CN115068492B - Application of linarin in preparation of drugs for preventing or treating pulmonary fibrosis - Google Patents

Abstract

The invention discloses application of linarin in preparation of a medicament for preventing or treating pulmonary fibrosis. In the in vivo and in vitro pulmonary fibrosis model, a series of experiments are carried outThe research shows that the linarin can regulate the expression of p-ERK1/2 and pulmonary fibrosis marker protein based on an ERK pathwayαExpression of SMA, collagen I, down-Regulation of TGF-β1 in lung tissue, inhibiting the release of inflammatory factors and improving inflammatory infiltration, plays a role in treating pulmonary fibrosis, and provides a theoretical basis for the research of new anti-pulmonary fibrosis drugs.

Description

Application of linarin in preparation of drugs for preventing or treating pulmonary fibrosis

Technical Field

The invention relates to the technical field of medicines, in particular to application of linarin in preparation of a medicine for preventing or treating pulmonary fibrosis.

Background

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal disease that is mainly characterized by myofibroblast proliferation and extracellular matrix deposition, promoting pulmonary remodeling and progression of the fibrotic plaque area. It is currently widely believed that the pathogenesis of pulmonary fibrosis is the persistent micro-damage of alveolar epithelium accompanied by abnormal repair process, characterized by abnormal activation of myofibroblasts, excessive accumulation of extracellular matrix, scarring of lung, and finally structural destruction and loss of function of lung. The prevalence rate of the idiopathic pulmonary fibrosis in the general population is 2/100 000-29/100 000, the incidence is more than that of the middle-aged and the old, and the prevalence rate of the idiopathic pulmonary fibrosis in the old men who smoke is more common.

At present, the drugs such as pirfenidone, nintedanib, N-acetylcysteine and the like which are commonly used in clinic delay the disease progression of pulmonary fibrosis, but specific drugs with obvious curative effect and low toxic and side effect are still lacked. Besides drug treatment, lung transplantation can effectively prolong the life of patients. However, the cost of lung transplantation is high, the overall survival rate of patients after lung transplantation is low, complications are more and complicated, and the clinical implementation and application are difficult. Most of the current treatment means have limited treatment effect from the clinical point of view, and no exact effective treatment means exists. The cost of lung transplantation is high, and the clinical implementation and application are difficult. Therefore, it is imperative to find safe, effective and inexpensive drugs.

In the current traditional Chinese medicine research, a plurality of researches report that the traditional Chinese medicine has good treatment effect on pulmonary fibrosis, and the value of the traditional Chinese medicine in treating pulmonary fibrosis is shown. The baicalein can improve the antioxidant activity, relieve inflammation, inhibit miR-21 and inhibit TGF-βSmad signaling to achieve therapeutic effect on pulmonary fibrosis, and relieve pulmonary fibrosis caused by Bleomycin (BLM); the triptolide can relieve radiation-induced pulmonary fibrosis symptoms and reduce collagen deposition in lung tissues; paeoniflorin can inhibit TGF-βActivation and increase of IFN by Smad pathwayγTo reduce the synthesis of Collagen I to inhibit the deposition of ECM in lung tissue, thereby achieving the effect of treating BLM-induced pulmonary fibrosis.

The research shows that the linarin has multiple pharmacological effects such as anti-inflammation, analgesia, antioxidation, anti-aging and the like, and has potential treatment value on various diseases. However, no literature report on the application of linarin in the preparation of drugs for pulmonary fibrosis is found at present.

Disclosure of Invention

In view of the above, the invention aims to provide the application of linarin in the preparation of the drugs for preventing or treating pulmonary fibrosis, and provide a theoretical basis for the research of new drugs for resisting pulmonary fibrosis.

