CN116370453A - Application of nuciferine in preparation of medicines for treating pulmonary fibrosis - Google Patents
Application of nuciferine in preparation of medicines for treating pulmonary fibrosis Download PDFInfo
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- CN116370453A CN116370453A CN202310053730.7A CN202310053730A CN116370453A CN 116370453 A CN116370453 A CN 116370453A CN 202310053730 A CN202310053730 A CN 202310053730A CN 116370453 A CN116370453 A CN 116370453A
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- nuciferine
- pulmonary fibrosis
- lung
- medicines
- treating
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Abstract
The invention discloses an application of nuciferine in preparing a medicine for treating pulmonary fibrosis. The nuciferine disclosed by the invention is applied to preparation of medicines for treating pulmonary fibrosis. Research results show that nuciferine can intervene in a mouse pulmonary fibrosis animal model established by air-tube instillation of bleomycin, and symptoms of inflammatory cell infiltration, alveolar space thickening, fibroblast activation, collagen deposition and lung function index reduction are all improved after nuciferine administration. Further in vitro cell experiments, nuciferine can improve pulmonary fibrosis by regulating and controlling the activation and proliferation of fibroblasts. Therefore, nuciferine is a novel compound with the function of resisting pulmonary fibrosis, and can be used for preparing medicines for resisting pulmonary fibrosis.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicine pharmacy, relates to application of nuciferine, and in particular relates to application of nuciferine in preparation of a medicine for treating pulmonary fibrosis.
Background
Pulmonary fibrosis (pulmonary fibrosis) is a chronic progressive disease characterized by alveolar epithelial cell damage, and the pathology manifests as diffuse alveolitis, alveolar structural disturbances, extracellular matrix (extracellular matrix, ECM) deposition, etc., ultimately leading to structural destruction and dysfunction of the lungs. The etiology of pulmonary fibrosis is highly diverse and uncertain and lacks reliable early biomarkers. Current treatments for pulmonary fibrosis are limited.
Pulmonary fibrosis is a fibroproliferative disease that repairs abnormalities following injury to lung tissue, and is closely associated with activation of fibroblasts and pathological deposition of collagen. When various damaging factors act on the lung, various cytokines and chemokines are secreted, a fibrosis microenvironment is created, and locally aggregated fibroblasts are further activated to become pulmonary muscle fibroblasts with high expression of smooth muscle actin (alpha-smooth muscle actin, alpha-SMA) and excessive secretion of extracellular matrix (extracellular matrix, ECM), which are considered to have the characteristics of fibroblasts and smooth muscle cells at the same time, and have a contractile function, promoting the occurrence and progress of pulmonary fibrosis. As a main constituent cell of the lung interstitium, the lung fibroblast is not only a simple effector cell, but also plays an important role in pathological processes such as inflammatory injury, abnormal repair, scarring and the like of the lung fibrosis. It follows that pulmonary fibroblast dysfunction is a key element in the progression of pulmonary fibrosis disease. It is important to investigate the need for effective anti-pulmonary fibrosis drugs that inhibit fibroblast activation and abnormal proliferation.
The drugs approved by the FDA for treating pulmonary fibrosis at present are pirfenidone and nidazole only, but the two drugs have longer treatment period, and the improvement of pulmonary function and the prolongation of progression-free survival period and the reduction of death risk are visible after 52 weeks of continuous use. Meanwhile, related researches suggest that the two medicaments can generate medicament resistance after long-term use, and reduce the treatment effect of the medicaments, but the change of the pulmonary fibroplasia structure cannot be reversed. Non-drug treatments for pulmonary fibrosis include oxygen therapy, mechanical ventilation, and lung transplantation, which are expensive and ineffective in alleviating the frequency of disease progression and acute exacerbations. Therefore, the searching of a low-cost, safe and effective pulmonary fibrosis drug therapy has important significance.
The lotus leaf is leaf of Nelumbo nucifera Gaertn (Nelumbo nuficera Gaertn) belonging to Nymphaeaceae, and also called Nelumbo nucifera Gaertn leaf and Nelumbo nucifera Gaertn leaf. Nuciferine (NF), an aporphine alkaloid compound, is one of the main active ingredients in lotus leaves. Nuciferine can improve hyperlipidemia and reduce lipase activity. Many studies have shown that nuciferine has pharmacological activity in the treatment of various diseases, such as cardiovascular diseases and cancers. The prior report indicates that nuciferine has biological activities of atherosclerosis resistance, bacteriostasis, virus resistance, tumor resistance and the like. Nuciferine is used as a substance in the existing weight-reducing health product, and has low cost and good safety.
