Application of 9 (Z), 11 (E)-octadecadienoic acid in treating and / or improving alcoholic liver injury

Abstract

The invention discloses an application of 9 (Z), 11 (E)-octadecadienoic acid in treating and / or improving alcoholic liver injury. The traditional Chinese medicine composition is good in druggability, clear in structure and easy in quality control and standardized production; the compound is relatively good in stability, has targeting optimization potential and good bioavailability, and has dual value potential of preventing and treating ALD (Atomic Lymphosis Disease).

Description

Technical Field

[0001] The present invention relates to the use of 9(Z),11(E)-octadecadienoic acid in the treatment and / or improvement of liver injury, belonging to the field of new drug uses. Background Art

[0002] Alcoholic liver disease (ALD) is a common liver disease caused by long-term excessive alcohol consumption. The prevalence of ALD continues to increase, especially among young people. The disease process of ALD includes alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis, and cirrhosis, etc. In severe cases, it can cause liver cancer and is one of the main causes of liver diseases and deaths globally. The pathogenesis of ALD is complex, involving genetics, metabolism, oxidative stress, immunity, gut microbiota, etc. After alcohol enters the body, it is absorbed by the gastrointestinal tract and enters the liver. Under the action of alcohol dehydrogenase and acetaldehyde dehydrogenase, it is successively metabolized into acetaldehyde and acetic acid. A large amount of NAD+ is consumed during the alcohol metabolism process, and a large amount of reactive oxygen species (ROS) are generated, which inhibits fatty acid oxidation, causes oxidative stress, further triggers cell death, and activates hepatic stellate cells. During the disease process of ALD, oxidative stress is its core pathological mechanism.

[0003] Oxidative stress refers to the pathological process in which the imbalance between ROS and the antioxidant defense system in the body leads to excessive accumulation of free radicals, causing oxidative damage to biological macromolecules such as lipids, proteins, and DNA. Its characteristics include excessive generation of ROS, accumulation of lipid peroxidation products (such as malondialdehyde), and decreased antioxidant enzyme activity, etc. The main pathogenic factors include environmental pollutants (such as PM2.5), ultraviolet radiation, smoking, high-fat diet, etc. Long-term oxidative stress is closely related to various diseases, including acute and chronic liver diseases (ALD, metabolic dysfunction-associated fatty liver disease, drug-induced liver disease, liver cancer, etc.), neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease), cardiovascular diseases (atherosclerosis), metabolic syndrome (diabetes), cancer, and inflammatory diseases.

[0004] Currently, the main clinical treatment drugs mainly include exogenous antioxidants (vitamin C / E, glutathione), ROS scavengers (N-acetylcysteine), and activators targeting the Nrf2 pathway (such as sulforaphane), etc. However, the above existing drugs have problems such as poor stability, low bioavailability, and poor targeting, so the drug-forming property is poor, and there is an urgent need to develop new and highly efficient antioxidant molecules.

[0005] Conjugated linoleic acid (CLA) belongs to the polyunsaturated fatty acid family and refers to a series of positional isomers and geometric isomers of linoleic acid (LA) containing conjugated double bonds. Its double bond can be located at any position of the fatty acid carbon chain, usually at positions 8-13; and has cis and trans configurations; therefore, it has multiple isomers. Due to the different positions of the double bonds, different CLAs have different physiological functions.

[0006] 9(Z),11(E)-octadecadienoic acid, also known as Bovinicacid, is a natural isomer of CLA and a type of LA containing cis- and trans-conjugated double bonds. Natural CLA is metabolized by bacteria in the rumen of ruminants and is commonly found in ruminant dairy products and meat. Summary of the invention

[0007] Purpose of the invention: The technical problem to be solved by the present invention is to provide an active ingredient of a drug that can be used to improve or treat alcoholic liver damage.

[0008] Technical solution: To solve the above technical problems, the present invention provides a conjugated linoleic acid, namely 9(Z), 11(E)-octadecadienoic acid, for the preparation of drugs for improving or treating alcoholic liver disease. 9(Z), 11(E)-octadecadienoic acid can significantly inhibit the generation of ROS and reduce the level of lipid peroxidation product MDA, providing an important basis for the development of new drugs for the treatment of alcoholic liver injury.

