Use of a quinolinone alkaloid for the preparation of a medicament for the treatment and / or prevention of liver damage

Abstract

The application relates to the field of medicinal chemistry, in particular to the use of a quinolinone alkaloid in the preparation of a medicine for treating and / or preventing liver injury. The compound has the following structural formula: The quinolinone alkaloid provided by the application has no damaging effect on HepG2 cells at a concentration of 0-100 micromoles, the compound can effectively inhibit the damaging effect of lipopolysaccharide LPS on HepG2 cells, reduce the activities of glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST), meanwhile, the compound can enhance the generation of anti-inflammatory factors IL-4 and IL-10, inhibit the release of pro-inflammatory factor TNF-alpha, and inhibit the expression of JAK1 / STAT3 signal pathway, thereby playing a role in protecting liver cells.

Description

Technical Field

[0001] This invention relates to the field of medicinal chemistry, and more specifically to the use of a quinolinone alkaloid in the preparation of medicaments for treating and / or preventing liver injury. Background Technology

[0002] Acute liver injury (ALI) is a severe disease characterized by a sudden onset of extensive hepatocyte necrosis or apoptosis, hepatocyte steatosis, inflammatory response, oxidative stress, and liver function impairment caused by multiple factors within a short period. Under the continuous influence of various pathogenic factors, ALI can easily progress to acute hepatitis, liver fibrosis, cirrhosis, and even severe conditions such as liver failure and liver cancer if not treated promptly. Currently, silymarin is often used to treat acute hepatitis, as it exerts a hepatoprotective effect by scavenging reactive oxygen species and maintaining cell membrane fluidity. However, its poor oral absorption and low bioavailability significantly limit its clinical application.

[0003] Graveoline, a quinolone alkaloid, was isolated from Rue. Current literature reports that Graveoline and its structural analogs possess anti-glioblastoma multiforme (Wu et al., Medicine (Philadelphia, PA, United States) (2022), 101(39), e30853), antifungal (Mohd Kamal et al., Mycopathologia (2021), 186(2), 221-236), anti-bladder cancer (Xiang et al., Latin American Journal of Pharmacy (2021), 40(6), 1227-1232), anti-atherosclerosis (Yao et al., Latin American Journal of Pharmacy (2021), 40(6), 1327-1332), and anti-melanoma (Samrat et al.). (Al., Phytotherapy Research (2014), 28(8), 1153-1162), anti-Staphylococcus aureus resistance activity (Stefano, et al., Journal of Medicinal Chemistry (2011), 54(16), 5722-5736), etc.)

[0004] The HepG2 cell line exhibits high differentiation and intact biotransformation characteristics of its metabolic enzymes, eliminating the need for exogenous activation systems. In drug-related studies, these metabolic enzymes remain stable and do not change with passage number. Furthermore, the biotransformation and metabolic enzymes it contains are homologous to those in normal human hepatocytes. Therefore, it is often used as an ideal cell line for in vitro hepatocyte metabolism or genotoxicity assays. Among these, HepG2.2.15 is a widely used cell line. As a derivative of HepG2, it serves as a good model for in vitro screening of anti-HBV drugs and is used as an in vitro research tool for the development of new anti-HBV drugs. Summary of the Invention

[0005] The present invention aims to provide the use of a quinolinone alkaloid in the preparation of a medicament for the treatment and / or prevention of liver injury.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0007] Use of a quinolinone alkaloid in the preparation of a medicament for treating and / or preventing liver injury, said compound having the following structural formula:

[0008]

[0009] According to some preferred embodiments of the present invention, the liver injury includes at least one of acute hepatitis, viral hepatitis, drug and toxic hepatitis, fatty liver, liver fibrosis, cirrhosis, and liver failure.

[0010] According to some preferred embodiments of the present invention, the medicament comprises a pharmaceutically effective amount of the quinolinone alkaloid and a pharmaceutically acceptable carrier.

[0011] According to some preferred embodiments of the present invention, the dosage form of the drug is a suspension, emulsion, tablet, capsule, granule, oral liquid or injection.

[0012] According to some preferred embodiments of the present invention, the quinolinone alkaloid is used to inhibit the release of pro-inflammatory factors, enhance the synthesis of anti-inflammatory factors, and reduce the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

[0013] According to some preferred embodiments of the present invention, the quinolinone alkaloid is used to inhibit hepatocyte damage and promote hepatocyte proliferation.

