mannose, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, polyvinylpyrrolidone, cellulose, water, sugar syrup, methylcellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, magnesium stearate, and mineral oil.

[0026] In particular, the dosage form of the drug is a capsule, a tablet, a powder, a granule, an oral solution, a liquor, a pill, a pellet, a mixture, or a tincture.

[0027] The present application has the following beneficial effects: (1) The composition provided by the present application has a significant improvement effect on alcohol-induced liver histopathological damage.

[0028] (2) The composition provided by the present application significantly reduces the lipid droplet area (fatty accumulation) on the surface of the liver, and relieves the fatty accumulation in the liver tissue caused by alcohol intake.

[0029] (3) The composition provided by the present application can effectively reduce the increase of ALT, AST, TG, and TC levels caused by alcoholic liver damage.

[0030] (4) The composition provided by the present application can significantly improve the levels of SOD, GSH-Px, and GSH in liver tissue, and significantly reduce the level of MDA, improve the ability of liver cells to scavenge free radicals, and relieve oxidative stress to improve liver damage.

[0031] (5) The composition provided by the present application can reduce the levels of TNF-α, IL-1β, and IL-6, which are related to liver inflammation.

[0032] (6) The composition provided by the present application can activate the ACC / AMPK signaling pathway, improve the ratio of p-ACC / ACC and p-AMPK / AMPK, inhibit the expression of SREBP-1c protein, promote fatty acid oxidation, reduce the synthesis of fatty acids and the accumulation of triglycerides in liver tissue, inhibit lipogenesis, and improve alcoholic liver damage.

[0033] (7) The composition provided by the present application significantly reduces the damage score of gastric mucosa tissue.

[0034] (8) The composition provided by the present application has a relatively obvious improvement effect on the condition of gastric mucosa, and shows a good treatment effect.

[0035] (9) The composition provided by the present application significantly improves the levels of SOD, GSH-Px, and GSH in the gastric mucosa tissue of mice, significantly reduces the level of MDA, improves the ability of gastric mucosa tissue to scavenge free radicals, and relieves oxidative stress to improve gastric mucosa damage.

[0036] (10) The composition provided by the present application can reduce the levels of alcohol-related gastric mucosal inflammation factors IL-6, TNF-alpha and IL-1beta.

[0037] (11) The composition provided by the present application can inhibit the specific increase of ERK phosphorylation level caused by alcohol, and thereby inhibit the activation of the ERK signal pathway, so as to regulate the proliferation and differentiation of inflammatory cells to achieve the effect of protecting the gastric mucosa; the composition can also inhibit the phosphorylation activity of p38 and JNK caused by alcohol, significantly reduce the p-p38 / p38 and p-JNK / JNK ratio, and effectively regulate the secretion of pro-inflammatory factors by blocking the activation of p-p38 and p-JNK signal pathways, thereby blocking the apoptosis process. BRIEF DESCRIPTION OF DRAWINGS

[0038] Figure 1 The pathological picture of acute liver injury (20x).

[0039] Figure 2 The pathological picture of acute gastric mucosal injury (40x). DETAILED DESCRIPTION

[0040] The present application will be further clarified by the following examples, which are only a part of the present application, and are not used to limit the present application, but only to illustrate the present application. The experimental methods used in the following examples are conventional experiments, and the materials, reagents, etc. used in the following examples are commercially available unless otherwise specified.

[0041] The purchase sources of the main raw materials of the present application are shown in Table 1: Table 1 Purchase sources of main raw materials

[0042] Example 1 1.1 Composition of the composition 35 parts of pueraria extract, 35 parts of honey locust fruit extract, 35 parts of radix codonopsis extract, 28 parts of salvia miltiorrhiza extract and 25 parts of atractylodes extract by weight.

[0043] 1.2 Preparation process of the composition Take the formula amount of pueraria extract, honey locust fruit extract, radix codonopsis extract, atractylodes extract and radix codonopsis extract, and sequentially put them into a rapid mixer for mixing (the mixer is kept in a low-speed running state when feeding), and then run at high speed for 5 min after feeding. Package to get the finished product.

[0044] Example 2 The difference from Example 1 is that the composition comprises: Pueraria extract 40 parts, Hovenia dulcis fruit extract 30 parts, Codonopsis extract 30 parts, Salvia extract 30 parts, and Atractylodes extract 30 parts. The rest is the same as Example 1.

[0045] Example 3 The difference from Example 1 is that the composition comprises: Pueraria extract 45 parts, Hovenia dulcis fruit extract 25 parts, Codonopsis extract 25 parts, Salvia extract 33 parts, and Atractylodes extract 35 parts. The rest is the same as Example 1.

[0046] Comparative Example 1 The difference from Example 1 is that the Atractylodes extract in Example 1 is replaced with an equal amount of Poria extract. The rest is the same as Example 1.

[0047] Comparative Example 2 The difference from Example 1 is that the Atractylodes extract in Example 1 is replaced with an equal amount of Astragalus extract. The rest is the same as Example 1.

[0048] Comparative Example 3: The difference from Example 1 is that no Atractylodes extract is added. The rest is the same as Example 1.

[0049] Comparative Example 4 The difference from Example 1 is that only Atractylodes extract 35 parts is contained.

[0050] Comparative Example 5 The difference from Example 1 is that only Poria extract 35 parts is contained.

[0051] Comparative Example 6 The difference from Example 1 is that only Astragalus extract 35 parts is contained.

[0052] Comparative Example 7 The difference from Example 1 is that no Pueraria extract is added. The rest is the same as Example 1.

[0053] Comparative Example 8 The difference from Example 1 is that no Pueraria extract and Atractylodes extract are added. The rest is the same as Example 1.