The invention selects SPF male C57BL/6J mice which are divided into a normal group, a model group and a pirfenidone group

(200mg·kg ^-1 ) The low and high dose group of linarin (12.5, 25 mg. Kg) ^-1 ) Each group has 6. Normal group is atomized with normal saline in trachea, the other groups are given BLM in the trachea to copy mouse pulmonary fibrosis model, the general condition of the mouse is observed in the administration period, the sample is collected after 14d is intervened by medicine, serum and lung tissue samples are taken, and lung index is weighed to calculate lung organ index; detecting serum by enzyme-linked immunosorbent assay (ELISA)Tumor necrosis factor-α(TNF-α) Transforming growth factor-β1(TGF-β1) And the level of interleukin-6 (IL-6) in lung tissue; pathological section observation is carried out on the lung tissue sample, and TGF-β1，α-protein expression level of SMA, collagen i, p-ERK 1/2; selecting TGF-β1 stimulating human embryonic lung fibroblast (HFL 1) adult in vitro pulmonary fibrosis model, which is divided into a normal group, a model group and a linarin administration group (6.25, 12.5, 25 mol. L) ^-1 ) Detection in cells by Western blotα-protein expression level of SMA, collagen I, ERK1/2,p-ERK 1/2.

Results in vivo experiments show that the lung index of mice in the model group is obviously increased compared with that in the normal group after 2 weeks of linarin intervention (P<0.01 ); the lung index of the mice with low linarin and high dose is obviously reduced compared with the model group (P< 0.05, P<0.01). HE and Masson staining results show that the lung tissue structure of the normal mice is intact and no obvious abnormality is found; the lung cells of the model group mice are vacuolated and denatured, have inflammatory infiltration and have a large amount of collagen deposition; the lung tissues of the mice in the low and high dose group of linarin are obviously reduced in vacuole degeneration compared with the lung tissues in the model group, the inflammatory infiltration is obviously improved, and the collagen deposition is obviously reduced. Compared with the normal group, the serum of the mice in the model group has TNF-α，TGF-β1,IL-6 content was significantly increased (P<0.01 ); TNF-α，TGF-β1,IL-6 content is significantly reduced (P<0.01). IHC results showed that in lung tissue of mice in the model group, compared with the normal groupα-elevated SMA, collagen i, p-ERK1/2 protein expression; comparing with the model group, each administration groupα-reduction of SMA, collagen I, p-ERK1/2 protein expression. Western blot results showed that the cells in the model group HFL1 cells were present in comparison with the normal groupαMarked increase in SMA, collagen I, p-ERK1/2 protein expression: (P< 0.05); menghuagan administration groupαThe expression of SMA, collagen I, p-ERK1/2 protein is obviously reduced (P< 0.05). In conclusion, in vivo results show that linarin may alleviate pulmonary fibrosis in mice through ERK and inflammatory pathways; in vitro results showIt is shown that linarin can alleviate TGF-β1 induced pulmonary fibrosis of HFL1 cells.

The pulmonary fibrosis is idiopathic pulmonary fibrosis or secondary pulmonary fibrosis, and is preferably idiopathic pulmonary fibrosis.

Further, the linarin acts to improve pulmonary fibrosis based on the ERK pathway.

Further, the linarin acts to improve pulmonary fibrosis by reducing inflammatory infiltration in lung tissue.

The invention also provides a medicament for preventing or treating pulmonary fibrosis, which comprises effective content of linarin and pharmaceutically acceptable salt

A carrier or excipient.

Preferably, the dosage form of the medicament comprises tablets, capsules, oral liquid or granules and the like.

The pharmaceutically acceptable carrier or excipient comprises a lubricant, a filler, a binder, a disintegrating agent, a surfactant, an antioxidant, a pH regulator and the like, and the dosage of the pharmaceutically acceptable carrier or excipient is the conventional dosage in the field.

The pharmaceutical dosage form of the invention can be prepared according to conventional preparation methods in the field.

Compared with the prior art, the invention has the following beneficial effects:

the invention provides a new application of linarin in preparing a medicament for preventing or treating pulmonary fibrosis, and a series of researches show that linarin can down-regulate the expression of p-ERK1/2 and down-regulate pulmonary fibrosis marker protein based on an ERK (extracellular signal-responsive kinase) pathway in an in vivo and in vitro pulmonary fibrosis modelαExpression of SMA, collagen I, down-Regulation of TGF-β1 in lung tissue, inhibits the release of inflammatory factors, improves inflammatory infiltration, plays a role in treating pulmonary fibrosis, and provides a theoretical basis for the research of new anti-pulmonary fibrosis drugs.