[0014] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0015] The quinolinone alkaloids provided by this invention have no damaging effect on HepG2 cells at concentrations of 0-100 μmol. These compounds effectively inhibit lipopolysaccharide (LPS)-induced damage to HepG2 cells. Their possible mechanism of action involves protecting hepatocytes by reducing the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Simultaneously, the quinolinone alkaloids can enhance the production of anti-inflammatory factors IL-4 and IL-10, inhibit the release of the pro-inflammatory factor TNF-α, and suppress the expression of the JAK1 / STAT3 signaling pathway. This provides a promising lead compound for the development of new drugs for the prevention and / or treatment of liver injury, and has significant research value and application prospects for the treatment of liver injury. Attached Figure Description

[0016] Figure 1 This is the high-resolution mass spectrum of compound 1 of the present invention;

[0017] Figure 2 The hydrogen spectrum (600 M Hz, MeOH-d4) of compound 1 of the present invention is shown.

[0018] Figure 3 The carbon spectrum (150 M Hz, MeOH-d4) of compound 1 of the present invention is shown.

[0019] Figure 4 The DEPT spectrum of compound 1 of this invention is shown below.

[0020] Figure 5 The 1H-1H COSY spectrum of compound 1 of the present invention is shown below.

[0021] Figure 6 The HSQC spectrum of compound 1 of this invention is shown below.

[0022] Figure 7 The HMBC spectrum of compound 1 of the present invention is shown below.

[0023] Figure 8 The effect of compound 1 of the present invention on the cell viability of HepG2 cells;

[0024] Figure 9 The expression of alanine aminotransferase (ALT) in HepG2 cells, an acute liver injury model, is shown by compound 1 of the present invention.

[0025] Figure 10 The expression of aspartate aminotransferase (AST) in HepG2 cells, an acute liver injury model, is shown by compound 1 of this invention.

[0026] Figure 11 The promoting effect of compound 1 of the present invention on IL-4, an inflammatory factor, in the supernatant of HepG2 cells in an acute liver injury model;

[0027] Figure 12 The promoting effect of compound 1 of the present invention on IL-10, an inflammatory factor in the supernatant of HepG2 cells in an acute liver injury model;

[0028] Figure 13 The inhibitory effect of compound 1 of the present invention on TNF-α, an inflammatory factor in the supernatant of HepG2 cells in an acute liver injury model; Figure 14 Compound 1 of this invention regulates the JAK1 / STAT3 signaling pathway in HepG2 cells; Gra is the drug group, and Sil is the positive silymarin group; compared with the model group, **P<0.01, *P<0.05; #P>0.05. Detailed Implementation

[0029] To explain in detail the technical content, objectives, and effects of the present invention, the following description is provided in conjunction with the embodiments and accompanying drawings.

[0030] Culture medium: MEM medium (high glucose) was mixed with 10% fetal bovine serum (FBS) and 1:1000 penicillin / streptomycin antibiotics.

[0031] HepG2 cell culture: HepG2 cells were cultured in a cell culture incubator at 37°C and 5% CO2 for 2–3 days. When the cells reached 80% confluence, they were digested with 0.5% trypsin for 2 minutes. The trypsin was removed, and medium containing 10% FBS was added to terminate the digestion. The cell suspension was aspirated into centrifuge tubes and centrifuged at 1000 rpm for 5 minutes to remove the medium. The cells were resuspended in fresh medium and passaged in culture dishes at a 1:2 ratio.

[0032] Data analysis was performed using Graphpad 7.0 software to calculate cell viability in each group.