In summary, no report is found on the use of nuciferine as a main active ingredient for preparing a medicament for treating pulmonary fibrosis.
Disclosure of Invention
The invention aims to provide application of nuciferine, in particular to application of nuciferine in preparation of medicines for treating pulmonary fibrosis.
The nuciferine is an effective component extracted from traditional Chinese medicine lotus leaves, belongs to aporphine alkaloid compounds, and has the molecular formula: C19H21NO2 has a molecular weight of 295.38 and a structural formula shown in the formula I.
The nuciferine provided by the invention is applied to preparation of medicines for treating pulmonary fibrosis.
The invention also provides application of nuciferine in preparing a medicament for treating bleomycin-induced pulmonary fibrosis.
The invention also provides application of nuciferine in preparing a medicament for treating TGF-beta 1 induced pulmonary fibrosis.
The invention also provides a medicine which comprises the nuciferine and the auxiliary agent as active ingredients.
In the medicine, the auxiliary agent is an aqueous solution of sodium carboxymethyl cellulose and/or pharmaceutically acceptable auxiliary materials.
In the present invention, the mass percentage concentration of the aqueous solution of sodium carboxymethyl cellulose may be specifically 0.05%.
In the above-mentioned medicines, the dosage form of the medicine is a dosage form for administration by intraperitoneal injection.
In the invention, the nuciferine is applied to the preparation of the medicine for treating pulmonary fibrosis, and after nuciferine is administered, the symptoms of inflammatory cell infiltration, alveolar space thickening, fibroblast activation and collagen deposition are all improved. Nuciferine can inhibit TGF-beta induced activation and proliferation of lung fibroblast, thereby exerting anti-pulmonary fibrosis effect.
According to the technical scheme, an in-vivo model of the pulmonary fibrosis of a mouse and a human pulmonary fibroblast cell line (MRC 5) are adopted, the effect of nuciferine on the expression condition of key proteins of pulmonary fibrosis indexes on the whole, in-vitro cell level and molecular level of the mouse is researched, the molecular mechanism of nuciferine for resisting the pulmonary fibrosis is explained, and an important experimental basis is provided for preparing the anti-pulmonary fibrosis medicine.
The invention has the following beneficial effects:
research results show that nuciferine can intervene in a mouse pulmonary fibrosis animal model established by air-tube instillation of bleomycin, and symptoms of inflammatory cell infiltration, alveolar space thickening, fibroblast activation, collagen deposition and lung function index reduction are all improved after nuciferine administration. Further in vitro cell experiments, nuciferine can improve pulmonary fibrosis by regulating and controlling the activation and proliferation of fibroblasts. Therefore, nuciferine is a novel compound with the function of resisting pulmonary fibrosis, and can be used for preparing medicines for resisting pulmonary fibrosis.
Drawings
FIG. 1 is a schematic view showing the effect of nuciferine on weight change in mice in example 1 of the present invention;
FIG. 2 shows the effect of nuciferine on pulmonary function change in mice in example 1 of the present invention;
FIG. 3 is a schematic representation of the effect of nuciferine on HE staining of mouse lung tissue in example 1 of the present invention;
FIG. 4 is a schematic representation of the effect of nuciferine on Masson staining of mouse lung tissue in example 1 of the present invention;
FIG. 5 is a graph showing the result of detecting the hydroxyproline content of the lung tissue of the mice by nuciferine in example 1 of the present invention;
FIG. 6 is a schematic representation of the effect of nuciferine on mouse lung tissue α -SMA immunohistochemistry in example 1 of the present invention;
FIG. 7 is a schematic representation of the effect of nuciferine on mouse lung tissue collagen-1 immunohistochemistry in example 1 of the present invention;
FIG. 8 is a schematic diagram of the western blot experiment in example 1 of the present invention for detecting the effect of nuciferine on the expression of mouse lung tissue alpha-SMA, fibronectin protein;
ctrl, NF, BLM, BLM +NF-low, BLM+NF-high in FIGS. 1-8 represent control, nuciferine, bleomycin, bleomycin+nuciferine (low), bleomycin+nuciferine (high), respectively;
FIG. 9 is a schematic diagram of the western blot experiment in example 2 of the present invention to detect the effect of nuciferine at different time points and concentrations on expression of alpha-SMA, fibronectin, collagen-1 protein in TGF-beta 1 induced MRC5 cells;
FIG. 10 is a schematic representation of immunofluorescence assay for detecting expression of alpha-SMA protein in TGF-beta 1 induced MRC5 cells by nuciferine in example 3 of the present invention; DAPI, α -SMA, mere in fig. 10 represent nuclei, target protein α -SMA, combined;
FIG. 11 is a schematic representation of immunofluorescence assay for detecting expression of a fibronectin protein in TGF-beta 1-induced MRC5 cells in example 3 of the present invention;
FIG. 12 is a graph showing the effect of Edu fluorescence assay in example 3 of the present invention on TGF-. Beta.1 induced proliferation of MRC5 cells;
FIG. 13 is a graph showing the effect of scratch assay in example 3 of the present invention on TGF-. Beta.1 induced proliferation of MRC5 cells;
wherein Ctrl, NF, TGF- β1 and TGF- β1+NF in FIGS. 9-13 represent control group, nuciferine drug control group, TGF- β1 induction model group, nuciferine drug treatment group, respectively.