[0054] Example 1 1.1 Establishment of an acute alcoholic liver injury animal model SPF Balb / c mice weighing 18-22 g were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. The mice had no significant difference in body weight (P>0.05). The mice were raised in a standard animal room with a humidity of 40-60% and a temperature of 23±2℃, with 12h of alternating light and dark. The mice were allowed to eat and drink freely during this period.

[0055] After 3 days of environmental adaptation feeding, they were randomly divided into 13 groups: blank control group, model control group, Example 1-Example 3 groups, Comparative Example 1-Comparative Example 8 groups, 10 in each group. The mice in Example 1-Example 3 and Comparative Example 1-Comparative Example 8 were respectively given 1668 mg / kg·BW of the corresponding composition (dissolved in distilled water) by gavage, with a volume of 20 mL / kg·BW. The normal control group and the model control group were given the same volume of distilled water by gavage, once a day, for 30 consecutive days. After that, except for the blank control group, the other groups were given 12 mL / kg of 50% (v / v) (diluted with distilled water) anhydrous ethanol by gavage to establish an acute alcoholic liver injury mouse model. The blank control group was given distilled water. After fasting for 16 h, the mice were anesthetized by intraperitoneal injection of 4% (m / v) chloral hydrate solution at 0.2 mL / 20 g. The mice were sacrificed by cervical dislocation after taking blood from the eyeball, and the blood was collected in 2 mL centrifuge tubes. After storage at 4℃ for 45 min, the blood was centrifuged at 4℃ at 3500 rpm for 15 min. The upper layer of light yellow transparent liquid was collected as serum and immediately stored in a -80℃ refrigerator. The mouse liver tissue samples were immersed in 4% (m / v) paraformaldehyde for pathological sectioning, and the remaining liver tissue was quickly frozen in liquid nitrogen and stored in a -80℃ refrigerator for detection of various indicators.

[0056] 1.2 Detection index 1.2.1 Determination of mouse serum indicators The collected mouse serum samples were taken out from the -80℃ refrigerator, thawed and placed in an ice bath. The AST (catalog number: C010-2-1, Nanjing Jiancheng Biological Engineering Institute), ALT (catalog number C009-2-1, Nanjing Jiancheng Biological Engineering Institute), TC (catalog number A111-1-1, Nanjing Jiancheng Biological Engineering Institute) and TG (catalog number A110-1-1, Nanjing Jiancheng Biological Engineering Institute) kits (Nanjing Jiancheng Biological Engineering Institute) were used to detect the activity of AST and ALT and the content of TC and TG in the mouse serum according to the instructions.

[0057] 1.2.2 Determination of oxidative stress factors in mouse liver tissue Take 0.5 g of liver tissue of each group of mice with residual blood removed, add 1:10 (m / v) of extraction solution, and grind in a homogenizer at low temperature until slurry. Centrifuge at low temperature (4°C, 10000 rpm) for 10 min, collect the supernatant and store in an EP tube in a -80°C refrigerator for standby. Use GSH-Px (item number A005-1-2, Nanjing Jiancheng Biological Engineering Institute), GSH (item number A006-2-1, Nanjing Jiancheng Biological Engineering Institute), MDA (item number A003-1-2, Nanjing Jiancheng Biological Engineering Institute), and SOD (item number A001-3-2, Nanjing Jiancheng Biological Engineering Institute) kits to determine the activity or content of GSH-Px, GSH, MDA, and SOD in mouse liver tissue. The experimental steps are operated in accordance with the kit instructions. During the experiment, the key parameters such as reaction system preparation, incubation temperature and time are accurately controlled to ensure the accuracy and reliability of the test results.

[0058] 1.2.3 Determination of inflammatory cytokines in mouse liver tissue Take 0.5 g of mouse liver tissue with residual blood removed, add 0.01 mol / L PBS solution (pH 7.4) at 1:9 (m / v), and add appropriate amount of protease inhibitor in a glass homogenizer. Grind in a homogenizer. Centrifuge the homogenate at 5000 rpm for 10 min, take the protein lysate supernatant of mouse liver tissue, and use enzyme-linked immunosorbent assay (ELISA) to detect the content of IL-1β (E-EL-M0037, Wuhan Elabscience Biotechnology Co., Ltd.), IL-6 (item number E-EL-M0044, Wuhan Elabscience Biotechnology Co., Ltd.), and TNF-α (item number E-EL-M3063, Wuhan Elabscience Biotechnology Co., Ltd.) in mouse liver tissue. The operation steps are strictly carried out according to the instructions in the ELISA kit.

[0059] 1.2.4 Detection of liver tissue protein expression level Select the key proteins p-AMPK, AMPK, SREBP-1c, p-ACC, and ACC in the lipid metabolism pathway of liver tissue as target detection proteins, and use immunoblotting to detect the expression levels of these proteins in liver tissue. The specific steps are as follows: (1) Protein extraction: 100 mg of liver tissue sample was accurately weighed and placed in a pre-cooled glass tissue grinder. 1 mL of premixed protease and phosphatase inhibitor RIPA lysis buffer was added, and low-temperature grinding was performed for 20 minutes to fully lyse. Then, centrifugation was performed for 10 minutes (12000 rpm, 4°C) to obtain total protein. The protein concentration was detected using a total protein quantification kit (with standard: BCA method) (microplate method) (item number A045-4-2, Nanjing Jiancheng Biological Engineering Institute). The concentration was adjusted to a uniform level with lysis buffer, and the supernatant was added to 4x protein loading buffer at a ratio of 3:1 (v / v). After mixing, boiling water bath was performed for 15 min, and the cooled sample was stored for use.