[0009] The applicant of the present invention first confirmed that after 9(Z),11(E)-octadecadienoic acid was administered to HepG2 under oxidative stress, the expression levels of ROS and MDA were significantly downregulated, and the expression levels of SOD and GSH were significantly upregulated; after 9(Z),11(E)-octadecadienoic acid was administered to ALD mouse model, the expression levels of ALT and AST were significantly downregulated, the expression level of MDA was significantly downregulated, and the expression level of SOD was significantly upregulated; liver pathology was significantly improved.

[0010] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: 1. Good drugability; 2. Clear structure, easy quality control and standardized production; 3. Good compound stability; 4. Potential for targeted optimization; 5. Good bioavailability; 6. Dual value potential for the prevention and treatment of ALD. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 Analysis of the toxicity of 9(Z),11(E)-octadecadienoic acid to HepG2 cells;

[0012] Figure 2 Analysis of the ROS level in HepG2 cells stimulated by ethanol with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0013] Figure 3 Analysis of the MDA level in HepG2 cells stimulated by ethanol with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0014] Figure 4 Analysis of the SOD level in HepG2 cells stimulated by ethanol with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0015] Figure 5 Analysis of the GSH level in HepG2 cells stimulated by ethanol with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0016] Figure 6 Analysis of the ROS level in HepG2 cells stimulated by tBHP with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0017] Figure 7 Analysis of the MDA level in HepG2 cells stimulated by tBHP with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0018] Figure 8 Analysis of the SOD level in HepG2 cells stimulated by tBHP with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0019] Figure 9 Analysis of the GSH level in HepG2 cells stimulated by tBHP with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0020] Figure 10 Analysis of the ALT level in the ALD model with 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0021] Figure 11Analysis of AST levels in the ALD model by 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0022] Figure 12 Effect of 9(Z),11(E)-octadecadienoic acid on liver pathology in the ALD model (HE staining, 10×20 magnification)

[0023] Figure 13 Analysis of MDA levels in the ALD model by 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01;

[0024] Figure 14 Analysis of SOD levels in the ALD model by 9(Z),11(E)-octadecadienoic acid, where: *P<0.05, **P<0.01, ***P<0.01. Detailed implementation manners

[0025] The technical solutions of the present invention will be further described below with reference to the accompanying drawings.

[0026] Example 1 Effect of 9(Z),11(E)-octadecadienoic acid on the cytotoxicity of HepG2 cells

[0027] 1 Experimental materials

[0028] The HepG2 cell line used in the present invention was purchased from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; the 9(Z),11(E)-octadecadienoic acid used in the present invention was purchased from Shanghai TargetMol Co., Ltd.; the CCK8 reagent was purchased from Nanjing Novozymes Biotech Co., Ltd.

[0029] 2 Experimental methods

[0030] The HepG2 cell suspension was added to a 96-well plate at a cell density of 6×10 4 cells / ml, 100 μl of cell suspension per well. After culturing for 24 h, the culture medium was discarded, and serum-free medium containing 9(Z),11(E)-octadecadienoic acid was added to make the final concentrations 0, 0.5, 5, 50, and 100 μM, respectively. After incubation for 24 h, the cell viability was measured using CCK8.

[0031] 3 Experimental results

[0032] According to the CCK8 results ([[]] Figure 1 ), in HepG2 cells cultured in vitro, when the cells were given different concentrations (0.5 - 100 μM) of 9(Z),11(E)-octadecadienoic acid, the viability of HepG2 cells was not affected.

[0033] Example 2 Effect of 9(Z),11(E)-octadecadienoic acid on oxidative stress of HepG2 cells stimulated by alcohol

[0034] 1 Experimental materials

[0035] The HepG2 cell line used in this invention was purchased from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; the 9(Z),11(E)-octadecadienoic acid used in this invention was purchased from Shanghai TargetMol Biotechnology Co., Ltd.; the MDA, SOD, and GSH assay kits were purchased from Nanjing Jiancheng Bioengineering Institute; H2DCFDA was purchased from MCE; the CCK8 reagent was purchased from Nanjing Novozymes Biotechnology Co., Ltd.; the BCA assay kit was purchased from Shanghai Beyotime Biotechnology Co., Ltd.