Drawings

FIG. 1 is a graph of the effect of linarin on the fibrotic changes in mouse lung tissue (HE,. Times.100);

FIG. 2 is a graph of the effect of linarin on the fibrotic changes in mouse lung tissue (Masson,. Times.100);

FIG. 3 shows the application of linarin to mouse lung tissueα-effect of SMA immunohistochemistry protein expression (IHC, x 100);

FIG. 4 shows the TGF-beta of mouse lung tissue induced by linarinβ1 effect of immunohistochemical protein expression (IHC, × 100);

FIG. 5 shows the effect of linarin on the expression of Collagen I immunohistochemical protein in mouse lung tissue (IHC,. Times.100);

FIG. 6 is a graph of the effect of linarin on the expression of p-ERK1/2 immunohistochemical protein in mouse lung tissue (IHC,. Times.100);

(in FIGS. 1-6, A is normal group; B is model group; C, D is low and high dosage of linarin group; E is pirfenidone group);

FIG. 7 shows the relation between linarin and HFL1 cellsαSMA, collagen I, ERK1/2 and p-ERK1/2 protein expression (A. Normal group; B. Model group; C, D, E Mongolian glycoside administration group (6.25, 12.5, 25. Mu. Mol. L) ^-1 ））。

Detailed Description

The present invention is further illustrated by the following specific embodiments, which are not intended to limit the scope of the invention.

Material

1.1 animals

30 SPF male C57BL/6J mice are 8 weeks old and 20 +/-2 g in body mass, are purchased from Guangdong province medical experimental animal center, and have an animal quality qualification certificate number of SCXK (Guangdong) 2018-0002. After the quarantine is qualified, the animal house (barrier environment) is raised in a traditional Chinese medicine pharmacology laboratory in traditional Chinese medicine institute in Zhongshan city, and the license number SYXK (Guangdong) 2020-0109 is used. Feeding conditions are as follows: the environmental temperature is 20-24 ℃, the relative humidity is 50% -70%, and the light and the shade are alternated to be 12 h respectively. All animal experimental procedures were approved by the institutional animal ethics committee in zhongshan city under the approval of No. 2022034.

Cell line human embryonic lung fibroblasts (HFL 1) were purchased from Wuhan Punuoise Life technologies, inc., under the product number CL-0106.

Medicaments and agents

Linarin (Sichuan Riboyurun Biotech Co., ltd., batch No. CYR-M0074210415);

bleomycin hydrochloride for injection (BLM, japan chemicals, lot number Y00720);

pirfenidone capsules (PFD, manufactured by Beijing Cortini pharmaceuticals Inc., lot number 20211105);

sodium pentobarbital, commercially available;

Recombinant Human TGF-β1 transforming growth factor (TGF-β1, peprotech corporation, usa, lot number: 1020209 );

HFL1 cell-specific medium (Wuhan Pond Life technologies, inc., batch No. WH2522P 161);

αsmooth muscle actin(s) (ii)αSMA) antibody, collagen type i (Collagen i) antibody, goat anti-rabbit immunoglobulin (Ig) G secondary antibody (Cell Signaling Technology, usa, lot numbers 8685T, 72026T, 7074P2, respectively);

glyceraldehyde-3-phosphate dehydrogenase (GAPDH), extracellular regulated protein kinase (ERK 1/2), phosphorylated extracellular regulated protein kinase (p-ERK 1/2) (Affinity, USA, batch No. AF7021, AF0155, AF 1015);

tumor necrosis factor-α(TNF-α) And transforming growth factor (TGF-β1) Enzyme-linked immunosorbent assay (ELISA) kit (Hangzhou Union Biotechnology GmbH, lot numbers A28220233 and A98111123, respectively);

interleukin-6 enzyme-linked immunosorbent assay (ELISA) kit (IL-6, jiangsu Jingmei Biotech Co., ltd., lot No. 202203);

phenylmethylsulfonyl fluoride (PMSF), SDS-PAGE protein loading buffer (Loadingbuffer, shanghai Bin Yuntian Biotechnology Co., ltd;

PBS buffer (Wuhan Punuouse Life technologies, inc., lot No. WH0021D 291);

dimethyl sulfoxide DMSO (SIGMA, usa, batch RHBB 3309);

a diquinuclidinecarboxylic acid BCA protein quantification kit (Thermo Co., USA, lot VI 311907).

Instrument for measuring the position of a moving object

A trace liquid intratracheal atomization device (Beijing Yuan Sen Kaided Biotechnology Co., ltd.); microplate readers (perkin elmer instruments ltd, usa); inverted fluorescence microscope (Nikon, japan); centrifuge (Hennuo instruments and Equipment Co., ltd., hunan); carbon dioxide cell culture chambers (japan and xijian medical devices limited).

