Application of glabridin in preparation of medicine for preventing and treating pulmonary fibrosis

Abstract

The invention discloses application of glabridin in preparation of a medicine for preventing and treating pulmonary fibrosis, and belongs to the technical field of pharmaceutical preparations. The new application of the glabridin in prevention and treatment of the pulmonary fibrosis is provided for the first time, and a bleomycin-induced mouse pulmonary fibrosis model verifies that the glabridin can obviously relieve pathological injury of lung tissue, reduce collagen deposition, obviously improve a pulmonary alveolar structure, play an anti-fibrosis role and improve lung functions; the application field of the natural compound in respiratory system diseases is expanded. Compared with an existing anti-fibrosis drug, glabridin is natural in source and high in safety, and has the potential of being further researched and developed into a novel anti-pulmonary fibrosis drug. The animal model and the human cell model are combined, the experimental design is scientific and reasonable, the result consistency is high, and the reliability and repeatability of the glabridin in the aspect of preventing and treating the pulmonary fibrosis are proved.

Description

Technical Field

[0001] This invention provides a novel use for glycyrrhizin, relating to the field of pharmaceutical formulation technology, specifically to the application of glycyrrhizin in the preparation of drugs for the prevention and treatment of pulmonary fibrosis. Background Technology

[0002] Pulmonary fibrosis is a chronic, progressive lung disease characterized by disordered lung tissue structure, abnormal proliferation of interstitial cells, and massive extracellular matrix deposition. It primarily manifests as alveolar structural destruction, decreased lung compliance, and loss of respiratory function. The most common clinical forms of pulmonary fibrosis are idiopathic pulmonary fibrosis and secondary pulmonary fibrosis induced by chemical factors such as bleomycin.

[0003] Currently, internationally approved drugs for treating pulmonary fibrosis include pirfenidone and nintedanib, but both have limited efficacy, are expensive, and have side effects such as gastrointestinal adverse reactions, making them unsuitable for long-term use. Organ transplantation, as a treatment option for end-stage patients, is also limited by donor shortages and high risks. Therefore, there is an urgent need to develop novel therapeutic drugs with clear targets and good tolerability.

[0004] Glabridin (GLA) is an important active ingredient in glycyrrhiza flavonoids. Although current research has not directly explored its mechanism of action in treating pulmonary fibrosis (PF), multiple experiments have shown that it may have potential therapeutic value for pulmonary fibrosis by regulating key processes such as inflammation, oxidative stress, signaling pathways, and epithelial-mesenchymal transition (EMT). Currently, there are no reports on anti-fibrotic effects of glabridin in China or abroad. Summary of the Invention

[0005] To overcome the shortcomings of the prior art, the present invention provides the application of glycyrrhizin in the preparation of drugs for the prevention and treatment of pulmonary fibrosis.

[0006] Furthermore, the pulmonary fibrosis is one or more of the interstitial pulmonary fibrosis diseases.

[0007] Furthermore, the pulmonary fibrosis is interstitial pulmonary fibrosis caused by bleomycin.

[0008] Furthermore, the drug is prepared using glycyrrhizin as its active ingredient, either alone or in combination with antifibrotic drugs, anti-inflammatory drugs, or antioxidant drugs.

[0009] Furthermore, the drug can inhibit FGFR1 phosphorylation.

[0010] Furthermore, the drug can be used to slow, prevent, or reverse the progression of pulmonary fibrosis.

[0011] Furthermore, the drug dosage form is an oral preparation, an injectable preparation, a lyophilized powder preparation, or an inhaler.

[0012] Furthermore, the oral formulation is a tablet, capsule, or oral liquid dosage form; the injectable formulation is a sustained-release formulation or a nano-formulation.

[0013] Furthermore, the drug formulation is administered via intraperitoneal injection, oral administration, intravenous injection, aerosol inhalation, or transdermal administration; the dosage of the drug formulation, calculated based on the mouse dosage, is 20-40 mg / kg per dose.

[0014] Furthermore, the dosage of the drug includes a single injection dose of 20 mg / kg or 40 mg / kg, administered once daily.