[0036] 2 Experimental methods

[0037] 2.1 Culture, modeling, and administration of HepG2 cell line

[0038] After the HepG2 cell line was cultured to 80% density, the culture medium was discarded, 1 ml of serum-free medium containing alcohol (alcohol concentration was 2000 mM) was added, and at the same time, 1 ml of serum-free medium containing 9(Z),11(E)-octadecadienoic acid (the concentrations of 9(Z),11(E)-octadecadienoic acid were 0, 1, 10, 100 μM) was added, so that the final concentration of alcohol in the cell culture system was 1000 mM, and the final concentrations of 9(Z),11(E)-octadecadienoic acid were 0, 0.5, 5, 50 μM. After incubation for 24 h, the cells were collected.

[0039] 2.2 Determination of cellular ROS

[0040] Discard the culture medium in the culture plate, add an equal volume of H2DCFDA working solution (10 μM), incubate for 30 min, then add PBS to wash the plate three times to ensure the removal of the residual H2DCFDA working solution, perform on-machine detection, measure the fluorescence intensity with an ELISA reader at 488 / 525 nm, record the values, and finally measure the cell viability with CCK8 and record the values. Among them, relative ROS content = cell fluorescence intensity / cell viability.

[0041] 2.3 Determination of MDA

[0042] The collected cells were ultrasonically disrupted. First, the protein concentration was measured according to the instructions of the BCA detection kit, and then the operation was carried out according to the instructions of the MDA detection kit. The absorbance was read at 532 nm with an ELISA reader, and the results were calculated.

[0043] 2.4 Determination of SOD

[0044] The collected cells were ultrasonically disrupted. First, the protein concentration was determined according to the instructions of the BCA assay kit, and then the operation was carried out according to the instructions of the SOD assay kit. The absorbance was read at 450 nm on an enzyme-linked immunosorbent assay (ELISA) reader, and the results were calculated.

[0045] 2.5 Determination of GSH

[0046] The collected cells were ultrasonically disrupted. First, the protein concentration was determined according to the instructions of the BCA assay kit, and then the operation was carried out according to the instructions of the GSH assay kit. The absorbance was read at 405 nm on an ELISA reader, and the results were calculated.

[0047] 3 Experimental results

[0048] 3.1 9(Z),11(E)-Octadecadienoic acid inhibits the ROS level in alcohol-stimulated HepG2 cells

[0049] According to the ROS results ( Figure 2 ), in HepG2 cells cultured in vitro, by giving alcohol stimulation to the cells, the ROS level in HepG2 cells was up-regulated (P<0.05). When the cells were given 9(Z),11(E)-octadecadienoic acid, the ROS level in HepG2 cells was down-regulated (P<0.05), and it showed a dose-dependent manner.

[0050] 3.2 9(Z),11(E)-Octadecadienoic acid inhibits the MDA level in alcohol-stimulated HepG2 cells

[0051] According to the MDA results ( Figure 3 ), in HepG2 cells cultured in vitro, by giving alcohol stimulation to the cells, the MDA level in HepG2 cells was up-regulated (P<0.05). When the cells were given 9(Z),11(E)-octadecadienoic acid, the MDA level in HepG2 cells was down-regulated (P<0.05), and it showed a dose-dependent manner.

[0052] 3.3 9(Z),11(E)-Octadecadienoic acid up-regulates the SOD level in alcohol-stimulated HepG2 cells

[0053] According to the SOD results ( Figure 4 ), in HepG2 cells cultured in vitro, by giving alcohol stimulation to the cells, the SOD level in HepG2 cells was down-regulated (P<0.05). When the cells were given 9(Z),11(E)-octadecadienoic acid, the SOD level in HepG2 cells was up-regulated (P<0.05), and it showed a dose-dependent manner.

[0054] 3.3 9(Z),11(E)-Octadecadienoic acid up-regulates the GSH level in alcohol-stimulated HepG2 cells

[0055] According to the results of GSH ( Figure 5 ), in HepG2 cells cultured in vitro, by giving alcohol stimulation to the cells, the GSH level of HepG2 cells was down-regulated (P<0.05). When the cells were given 9(Z),11(E)-octadecadienoic acid, the GSH level of HepG2 cells was up-regulated (P<0.05), and it was dose-dependent.

