Use of syringaldehyde in the preparation of a drug for treating silicosis

Abstract

The application discloses application of syringaldehyde in preparation of a drug for treating silicosis, and belongs to the technical field of medical uses. The application finds for the first time that syringaldehyde can significantly improve lung function of a silicosis mouse model, reduce lung inflammatory factors IL-6, IL-1beta and TNF-alpha levels, inhibit collagen deposition and hydroxyproline content, and reduce lung fibrosis, and has no hepatorenal toxicity under a treatment dose. The application shows through research that syringaldehyde reduces lung inflammation of a silicosis model, syringaldehyde reduces lung fibrosis of a silicosis model, and syringaldehyde reduces lung inflammation and lung fibrosis of a silicosis model by inhibiting a beta-catenin / Cyclin D1 signal axis. The application provides a safe and effective new drug selection for silicosis, a professional lung disease for which there is no specific drug.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a novel use of eugenol in the preparation of drugs for treating silicosis, as well as pharmaceutical compositions and formulations containing eugenol. Background Technology

[0002] Silicosis is an interstitial lung disease caused by long-term inhalation of respirable crystalline silica (RCS) during occupational activities. It is characterized by diffuse fibrosis of the lung tissue, progressive lung inflammation, silicotic nodule formation, and irreversible interstitial fibrosis, ultimately leading to respiratory failure and death. Besides being common in traditional industries such as mining, metallurgy, construction, and ceramics, silicosis is also relatively common in emerging industries such as sandblasting jeans and cutting artificial stone. Despite active prevention and control measures worldwide, the incidence and prevalence of silicosis continue to rise. According to the Global Burden of Disease Report, from 1990 to 2019, the incidence and prevalence of silicosis increased by 64.6% and 91.4%, respectively, posing a serious global public health problem.

[0003] Silicosis, a serious global occupational disease, has a complex and incompletely understood pathogenesis, which limits its treatment options. Pirfenidone (PFD) is a drug used to treat idiopathic pulmonary fibrosis and has significant anti-inflammatory and anti-fibrotic properties. Furthermore, in vitro and in vivo studies have confirmed that PFD can slow the progression of silicosis. However, PFD suffers from hepatotoxicity and a short half-life, limiting its widespread clinical application. Given that current clinical drugs can only alleviate silicosis symptoms and improve respiratory function, but cannot halt the progression of pulmonary fibrosis caused by silica dust, exploring safer and more effective treatments has become an urgent clinical need.

[0004] Natural products offer an attractive option for treating a variety of acute and chronic inflammatory and fibrotic conditions. Syringaldehyde (SA), a natural phenolic compound found in cassava and magnolia bark, is traditionally known for its anti-inflammatory and antioxidant properties.

[0005] The chemical structural formula of eugenol is as follows:

[0006]

[0007] Recent reports indicate that styrax (SA) inhibits inflammation and oxidative stress by modulating the Nrf2 / NF-κB / HO-1 signaling pathway. Other reports suggest that SA suppresses mycobacterial infection-induced inflammatory responses by activating the AMPK-α1 / AKT / GSK-3β signaling pathway. Furthermore, SA alleviates Deltamethrin-induced liver injury by inhibiting the Nrf2 / HO-1 signaling axis. Based on a mouse arthritis model, SA improves arthritis by inhibiting dendritic cell maturation and pro-inflammatory cytokine secretion, and downregulating MAPK and NF-κB levels.

[0008] A search revealed existing reports of aldehyde compounds used to treat pulmonary fibrosis, but none specifically disclosed syringaldehyde, and the treatment targets were broadly defined as pulmonary fibrosis, not silicosis of a specific etiology. Other studies disclosed the application of syringaldehyde in the preparation of immunosuppressive drugs, but the indication for this patent was autoimmune arthritis, and the mechanism of action focused on dendritic cells and T cell subsets, without addressing silica-induced lung injury, pulmonary fibrosis, or the β-catenin signaling pathway. To date, there are no reports of syringaldehyde being used to treat silicosis, and even fewer studies have been found on its mechanism of reducing pulmonary inflammation and fibrosis in silicosis by inhibiting the β-catenin / Cyclin D1 signaling axis. Summary of the Invention

[0009] The technical problem to be solved by this invention is to provide a new use for eugenol in the preparation of drugs for treating silicosis. Specifically, it provides a drug application with eugenol as the active ingredient that can effectively reduce lung inflammation and pulmonary fibrosis in silicosis models, and clarifies its mechanism of action, providing a safe and effective treatment option for silicosis, an occupational lung disease for which there is currently no specific drug.