[0015] Since this invention discloses for the first time the role of glycyrrhizin in the preparation of drugs for the prevention and treatment of pulmonary fibrosis, any preparation of glycyrrhizin alone or in combination with other active ingredients or pharmaceutical excipients, as long as the preparation is used for the prevention and treatment of pulmonary fibrosis, regardless of the dosage form or route of administration, falls within the scope of protection of this invention.

[0016] Furthermore, the glycyrrhizin can also be used in the prevention and treatment of other fibrotic diseases such as liver fibrosis, kidney fibrosis, myocardial fibrosis, or skin fibrosis.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention proposes a novel application of glycyrrhizin in the prevention and treatment of pulmonary fibrosis for the first time. Validated using a bleomycin-induced mouse pulmonary fibrosis model, glycyrrhizin significantly reduces pathological damage to lung tissue, decreases collagen deposition, and significantly improves alveolar structure, thus exerting an anti-fibrotic effect. Glycyrrhizin also reduces the lung index and hydroxyproline levels in lung tissue of experimental animals, while alleviating weight loss, demonstrating significant advantages in maintaining and improving lung function. This expands the application field of this natural compound in respiratory diseases and is highly innovative.

[0018] (2) The present invention demonstrates through in vitro and in vivo experiments that glycyrrhizin can effectively inhibit FGFR1 phosphorylation. In addition, glycyrrhizin can significantly inhibit the proliferation and migration of human embryonic lung fibroblasts (HFL-1) and reverse lactate-induced fibrotic phenotype, proving that it has a good anti-fibrotic effect at the cellular level.

[0019] (3) Compared with existing anti-fibrotic drugs, glycyrrhizin is derived from natural plants and has a higher safety profile. It has the potential to be further developed into a new anti-pulmonary fibrosis drug. This invention uses a combination of animal models and human cell models. The experimental design is scientific and reasonable, and the results are highly consistent, which proves the reliability and reproducibility of glycyrrhizin in the prevention and treatment of pulmonary fibrosis, providing a new option for clinical treatment. Attached Figure Description

[0020] Figure 1 The diagram shows the chemical molecular structure of glycyrrhizin and the intraperitoneal injection administration procedure in mouse experiments of this invention. Figure A shows the chemical molecular structure of glycyrrhizin, and Figure B shows the administration procedure.

[0021] Figure 2 The images show the appearance of the lung tissue, the results of HE and Masson staining, the lung index, the hydroxyproline content, and the changes in body weight of the mice in each group. Figure A shows the appearance of the mouse lung tissue, the results of H&E and Masson staining, Figure B shows the lung index statistics of each group of mice, Figure C shows the results of the hydroxyproline content in the lung tissue of each group of mice, and Figure D shows the changes in body weight of each group of mice.

[0022] Figure 3 From top to bottom, the images show WB representations and semi-quantitative statistical charts of the protein levels of type I collagen and α-SMA in the lung tissues of mice in each group.

[0023] Figure 4 Effects of glycyrrhizin on the vitality of human lung fibroblasts.

[0024] Figure 5 Effects of 24h treatment with glycyrrhizin on the migration ability of lactate-induced fibroblasts and the results of Transwell assay.

[0025] Figure 6 The results of EdU fluorescence detection in human pulmonary fibrosis epithelial cells before and after treatment with glycyrrhizin.

[0026] Figure 7 To illustrate the effects of glycyrrhizin on the mRNA and protein expression levels of type I collagen and α-actin in lactate-stimulated human primary fibroblasts, Figure A shows the Western blot representation of the protein levels of type I collagen and α-SMA in each group of cells, Figures B and C are semi-quantitative statistical charts, and Figure D shows the mRNA levels of type I collagen and α-SMA in each group of cells from left to right. Figure 8 A schematic diagram of the molecular docking between glycyrrhizin and the core target; Figure 9 This is a schematic diagram of the KEGG enrichment results; Figure 10 Schematic diagram of the binding of glycyrrhizin to FGFR1; Figure 11 The results of CETSA and Western blot experiments on human embryonic lung fibroblasts are shown. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the following embodiments are given for illustrative purposes only and are not intended to limit the scope of the invention. Those skilled in the art can make various modifications and substitutions to this invention without departing from its spirit and intent. Unless otherwise specified, the materials and components used in the following embodiments are commercially available.