[0056] Example 3 Effect of 9(Z),11(E)-octadecadienoic acid on oxidative stress of tBHP-stimulated HepG2 cells

[0057] 1 Experimental materials

[0058] The HepG2 cell line used in the present invention was purchased from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; the 9(Z),11(E)-octadecadienoic acid used in the present invention was purchased from TargetMol; the MDA, SOD, and GSH kits were purchased from Nanjing Jiancheng Company; H2DCFDA was purchased from MCE Company; the CCK8 reagent was purchased from Novoprotein; the BCA kit was purchased from Beyotime Reagent Company.

[0059] 2 Experimental methods

[0060] 2.1 Culture, modeling, and administration of HepG2 cell line

[0061] After the HepG2 cell line was cultured to 80% density, the medium was discarded, 1 ml of serum-free medium containing tert-butyl hydroperoxide (tBHP) (tBHP concentration was 800 μM) was added, and at the same time, 1 ml of serum-free medium containing 9(Z),11(E)-octadecadienoic acid (the concentrations of 9(Z),11(E)-octadecadienoic acid were 0, 1, 10, 100 μM) was added, so that the final concentration of tBHP in the cell culture system was 400 μM, and the final concentrations of 9(Z),11(E)-octadecadienoic acid were 0, 0.5, 5, 50 μM. The cells were collected after incubation for 4 h.

[0062] 2.2 Determination of cellular ROS

[0063] The experimental method was the same as that in Example 1.

[0064] 2.3 MDA determination

[0065] The experimental method was the same as that in Example 1.

[0066] 2.4 SOD determination

[0067] The experimental method was the same as that in Example 1.

[0068] 2.5 GSH determination

[0069] The experimental method was the same as that in Example 1.

[0070] 3 Experimental Results

[0071] 3.1 9(Z),11(E)-Octadecadienoic Acid Inhibits the ROS Level in tBHP-Stimulated HepG2 Cells

[0072] According to the ROS results ( Figure 6 ), in HepG2 cells cultured in vitro, by stimulating the cells with tBHP, the ROS level in HepG2 cells was up-regulated (P<0.05). When the cells were treated with 9(Z),11(E)-octadecadienoic acid, the ROS level in HepG2 cells was down-regulated (P<0.05), and it showed a dose-dependent manner.

[0073] 3.2 9(Z),11(E)-Octadecadienoic Acid Inhibits the MDA Level in tBHP-Stimulated HepG2 Cells

[0074] According to the MDA results ( Figure 7 ), in HepG2 cells cultured in vitro, by stimulating the cells with tBHP, the MDA level in HepG2 cells was up-regulated (P<0.05). When the cells were treated with 9(Z),11(E)-octadecadienoic acid, the MDA level in HepG2 cells was down-regulated (P<0.05), and it showed a dose-dependent manner.

[0075] 3.3 9(Z),11(E)-Octadecadienoic Acid Up-regulates the SOD Level in tBHP-Stimulated HepG2 Cells

[0076] According to the SOD results ( Figure 8 ), in HepG2 cells cultured in vitro, by stimulating the cells with tBHP, the SOD level in HepG2 cells was down-regulated (P<0.05). When the cells were treated with 9(Z),11(E)-octadecadienoic acid, the SOD level in HepG2 cells was up-regulated (P<0.05), and it showed a dose-dependent manner.

[0077] 3.3 9(Z),11(E)-Octadecadienoic Acid Up-regulates the GSH Level in tBHP-Stimulated HepG2 Cells

[0078] According to the GSH results ( Figure 9 ), in HepG2 cells cultured in vitro, by stimulating the cells with tBHP, the GSH level in HepG2 cells was down-regulated (P<0.05). When the cells were treated with 9(Z),11(E)-octadecadienoic acid, the GSH level in HepG2 cells was up-regulated (P<0.05), and it showed a dose-dependent manner.