Detailed Description
The experimental methods used in the following examples are conventional methods unless otherwise specified.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
The technical scheme of the present invention is further described below with reference to examples, and the scope of protection of the present invention is not limited thereto.
The present invention provides a potential anti-pulmonary fibrosis drug for the treatment of pulmonary fibrosis, as described in further detail below in connection with the detailed description of the invention:
example 1: in vivo experiment-nuciferine improving effect of bleomycin-induced pulmonary fibrosis of mice
1 Experimental materials
C57BL/6 mice, purchased from Guangzhou Kangdong animal Co., ltd; bleomycin, purchased from the vast glory pharmaceutical limited, approval document: chinese medicine standard character H20055883; nuciferine, available from MCE.
2 Experimental methods
C57BL/6 mice at 6-8 weeks, the trachea was isolated by surgery, bleomycin (3.5U/kg) was injected intratracheally with a microinjector, nuciferine was injected intraperitoneally at 10 days post-surgery, the nuciferine low concentration group was: the drug dose of each Kg of mice is 3mg, namely 3mg/Kg; nuciferine high concentration group: the drug dose of each Kg of mice is 15mg, namely 15mg/Kg (the solvent is an aqueous solution of sodium carboxymethylcellulose with the mass percent of 0.05 percent), and after 21 days, the mice are anesthetized and sequentially subjected to lung function detection and lung tissue collection for subsequent experiments.
2.1 detection of pulmonary function
The detection of lung function was performed according to the RC system (anaesthetised animal airway resistance and dynamic lung compliance detection analysis system) provided by the apparatus according to the instructions for the use of the apparatus.
2.2 Paraffin embedding and sectioning of tissue
The left lung of the mice was fixed in a 10mL centrifuge tube containing 4% formalin for 48h, during which time it was not possible to shake randomly and ensure complete infiltration of the whole lung tissue in formalin reagent. The embedding boxes are marked in advance, lung tissues are taken out and then transversely cut, two uniform pieces are guaranteed, and the two pieces are placed in the same embedding box, covered tightly, and then placed in dehydrated reagent. The lung tissue dehydration reagent sequence is as follows: 30% ethanol (30 min), 50% ethanol (30 min), 70% ethanol (30 min), 80% ethanol (30 min), 90% ethanol (30 min), 100% ethanol (30 min); continuing with the transparency of the lung tissue: xylene l (30 min), xylene II (30 min); finally, waxing of lung tissues is carried out: paraffin I (30 min), paraffin II (30 min); cutting the tissue into continuous slices with the thickness of 3-5 mu m by using a slicing machine, and flatly placing the slices on a flat plate with the light surface facing upwards; placing the paraffin thin slice on the water surface (water temperature 40 ℃) to extend the paraffin thin slice, and then attaching the paraffin thin slice on a pretreated slide;
2.3HE staining procedure
The pre-placed slices were taken out of the oven for dying (1 h in an incubator at 80 ℃). (1) Dewaxing of lung tissue sections to hydration once is: xylene I (5 min), xylene II (5 min), 100% ethanol (3 min), 90% ethanol (3 min), 80% ethanol (3 min), 70% ethanol (3 min), PBS (3 min); (2) hematoxylin (2 min); (3) washing redundant fuel around the slice by tap water; (4) differentiation of the differentiation solution for 1s; (5) returning tap water to blue for 15min; (6) eosin 1min; (7) 100% ethanol (30 s) after 95% ethanol (30 s); (8) air drying, sealing with neutral resin, and air drying at normal temperature (25deg.C); (9) photographing.