[0028] Example 1: Effects of intraperitoneal injection of glycyrrhizin on the degree of pulmonary fibrosis, lung function, and lung pathology in mice. 1. Experimental materials Laboratory animals: Male C57BL / 6 mice (6–8 weeks old, weighing 20±2 g) were purchased from Hunan Silek Jingda Laboratory Animal Co., Ltd. Mice were housed in a specific pathogen-free (SPF) barrier environment, and all experiments were approved by the Animal Ethics Committee of Hubei University of Traditional Chinese Medicine.

[0029] Drugs and reagents: Bleomycin (Abmole), Glabridin (purity ≥98%, MedChemExpress), Hydroxyproline assay kit (Solarbio), 4% paraformaldehyde, HE staining solution, Masson staining solution (Solarbio).

[0030] 2. Experimental Methods After 7 days of acclimatization, mice were randomly divided into four groups (n=6): Control group, Model group, Glycyrrhizin (GLA) (20 mg / kg) group, and Glycyrrhizin (GLA) (40 mg / kg) group. Except for the control group, the other three groups of mice were given a single intratracheal infusion of bleomycin (3 mg / kg) to establish a pulmonary fibrosis model. Starting from day 1, the Glycyrrhizin group received intraperitoneal injections of Glycyrrhizin once daily for 21 consecutive days. The control and model groups received an equal volume of physiological saline. On day 22, mice were sacrificed, their body weight was measured, and lung tissue was harvested and weighed to calculate the lung index (lung weight / body weight × 100%). The left lung was used for histological processing, and the right lung was used for biochemical index detection. The left lung tissue was fixed in 4% paraformaldehyde for 24 h, embedded in paraffin, and then stained with hematoxylin and eosin (HE) and Masson's stain. Alveolar structure, inflammatory infiltration, and collagen deposition were observed under a microscope. Collagen metabolism parameters in lung tissue were measured using a hydroxyproline kit according to the manufacturer's instructions. In lung tissue, hydroxyproline is a classic, stable, and quantitative biochemical indicator for measuring the degree of collagen deposition and fibrosis; its elevation usually indicates the progression of pulmonary fibrosis or enhanced collagen remodeling.

[0031] 3. Experimental Results Lung tissue was taken for external observation, HE staining, and Masson staining analysis. Figure 2 (A) The degree of pulmonary fibrosis was significantly reduced in the glycyrrhizin-treated group. Lung index (lung weight / body weight ratio) and hydroxyproline content in lung tissue were respectively shown in Figures A and B. Figure 2 B and Figure 2 The C-value in the glycyrrhizin treatment group was significantly lower than that in the model group, suggesting a decrease in the degree of fibrosis. Figure 2 The results showed that during the experiment, the weight loss trend of mice in the glycyrrhizin-treated group was significantly slowed down, indicating good tolerance.

[0032] Example 2: Inhibitory effect of glycyrrhizin on fibrosis markers in mouse lung tissue 1. Experimental materials The experimental materials were the same as those used in Example 1.

[0033] 2. Experimental Methods Lung tissue was harvested, lysed using RIPA, quantified using the BCA method, and then subjected to SDS-PAGE electrophoresis. After transfer to a membrane, the tissue was incubated overnight at 4°C with primary antibody (anti-Collagen I, anti-α-SMA, 1:1000). Secondary antibody was added, and the membrane was incubated at room temperature for 30 min. The membrane was then washed four times with TBST on a shaker at room temperature for 5 min each time. Freshly prepared ECL mixed solution (A:B=1:1) was added to the protein side of the membrane, and the membrane was exposed in a dark room.