Method

2.1 preparation of the medicinal solution

The bleomycin is prepared into 1.2 mg/mL by adopting normal saline ^-1 In animal administration, pirfenidone capsule is suspended to 200 mg/kg using 0.5% CMCNa ^-1 The linarin is suspended by 0.5% into 12.5, 25 mg. Kg ^-1 (ii) a In the cell administration, linarin is prepared into 6.25, 12.5, 25 with DMSOμmol·L ^-1 。

Animal grouping, modeling and intervention method

After the mice are adaptively fed for 1 week, the mice are randomly divided into a normal group, a model group, a linarin low-dose group, a linarin high-dose group and a pirfenidone group, and 6 mice are selected in each group. Each group of mice was anesthetized by intraperitoneal injection of 1% sodium pentobarbital, fixed on an operating table, and administered with bleomycin (3 mg. Kg) by a micro-liquid intratracheal atomization device ^-1 ) The pulmonary fibrosis model was induced, and the normal group was given an equal amount of physiological saline in the same treatment manner. After 24h of modeling, the intragastric administration is started, 1 time a day, the administration is continued for 14 days, the intragastric administration dosage is 12.5, 25 mg. Kg respectively according to the preliminary experiment investigation dosage in the group with low and high linarin ^-1 ·d ^-1 The linarin and pirfenidone group of the formula (II) is administered with a clinical equivalent dose (200 mg kg) through intragastric administration ^-1 ·d ^-1 ) The normal group and the model group were gavaged with an equivalent amount of 0.5% CMCNa per day. During the feeding process, the mice freely drink and eat water.

General observations in mice

The general conditions of activity, hair, diet, body mass and the like of each group of mice were observed every day during the experiment.

Taking materials

Recording the body mass of each group of mice before the last administration, 2h after the last administration, collecting blood from eyeball after anesthesia, standing the obtained whole blood at 4 deg.C for 2 hr, 3500 r.min ^-1 Centrifuge 15mAnd in, collecting the upper serum, and freezing and storing in a refrigerator at the temperature of 80 ℃ below zero for testing. After blood collection, mice were sacrificed and lung tissue dissected and dissected.

Index of lung

The stripped clean lung tissue was weighed and the mouse lung index was calculated according to the formula, lung index = lung mass (mg)/mouse body mass (g) before the last dose.

Pathological examination of lung tissue

After weighing lung tissue, the left lung of each group of mice was taken, fixed in formalin solution for 24 hours, dehydrated, paraffin-embedded, sectioned (thickness 4 μm), and HE-stained and Masson-stained. The pathological morphology of lung tissue was observed using an optical microscope (x 100) and images were collected, and pulmonary fibrosis scores were made with reference to Ashcroft scoring criteria, with higher scores indicating more severe pulmonary fibrosis. The Ashcroft score criteria are as follows, score 0: normal lung tissue; 1 minute: slight thickening of the alveolar or bronchial wall; and 3, dividing: moderate thickening of the alveolar or bronchial walls, but no apparent destruction of the alveolar structure; and 5, dividing: a cord-like fibrous band or a small-range fibrous foci is formed, and the alveolar structure is obviously damaged; 7, dividing: the alveolar structure is seriously deformed, and a wide fibrous focus is formed and presents as a honeycomb lung; 8 min: pulmonary tissue full-field fibrosis lesions, 2, 4, 6 points between corresponding fractions.

Detection by ELISA method

Detection of serum TGF-β1，TNF-αHorizontal; collecting right lung tissue, adding PBS (containing 1% of PMSF), grinding in a refrigerated ultrasonic grinder at 10000r min ^-1 Centrifuging for 15min, taking the homogenate for later use, and detecting the IL-6 level in the lung homogenate according to the ELISA kit specification.

Immunohistochemical detection

TGF-β1，αExpression of SMA, collagen I, p-ERK mice Lung tissue sections, thickness 3 μm, after conventional dewaxing and corresponding treatment, rabbit anti-TGF-β1，α-SMA, collagen I, p-ERK1/2 polyclonal antibody, according to the kit instruction method operation, mounting after microscope examination, collecting image analysis, according to the dyeing degree to judge the result.