2.4Masson staining procedure
Taking out the pre-placed slices from the oven for dyeing. (1) Lung tissue sections were routinely dewaxed to water; (2) dyeing with Masson composite dye liquor for 8 minutes; (3) soaking and washing the mixture in 2% glacial acetic acid water solution for a moment; (4) placing in 1% phosphoric acid water solution for 3min, and spin-drying; (5) dyeing with aniline blue water solution for 5min; (6) alcohol gradient dehydration, xylene I, II transparency, neutral resin sealing.
2.5 Immunohistochemistry (IHC)
Taking out the pre-placed slices from the oven for dyeing. (1) Lung tissue sections were routinely dewaxed to water; (2) antigen retrieval: adding a pre-prepared citrate buffer with PH=6.0, boiling, adding a glass slide, lasting for 15min, naturally cooling at room temperature, and washing with PBS; (3) blocking endogenous peroxidases: adding 3% hydrogen peroxide, and incubating in a wet box at room temperature for 15min; (4) closing: dripping goat serum, and incubating for 30min in a wet box at room temperature; (5) after pouring the serum, 20. Mu.l of primary antibody (. Alpha. -SMA, collagen-1; dilution ratio 1:200) was added and incubated overnight at 4℃in a wet box; (6) adding corresponding secondary antibody (the secondary antibody is goat anti-rabbit IgG; 1:400), and incubating in a wet box for 20min at room temperature; (7) color development: dripping DAB color development liquid for observation and recording termination time; (8) nuclear dyeing: nuclear staining is carried out by using hematoxylin, counterstaining is carried out for 30s at room temperature, and tap water is used for flushing; (9) dehydration and transparency: immersing in the following solutions in sequence: 80% ethanol (2 min), 95% ethanol (2 min), 100% ethanol (2 min), xylene I (5 min), xylene II (5 min); and (3) sealing the sheet: the encapsulation was performed using neutral gum and the pictures were taken after drying at room temperature.
2.6 hydroxyproline detection
In the case of pulmonary fibrosis, the components added to the interstitial parts of the lung are collagen fibers, and hydroxyproline is unique to the collagen fibers, and the content of the hydroxyproline is measured and can be converted into the content of collagen in the interstitium to reflect the degree of pulmonary fibrosis. (1) Preparing lung tissue; (2) adding corresponding reagents according to the instruction book; (3) according to the formula:
2.7 intracellular protein expression detection (Western Blot method)
Detection Using whole protein extraction kit
2.8mRNA detection (RT-qPCR)
Prime Script (TM) reverse transcription kit reverse transcribes total RNA into cDNA and then performs RT-qPCR detection.
Conclusion of results
Results: nuciferine was administered therapeutically in a bleomycin-induced pulmonary fibrosis mouse model, i.e. nuciferine drug treatment was performed on day 10 of the pulmonary fibrosis model. Mice in the normal control group and nuciferine alone treated group continued to increase in weight, and mice in the pulmonary fibrosis model group decreased significantly, but the pulmonary fibrosis mice decreased in weight after treatment with nuciferine at high (15 mg/kg) and low concentrations (3 mg/kg), with the high dose group being more pronounced (fig. 1). Because of the diffuse fibrotic focus of the lung, the ventilation function and the ventilation function of the patient with pulmonary fibrosis are seriously affected, and finally respiratory failure is caused. Improving lung function in patients with pulmonary fibrosis is therefore also one of the important tasks for treating pulmonary fibrosis. Compared with the normal control group, the pulmonary fibrosis model group mice have severely reduced pulmonary function, mainly manifested by reduced total lung volume, reduced airway compliance and increased airway resistance, but the pulmonary function related index is significantly improved after nuciferine treatment (fig. 2). As shown in the graph HE (fig. 3), the control group shows the normal lung structure, and the bleomycin-induced mouse lung fibrosis model group HE staining found that the alveoli were significantly collapsed and fused, the lung structure was disordered, the alveoli wall was thickened, and inflammatory cells were diffusely infiltrated. Nuciferine treatment group showed a reduction in alveolar space and a significant improvement in pulmonary structural disorder compared to model group. Masson staining suggested that deposition of pulmonary interstitial collagen could be significantly reduced following nuciferine treatment compared to model group mice (fig. 4). The hydroxyproline experiment quantitatively detects the collagen deposition of lung tissues, and the results are the same as the Masson results, and all suggest that nuciferine obviously reduces the collagen deposition of lung tissues (figure 5). Immunohistochemistry suggested that the expression of the model constituent fibroblast activation marker α -SMA and extracellular matrix fibronectin collagen-1 of pulmonary fibrosis was significantly increased, and significantly decreased after nuciferine treatment (fig. 6-7). To further quantify the expression of fibrosis-associated proteins in lung tissue, the experiment used Western Blot to detect the expression of α -SMA, fibronectin, suggesting that activation of fibroblasts and deposition of extracellular matrix can be significantly inhibited following nuciferine treatment (fig. 8).