[0033] Example 1: Isolation of the target compound

[0034] 10 kg of dried rue aerial parts were collected. The coarse stems were pulverized using a pulverizer and extracted twice with pure water using ultrasound at room temperature (8 L of pure water for 1 hour each time). The extracts were filtered, and the filtrates from both extractions were combined to obtain an aqueous extract of dried rue. The aqueous extract was concentrated to 1823.7 g under reduced pressure and coarsely separated using a macroporous resin (D101, approximately 2 kg). The extract was then eluted sequentially with water, 50% ethanol, and 90% ethanol until no significant color change was observed, yielding three fractions (Fr. A to Fr. C) with volumes of 5 L, 4 L, and 5 L, respectively. Fr. C was further concentrated under reduced pressure to obtain 14.3 g of extract. Fr.C was dissolved in methanol, mixed with silica gel, and dry-coated onto a column for further silica gel column chromatography, followed by thin-layer chromatography (TLC) analysis. Finally, a dichloromethane-methanol system was used for gradient separation on silica gel column chromatography. The elution gradients were successively 800 ml of 100% dichloromethane, 800 ml of dichloromethane:methanol mixtures (100:1, 50:1, 30:1, 20:1, 10:1, and 1:1), and 800 ml of 100% methanol. Formic acid solution of 0.1% was added to each eluent. Fractions were collected and spotted onto a TLC plate for color development. Similar components were combined to obtain 12 fractions (Fr.C-Ⅰ~Fr.C-Ⅻ). Fr.C-Ⅵ was again subjected to Sephadex LH-20 column chromatography with methanol elution. Fractions were spotted onto a TLC plate for color development and combined to obtain 11 components (Fr.C-Ⅵ-1~Fr.C-Ⅵ-11). Fr.C-Ⅵ-2 precipitated needle-like crystals at room temperature, which is compound 1 (6.2 mg). The structural formula of compound 1 is as follows:

[0035]

[0036] Example 2: Structural confirmation of the target compound

[0037] The structure of the compound was confirmed by mass spectrometry and nuclear magnetic resonance, and the data obtained are as follows:

[0038] 1. Mass spectrometry: HRESIMS: m / z: 280.09777 [M+H] + (calcd.for C 17 H 14 NO3, 280.0969); mass spectrum as shown Figure 1 As shown.

[0039] 2. Nuclear magnetic resonance (NMR): Proton spectrum (H NMR) Figure 2 ), carbon spectrum ( Figure 3 DEPT Figure 4 ), 1 H- 1 H COSY( Figure 5 ), HSQC ( Figure 6 ),HMBC( Figure 7The spectral information was used to determine the structure of the compound. The proton and carbon spectral data are shown in Table 1 below. The solvent was MeOH-d4. The proton spectrum was 600 MHz, and the carbon spectrum was 150 MHz.

[0040] Table 1. Signal assignments for the 1H and 1C spectra of the target compounds (δ is in ppm).

[0041]

[0042]

[0043] Based on the above NMR and mass spectrometry data, the compound was identified as Graveoline, and its structural formula is as follows:

[0044]

[0045] Example 3: Effects of Graveoline on the viability of human cells (HepG2)

[0046] 1. Take HePG2 cells in the logarithmic growth phase, discard the culture medium, digest them with 0.5% trypsin containing EDTA, count the cells, and prepare a cell suspension;

[0047] 2. Using 5×10 3 Cells were seeded at a density of 100 μL per well in 96-well plates, with 3 replicates for each group. The cells were placed in MEM medium (high glucose) containing 10% fetal bovine serum (FBS) and 1:1000 penicillin / streptomycin antibiotics, and cultured at 37°C in a 5% CO2, saturated humidity incubator.

[0048] 3. Add different concentrations of Graveoline to make the final concentrations 0 μM, 10 μM, 20 μM, 40 μM, 60 μM, 80 μM, and 100 μM, and continue culturing for 24 h.

[0049] 4. After removing the drug-containing culture medium, mix 10 μl / well of CCK8 reagent with 150 μl / well of culture medium, and then add the mixture to the treated cell culture plate.

[0050] 5. After incubation at 37℃ and 5% CO2 for 4 hours, analyze the absorbance (OD) value at 450nm using a microplate reader and plot the average value as a line graph.

[0051] The obtained cell viability results are as follows Figure 8As shown, the study indicates that the compound Graveoline at concentrations of 0-100 μM has no significant toxic effect on HepG2 cell viability and can promote cell proliferation within this concentration range, exhibiting a certain dose-response effect. The effect on cell proliferation is relatively small at a concentration of 10 μM; therefore, this concentration was selected as the optimal concentration for subsequent experiments.