[0010] The inventors have discovered for the first time that syringaldehyde has a significant therapeutic effect on silica-induced silicosis. Experiments have shown that syringaldehyde can effectively alleviate lung inflammation and fibrosis in a mouse model of silicosis by improving lung function, reducing the level of pulmonary inflammatory factors, decreasing collagen deposition, and inhibiting the expression of pulmonary fibrosis markers. Further mechanistic studies have shown that syringaldehyde blocks the silica-induced pro-inflammatory and pro-fibrotic cascade by inhibiting the activation of the β-catenin / Cyclin D1 signaling axis in fibroblasts.

[0011] The objective of this invention is achieved through the following technical solution:

[0012] Application of eugenol in the preparation of drugs for treating silicosis.

[0013] To further illustrate, the eugenol effectively reduces lung inflammation and / or pulmonary fibrosis in the silicosis model.

[0014] To further illustrate, the eugenol reduces lung inflammation and pulmonary fibrosis in a silicosis model by inhibiting the β-catenin / Cyclin D1 signaling axis.

[0015] To further clarify, the drug is an oral preparation made with eugenol as the active ingredient and pharmaceutically acceptable excipients.

[0016] To further clarify, the oral preparation is a capsule or tablet, and the content of eugenol in the oral solid preparation is 1% to 50% (w / w).

[0017] In the above technical solution, "silicosis" specifically refers to occupational pneumoconiosis caused by inhaling silica dust.

[0018] Typically, pharmaceuticals are clinically used only after being formulated into a pharmaceutical preparation. The pharmaceutical product described in this invention can be prepared according to methods known in the art. It can be formulated into any dosage form suitable for human or animal use by combining the pharmaceutical product of this invention with one or more pharmaceutically acceptable solid or liquid excipients and / or adjuvants.

[0019] The drug of this invention or a drug containing it can be administered in unit dose form, and the route of administration can be enteric or non-enteric, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum, etc.

[0020] Dosage forms can be liquid, solid, or semi-solid. Liquid dosage forms can include solutions (including true solutions and colloidal solutions), emulsions (including o / w, w / o, and double emulsions), suspensions, injections (including aqueous injections, powder injections, and infusions), eye drops, nasal drops, lotions, and liniments, etc.; solid dosage forms can include tablets (including regular tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, and orally disintegrating tablets), capsules (including hard capsules, soft capsules, and enteric-coated capsules), granules, powders, microcapsules, pellets, suppositories, films, patches, aerosols, and sprays, etc.; semi-solid dosage forms can include ointments, gels, and pastes, etc.

[0021] The drug of this invention can be formulated into conventional formulations, sustained-release formulations, controlled-release formulations, targeted formulations, and various microparticle delivery systems. To formulate the drug of this invention into tablets, a wide range of excipients known in the art can be used, including diluents, binders, wetting agents, disintegrants, lubricants, and flow aids. Diluents can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, dicalcium phosphate, calcium carbonate, etc.; wetting agents can be water, ethanol, isopropanol, etc.; binders can be starch paste, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic paste, gelatin paste, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.; disintegrants can be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose, croscarmellose sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitol fatty acid ester, sodium dodecyl sulfonate, etc.; lubricants and flow aids can be talc, silica, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc.

[0022] Tablets can also be further processed into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or bilayer and multilayer tablets.

[0023] To formulate the drug delivery unit into capsules, the active ingredient of the present invention can be mixed with a diluent and a disintegrant, and the mixture can be placed directly into hard or soft capsules. Alternatively, the active ingredient of the present invention can be first formed into granules or microspheres with a diluent, binder, and disintegrant, and then placed into hard or soft capsules. The diluents, binders, wetting agents, disintegrants, and disintegrants used to prepare tablets of the present invention can also be used to prepare capsules of the present invention.

[0024] To prepare the drug of this invention into an injectable formulation, water, ethanol, isopropanol, propylene glycol, or mixtures thereof can be used as solvents, and appropriate amounts of commonly used solubilizers, co-solvents, pH adjusters, and osmotic pressure regulators can be added. Solubilizers or co-solvents can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin, etc.; pH adjusters can be phosphates, acetates, hydrochloric acid, sodium hydroxide, etc.; osmotic pressure regulators can be sodium chloride, mannitol, glucose, phosphates, acetates, etc. If preparing a lyophilized powder for injection, mannitol, glucose, etc., can also be added as a support agent.