[0079] Example 4 Effects of 9(Z),11(E)-Octadecadienoic Acid on the ALD Model

[0080] 1 Experimental materials

[0081] The experimental mice (C57BL / 6JNifdc) used in this invention were purchased from Zhejiang Vital River Laboratory Animal Technology Co., Ltd.;

[0082] 9(Z),11(E)-Octadecadienoic acid used in this invention was purchased from Merck; ALT and AST kits were purchased from Neusoft Witman Biotechnology (Nanjing) Co., Ltd.; MDA and SOD kits were purchased from Nanjing Jiancheng Co., Ltd.; BCA kit was purchased from Beyotime Institute of Biotechnology.

[0083] 2 Experimental methods

[0084] 2.1 Mouse modeling and drug administration

[0085] After one week of adaptive feeding, the mice were randomly divided into 3 groups, with 6 mice in each group, a total of 18 mice. They were the control group, the model group, and the 9(Z),11(E)-octadecadienoic acid administration group. Among them, the model group was given an ethanol solution (50%, dissolved in ultrapure water) by intraperitoneal gavage, and the control group was given the corresponding volume of solvent (ultrapure water), once a day, for a total of 10 days.

[0086] Preparation of the solution containing 9(Z),11(E)-octadecadienoic acid: Take 17.56 ul (density is 0.911 g / cm3, 17.56 ul of 9(Z),11(E)-octadecadienoic acid is about 16 mg) of 9(Z),11(E)-octadecadienoic acid and add it to 782.44 ul of ultrapure water, vortex to mix it evenly to obtain a 20 mg / ml solution.

[0087] At the same time of modeling, the above solution was given to the mice by gavage, with a dosing volume of 5 ml / kg for each mouse, once a day, for 10 consecutive days. After the dosing cycle ended, the mice were sacrificed, and the serum and liver were collected and preserved for later use.

[0088] 2.2 Determination of serum ALT

[0089] The collected serum was operated according to the ALT detection kit instruction manual. The absorbance was read at 340 nm on an enzyme-labeled instrument, measured once every 180 s, and the result was calculated according to the formula in the instruction manual: ALT activity = △A / min × F.

[0090] When calculating the factor (F value) and the measured F value for enzyme activity determination by the continuous monitoring method, it is not necessary to make a standard tube or standard curve. According to the molar absorption coefficient, it is very easy to calculate the enzyme activity concentration. First, measure the change in absorbance per minute (△A / min) within the linear range. When representing the enzyme activity concentration in U / L, it can be calculated according to the following formula:

[0091] U / L, t℃ = ΔA / min × F = ΔA / min × V × 10 6 / (ε × v × L)

[0092] where V: total volume of the reaction system (mL); 10 6 : convert mol to μmol; ε: molar extinction coefficient (cm 2 / mol); v: sample volume (mL); L: light path of the cuvette (cm). When the conditions are fixed, theoretically V, v, and L are all fixed values, and the ε value is a constant, so the F value is constant. The F value may be different on different biochemical analyzers. It is recommended that each laboratory establish its own F value.

[0093] ALT activity = ΔA / ΔA standard.

[0094] 2.3 Determination of serum AST

[0095] Operate the collected serum according to the instructions of the AST detection kit, read the absorbance at 340 nm on the microplate reader, measure once every 250 s, and calculate the result according to the formula in the instructions: AST activity = ΔA / min × F.

[0096] Calculation factor (F value) and measured F value When using the continuous monitoring method for enzyme activity determination, there is no need to prepare a standard tube or standard curve. According to the molar extinction coefficient, it is very easy to calculate the enzyme activity concentration. First, measure the change in absorbance per minute (ΔA / min) within the linear range. When representing the enzyme activity concentration in U / L, the following formula can be used for calculation:

[0097] U / L, t℃ = ΔA / min × F = ΔA / min × V × 10 6 / (ε × v × L)

[0098] where V: total volume of the reaction system (mL); 10 6 : convert mol to μmol; ε: molar extinction coefficient (cm 2 / mol); v: sample volume (mL); L: light path of the cuvette (cm). When the conditions are fixed, theoretically V, v, and L are all fixed values, and the ε value is a constant, so the F value is constant. The F value may be different on different biochemical analyzers. It is recommended that each laboratory establish its own F value.

[0099] 2.4 MDA determination

[0100] Weigh a part of the liver tissue, first pretreat the liver sample according to the instructions of the MDA detection kit to obtain the solution to be measured, then measure the protein concentration according to the instructions of the BCA detection kit, and finally operate according to the instructions of the MDA detection kit, read the absorbance at 532 nm on the microplate reader, and calculate the result.