[0034] 3. Experimental Results Figure 3 The A-value in the study showed that the protein levels of α-SMA and Collagen I in the glycyrrhizin-treated group were significantly lower than those in the model group, indicating that the protein expression levels were significantly inhibited (P<0.01), suggesting that glycyrrhizin can effectively reduce the degree of pulmonary fibrosis in mice.

[0035] Example 3: Effect of glycyrrhizin on the viability of human primary fibroblasts 1. Experimental materials Human embryonic lung fibroblasts HFL-1 (purchased from Cybio Biotechnology Co., Ltd.), CCK-8 kit (purchased from Beyotime Biotechnology Co., Ltd.).

[0036] 2. Experimental Methods To determine the appropriate drug concentration, cell viability was assessed using the CCK8 cell proliferation and toxicity assay kit. Logarithmic growth phase cells were digested with trypsin to prepare a formulation with a concentration of 1×10⁻⁶. 5 Cell suspension of cells / mL, at 1×10 4Cells were seeded per well in 96-well plates at 100 μL each, and incubated at 37°C in a 5% CO2 incubator until cell adhesion was achieved. The culture medium for each group was then replaced with 100 μL of serum-free basal medium containing 1% BSA, and the cells were starved for 12 h. The culture medium for each group was then replaced with 100 μL of the corresponding medium containing a specific concentration of the drug for each cell sample. The control group was replaced with medium containing the solvent, and corresponding blank wells (wells containing only the corresponding medium and no cells) were set up. The cells were incubated for an appropriate time. 10 μL of CCK-8 solution was added to each well, and the cells were incubated for 1–4 hours. The absorbance at 450 nm was measured using a microplate reader. Cells treated with the solvent were used as the control group, and the blank wells were used as the blank wells. The cell viability was calculated using the formula.

[0037] 3. Experimental Results The CCK8 results showed that glycyrrhizin inhibited HFL-1 cell proliferation in a concentration-dependent manner, with a significant decrease in cell proliferation at concentrations of 20 μM and above (P < 0.01), indicating its anti-fibrotic cell activity. Figure 4 The effect of different concentrations of glycyrrhizin A on cell viability was investigated. As the concentration of glycyrrhizin A increased, cell viability gradually decreased, with the most significant decrease observed at 60 μM.

[0038] Example 4: Glycyrrhizin inhibits lactate-induced fibroblast migration. 1. Experimental materials Human embryonic lung fibroblasts HFL-1, lactate (10 mM), Transwell plates (8 μm), crystal violet staining solution.

[0039] 2. Experimental Methods In the Transwell assay, HFL-1 cells were treated with lactate (10 mM) and then treated with glycyrrhizin for 24 h. The cell suspension was then added to the upper chamber, and culture medium containing 10% FBS was added to the lower chamber. After 24 h, the upper chamber was removed, the culture medium was washed off with PBS, and the cells on the membrane were wiped clean with a cotton swab. The cells were fixed with paraformaldehyde for 20 min, gently washed twice with PBS, and stained with crystal violet staining working solution at room temperature for 10 min. The cells were then gently washed three times with PBS to remove the surface crystal violet, and the non-cell-inoculated side was photographed under an inverted microscope.

[0040] 3. Experimental Results like Figure 4 In Figure B, HFL-1 cells treated with lactate (10 mM) followed by the addition of glycyrrhizin showed lower overall cell viability compared to the control group. The inhibitory effect of glycyrrhizin on cell viability was more pronounced under lactate conditions, especially at higher concentrations; at concentrations of 5 μM and above, cell proliferation decreased significantly (P < 0.01), indicating its anti-fibrotic cell activity.

[0041] Lactic acid is an important metabolic-inflammatory-fibrotic signaling molecule. Extensive evidence suggests that elevated lactate levels promote mesenchymal cell activation, extracellular matrix (ECM) deposition, and tissue remodeling through multiple pathways in the development and progression of pulmonary fibrosis. Lactic acid activates GPR81 and MCT1 / 4-H... + The mild acidification caused by influx activates PI3K-Akt, ERK / p38, FAK / Src, and RhoA-ROCK, enhancing migration, stress fiber formation, and adhesion plaque formation. Lactic acid also promotes the expression / activity of MMP-2 / 9 and LOX, facilitating cell migration and promoting collagen cross-linking to form a stiffer matrix.