[0025] In addition, colorants, preservatives, flavorings, tasters or other additives may be added to pharmaceutical preparations if necessary.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The inventors have discovered a novel use for eugenol in the treatment of silicosis. No existing technologies have reported any therapeutic effects of eugenol on silicosis, and this invention fills this technological gap. Animal experiments show that oral administration of eugenol at 50-200 mg / kg for 28 days significantly improves lung function, reduces CT lesions, and lowers inflammation and fibrosis scores in silicosis-affected mice, with effects comparable to or better than the positive control drug pirfenidone. Furthermore, this invention reveals for the first time that eugenol inhibits the β-catenin / Cyclin D1 signaling axis, blocking silica-induced fibroblast activation and collagen deposition—a mechanism distinct from the known immunosuppressive effects of eugenol. At therapeutic doses (50-200 mg / kg), eugenol has no significant effect on liver and kidney function (ALT, AST, CRE) in silicosis-affected mice, demonstrating superior safety potential compared to pirfenidone. Eugenol can be extracted from natural plants such as cassava and magnolia officinalis or chemically synthesized, making it cost-effective and suitable for industrial production. Attached Figure Description

[0028] Figure 1 This is a graph showing the effect of eugenol on lung function in a silicosis mouse model in the experimental examples of this invention. Wherein: AC represents changes in lung function parameters, F is respiratory rate; sRAW is specific airway resistance; and TV is tidal volume.

[0029] Figure 2 This is a diagram illustrating the effect of eugenol on chest Micro-CT scans in a silicosis mouse model, as shown in the experimental examples of this invention. A) Chest Micro-CT scan image; B) Quantitative lung volume analysis based on Micro-CT data.

[0030] Figure 3 This is a diagram illustrating the effect of eugenol on lung inflammation in a silicosis mouse model, as shown in the experimental examples of this invention. Wherein: AB, H&E staining of lung tissue sections (scale bars are 500 μm and 100 μm, respectively); C, H&E staining inflammation score; D, number of inflammatory cells in bronchoalveolar lavage fluid; EG, concentration of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in BALF; HJ, concentration of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in serum.

[0031] Figure 4 This is a diagram illustrating the effect of eugenol on pulmonary fibrosis in a mouse model of silicosis, as shown in the experimental examples of this invention. The figures are as follows: AB, Masson's trichrome staining of lung tissue sections (scale bars at 500 μm and 100 μm, respectively); CD, immunohistochemistry of Collagen-I and Fibronectin in lung tissue (scale bar at 100 μm); E, fibrosis score based on Masson's trichrome staining; FG, quantitative analysis of the percentage of positive areas for Collagen-I and Fibronectin; H, determination of HYP content in lung tissue.

[0032] Figure 5 The graph shows that eugenol at therapeutic doses has no significant liver and kidney toxicity in a mouse model of silicosis.

[0033] Figure 6 This is a diagram illustrating the effect and mechanism of eugenol on human fetal lung fibroblasts in experimental examples of this invention. Specifically: A) RT-qPCR detection of mRNA expression of IL-6, IL-1β, and TNF-α in human fetal lung fibroblasts; B) Western blot detection of protein expression and relative quantification of Collagen-I and Fibronectin in human fetal lung fibroblasts; C) Western blot detection of protein expression and relative quantification of β-catenin and Cyclin D1 in human fetal lung fibroblasts. Detailed Implementation

[0034] The specific embodiments of the present invention will be further described below with reference to examples.

[0035] Example 1: Preparation of Eugenol Oral Capsules

[0036] Take 200g of eugenol raw material (purity ≥98%), 140g of microcrystalline cellulose, 40g of starch, 16g of croscarmellose sodium, and 4g of magnesium stearate, for a total weight of 400g.

[0037] Preparation method: Syringaldehyde is mixed evenly with microcrystalline cellulose, starch, and croscarmellose sodium, and then passed through an 80-mesh sieve three times; magnesium stearate is added and the mixture is stirred; the mixture is then filled into No. 0 gelatin hard capsules using a fully automatic capsule filling machine, with each capsule containing 200 mg of syringaldehyde. After passing inspection, the capsules are packaged.

[0038] This product is used as an adjunct treatment for silicosis. The recommended oral dose is 400-800 mg (calculated as eugenol) daily, divided into two doses.