[0060] (2) Western blotting: After preparing 15% (wt) separating gel and 5% (wt) concentrated gel, add enough electrophoresis solution to the electrophoresis tank, complete the sample protein and pre-stained Marker loading, and perform SDS-PAGE electrophoresis at a constant voltage of 150V. After electrophoretic separation, the proteins in the gel were transferred to a 0.45μm PVDF membrane by wet transfer method, and a constant current of 200mA and ice bath were maintained during the transfer process. Then the PVDF membrane was blocked with 5%wt blocking solution at room temperature for 1h, and then incubated with the first antibody at 4°C overnight, washed with TBST for 3 times (10min each time), incubated with the second antibody at room temperature for 1h, and washed with TBST for 5 times (10min each time). Finally, the target protein was developed using the ultra-sensitive ECL chemiluminescence kit (item number P0018FS, Shanghai Biyun Tian Biological Technology Co., Ltd.), the gel imaging system was used to collect the image, and the Image J software was used to quantitatively analyze the optical density of the target protein band. The liver tissue protein was used as an internal reference.

[0061] 1.2.5 Liver tissue pathological score (1) Experimental materials: Take samples from the middle of the left lobe of the liver, freeze sections, and perform staining.

[0062] (2) Microscopy: Record the pathological changes of cells from the field of view at one end of the liver, and continuously observe the entire tissue section with a 40x objective lens. The distribution, range and area of lipid droplets in the liver were observed.

[0063] (3) The scoring criteria are shown in Table 2: Table 2 Scoring criteria

[0064] (4) Data processing Analyze the variance, but need to conduct variance homogeneity test according to the procedure of variance analysis, if the variance is homogeneous, calculate F value, F value < F0.05. Conclusion: There is no significant difference between the means of each group: F value > F0.05, P≤0.05, use the pairwise comparison method between the means of multiple experimental groups and a control group for statistics; for non-normal or non-homogeneous variance data, perform appropriate variable transformation, and after meeting the requirements of normality or homogeneity of variance, use the transformed data for statistics; if the variable transformation still does not meet the requirements of normality or homogeneity of variance, use rank sum test for statistics.

[0065] 1.3 Experimental results 1.3.1 Protective effect of the composition on liver damage (1) Liver histopathological results Prepare mouse liver histopathological sections by HE staining method to observe the morphological characteristics of liver cells, cell structure integrity and inflammatory cell infiltration and other histopathological changes, and analyze the effects of the examples and comparative examples on the liver tissue of chemical liver injury mice. From Figure 1 It can be seen that the liver tissue structure of the blank control group mice is complete and clear, the liver cell structure integrity is good, the size is basically consistent, the arrangement is neat and close, the cytoplasm is uniformly dyed, the nucleus is clear and large and round, and no fatty degeneration is found. In contrast, the image of the model control group shows that the liver cell morphological structure is severely damaged, the cells are arranged in disorder and loose, there are a large number of fat vacuoles, and the cytoplasm is lightly dyed. And the liver cell volume increases, the cell swells, the cell boundary is blurred, and there may be inflammatory cell infiltration, indicating that the large intake of alcohol causes pathological changes in liver tissue.

[0066] After the intervention of examples 1-3, most of the liver cells of the mice are complete in morphological structure, the cells are arranged in neat and close, and the broken cells and fat vacuoles are significantly reduced, which has obvious improvement effect on the pathological damage of liver tissue caused by alcohol. In summary, examples 1-3 improve the pathological damage of liver tissue caused by alcohol.

[0067] Compared with examples 1-3, the liver images of mice after the intervention of comparative examples 1-8 show that part of the liver cells are broken, the cell size is not uniform, the intercellular space is large, there are many fat vacuoles, and the cytoplasm is lightly dyed. It can be seen that the relief effect of comparative examples 1-8 on liver tissue damage is poor. Among them, compared with comparative examples 5-6, the intercellular space of liver cells of mice after the intervention of comparative example 4 is large, and there are many fat vacuoles, which is consistent with the liver damage pathological score results in table 2.

[0068] (2) Liver damage pathological score The liver histopathology was scored by observing the area of hepatocytes containing lipid droplets, and the results are shown in Table 3. The liver histopathology scores of Examples 1-3 were significantly lower than those of Comparative Examples 1-8 (p<0.05), and Examples 1-3 significantly reduced the area of lipid droplets on the surface of the liver (fatty accumulation) and alleviated the fatty accumulation in the liver tissue caused by alcohol intake.

[0069] There was no significant difference between Comparative Examples 3, 7, and 8 (p>0.05), but the degree of lipid droplet area on the surface of the liver (fatty accumulation) after intervention was significantly higher than that of Examples 1-3 (p<0.05). Pueraria extract and Atractylodes extract had a synergistic effect in improving fatty accumulation in liver tissue.

[0070] The liver injury pathology score of mice after intervention in Comparative Example 4 was significantly higher than that of Comparative Examples 5 and 6 (p<0.05), but the liver injury pathology score of mice after intervention in Examples 1-3 was significantly higher than that of Comparative Examples 1 and 2 (p<0.05), which indicated that Atractylodes extract and the components other than Atractylodes extract in Examples 1-3 had a synergistic effect in improving the pathological state of alcoholic liver injury.

[0071] Table 3 Liver injury pathology scores of examples and comparative examples

[0072] Note: The same letter means no significant difference (p>0.05), and different letters mean significant difference (p<0.05).

[0073] 1.3.2 Influence on serum indicators related to liver function Triglycerides (TG) is one of the main lipid components in blood, mainly synthesized by the liver and stored in adipose tissue. Changes in TG levels can reflect the state of lipid metabolism in the body and are closely related to various liver diseases, especially in alcoholic liver disease. Total cholesterol (TC) refers to the total amount of cholesterol in all lipoprotein forms in the blood, including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and cholesterol in other lipoproteins. Aspartate aminotransferase (AST) is an enzyme widely present in various tissues of the human body, including the liver, heart, kidneys, and skeletal muscles. In a physiological state, the concentration of AST in serum is low. When these tissues are damaged, the permeability of the cell membrane increases, causing AST to be released from the cells into the blood circulation, thereby increasing the level of AST in serum.