Cell culture

Inoculating HFL1 cells with appropriate density into special culture medium for HFL1 cells, and placing at 37 deg.C and 5% CO ₂ Culturing in an incubator, and carrying out subculture liquid change every three days to ensure the optimal state of cell activity.

Western blot

Spreading HFL1 cells in logarithmic growth phase on six-well plate, and dividing into blank group, model group and linarin administration group after wall adhesion next day, wherein the blank group is added with culture medium, and the model group is added with TGF-β1(10ng·ml ^-1 ) Stimulation of formation of pulmonary fibrosis cell model ^[15] The linarin administration group is simultaneously added with TGF-β1(10ng·ml ^-1 ) Co-culturing with linarin (25, 12.5, 6.25 μ M) for 48h, adding RIPA lysate for lysis, centrifuging, collecting supernatant, determining protein concentration by BCA method, adding Loading buffer, and decocting at 96 deg.C in metal bath for 10min to denature protein. Separating protein components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transferring the protein onto polyvinylidene fluoride (PVDF) membrane by wet transfer method, sealing with 5% skimmed milk powder, and washing with PBST. Primary antibody (1. PBST washing. Adding goat anti-rabbit secondary antibody (1.

Statistical method

Statistical processing is carried out by SPSS 22.0 version statistical analysis software, and data measurement is carried out by average number +/-standard deviation (

±s) Showing that the single-factor variance analysis is adopted for the inter-group mean comparison, and the LSD-tAnd (6) checking. To be provided withPDifferences < 0.05 are statistically significant.

As a result, the

3.1 influence of Mongolian glycosides on BLM-induced pulmonary fibrosis model in mice and organ index

In animal experiments, the administration group adopts the same induction mode as the model group to establish a mouse pulmonary fibrosis model. From the general condition of the mice, it can be observed that the normal group of mice ingests and drinks water normally and acts normally. The eyes have spirit, the fur is soft and smooth, and abnormal breathing sound is avoided. The mice in the model group have the defects of gradual reduction of food and water intake, slow action, rough fur, serious shedding, laziness in behavior and obvious decline of physical functions, and are mainly characterized by poor limb coordination, insensitive action, unsmooth breathing and abnormal breathing sound. Compared with the model group, the symptoms and the performances of the mice in various dose groups of the linarin and the pirfenidone group are obviously improved.

As observed from the mouse body weight, a significant reduction in the mouse body weight as compared with the normal group was observed in the model group mice (P< 0.01); the weight of the positive drug pirfenidone group is larger than that of the model group, and the significant difference is shown in (A)P< 0.05); the weight of the mice in the high-dose group of the linarin is higher than that in the low-dose group of the linarin, and the weights of the mice in the high-dose group and the low-dose group of the linarin are both higher than those in the pirfenidone group and the model group, and the significant difference is shown (the weight of the mice in the high-dose group and the low-dose group of the linarin are higher than that in the pirfenidone group and the model group of the linarinP＜0.05)。

The lung organ index of the model group was significantly increased compared to that of the normal group, as observed from the organ index of mouse lung: (P＜0.01 ); compared with the model group, the pulmonary organ indexes of the pirfenidone group, the high-Mongolian glycoside and the low-dose group are all obviously reduced (P< 0.05), close to the normal group.

Based on the above analysis, the safety of the linarin high-dose group and the linarin low-dose group is better than that of the positive drug pirfenidone group from the comprehensive points of the general condition, the body weight and the pulmonary organ index of mice. Compared with the model group, the high-low dose group of the linarin shows the improvement effect on the pulmonary fibrosis model on the improvement of the body weight and the pulmonary organ index. See table 1.

Effect of linarin on pathological section of lung

The results of the lung tissue staining for each group were scored in combination with the results of the HE and Masson staining experiments, and the scores are shown in table 2. In the normal group, the lung tissue structure is normal, and the alveolar wall and cells all show structuresThe preparation is complete and has no phenomena such as inflammation infection, cell necrosis, fibrosis and the like related to pathology; the thickening of alveolar wall in the model group is significant compared with that in the normal group (PLess than 0.05), alveoli all present pathological states, and a large amount of inflammatory infection and increased cell fibrosis exist; compared with the model group, the lung tissue inflammatory lesions of the high and low dose Mongolian and pirfenidone groups are obviously reduced (PLess than 0.05), the alveolar wall thickening is obviously improved, the fibrosis deposition is obviously reduced, the inflammatory infection is obviously improved, and the performances of the linarin high-dose group and the pirfenidone group are superior to those of the linarin low-dose group and are more close to those of the normal group. See fig. 1, fig. 2, table 2.