[0042] Figure 5 A in the diagram illustrates cell migration under different treatment conditions. Figure 5 B in the study showed that lactate significantly promoted cell migration, and the number of Transwell cells in the glycyrrhizin-treated group was significantly reduced (P<0.01), suggesting that glycyrrhizin can effectively inhibit lactate-induced HFL-1 cell migration.

[0043] Example 5: EdU assay for cell proliferation 1. Experimental materials Human embryonic lung fibroblasts (HFL-1), lactate (10 mM), EdU assay kit (Invitrogen).

[0044] 2. Experimental Methods Lactate-induced cells were collected in 96-well plates. When the cell density reached approximately 70%, the cells were divided into three groups, and glycyrrhizin at specified concentrations (5, 10, and 20 μM) was added to each well. Cells were then cultured for another 24 hours. Cell proliferation activity was assessed using the EdU assay, and the cells were observed and photographed under a fluorescence microscope for statistical analysis.

[0045] 3. Experimental Results Figure 6 B in the study showed that lactate stimulation significantly induced abnormal cell proliferation. After treatment with glycyrrhizin, the positive rate of EdU (proliferating cells) decreased significantly, suggesting that it can reverse lactate-induced excessive proliferation and antagonize lactate-mediated enhanced proliferation.

[0046] Example 6: Glycyrrhizin inhibits the primary pulmonary fibrosis phenotype under lactate stimulation. 1. Experimental materials Human embryonic lung fibroblasts HFL-1, lactate (10 mM).

[0047] 2. Experimental Methods Cells were stimulated with lactate for 24 hours, then incubated with glycyrrhizin for another 24 hours. The mRNA and protein expression of Collagen I and α-SMA were then detected.

[0048] Rinse cells 2-3 times with PBS buffer. Add total cell protein extraction reagent for lysis for 3-5 min. Incubate on ice for 30 min, repeatedly pipetting to ensure complete cell lysis. Centrifuge at 12000g for 5 min at 4℃, and determine protein concentration using the supernatant (BCA method). Perform SDS-PAGE electrophoresis. After transfer, incubate overnight at 4℃ with primary antibody (anti-Collagen I, anti-α-SMA, 1:1000). Add secondary antibody and incubate at room temperature for 30 min. Wash four times with TBST on a shaker at room temperature for 5 min each time. Add freshly prepared ECL mixture (A:B=1:1) to the protein side of the membrane and expose in the dark.

[0049] Total RNA was extracted using Trizol reagent, and after purity testing, it was reverse transcribed into cDNA. RT-PCR was performed using GAPDH as an internal control to detect the mRNA levels of type I collagen and α-SMA. Primer sequences are shown in Table 1.

[0050] Reaction system: 5.0 μL 2×Master Mix, 1.0 μL primer working solution (2.5 μM), 1.0 μL template, 2.0 μL ddH2O, 1.0 μL Rox. Reaction program: 95℃ pre-denaturation for 3 min; cycles (40 times): 95℃, 10 s → 58℃, 30 s → 72℃, 30 s.

[0051] Table 1. List of primers corresponding to the target gene

[0052] 3. Experimental Results Figure 7 Results A, B, and C showed that, compared with lactate-stimulated human embryonic lung fibroblasts, the transcriptional and protein expression levels of type I collagen and α-actin were significantly reduced in cells treated with glycyrrhizin, further verifying its anti-pulmonary fibrosis effect.

[0053] Example 7: Predicting the target of glycyrrhizin in the anti-pulmonary fibrosis based on network pharmacology and molecular docking technology 1. Method 1.1 Acquisition of glycyrrhizin and pulmonary fibrosis targets Potential targets of glycyrrhizin were searched using databases such as TCMSP and SwissTargetPrediction. Identify pulmonary fibrosis-related targets using GeneCards and OMIM databases; The target names were standardized using the Uniprot database; The Venn plot of the intersection target of glycyrrhizin and pulmonary fibrosis was drawn using the Venny tool.