[0074] From Table 4, it can be seen that Examples 1-3 can effectively reduce the increase of AST and ALT levels caused by alcoholic liver injury. Comparative Examples 1 and 2, Comparative Examples 7 and 8 have a certain inhibitory effect on the increase of AST and ALT caused by alcoholic liver injury.

[0075] The effect of Examples 1-3 on reducing AST and ALT is significantly better than that of Comparative Examples 3, 7 and 8, and there is no significant difference between Comparative Examples 3, 7 and 8 (p<0.05), which indicates that the pueraria extract and the atractylodes extract have a synergistic effect in improving the increase of ALT, AST and TG content caused by alcoholic liver injury.

[0076] The effect of Comparative Example 4 on reducing ALT, AST and TG is significantly worse than that of Comparative Examples 5 and 6, but the effect of Examples 1-3 on reducing ALT, AST and TG is significantly better than that of Comparative Examples 1 and 2, which indicates that the atractylodes extract and the components other than the atractylodes extract in Examples 1-3 have a synergistic effect in improving the increase of ALT, AST and TG content caused by alcoholic liver injury.

[0077] Table 4 Effects of examples and comparative examples on serum indexes

[0078] Note: The same letter means no significant difference (p>0.05), and different letters mean significant difference (p<0.05).

[0079] 1.3.3 Effects on liver-related oxidative stress indexes (SOD, GSH, GSH-Px, MDA) Alcohol liver injury is closely related to the level of malondialdehyde (MDA) in liver tissue. Reactive oxygen species (ROS) produced during alcohol metabolism can attack polyunsaturated fatty acids in biological membranes, trigger lipid peroxidation, and ultimately form lipid peroxides. Malondialdehyde (MDA) is one of the end products of lipid peroxidation, has cytotoxicity, can damage hepatocytes, and cause hepatocyte dysfunction and tissue damage. Superoxide dismutase (SOD) is an antioxidant metal enzyme present in the body, which can catalyze the dismutation of superoxide anion radicals to form oxygen and hydrogen peroxide, and plays a crucial role in the balance between oxidation and antioxidant in the body, and is closely related to the occurrence and development of many diseases. Oxidative metabolism of alcohol in the body, 90% of which occurs in the liver, increases the production of free radicals, and excessive free radicals can trigger oxidative stress symptoms. Under oxidative stress, the contents of antioxidant enzymes glutathione peroxidase (GSH-Px) and glutathione (GSH) change. These enzymes can scavenge intracellular free radicals and promote the resolution of oxidative stress.

[0080] As can be seen from Table 5, Examples 1-3 significantly increased the levels of SOD, GSH-Px and GSH in the liver tissue of mice (p<0.05), significantly reduced the level of MDA (p<0.05), improved the ability of hepatocytes to scavenge free radicals, and alleviated oxidative stress in the body to improve liver damage.

[0081] There was no significant difference between Comparative Examples 3, 7 and 8 (p>0.05), and the levels of SOD, GSH-Px and GSH after intervention were significantly lower than those of Examples 1-3 (p<0.05), and the level of MDA was significantly higher than that of Examples 1-3 (p>0.05), which indicated that the pueraria extract and the atractylodes extract had a synergistic effect on improving the oxidative stress indicators caused by alcoholic liver injury.

[0082] The levels of SOD, GSH-Px and GSH after intervention of Comparative Example 4 were significantly lower than those of Comparative Examples 5 and 6, and the level of MDA after intervention of Comparative Example 4 was significantly higher than that of Comparative Examples 5 and 6, but the levels of SOD, GSH-Px and GSH after intervention of Examples 1-3 were significantly higher than those of Comparative Examples 1 and 2, and the level of MDA after intervention of Examples 1-3 was significantly lower than that of Comparative Examples 1 and 2, which indicated that the atractylodes extract and the components other than the atractylodes extract in Examples 1-3 had a synergistic effect on improving the oxidative stress indicators caused by alcoholic liver injury.

[0083] Table 5 Effects of examples and comparative examples on liver oxidative stress indicators

[0084] Note: The same lowercase letter means no significant difference (p>0.05), and different lowercase letters mean significant difference (p<0.05).

[0085] 1.3.4 Effect on liver-related inflammatory factors (IL-1β, IL-6, TNF-α) TNF-α, IL-1β and IL-6, as important pro-inflammatory cytokines, play an indispensable role in the inflammatory response. They work together and interact with each other to jointly regulate the immune response and inflammatory response of the body to various external stimuli and damage. TNF-α, IL-1β and IL-6 often do not act in isolation, but synergistically and interact with each other. For example, TNF-α can induce the production of IL-1β and IL-6, while IL-6 can in turn enhance the effects of TNF-α and IL-1β. IL-1β, IL-6 and TNF-α play a key role in alcoholic liver injury. After alcohol intake, the levels of these inflammatory factors in the liver usually increase, which is closely related to the severity of liver inflammation and damage. These factors can promote the inflammatory response, leading to liver cell damage and liver dysfunction.

[0086] Excessive alcohol intake can activate liver inflammatory genes to induce an inflammatory response, leading to increased levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, exacerbating liver inflammation, and further causing liver cell damage and liver dysfunction. As can be seen from Table 6, the levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in the liver tissues after the intervention of Examples 1-3 were significantly lower than those of Comparative Examples 1-8 (p<0.05), and there was no significant difference between Comparative Examples 3, 7 and 8 (p>0.05). The levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in the liver tissues of mice after the intervention of Comparative Examples 3, 7 and 8 were significantly higher than those of Examples 1-3 (p<0.05), indicating that there is a synergistic effect between Pueraria and Atractylodes in improving inflammation caused by alcoholic chemical liver injury.