[0039] Example 2: Preparation of Syringaldehyde Oral Tablets

[0040] Take 100 g of eugenol raw material, 80 g of lactose, 60 g of pregelatinized starch, 15 g of low-substituted hydroxypropyl cellulose, and 2 g of magnesium stearate.

[0041] Preparation method: Syringaldehyde is mixed evenly with lactose, pregelatinized starch and low-substituted hydroxypropyl cellulose, and a soft mass is prepared by using 50% ethanol as a wetting agent. The mass is granulated by passing through a 20-mesh sieve, dried at 50°C for 2 hours, granulated, magnesium stearate is added, and the mass is compressed into tablets. Each tablet contains 200 mg of syringaldehyde.

[0042] This product is used to treat silicosis. The oral dose is 400-800 mg daily, divided into two doses.

[0043] Example 3: Preparation of Syringaldehyde Oral Suspension

[0044] Take 20 g of eugenol, 5 g of sodium carboxymethyl cellulose, 20 mL of glycerol, 2 mL of polysorbate 80, and 1.5 g of sodium benzoate, and add purified water to 1000 mL.

[0045] Preparation method: Disperse sodium carboxymethyl cellulose in an appropriate amount of hot purified water and cool; add glycerol, polysorbate 80 and sodium benzoate, and stir to dissolve; slowly add syringaldehyde while stirring, add purified water to the total volume, homogenize at high speed for 10 minutes to obtain a uniform suspension. Each milliliter contains 20 mg of syringaldehyde.

[0046] This product is used to treat silicosis. The oral dosage is 20-40 mL daily, divided into two doses.

[0047] Experiment Example 4: Pharmacodynamic Experiment of Syringaldehyde on a Mouse Model of Silicosis

[0048] I. Purpose

[0049] To explore the effects of eugenol on lung inflammation and pulmonary fibrosis in a silica-induced silicosis mouse model.

[0050] II. Materials and Methods

[0051] Animals: Male C57BL / 6J mice (n=60) aged 8 weeks and weighing approximately 22-26g were purchased from Jiangsu Huachuang Xinno Pharmaceutical Technology Co., Ltd. (License No.: SCXK(Su)2020-0009). They were housed in a constant temperature (22±2℃), constant humidity (50±10%), 12h light / dark cycle environment with free access to food and water. The experimental protocol was approved by the Animal Ethics Committee of Guilin Medical University (Approval No.: GLMU-IACUC-202510136).

[0052] Silicosis model grouping and establishment: Sixty mice were randomly divided into 6 groups of 10 mice each.

[0053] Control group: saline group;

[0054] Model group (SiO2): Silicon dioxide model group;

[0055] Experimental group (SiO2+SA-L): low concentration group of silicon dioxide + syringaldehyde (50mg / kg);

[0056] ④ Experimental group (SiO2+SA-M): Silicon dioxide + medium concentration of syringaldehyde (100mg / kg);

[0057] Experimental group (SiO2+SA-H): High concentration of silica + syringaldehyde (200mg / kg);

[0058] ⑥ Positive control group (SiO2+PFD): Silicon dioxide + PFD group (400mg / kg).

[0059] Modeling period: 40 μL of physiological saline was instilled into the trachea of ​​the control group, and 40 μL of silica suspension (300 mg / mL) prepared with physiological saline was instilled into the trachea of ​​the model group.

[0060] Administration period: Intervention began the day after modeling. The control group and the model group were administered 1% sodium carboxymethyl cellulose by gavage daily. The silica + eugenol low, medium and high concentration groups were administered eugenol by gavage at 50 mg / kg, 100 mg / kg and 200 mg / kg respectively. The silica + PFD group was administered pirfenidone (PFD) by gavage at 400 mg / kg. The administration was continued for 28 days.

[0061] Sample collection: On day 29, mice were euthanized by an overdose of anesthetic drugs after undergoing a micro-CT scan of the chest and lung function measurement. Bronchoalveolar lavage fluid, serum and lung tissue were collected for analysis.

[0062] Statistical methods: Data are expressed as mean ± standard deviation (Mean ± SD). One-way ANOVA was used for comparisons among multiple groups, and Tukey's multiple comparisons were used for post-hoc tests. P < 0.05 was considered statistically significant.