。

Effect of linarin on BLM-induced inflammatory factor content in mice with pulmonary fibrosis

TGF-one in the serum of the model group compared with the normal groupβ1，TNF-αThe IL-6 content is obviously increased (P＜0.05，PLess than 0.01), indicating that more inflammation exists in the body of the mice in the pulmonary fibrosis model group; compared with the model group, TGF-β1，TNF-αThe IL-6 content is obviously reduced (P＜0.05，PLess than 0.01) is relatively close to a normal group, and shows that the linarin has a remarkable improvement effect on inflammation of an in-vivo pulmonary fibrosis model. See Table 3

。

Linarin in lung tissueα-SMA、TGF-β1. Effect of p-ERK1/2 and Collagen I protein expression

Of the model group compared with the normal groupα-SMA、TGF-β1. p-ERK1/2 and Collagen I are obviously expressed, which shows that the model making of the in vivo pulmonary fibrosis model is successful; compared with the model group, the expression of alpha-SMA, TGF-beta 1, p-ERK1/2 and Collagen I of the high and low dosage Mongolian glycoside group and the pirfenidone group is obviously improved and is close to normalIn the group, the linarin has obvious improvement effect on the pulmonary fibrosis in-vivo model. See fig. 3-6.

For TGF-β1 induced HFL1 cellsαInfluence of the expression of SMA, collagen I, ERK1/2 and p-ERK1/2 proteins

Of the model group compared with the normal groupαThe expression levels of SMA, collagen I and P-ERK1/2 are obviously increased (P is less than 0.05, P is less than 0.01), which indicates that the model making of the in vitro pulmonary fibrosis model is successful; in the 25 μ M dose group of linarin compared to the model groupαThe expression of SMA, collagen I and P-ERK1/2 is obviously reduced (P < 0.05, P < 0.01), and the expression is dose-dependent, while the expression of ERK1/2 among groups is not obviously changed. Suggesting that linarin can be down-regulatedαThe expression of-SMA, collagen I and p-ERK1/2 protein has no obvious influence on ERK1/2 protein. See fig. 7, table 4;

。

from the above results, it was found that, in the study of the BLM-induced lung fiber model in mice, the body weight and pulmonary organ index of the mice in the linarin-administered group were improved to different degrees compared to the model group, and the body weight and organ index were superior to those in the positive drug pirfenidone group. In addition, HE staining and Masson staining results showed that linarin significantly improved lung pathology induced by BLM.

In the research of the invention, the linarin can reduce TGF-one in lung tissues of a BLM-induced pulmonary fibrosis modelβ1, reduction of inflammatory factor TGF-β1、TNF-αIL-6 levels, act to ameliorate pulmonary fibrosis by reducing inflammatory infiltration in lung tissue.

In an in-vivo and in-vitro model of pulmonary fibrosis, the linarin can obviously reduce the expression of p-ERK1/2 and reduce pulmonary fibrosis marker proteinαExpression of SMA, collagen i, acting to improve pulmonary fibrosis based on the ERK pathway.

In conclusion, in an in vivo and in vitro pulmonary fibrosis model, the linarin can inhibit the release of inflammatory factors to improve inflammatory infiltration by regulating ERK and inflammation-related pathways, so that the function of improving pulmonary fibrosis is achieved.

Claims (7)

1. Application of linarin in preparing medicine for preventing or treating pulmonary fibrosis is provided.

2. The use according to claim 1, wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis or secondary pulmonary fibrosis.

3. The use according to claim 2, wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis.

4. The use of claim 1, wherein the linarin acts to improve pulmonary fibrosis based on the ERK pathway.

5. The use of claim 1, wherein the linarin acts to improve pulmonary fibrosis by reducing inflammatory infiltration in lung tissue.

6. The use of claim 1, wherein the medicament comprises an effective amount of linarin and a pharmaceutically acceptable carrier or excipient.

7. The use according to claim 6, wherein the medicament is in the form of tablets, capsules, oral liquid or granules.

Images