[0087] The levels of IL-1β, IL-6 and TNF-α in the liver tissues of mice after the intervention of Comparative Example 4 were significantly higher than those of Comparative Examples 5 and 6 (p<0.05), but the levels of IL-1β, IL-6 and TNF-α in the liver tissues after the intervention of Examples 1-3 were significantly lower than those of Comparative Examples 1 and 2 (p<0.05), indicating that the extract of Atractylodes has a synergistic effect with the components other than the extract of Atractylodes in Examples 1-3 in improving inflammation caused by alcoholic chemical liver injury.

[0088] Table 6 Effect of example and comparative example compositions on inflammatory factors

[0089] Note: The same lowercase letter means no significant difference (p>0.05), and different lowercase letters mean significant difference (p<0.05).

[0090] 1.3.5 Effects on the expression of liver-related proteins AMPK is a key regulator of cellular energy balance and metabolic regulation, known as the "cellular energy regulator", and the relative change in its expression level can reflect the metabolic state of the cell. When alcohol intake leads to energy depletion of liver cells, AMPK is activated, which in turn regulates metabolic pathways such as glycolysis and fatty acid oxidation to maintain cellular energy balance. ACC is a rate-limiting enzyme of fatty acid metabolism, involved in the synthesis and oxidation of fatty acids. When the body is in a state of stress, cells activate AMPK to start the energy metabolism regulation mechanism, and activated AMPK phosphorylates the 79th threonine residue of the key regulator of lipid metabolism ACC, inhibits the activity of the enzyme, inhibits fatty acid synthesis, promotes fatty acid oxidation, reduces the deposition of fat in tissues, and improves lipid metabolism. Sterol regulatory element binding proteins-1c (SREBP-1c) is a key transcription factor that regulates fatty acid and triglyceride synthesis. During alcohol metabolism, the activity of SREBP-1c may increase, thereby promoting the synthesis of fatty acids and the accumulation of triglycerides. Excessive accumulation of these lipids in the liver can lead to fatty degeneration, which in turn triggers an inflammatory response and liver cell damage.

[0091] As can be seen from Table 7, compared with Comparative Examples 1-8, Examples 1-3 significantly promoted AMPK phosphorylation, significantly reduced SREBP-1c protein expression level, and significantly promoted ACC phosphorylation leading to its inactivation (P<0.05). This indicates that Examples 1-3 inhibit SREBP-1c protein expression by increasing the expression of p-ACC / ACC and p-AMPK / AMPK proteins, promote fatty acid oxidation, reduce liver tissue fatty acid synthesis and triglyceride accumulation, inhibit lipogenesis, and improve alcoholic liver injury.

[0092] The ratio of p-ACC / ACC and p-AMPK / AMPK after intervention of Examples 1-3 is significantly higher than that of Comparative Examples 3, 7 and 8 (p<0.05), and there is no significant difference in the expression level of SREBP-1c protein and the ratio of p-ACC / ACC and p-AMPK / AMPK between Comparative Examples 3, 7 and 8 (p>0.05), which indicates that, in terms of improving alcoholic liver injury, atractylodes and pueraria have a synergistic effect in reducing fatty acid synthesis, promoting fat oxidation and inhibiting fat production.

[0093] The ratio of p-ACC / ACC and p-AMPK / AMPK after intervention of Comparative Example 4 is significantly lower than that of Comparative Examples 5 and 6 (p<0.05), and the expression level of SREBP-1 protein after intervention of Comparative Example 4 is significantly higher than that of Comparative Examples 5 and 6 (p<0.05), but the ratio of p-ACC / ACC and p-AMPK / AMPK after intervention of Examples 1-3 is higher than that of Comparative Examples 1 and 2 (p<0.05), and the expression level of SREBP-1 protein after intervention of Examples 1-3 is significantly lower than that of Comparative Examples 1 and 2 (p<0.05), which indicates that, in terms of improving alcoholic liver injury, the atractylodes extract and the components in Examples 1-3 except the atractylodes extract have a synergistic effect in reducing fatty acid synthesis, promoting fat oxidation and inhibiting fat production.

[0094] Table 7 Ratio of p-ACC / ACC, p-AMPK / AMPK and expression of SREBP-1 protein

[0095] Note: the same lowercase letter means no significant difference (p>0.05), and different lowercase letters mean significant difference (p<0.05).

[0096] Therefore, the composition provided by the present application has a significant improvement effect on the biochemical indicators related to alcoholic liver injury. After excessive drinking, the levels of TG, TC, AST and ALT in the blood are significantly increased. At the same time, the activities of GSH-px and GSH are reduced, MDA is increased, and the activity of SOD is reduced. In addition, the expression levels of pro-inflammatory factors IL-6, IL-1β and TNF-α are increased.

[0097] In addition, the composition can activate AMPK to promote ACC phosphorylation and inactivation, inhibit SREBP-1c protein expression, reduce hepatic tissue fatty acid synthesis and triglyceride accumulation, relieve liver lipid metabolism disorder, and protect liver function. The composition can activate AMPK to promote ACC phosphorylation and inactivation, inhibit SREBP-1c protein expression, reduce hepatic tissue fatty acid synthesis and triglyceride accumulation, relieve liver lipid metabolism disorder, and protect liver function. To confirm these biochemical results, histological examination of liver tissue was performed. Test substance B significantly improved the structural integrity of hepatocytes. Treatment reduced the disorganization and looseness of cell arrangement, reduced the presence of fat vacuoles, and improved the overall histopathological appearance of liver tissue, indicating its protective effect on alcohol-induced liver damage.