[0063] III. Results:

[0064] 1. Lung Function Testing: To clarify the effect of eugenol on lung function in a silicosis mouse model, respiratory rate (F), specific airway resistance (sRAW), and tidal volume (TV) were monitored in real time using a pulmonary function analyzer. The data were then collected and analyzed to determine the changes in lung function in the experimental mice. Results are as follows: Figure 1 The results showed that, compared with the control group, the model group mice had significantly increased F and sRAW and significantly decreased TV (P < 0.0001), indicating that silicosis leads to severe lung dysfunction. Compared with the model group, the medium and high dose syringaldehyde groups and the PFD group all significantly decreased F and sRAW and increased TV (P < 0.05 or P < 0.01), in a dose-dependent manner.

[0065] The low-dose group showed some improvement trends in certain indicators, but the differences were not statistically significant. These results indicate that eugenol can effectively improve lung ventilation and compliance in silicosis mice.

[0066] 2. Micro-CT Imaging: To clarify the effect of eugenol on lung lesions in a mouse model of silicosis, mice underwent chest micro-CT scans, and lung volume was quantified using PMOD software.

[0067] The results are as follows Figure 2 The results showed that the lung fields of the control group mice had good translucency and clear lung markings, with no abnormal dense shadows. In contrast, the lung fields of the silicosis model group mice showed increased density, with multiple high-density nodules and areas of consolidation of varying sizes, mostly distributed around the bronchi, accompanied by a significant reduction in lung volume. After treatment with syringaldehyde or pirfenidone, the distribution range and shadow density of the high-density lesions in the lungs of the mice were significantly reduced, and the lung ventilation volume was effectively restored.

[0068] 3. Evaluation of lung inflammation: In order to clarify the effect of eugenol on lung inflammation in a mouse model of silicosis, H&E staining was performed on mouse lung tissue sections, and ELISA was used to detect pro-inflammatory cytokines in mouse bronchoalveolar lavage fluid and serum.

[0069] The results are as follows Figure 3 As shown:

[0070] Results of H&E staining of lung tissue are shown in Figure 3 In the AB control group, the alveolar structure of the mice remained intact, with no obvious inflammatory cell infiltration. In contrast, the silica model group exhibited a severe pulmonary inflammatory response, with a large number of inflammatory cells accumulating around small blood vessels and bronchioles; typical silicotic nodules were also observed, with dense collagen fibers and significant hyaline degeneration within the nodules. After SA treatment, the pulmonary inflammatory response was significantly improved, and the degree of damage was alleviated. Figure 3 C showed that the model group score was significantly higher, while the high-dose syringaldehyde group score was significantly lower (P < 0.001). Lung histology further confirmed that the inflammation score in the SA group was significantly lower than that in the model group, and the high-dose group showed the most significant improvement. Furthermore, as... Figure 3 As shown in Figure D, the total cell count in the model group BALF was significantly increased (P < 0.0001), while it was significantly decreased in the medium and high dose syringaldehyde groups (P < 0.001, P < 0.0001). This indicates that SA treatment significantly reversed the silica-induced surge in the total number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and this effect was particularly pronounced in the medium and high dose groups. Figure 3 As shown in EJ, SA also significantly inhibited the levels of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) in BALF and serum, demonstrating strong systemic and local anti-inflammatory effects.

[0071] 4. Evaluation of pulmonary fibrosis: To clarify the effect of eugenol on pulmonary fibrosis in a mouse model of silicosis, Masson's trichrome staining was performed on mouse lung tissue sections, and the expression levels of classic fibrosis markers type I collagen (Collagen-I) and fibronectin were detected by immunohistochemical staining. In addition, hydroxyproline (HYP) in lung tissue was also detected.

[0072] like Figure 4 The Masson trichrome staining results shown in Figure AB indicate that the alveolar structure of the control group mice was intact, the airway boundaries were clear, and no obvious collagen deposition was observed. However, the normal lung tissue structure of the SiO2 model group mice was disrupted, accompanied by the formation of numerous typical silicotic nodules, with significant abnormal deposition of collagen fibers visible within and around the nodules. Figure 4 As shown in Figure E, compared to the model group, medium and high doses of SA and PFD treatments significantly reduced collagen deposition and effectively improved fibrotic lesions. Stain-based fibrosis pathology scores further confirmed that the treatment group's score was significantly lower than the model group. Immunohistochemical staining results further indicated that, as... Figure 4 As shown in CD and 4F-G, the expression of classic fibrosis markers Collagen-I and Fibronectin in the lung tissue of the model group was significantly upregulated, while SA intervention dose-dependently inhibited the abnormally high expression of these two proteins. Figure 4 As shown in Figure H, biochemical tests revealed a sharp increase in HYP levels in the lung tissue of the model group. SA treatment significantly restored HYP levels, with the inhibitory effect being particularly pronounced in the high-dose group.