[0054] 1.2 Construction of protein interaction network Intersecting targets were imported into the STRING database to construct a protein-protein interaction (PPI) network; Use Cytoscape software to perform network topology analysis and screen key targets.

[0055] 1.3 GO enrichment and KEGG enrichment analysis GO biological function and KEGG pathway enrichment analysis were performed on the intersecting targets. GO bar charts and KEGG Sankey diagrams were visualized using the MicroBioinformatics online platform.

[0056] 1.4 Molecular docking of glycyrrhizin with the core target The three-dimensional crystal structure of the core target was obtained from the PDB database and preprocessed (removing water molecules and ligands, adding hydrogen, calculating charges, etc.); the target was saved as a pdbqt format acceptor using AutoDockTools; the SDF structure file of glycyrrhizin was obtained, converted to mol2, and then converted to pdbqt format as a ligand; molecular docking was run in AutoDock to obtain the binding energy results; a binding energy < 0 indicates spontaneous binding, and a binding energy ≤ -5.0 kcal / mol indicates stable binding; The docking results are imported into Pymol software for visualization.

[0057] 2 Experimental Results 2.1 Venn analysis showed that glycyrrhizin and pulmonary fibrosis have 48 overlapping target sites ( Figure 8 (as shown in A in the diagram). 2.2 PPI network analysis showed that FGFR1 (fibroblast growth factor receptor 1) was one of the core targets. Figure 8 (as shown in B in 8 and C in 8). 2.3 GO enrichment results showed that these targets are mainly involved in receptor signaling pathways, lesion adhesion, extracellular space, and protein tyrosine kinase activity, suggesting that they are closely related to cell-matrix interactions and metabolic regulation. Figure 9 (As shown in A in the diagram).

[0058] KEGG enrichment results showed significant enrichment of central carbon metabolism pathways in cancer, suggesting that the relevant targets are involved in fibrosis-related signaling pathways. Figure 9 (As shown in B in the diagram).

[0059] 2.4 Molecular docking results showed that the binding energy between glycyrrhizin and FGFR1 was -7.1 kcal / mol, indicating a relatively stable binding. Figure 10 (As shown).

[0060] Example 8: Experimental Validation of the Target of Glycyrrhizin in the Anti-pulmonary Fibrosis Effect 1. Method 1.1 CETSA Experiment Human embryonic lung fibroblasts (HFL-1, ATCC-derived) were cultured in DMEM medium containing 10% fetal bovine serum at 37°C and 5% CO2. Cells were divided into a control group and a glycyrrhizin treatment group, the latter treated with a final concentration of 20 μM glycyrrhizin for 24 h. After treatment, cells were collected, lysed using RIPA lysis buffer containing a protease inhibitor, aliquoted, and heated at 40°C to 60°C (5°C intervals) for 3 min, followed by rapid cooling on ice. After high-speed centrifugation to remove the precipitate, the supernatant was collected and subjected to SDS-PAGE electrophoresis and Western blotting. Incubation with anti-FGFR1 primary antibody (1:1000 dilution) was followed by HRP-labeled secondary antibody (1:5000 dilution) and ECL development. The amount of soluble protein remaining after heating at different temperatures was measured to infer whether the drug bound to the target protein. The FGFR1 protein signal intensity was compared at different temperatures to evaluate changes in thermostability.

[0061] 1.2 Western blot experiment Cells were stimulated with lactate for 24 hours, then incubated with glycyrrhizin for another 24 hours. Protein expression of FGFR1 and phosphorylated FGFR1 (p-FGFR1) was then detected. GAPDH was used as an internal control; band grayscale analysis was performed using ImageJ software.

[0062] 2 Experimental Results 2.1 CETSA results showed that the FGFR1 band signal could still be detected in the glycyrrhizin-treated group under higher temperatures (50–60℃), while the signal in the control group was significantly weakened. This indicates that glycyrrhizin binds to FGFR1, making the protein more "heat-resistant" and less prone to denaturation and precipitation at high temperatures, thus enhancing the thermal stability of FGFR1. Figure 11 (As shown in A and B in the diagram).