[0098] In summary, the composition showed a protective effect on alcoholic liver injury by regulating a series of biochemical and inflammatory markers and by improving the histopathological characteristics of liver tissue.

[0099] Example 2 Randomly selected 130 mice (SPF level Balb / c mice, body weight 18-22 g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.), the body weight of mice had no significant difference (P>0.05), the mice were raised in a standard animal room with humidity of 40-60% and temperature of 23±2℃, 12h alternating light, during which the mice were free to eat and drink water.

[0100] After 3 days of environmental adaptability feeding, all mice were randomly divided into 13 groups, 10 mice in each group: normal control group, model control group, Example 1-Example 3 group, Comparative Example 1-Comparative Example 8 group. Except for the normal control group and the model control group, the mice of Example 1-Example 3 and Comparative Example 1-Comparative Example 8 were respectively gavaged with 1668 mg / kg·BW of the corresponding composition (dissolved in distilled water), with a volume of 20 mL / kg·BW. The normal control group and the model control group were gavaged with the same volume of distilled water, once a day, for 30 consecutive days.

[0101] At the end of administration of the composition, all animals were strictly fasted for 24 hours (without water restriction). Except for the blank control group, the other groups were once gavaged with anhydrous ethanol 10 mL / kg body weight to establish an acute gastric mucosal injury model. Two hours after modeling, the mice were anesthetized by intraperitoneal injection of 4% (m / v) chloral hydrate solution 0.2 mL / 20 g, and then the mice were sacrificed by cervical dislocation after removal of the eyeball to collect blood. The blood was collected in a 2 mL centrifuge tube and stored at 4°C for 45 min, then centrifuged at 4°C at 3500 rpm for 15 min. The upper light yellow transparent liquid was collected as serum and immediately stored in a -80°C refrigerator. The gastric mucosa tissue samples of the mice were immersed in 4% (m / v) paraformaldehyde for pathological sectioning, and the remaining gastric mucosa tissue was quickly frozen in liquid nitrogen and stored in a -80°C refrigerator for detection of various indicators.

[0102] 1.1 Pathological analysis of gastric mucosal injury 1.1.1 Gastric mucosal tissue injury score After the mice were sacrificed, the complete stomach was exposed, the pylorus was ligated, and an appropriate amount of 10% formaldehyde solution was perfused for 20 min. Then the stomach was cut along the greater curvature, the contents were washed out, and the gastric mucosa was unfolded. The length and width of the bleeding points or bleeding bands were measured under a stereomicroscope or by the naked eye using a vernier caliper. Since the width represents the severity of the injury much more than the length, it is doubled for scoring. The scoring criteria are shown in Table 8.

[0103] Table 8 Scoring criteria for acute alcohol-induced gastric mucosal injury under naked eye observation

[0104] 1.1.2 Pathological histological observation and scoring After gross examination, the most severely injured part of the gastric mucosa of each animal was cut off and fixed in 10% formaldehyde solution. Routine sectioning was performed, and H&E staining was carried out for microscopic observation. Care should be taken to select a cross-section of the gastric mucosa that includes the entire mucosal layer for observation.

[0105] Scoring method: The involvement of congestion, bleeding, and mucosal cell degeneration and necrosis in the entire mucosal epithelial layer was scored on a scale of 1 to 5. Congestion was weighted as 1, bleeding as 2, and epithelial cell degeneration and necrosis as 3. The scoring criteria and total lesion score formula are shown in Table 9.

[0106] Table 9 Scoring criteria for acute gastric mucosal injury under a microscope

[0107] 1.1.3 Protective effect of the composition on gastric mucosal injury 1.1.3.1 Pathological analysis of gastric mucosal injury (1) Gastric mucosal tissue injury score Compared with Comparative Example 1-Comparative Example 8, the gastric mucosa tissue injury scores of the mice after intervention of Example 1-Example 3 were significantly reduced (p<0.05). There was no significant difference (p>0.05) between the gastric mucosa tissue injury scores of Comparative Example 3, Comparative Example 7 and Comparative Example 8, which indicated that the Pueraria extract and the Atractylodes extract had a synergistic effect in improving the gastric mucosa injury.

[0108] The gastric mucosa injury score after intervention of Comparative Example 4 was significantly higher than that of Comparative Example 5 and Comparative Example 6, but the gastric mucosa injury scores after intervention of Example 1-Example 3 were significantly lower than those of Comparative Example 1 and Comparative Example 2, which indicated that the Atractylodes extract had a synergistic effect with the components other than the Atractylodes extract in Example 1-Example 3 in improving the pathological state of alcoholic gastric mucosa injury.

[0109] Table 10 Influence of acute alcoholic gastric mucosa injury score

[0110] Note: the same letter means no significant difference (p>0.05), and different letters mean significant difference (p<0.05).

[0111] (2) Gastric mucosa tissue histopathology examination The pathological results of the gastric mucosa tissue injury are shown in Table 10. Figure 2

[0112] The gastric mucosa of the mice in the blank control group: the epithelial cells were arranged closely and orderly; the glands in the lamina propria were arranged in order; the tissue had no necrosis, cell separation, shedding, or irregular arrangement; the submucosa had no edema; the cell nuclei had no pyknosis or lysis; the capillaries had no dilation or compression; red blood cells had no exosmosis; and inflammatory cells had no infiltration. The gastric mucosa of the mice in Example 1-Example 3: the degree of injury was significantly lighter than that of the model control group. The damage to the mucosa surface was relatively light and reddish. The bleeding was less in the form of cord-like and the width was narrowed. The gastric mucosa tissue structure of the normal mice was complete, while Comparative Example 1-Comparative Example 8 showed obvious signs of tissue injury and inflammation. The gastric mucosa injury of the mice in Example 1-Example 3 was improved more obviously, showing a better therapeutic effect.