[0073] 5. Preliminary Safety Assessment: To determine whether eugenol has hepatotoxicity or nephrotoxicity in a mouse model of silicosis, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CRE) levels were measured in mice.

[0074] like Figure 5 As shown, eugenol at therapeutic doses had no significant hepatotoxic or nephrotoxic effects on the silicosis mouse model. Liver and kidney function tests revealed no statistically significant differences in serum ALT, AST, and CRE levels between SA-treated silicosis mice and the control group. These results indicate that therapeutic doses of SA do not produce significant hepatotoxicity or nephrotoxicity.

[0075] Example 5: Effects and mechanisms of eugenol on human fetal lung fibroblasts (HFL-1) in a silicosis model

[0076] 1. Cell culture: Human fetal lung fibroblasts HFL-1 were purchased from the Cell Bank of the Chinese Academy of Sciences and cultured in HFL-1-specific medium in a humidified incubator at 37°C and 5% CO2.

[0077] 2. Modeling and Drug Administration: Cells were seeded in 6-well plates. When the cells reached 60-70% confluence, the SiO2+SA group was pretreated with 25 μM SA for 6 hours; the control group and SiO2 model group were pretreated with an equal volume of PBS for 6 hours simultaneously. After pretreatment, the SiO2 model group and SiO2+SA group were added with a final concentration of 100 μg / mL SiO2, and the cells were collected after culturing for another 24 hours.

[0078] 3. Detection indicators: RT-qPCR was used to detect the mRNA expression levels of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), and Western blot was used to detect the protein levels of Collagen-I, Fibronectin, β-catenin and Cyclin D1.

[0079] qPCR results showed ( Figure 6 A) The mRNA levels of IL-6, IL-1β, and TNF-α in the model group were significantly higher than those in the control group, and SA could significantly reverse this effect, suggesting that syringaldehyde can inhibit the expression of SiO2-induced pro-inflammatory cytokines. Western blot results showed that ( Figure 6 B and Figure 6 (C) The expression of Collagen-I and Fibronectin proteins was significantly upregulated in the model group, and their expression levels decreased significantly after SA treatment, indicating that syringaldehyde can effectively alleviate SiO2-induced fibrosis in human fetal lung fibroblasts. Furthermore, we found that the expression of β-catenin and Cyclin D1 proteins was upregulated in the model group, and this phenomenon could be reversed after SA intervention, suggesting that SA alleviates lung inflammation and pulmonary fibrosis in the silicosis model by inhibiting the β-catenin / Cyclin D1 signaling axis.

[0080] In summary, this invention discloses for the first time the application of eugenol in the preparation of drugs for treating silicosis. In vivo animal experiments and in vitro cell experiments have confirmed that eugenol can significantly improve lung function decline caused by silicosis, reduce pulmonary inflammation, and inhibit the progression of pulmonary fibrosis, with no significant hepatotoxicity or nephrotoxicity observed at therapeutic doses. Mechanistic studies reveal that eugenol blocks silica-induced pro-inflammatory and pro-fibrotic effects on fibroblasts by inhibiting the activation of the β-catenin / Cyclin D1 signaling axis.

[0081] The above description is a detailed description of the preferred embodiments of the present invention. However, the embodiments are not intended to limit the scope of the patent application of the present invention. All equivalent changes or modifications made under the technical spirit of the present invention should fall within the patent scope covered by the present invention.

Claims

1. Application of eugenol in the preparation of drugs for treating silicosis.

2. The application according to claim 1, characterized in that, The eugenol effectively reduced lung inflammation and / or pulmonary fibrosis in the silicosis model.

3. The application according to claim 1 or 2, characterized in that, Syringaldehyde alleviates lung inflammation and pulmonary fibrosis in a silicosis model by inhibiting the β-catenin / Cyclin D1 signaling axis.

4. The application according to any one of claims 1-3, characterized in that, The drug is an oral preparation made with eugenol as the active ingredient and pharmaceutically acceptable excipients.

5. The application according to claim 4, characterized in that: The oral preparation is a capsule or tablet, and the content of eugenol in the oral solid preparation is 1% to 50% (w / w).

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