[0052] Simultaneously, the toxicity of 4(1H)-quinolinone, 2-(3,4-dihydroxyphenyl)-1-methyl to HepG2 cell viability was tested at 0-100 μM. The results showed that the compound Graveoline was less toxic than 4(1H)-quinolinone, 2-(3,4-dihydroxyphenyl)-1-methyl. The molecular formula of 4(1H)-quinolinone, 2-(3,4-dihydroxyphenyl)-1-methyl is C1 16 H 13 NO3, Structure

[0053] The formula is as follows:

[0054]

[0055] II. Effects of Graveoline on the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in HepG2 cells, an acute liver injury model.

[0056] 1. Establishment of an acute liver injury model:

[0057] (1) HepG2 cells in the logarithmic growth phase were digested with 0.5% trypsin, resuspended and counted, and cultured in 6-well plates for 24 h in groups: control group (CON), LPS-induced model group (MOD), positive control silymarin group (SIL), low-dose graveoline group (10 μM), medium-dose graveoline group (20 μM), high-dose graveoline group (40 μM), low-dose water extract of dried rue group (10 μM), medium-dose water extract of dried rue group (20 μM), and high-dose water extract of dried rue group (40 μM).

[0058] (2) LPS modeling: After culturing for 24 hours, the medium was changed. The model group, the positive drug silymarin group and the Graveoline group were replaced with medium containing LPS (100 μM) and cultured for another 24 hours.

[0059] (3) Drug addition: After culturing for 24 hours, the medium was changed. The positive drug milk thistle group (20 μM) and Graveoline group were replaced with the drug-added medium containing the corresponding concentration of drug and cultured for another 24 hours.

[0060] 2. Pretreatment of cell culture samples: Wash the collected cells 1-2 times with isotonic buffer (0.1 mol / L pH 7-7.4 phosphate buffer or physiological saline is recommended); centrifuge at 1000 rpm for 10 minutes, discard the supernatant, keep the cell pellet, add homogenizing medium (0.1 mol / L pH 7-7.4 phosphate buffer or physiological saline is recommended), sonicate or homogenize manually under ice-water bath conditions, do not centrifuge the prepared homogenate, and wait for analysis.

[0061] 3. Detect ALT and AST levels in cell supernatant: Detect serum ALT (Nanjing Jiancheng, Cat. No. C009-2-1) and AST (Nanjing Jiancheng, Cat. No. C0010-2-1) levels according to the transaminase reagent instructions. Specific procedures are as follows:

[0062] Table 2. Procedure for Measuring ALT and AST Levels in Cells

[0063]

[0064] 3. Gently shake the 96-well plate horizontally to mix, let it stand at room temperature for 15 minutes, and measure the OD value of each well with a microplate reader at a wavelength of 510 nm. Use the absolute OD value (OD value of the test well minus the OD value of the control well) to find the corresponding ALT / GPT activity units from the standard curve.

[0065] Experimental results

[0066] Table 3. Expression of ALT and AST in HepG2 cells after treatment.

[0067]

[0068] The results showed that, compared with the blank control group, the expression of ALT and AST in the LPS-induced HepG2 cell acute liver injury model group was significantly increased (**P<0.01), indicating successful model establishment. The addition of different concentrations of Graveoline significantly inhibited ALT expression. Figure 9 ) and AST( Figure 10 Graveoline significantly inhibited the expression levels of ALT and AST in HepG2 cells at a concentration of 10 μM. However, the addition of 10-40 μM of water extract from dried rue had no significant effect on ALT and AST levels in the HepG2 cell acute liver injury model group.

[0069] III. Effects of Graveoline on Inflammatory Factors in HepG2 Cell Supernatant

[0070] An LPS-induced HepG2 cell model was established. The levels of inflammatory factors IL-4, IL-10, and TNF-α in the supernatant of the cell model were detected by ELISA to evaluate the inhibitory effect of Graveoline on inflammatory factors in an acute liver injury model.

[0071] 1. Cell treatment

[0072] (1) HepG2 cells in the logarithmic growth phase were digested with 0.5% trypsin, resuspended and counted, and grouped into 6-well plates for 24 h: control group, LPS-induced model group, positive control silymarin group, low-dose graveoline group (10 μM), medium-dose graveoline group (20 μM), and high-dose graveoline group (40 μM).

[0073] (2) LPS modeling: After culturing for 24 hours, the medium was changed. The model group, silymarin group and Graveoline group were replaced with medium containing LPS (100 μM) and cultured for another 24 hours.