[0113] ​Compared with Example 1-Example 3, the damage degree of the stomach mucosa of the mice in Comparative Example 1-Comparative Example 8 was more serious, the improvement effect was poor, and to some extent, there was tissue necrosis; the epithelial cells were separated, shed, and arranged irregularly; the submucosal layer was obviously edematous; the cell nuclei were pyknotic or even dissolved; the capillaries were dilated and compressed; red blood cells were exuded; and some inflammatory cell infiltration was observed. It can be seen that the relief effects of Comparative Example 1-Comparative Example 8 on the gastric mucosa damage were all poor. Among them, Comparative Example 4 was weaker than Comparative Example 5 and Comparative Example 6 in improving the tightness of the epithelial cell arrangement, the degree of cell separation and shedding, and the degree of cell nucleus dissolution, which was consistent with the liver damage pathological score results in Table 9.

[0114] (3) Oxidative stress indicators (SOD, GSH, GSH-Px, MDA) related to gastric mucosa GSH-Px, MDA and SOD are important indicators reflecting oxidative stress damage of tissues and organs. The increase of MDA indicates the occurrence and aggravation of oxidative stress damage, and the decrease of SOD and GSH-Px activity means that the self-regulation ability of gastric mucosa tissue cells decreases after suffering oxidative stress damage.

[0115] As can be seen from Table 11, Example 1-Example 3 significantly increased the levels of SOD, GSH-Px and GSH in the gastric mucosa tissue of mice (p<0.05), and significantly reduced the level of MDA (p<0.05), thereby improving the ability of the gastric mucosa tissue to scavenge free radicals and relieving oxidative stress to improve gastric mucosa damage. The levels of SOD, GSH-Px and GSH after the intervention of Comparative Example 3, Comparative Example 7 and Comparative Example 8 were significantly lower than those of Example 1-Example 3 (p<0.05), and the level of MDA was significantly higher than that of Example 1-Example 3 (p>0.05), which indicated that the pueraria extract and the atractylodes extract had a synergistic effect in improving the oxidative stress indicators caused by alcoholic gastric mucosa damage.

[0116] The level of SOD after the intervention of Comparative Example 4 was significantly lower than that of Comparative Example 5 and Comparative Example 6 (p<0.05), the level of MDA was significantly higher than that of Comparative Example 5 and Comparative Example 6 (p<0.05), and the levels of GSH and GSH-Px were not significantly different from those of Comparative Example 5 and Comparative Example 6 (p>0.05), while the levels of SOD, GSH and GSH-Px after the intervention of Example 1-Example 3 were significantly higher than those of Comparative Example 1 and Comparative Example 2 (p<0.05), and the level of MDA was significantly lower than that of Comparative Example 1 and Comparative Example 2 (p<0.05), which indicated that the atractylodes extract had a synergistic effect with the components other than the atractylodes extract in Example 1-Example 3 in improving the oxidative stress indicators caused by alcoholic gastric mucosa damage.

[0117] Table 11 Influence of examples and comparative examples on oxidative stress indicators of gastric mucosa

[0118] Note: The same letter indicates no significant difference (p>0.05), and different letters indicate a significant difference (p<0.05).

[0119] (4) Effects of gastric mucosa-related inflammatory factors (IL-1β, IL-6, TNF-α) TNF-α and IL-1β, as important pro-inflammatory cytokines, play indispensable roles in inflammatory responses. They work synergistically and interactively to regulate the body's immune response and inflammatory response in response to various external stimuli and damage. IL-1β, IL-6, and TNF-α often do not act in isolation in inflammatory responses, but rather synergistically and mutually influence each other. For example, TNF-α can induce the production of IL-1β and IL-6. IL-1β, IL-6, and TNF-α play a key role in alcoholic gastric mucosal injury. After alcohol intake, the levels of these inflammatory factors in the gastric mucosa usually increase, which is closely related to the severity of gastric mucosal inflammation and injury.

[0120] Table 12 shows that Examples 1-3 can reduce the levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α. There were no significant differences in the levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α among Comparative Examples 3, 7, and 8 (p > 0.05). However, the levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α in the gastric mucosa tissue of mice after intervention in Comparative Examples 3, 7, and 8 were significantly higher than those in Examples 1-3 (p < 0.05). This indicates that there is a synergistic effect between Pueraria lobata extract and Atractylodes macrocephala extract in reducing the levels of factors related to alcoholic gastric mucosal inflammation.

[0121] The levels of IL-1β, IL-6, and TNF-α after intervention in Comparative Example 4 were significantly higher than those in Comparative Examples 5 and 6 (p < 0.05), but the levels of IL-1β, IL-6, and TNF-α after intervention in Examples 1-3 were significantly lower than those in Comparative Examples 1 and 2 (p < 0.05). This indicates that the Atractylodes macrocephala extract has a synergistic effect with the components other than the Atractylodes macrocephala extract in Examples 1-3 in improving inflammation caused by alcoholic chemical liver injury.

[0122] Table 12 Effects of Examples and Comparative Examples on Gastric Mucosal Inflammatory Factors

[0123] Note: The same letter indicates no significant difference (p>0.05), and different letters indicate a significant difference (p<0.05).