[0101] 2.5 SOD Assay

[0102] Weigh a part of the liver tissue. First, pretreat the liver samples according to the instructions of the SOD detection kit to obtain the solution to be tested. Then, measure the protein concentration according to the instructions of the BCA detection kit. Finally, operate according to the instructions of the SOD detection kit, read the absorbance at 450 nm with an enzyme-labeling instrument, and calculate the results.

[0103] 3 Experimental Results

[0104] 3.1 9(Z),11(E)-Octadecadienoic Acid Inhibits the ALT Level in ALD Model Mice

[0105] According to the ALT results ([[]] Figure 10 Figure 10 ), in the in vivo mouse model, by intraperitoneal gavage of ethanol to mice, the ALT level of mice was up-regulated (P<0.05). When 9(Z),11(E)-octadecadienoic acid was given to mice, the ALT level of mice was down-regulated (P<0.05).

[0106] 3.2 9(Z),11(E)-Octadecadienoic Acid Inhibits the AST Level in ALD Model Mice

[0107] According to the AST results ([[]] Figure 11 Figure 11 ), in the in vivo mouse model, by intraperitoneal gavage of ethanol to mice, the AST level of mice was up-regulated (P<0.05). When 9(Z),11(E)-octadecadienoic acid was given to mice, the AST level of mice was down-regulated (P<0.05).

[0108] 3.3 9(Z),11(E)-Octadecadienoic Acid Improves the Liver Pathology in ALD Model Mice

[0109] According to the liver pathology results ([[]] Figure 12 Figure 12 ), the liver tissue morphology of mice in the blank control group was normal, the structure of the portal area was normal, the liver lobule tissue morphology was complete, and the hepatocytes were arranged neatly in an obvious radial pattern, without inflammation or lesions. In the model group, the arrangement of liver cords was disordered, the liver cell nuclei were swollen, the structure of liver lobules was unclear, small lipid droplets appeared in a small number of hepatocytes, a large number of inflammatory cells infiltrated, and hepatocyte hemorrhage occurred. Compared with the model group, the cell morphology of the group given 9(Z),11(E)-octadecadienoic acid to mice was better and the infiltration of inflammatory cells was less.

[0110] 3.3 9(Z),11(E)-Octadecadienoic Acid Inhibits the MDA Level in ALD Model

[0111] According to the MDA results ([[]] Figure 13 Figure 13) In the in vivo mouse model, by intraperitoneal gavage of ethanol to mice, the MDA level in the mouse liver was up-regulated (P < 0.05). When 9(Z),11(E)-octadecadienoic acid was given to mice, the MDA level in the mouse liver was down-regulated (P < 0.05).

[0112] 3.3 9(Z),11(E)-Octadecadienoic acid promotes the SOD level in the ALD model

[0113] According to the SOD results ([[]] Figure 14 ) In the in vivo mouse model, by intraperitoneal gavage of ethanol to mice, the SOD level in the mouse liver was down-regulated (P < 0.05). When 9(Z),11(E)-octadecadienoic acid was given to mice, the SOD level in the mouse liver was up-regulated (P < 0.05).

Claims

Use of 1.9(Z),11(E)-octadecadienoic acid in the preparation of a drug for treating and / or improving alcoholic liver injury.

2. The application according to claim 1, wherein The alcoholic liver injury includes alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis or cirrhosis.

3. The application according to claim 1, characterized in that, The concentration of the 9(Z),11(E)-octadecadienoic acid is 0.5 - 50 μM.

4. A drug or pharmaceutical composition for treating and / or improving alcoholic liver injury, characterized in that, It contains 9(Z),11(E)-octadecadienoic acid.

5. The drug or pharmaceutical composition according to claim 4, wherein The concentration of the 9(Z),11(E)-octadecadienoic acid is 0.5 - 50 μM.

6. The drug or pharmaceutical composition according to claim 4, wherein The alcoholic liver injury includes alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis or cirrhosis.

7. The drug or pharmaceutical composition according to claim 4, wherein The dosage form includes tablets, capsules, granules, pills, powders or injections.

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