[0063] 2.2 Western blot results showed that lactate stimulation significantly upregulated the p-FGFR1 / FGFR1 ratio in HFL-1 cells. Phosphorylation of FGFR1 (p-FGFR1) signifies signal activation, driving the fibrosis process. In the glycyrrhizin treatment group, this ratio was significantly lower than in the lactate group, approaching the control level. Figure 11 As shown in C and D), this indicates that glycyrrhizin can exert its anti-fibrotic effect by inhibiting FGFR1 phosphorylation.

[0064] FGFR1 is a receptor tyrosine kinase that plays a crucial role in pulmonary fibrosis. Its activation (especially the phosphorylated form p-FGFR1) can promote fibroblast proliferation and collagen deposition through downstream signaling pathways (such as MAPK and PI3K). Animal models and partial clinical trial data from the above examples demonstrate that glycyrrhizin treatment can improve lung tissue structure, reduce inflammation and collagen deposition, and improve lung function indicators, showing high therapeutic potential and good safety.

[0065] Related studies have shown that glycyrrhizin can exert significant anti-inflammatory and antioxidant effects by inhibiting NF-κB activation, reducing the expression of pro-inflammatory factors such as TNF-α, IL-1β and IL-6, and clearing intracellular ROS. It can also effectively inhibit epithelial-mesenchymal transition (EMT) and fibroblast activation by intervening in the TGF-β1 / Smad and PI3K / Akt / mTOR signaling pathways. It has the ability to both fight inflammation and oxidation and inhibit fibrosis-related cellular processes. Further optimization of formulation and delivery system can improve the therapeutic effect of glycyrrhizin.

[0066] In conclusion, glycyrrhizin shows great potential in the treatment of lung diseases and is expected to become a new option for the treatment of pulmonary fibrosis through multiple systematic studies in the future.

[0067] Although the above embodiments have described the present invention and its implementation in detail, it should be noted that for those skilled in the art, any changes, modifications, substitutions, combinations, simplifications, etc., made to the corresponding conditions without departing from the technical principles of the present invention should be considered as equivalent substitutions, and these improvements should also be considered within the scope of protection of the present invention.

Claims

1. Application of glycyrrhizin in the preparation of drugs for the prevention and treatment of pulmonary fibrosis.

2. The application according to claim 1, characterized in that, The pulmonary fibrosis disease mentioned is one or more of the interstitial pulmonary fibrosis diseases.

3. The application according to claim 1, characterized in that, The pulmonary fibrosis mentioned refers to interstitial pulmonary fibrosis caused by bleomycin.

4. The application according to claim 1, characterized in that, The drug is prepared using glycyrrhizin as its active ingredient, either alone or in combination with antifibrotic drugs, anti-inflammatory drugs, or antioxidant drugs.

5. The application according to claim 1, characterized in that, The drug can inhibit FGFR1 phosphorylation.

6. The application according to claim 1, characterized in that, The drug can be used to slow, prevent, or reverse the progression of pulmonary fibrosis.

7. The application according to claim 1, characterized in that, The drug dosage form is an oral preparation, an injectable preparation, a lyophilized powder preparation, or an inhaler.

8. The application according to claim 1, characterized in that, The oral formulation is a tablet, capsule, or oral liquid dosage form; the injectable formulation is a sustained-release formulation or a nano-formulation.

9. The application according to claim 1, characterized in that, The drug formulation can be administered via intraperitoneal injection, oral administration, intravenous injection, aerosol inhalation, or transdermal administration; the dosage of the drug formulation, calculated based on the mouse dose, is 20-40 mg / kg per dose.

10. The application according to claims 1-9, characterized in that, The glycyrrhizin can also be used in the prevention and treatment of other fibrotic diseases such as liver fibrosis, kidney fibrosis, myocardial fibrosis, or skin fibrosis.

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