[0074] (3) Drug addition: After culturing for 24 hours, the medium was changed. The milk thistle group and the Graveoline group were replaced with a drug-added medium containing the corresponding concentration of drug and cultured for another 24 hours.

[0075] 2. ELISA experiment

[0076] (1) Establish standard curves according to the kit instructions (IL-4: Proteintech, KE00016; IL-10: Proteintech, KE00170; TNF-α: Proteintech, KE00154). Perform serial dilutions of the standards as follows:

[0077] Table 4. Steps for gradient dilution of standards

[0078]

[0079] (2) Add samples separately, and set up zero wells, standard wells, and test sample wells separately. Add 100 μL of sample diluent to the zero well, and add 100 μL of serially diluted standard or test sample to the remaining wells respectively;

[0080] (3) Cover the enzyme-labeled plate with a film and incubate at 37°C for 2 hours;

[0081] (4) Remove the sealing film, discard the liquid, and pat dry; wash the strip with washing solution (1×), 350-400μL per well. After washing, shake off the liquid and pat dry the strip. Repeat this step 4 times to avoid foreign objects entering the well and to prevent the strip from drying.

[0082] (5) Add 100 μL of detection antibody (1×) to each well, cover with sealing film, and incubate at 37°C for 1 h;

[0083] (6) Repeat step (4);

[0084] (7) Add 100 μL of HRP-labeled streptavidin (1×) to each well, cover with sealing film, and incubate at 37°C for 40 min;

[0085] (8) Repeat step (4);

[0086] (9) Color development: Add 100 μL of TMB color development solution to each well and develop color at 37℃ in the dark for 15-20 min;

[0087] (10) Termination: Add 100 μL of stop solution to each well; the blue color will turn yellow. The order of adding the stop solution is the same as that of adding the TMB colorimetric solution.

[0088] (11) Shake for 5 min, and then measure the absorbance at 450 nm using an ELISA reader within 15 min.

[0089] (12) Create a standard curve in Excel and calculate the concentration.

[0090] Experimental results

[0091] ELISA results showed significant changes in inflammatory factors after Graveoline intervention in the HepG2 cell acute liver injury model. As shown in the figure, compared with the control group, the anti-inflammatory factor IL-4 (…)… Figure 11 ) and IL-10 ( Figure 12 All decreased significantly (**P<0.01), TNF-α ( Figure 13 The levels of IL-4 and IL-10 increased significantly (**P<0.01). All three doses of Graveoline significantly increased the levels of anti-inflammatory factors IL-4 and IL-10 (**P<0.01) and significantly decreased the levels of pro-inflammatory factor TNF-α (**P<0.01).

[0092] IV. Graveoline regulates the LPS-induced JAK1 / STAT3 signaling pathway in HepG2 cells.

[0093] 1. Target compound

[0094] 1) Sample preparation

[0095] a) Cell plating: HepG2 cells in the logarithmic growth phase were taken, the culture medium was discarded, washed once with PBS, digested with 0.5% trypsin containing EDTA, the cell suspension was terminated with fresh culture medium and dispersed by pipetting, and the cells were counted to prepare a cell suspension.

[0096] b) Adjust the cell density to 3 × 10⁶ cells using MEM medium. 5Cells / well, seeded into 6-well plates, 2 mL / well, and incubated in an incubator at 37°C, 5% CO2, and 100% relative humidity for 24 h;

[0097] c) Drug administration: ① Blank control group: HepG2 cells cultured normally; ② Model group: HepG2 cells treated with 100 μM LPS for 24 h; ③ Positive control group: HepG2 cells treated with 100 μM LPS + 20 μM silymarin for 24 h; ④ Drug group: HepG2 cells treated with 100 μM LPS + 10 μM Graveoline for 24 h;

[0098] d) After culturing for 24 hours, collect the cells, discard the culture supernatant, wash once with PBS, digest with 0.5% trypsin containing EDTA, stop digestion with 1 mL of culture medium, centrifuge at low speed to collect the cells, and wash once more with PBS.

[0099] e) per 1×10 6 Each cell was resuspended in 100 μL of RIPA lysis buffer and lysed on ice for 15–30 min; then centrifuged at 12000 g for 10 min at 4 °C.

[0100] f) Take a small amount of supernatant and perform BCA quantification using a BCA kit (Abiowell, AWB0104). Prepare the detection working solution by mixing solution A and solution B in a ratio of 50:1. Add 5 μL of supernatant or standard, incubate at 37°C for 30 min, and detect the absorbance at a wavelength of 562 nm.