[0124] (5) Gastric mucosa-associated protein expression Mitogen-activated protein kinase (MAPK) signaling pathway is one of the important signal transduction systems in the body, mainly involved in cell proliferation, differentiation and apoptosis, and plays a crucial role as the main signaling pathway in oxidative stress response. MAPK signaling pathway mainly includes three signal regulatory kinases, extracellular signal-regulated kinase (ERK) protein regulating cell proliferation and differentiation, Protein 38 MAPK (P38) protein regulated inflammatory response of the body, and Jun N-terminal kinase (JNK) protein promoting cell apoptosis. MAPK signaling pathway will undergo phosphorylation under the activation of inflammatory stimuli, giving MAPK pathway strong activity, and regulating intracellular genes through phosphorylated transcription factors. ERK can be activated by alcohol-induced oxygen free radicals in the body in a phosphorylated state, and a series of stimulating responses to the body. P38 protein can be activated by a variety of stimuli and produce inflammatory mediators, and its cascade reaction can promote the occurrence of inflammatory response. JNK is the central pathway of apoptosis, which can be activated by oxidative stress transcription expression. Under the stimulation of alcohol, the gastric mucosa has an inflammatory response, and inflammatory factors activate apoptosis and oxidative stress response, and through a series of cascade reactions, P38 and JNK are activated in a phosphorylated state.

[0125] As can be seen from Table 13, compared with Comparative Examples 1-8, the ratio of p-ERK / ERK in the gastric mucosa tissue of mice after intervention of Examples 1-3 significantly decreased (p<0.05), indicating that Examples 1-3 can inhibit the specific increase of ERK phosphorylation level caused by alcohol, and thereby inhibit the activation of ERK signaling pathway, so as to regulate the proliferation and differentiation of inflammatory cells to protect the gastric mucosa; the ratio of p-p38 / p-38 and p-JNK / JNK in the gastric mucosa tissue of mice after intervention of Examples 1-3 significantly decreased (p<0.05), indicating that Examples 1-3 can significantly inhibit the specific increase of p-p38 and p-JNK levels caused by alcohol, and effectively regulate the secretion of pro-inflammatory factors by blocking the activation of p-P38 and p-JNK signaling pathways, thereby blocking the apoptosis process.

[0126] The ratio of p-ERK / ERK, p-p38 / p38 and p-JNK / JNK in the gastric mucosa tissue of the mice after intervention of Examples 1-3 was significantly lower than that of Comparative Examples 3, 7 and 8 (p<0.05), but there was no significant difference between Comparative Examples 3, 7 and 8 (p>0.05), which indicated that the Atractylodes lancea extract and the Pueraria lobata extract had synergistic effect in improving the alcoholic gastric mucosa injury by inhibiting the secretion of pro-inflammatory factors, inhibiting the proliferation and differentiation of inflammatory cells, improving the inflammatory reaction and the like through inhibiting the ERK, p38 and JNK signal pathways.

[0127] The ratio of p-ERK / ERK, p-p38 / p38 and p-JNK / JNK after intervention of Comparative Example 4 was significantly higher than that of Comparative Examples 5 and 6, and the ratio of p-ERK / ERK, p-p38 / p38 and p-JNK / JNK after intervention of Examples 1-3 was significantly lower than that of Comparative Examples 1 and 2, which indicated that the Atractylodes lancea extract and the components other than the Atractylodes lancea extract in Examples 1-3 had synergistic effect in reducing the phosphorylation level of the MAPK pathway related proteins, reducing the proliferation and differentiation of inflammatory cells, controlling the secretion of pro-inflammatory factors, blocking the apoptosis process and the like in improving the alcoholic gastric mucosa injury.

[0128] Table 13 Optical density of p-ERK / ERK, p-p38 / p38 and p-JNK / JNK protein expression

[0129] Note: the same letter means no significant difference (p>0.05), and different letters mean significant difference (p<0.05).

[0130] The above detailed description is a specific description of one of the feasible embodiments of the present application, which is not used to limit the patent scope of the present application. It should be noted that any equivalent implementation or change made without departing from the present application should be included in the scope of the technical solutions of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A composition for adjuvant protection against chemically induced liver injury and gastric mucosal injury, characterized in that, The composition comprises, by weight, the following components: 35-45 parts of kudzu root extract, 25-35 parts of Japanese raisin tree fruit extract, 25-35 parts of codonopsis root extract, 25-35 parts of atractylodes macrocephala extract, and 28-33 parts of salvia miltiorrhiza extract.

2. The composition according to claim 1, characterized in that, The composition, by weight, comprises one of the following combinations (1)-(3). composition: (1) 35 parts of kudzu root extract, 35 parts of Japanese raisin tree fruit extract, 35 parts of codonopsis root extract, 28 parts of salvia miltiorrhiza extract and 25 parts of atractylodes macrocephala extract; (2) 40 parts of kudzu root extract, 30 parts of Japanese raisin tree fruit extract, 30 parts of codonopsis root extract, 30 parts of salvia miltiorrhiza extract and 30 parts of atractylodes macrocephala extract; (3) 45 parts of kudzu root extract, 25 parts of Japanese raisin tree extract, 25 parts of codonopsis root extract, 33 parts of salvia miltiorrhiza extract and 35 parts of atractylodes macrocephala extract.

3. The use of the composition according to claim 1 or 2 in the preparation of products that provide auxiliary protection against chemically induced liver damage and gastric mucosa.

4. The application according to claim 3, characterized in that, The product is a medicine or health product.

5. The application according to claim 4, characterized in that, The drugs or health products mentioned also include pharmaceutical excipients.

6. The application according to claim 5, characterized in that, The pharmaceutical excipients are one or more of dextrin, starch, microcrystalline cellulose, talc, and magnesium stearate.

7. The application according to claim 6, characterized in that, The dosage form of the drug or health product is capsule, tablet, powder, granule, oral liquid, medicated wine, pill, mixture or tincture.

8. A method for preparing the composition according to claim 1 or 2, characterized in that, The ingredients include weighing out kudzu root extract, Japanese raisin tree fruit extract, codonopsis root extract, atractylodes macrocephala extract, and salvia miltiorrhiza extract according to their weight parts and mixing them together.

9. A health product, characterized in that, The health product includes the composition according to claim 1 or 2.

10. A drug, characterized in that, The drug comprises the composition according to claim 1 or 2.

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