Conclusion: nuciferine can inhibit bleomycin-induced progression of pulmonary fibrosis in mice.
Example 2: in vitro experiments-action of nuciferine on TGF-beta 1 induced activation of human lung fibroblasts
1 Experimental materials
In vitro experiments with human fibroblast line MRC5
2 Experimental methods
Taking human fibroblast line MRC5 in logarithmic growth phase, inoculating into 6-well plate, placing at 37deg.C and 5% CO 2 And culturing the cell length in a saturated humidity incubatorAt 70% fusion, the control group was given DMSO, the model group was given TGF-beta (10 ng/mL) to stimulate cells, the drug group was given nuciferine (the drug solvent was DMSO, the final concentration was 20. Mu.M), TGF-beta (10 ng/mL) was added to stimulate cells per well, cellular proteins were extracted 24h after TGF-beta addition, and lung fibrosis related indicators were detected by Western Blot, RT-qPCR, immunofluorescence.
2.1Western blot
Pre-treated well plates: (1) removing the culture medium, extracting protein by using a whole protein extraction kit, measuring the protein concentration, and then adding a Loading Buffer for denaturation at 95 ℃; (2) taking 40 mug for sample loading, carrying out electrophoresis at 90V for 40min, and then 120V for 20min; and then carrying out die turning under the conditions of 350mA and 70 min. Diluting beta-actin, alpha-SMA, col-1 and fibrauretin antibody in the ratio of 1 to 1000, and incubating at 4 ℃ overnight; (3) the secondary antibodies (the secondary antibodies corresponding to alpha-SMA, col-1 and fibractin are goat anti-rabbit IgG) are diluted 1:10000, and the secondary antibodies corresponding to beta-actin are goat anti-mouse IgG) are incubated for 2 hours and then subjected to chemical development.
2.2RT-qPCR
Pre-treated well plates: (1) the medium was discarded, the cells were washed 3 times with pre-chilled PBS, the medium was removed thoroughly, 300. Mu.l Trizol was added to each dish, and the mixture was repeatedly blown for 1min and transferred to a 1.5ml ep tube; (2) 60 μl of chloroform was added per 300 μl Trizol, the sample tube was capped, shaken vigorously by hand for 15s and allowed to stand at room temperature for 3min. Centrifuging at high speed for 15min at 4deg.C with 12000r centrifuge; (3) the upper water sample layer was transferred to a new 1.5ml centrifuge tube, 150. Mu.l of isopropanol was added and mixed well (inverted several times), and the mixture was allowed to stand at room temperature for 10min, centrifuged at 12000r for 10min, and RNA was attached to the bottom of the tube. The supernatant was discarded, 300. Mu.l of 75% ethanol was added, the tube wall was flicked, and the mixture was centrifuged at 4℃and 7400r for 5min. (4) The supernatant was decanted, left in a fume hood for 20min, and after ethanol evaporation, 20. Mu.l DEPC water was added and reverse transcription and amplification experiments were performed according to the instructions in the kit.
2.3 cell immunofluorescence assay
Preparing cells: cells were seeded in confcol dishes and placed in a cell culture incubator overnight using complete media. Corresponding stimulation was given after cell fusion at 30-40%. (1) Cells were fixed with 4% paraformaldehyde for 15min, and immersed 3 times with PBS for 5min each; (2) 0.5% Triton X-100 (PBS) was allowed to permeate for 20min at room temperature; (3) the absorbent paper blots the PBS around the confcol petri dish, using 3% BSA in the petri dish, and blocking for 30min at room temperature; (4) adding a primary antibody diluted in advance into a small dish, putting the small dish into a wet box, and incubating overnight at 4 ℃; (5) adding immunofluorescence secondary antibody (goat anti-rabbit IgG), incubating for 2h at room temperature, and performing shaking table pickling with PBS for 3 times each for 5min; (6) nuclear counterstain: dripping diluted DAPI, incubating for 5min in dark, and carrying out shaking table pickling for 3 times by using PBS for 5min each time; (7) the images were observed and collected under a fluorescence microscope.