[0101] g) Plot a linear graph based on the standard concentrations, calculate the total protein concentration in the supernatant, and prepare an appropriate concentration using buffer. Add 5×SDS loading buffer at a ratio of 4:1, boil in a metal bath for 10 min, and store at -80℃.

[0102] 2) Electrophoresis

[0103] a) Load the sample onto the prepared gel;

[0104] b) Electrophoresis: Adjust the voltage to 60V. After the protein is concentrated, adjust the voltage to 120V until the bromophenol blue front reaches the bottom of the gel, then stop the electrophoresis.

[0105] c) Transfer: Constant current applied, 300mA, transfer time 1.5h;

[0106] d) Sealing: Remove the membrane and place it in a 5% skim milk powder sealing solution, and shake it on a shaker at room temperature for 1 hour;

[0107] e) Primary antibody incubation: Add primary antibodies (Jak1: Proteintech, 66466-1-Ig; P-Jak1: Affinity Biosciences, AF2012; P-STAT3: abcam, ab76315; STAT3: Proteintech, 10253-2-AP; β-actin: Proteintech, 66009-1-Ig) to each group and incubate overnight at 4°C.

[0108] f) Secondary antibody incubation: After primary antibody incubation, remove the PVDF membrane and wash it three times with TBST for 10 min each time. Add secondary antibodies (Goat anti-Mouse: Abiowell, Cat. No. AWS0001; Goat anti-Rabbit: Abiowell, Cat. No. AWS0002) to each group and incubate at room temperature for 1 h. Remove the membrane and wash it three times with TBST for 10 min each time.

[0109] g) Turn on the developer, prepare the ECL developer solution, spread it evenly on the membrane, and perform development.

[0110] Experimental results

[0111] Graveoline significantly inhibited the expression of p-JAK1 and p-STAT3 proteins, key indicators of inflammation in the IL-10 / JAK1 / STAT3 signaling pathway. Figure 14 A). Compared with the normal group, p-JAK1 levels were significantly increased in the model group (P<0.05), while p-JAK1 levels were significantly downregulated in the drug group after the addition of Graveoline (P<0.01). Figure 14 B). Compared with the normal group, p-STAT3 was also significantly increased in the model group (P<0.01). Figure 14 C), the addition of Graveoline to the drug group significantly downregulated p-STAT3 (P<0.01). There were no significant differences in JAK1 and STAT3 between the model group, the normal group, and the drug group. Figure 14 D,14E).

[0112] Meanwhile, 4(1H)-quinolinone and 2-(3,4-dihydroxyphenyl)-1-methyl were also tested and found to downregulate p-STAT3 at 0-100 μM, but the downregulation was significantly less than that of Graveoline.

[0113] In summary, the compounds provided by this invention can cause no damage to HepG2 cells at concentrations of 0-100 μmol. These compounds effectively inhibit lipopolysaccharide (LPS)-induced damage to HepG2 cells. Their mechanism of action involves reducing the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), while simultaneously enhancing the production of anti-inflammatory factors IL-4 and IL-10, inhibiting the release of pro-inflammatory factor TNF-α, and suppressing the expression of the JAK1 / STAT3 signaling pathway, thereby exerting an anti-inflammatory effect. This provides a promising lead compound for developing new drugs to prevent and / or treat acute liver injury, and has significant research value and application prospects for the treatment of liver injury.

[0114] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent modifications made based on the content of the present invention specification and drawings, or direct or indirect applications in related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. The use of a quinolinone alkaloid in the preparation of a medicament for treating and / or preventing acute liver injury, characterized in that, The compound has the following structural formula: 。 2. The use according to claim 1, characterized in that, The acute liver injury mentioned is acute hepatitis.

3. The use according to claim 1, characterized in that, The drug comprises a pharmaceutically effective amount of the quinolinone alkaloid and a pharmaceutically acceptable carrier.

4. The use according to claim 1, characterized in that, The dosage form of the drug is a suspension, emulsion, tablet, capsule, granule, oral liquid or injection.

5. The use according to any one of claims 1-4, characterized in that, The quinolinone alkaloids are used to inhibit hepatocyte damage and promote hepatocyte proliferation.

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