Conclusion of results
Results: the influence of nuciferine on fibroblast activation and extracellular matrix related proteins was detected by Western Blot. Experimental results show that the lung fibrosis related protein (alpha-SMA, collagen-1, fibronectin) is obviously increased in a TGF-beta 1 induced mouse lung fibroblast model, the expression level of the fibroblast activation marker protein alpha-SMA is obviously reduced after nuciferine treatment is given, and meanwhile, the expression level of the extracellular matrix related protein (fibronectin, collagen-1) shows a obvious descending trend, and the difference has a statistical significance (figure 9). In order to further verify the influence of nuciferine on fibroblast activation and extracellular matrix proteins, immunofluorescence experiments are used, so that the expression of proteins can be more intuitively counted. The experimental results suggest that TGF- β1-induced expression of α -SMA, collagen-1, was significantly reduced following nuciferine treatment, consistent with the results of Western Blot (FIGS. 10-11).
Conclusion: nuciferine can significantly inhibit TGF- β1-induced activation of lung fibroblasts.
Example 3: in vitro experiment-inhibition of nuciferine on TGF-beta 1 induced human lung fibroblast proliferation 1 experiment material
In vitro experiments with human fibroblast line MRC5
2 Experimental methods
Taking human fibroblast line MRC5 in logarithmic growth phase, inoculating into 6-well plate, placing at 37deg.C and 5% CO 2 And in an incubator with saturated humidity, culturing cells until the cells grow to 70% fusion degreeThe control group was given DMSO, the model group was given TGF-beta (10 ng/mL) to stimulate cells, the drug group was given nuciferine (the drug solvent was DMSO, the final concentration was 20. Mu.M), TGF-beta (10 ng/mL) was added to stimulate cells per well, and the proliferation capacity of lung fibroblasts was examined by Edu and scratch experiments 24h after adding TGF-beta.
2.1 detection of cell proliferation (EdU)
Detecting the proliferation capacity of cells: (1) placing the cell pore plate added with the EdU working solution back into the cell culture dressing box for continuous incubation for 2 hours; (2) adding 1mL of cell fixing solution prepared in advance, and fixing at room temperature for 20min; (3) adding click reaction solution after 0.5% Triton X-100 is penetrated for incubation for 30min; (4) the nuclei were stained and photographed.
2.2 scratch test
And (3) scribing the cell growth central area on the pre-cultured and attached fibroblast pore plate by using a micro gun head, removing the cells at the central area, culturing for 24 hours after stimulation, taking out the cell culture plate, observing whether peripheral cells migrate to the central scratch area or not under a microscope, and photographing.
Conclusion of results
Results: in the progression of pulmonary fibrosis, proliferation of lung (muscle) fibroblasts plays an important role. Edu-fluorescence experiments suggest that TGF-beta 1 induced lung fibroblasts have a strong proliferation potency, and that the proliferation potency of lung fibroblasts is significantly inhibited after nuciferine administration (FIG. 12). Meanwhile, the proliferation ability of cells was observed using a cell scratch test, and the result was the same as that of the Edu test (fig. 13).
Conclusion: nuciferine can improve pulmonary fibrosis by inhibiting proliferation of fibroblasts.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (6)
1. The application of nuciferine in preparing medicine for treating pulmonary fibrosis is provided.
2. Use of nuciferine in preparing medicine for treating bleomycin-induced pulmonary fibrosis is provided.
3. Use of nuciferine in the preparation of a medicament for treating TGF-beta 1 induced pulmonary fibrosis.
4. The medicine is characterized by comprising the nuciferine and an auxiliary agent as active ingredients.
5. The medicament according to claim 4, wherein the auxiliary agent is an aqueous solution of sodium carboxymethyl cellulose and/or a pharmaceutically acceptable auxiliary agent.
6. The medicament according to claim 3 or 4, wherein the dosage form of the medicament is a dosage form for intraperitoneal administration.
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