Use of a drug for suppressing fibrosis of silicosis
By inhibiting lung inflammation and fibrosis in silicosis mice with rhodioloside, this study addresses the issues of individual variability in efficacy and toxicity associated with existing drugs, providing an effective solution to inhibit silicosis fibrosis with superior efficacy compared to existing medications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY
- Filing Date
- 2026-06-01
- Publication Date
- 2026-07-03
AI Technical Summary
Current clinical treatments for silicosis fibrosis suffer from significant individual differences in efficacy, marked hepatotoxicity and nephrotoxicity, and insufficient specificity, resulting in a lack of effective drugs to inhibit silicosis fibrosis.
Using rhodioloside as the active ingredient, it can reduce the number and area of silicotic nodules in the pulmonary interstitial region by inhibiting the pulmonary inflammatory response induced by SiO2 exposure, inhibiting the expression of pulmonary fibrosis-related proteins Collagen 1 and α-SMA, and downregulating the transdifferentiation of fibroblasts into myofibroblasts, and can be prepared into a suitable health care product or drug dosage form.
Rhodioloside significantly inhibits lung inflammation and fibrosis in silicosis mice, showing better efficacy than the existing drug tetrandrine, and has no obvious liver and kidney toxicity, providing an innovative theoretical basis for inhibiting silicosis fibrosis.
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Figure CN122320971A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical technology, and more specifically, to the application of a drug that inhibits silicosis fibrosis. Background Technology
[0002] Silicosis is a progressive, irreversible, and incurable respiratory disease characterized by diffuse fibrosis of the lungs. With economic development, pneumoconiosis cases are no longer limited to traditional industries; workers in many emerging industries are also at risk, such as those involved in denim washing, artificial stone processing (e.g., kitchen countertops), denture manufacturing, jewelry polishing, and shale gas hydraulic fracturing. Furthermore, the newly exposed populations show a significant trend of developing the disease at younger ages, imposing a huge economic burden on families and society. Current clinical treatments primarily rely on antifibrotic drugs such as pirfenidone and nintedanib, but these have drawbacks including significant individual differences in efficacy, marked hepatotoxicity and nephrotoxicity, and insufficient targeting of pulmonary fibrosis caused by silica dust exposure.
[0003] Salidroside (SAL) is the main active ingredient of Rhodiola rosea L., a precious traditional Chinese medicine, and is hailed as the core essence of "plateau ginseng" or "golden plant." As a highly promising "food and medicine homology" active substance, salidroside possesses various biological effects, including anti-fatigue, anti-hypoxia, antioxidant, immunomodulatory, and anti-tumor properties. Widely distributed in high-altitude regions of Tibet and Qinghai in my country, its application has a long history. As early as the *Shennong Bencao Jing* (Shennong's Classic of Materia Medica), it was listed as a "superior" herb, stating that it "nourishes life to accord with nature, is non-toxic, and does not harm the body even with prolonged or excessive use." The *Compendium of Materia Medica* also records that it can "lighten the body, invigorate qi, and prolong life." Modern medical research has proven that salidroside exhibits excellent performance in cardiovascular protection, nervous system regulation, and anti-aging, and has been widely used in clinical drug development and high-end health foods. Preparations with rhodioloside as the core extract are widely regarded as a natural remedy for enhancing physical fitness and resisting altitude sickness because they can significantly improve the body's defense against harmful stimuli.
[0004] However, current research and applications of rhodioloside are mostly focused on combating high-altitude hypoxia, improving exercise-induced fatigue, protecting the myocardium, and intervening in neurodegenerative diseases. There is a lack of systematic literature support and clinical trial evidence regarding its application in occupational disease prevention, particularly whether rhodioloside can alleviate pulmonary inflammation and fibrosis caused by silicosis. Therefore, this paper proposes the application of a drug to inhibit silicosis fibrosis. Summary of the Invention
[0005] The purpose of this invention is to demonstrate that rhodioloside can inhibit lung inflammation and fibrosis in silicosis mice, thereby proving that rhodioloside can be developed into a health product or drug that can alleviate the progression of silicosis. This invention uses free silica (SiO2) dust as an exposure factor and, from the perspective of SiO2 exposure to lung inflammation and fibrosis in mice, comprehensively observes whether rhodioloside can regulate silicosis and fibrosis, providing an innovative theoretical basis for rhodioloside to alleviate silicosis.
[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: the application of a drug to inhibit silicosis fibrosis, specifically the application of rhodioloside in the preparation of drugs to alleviate silicosis and pulmonary fibrosis.
[0007] As a preferred technical solution of the present invention, the application of rhodioloside in the preparation of drugs to inhibit silicosis fibrosis.
[0008] As a preferred technical solution of the present invention, rhodioloside is used to inhibit the inflammatory response of the lungs caused by SiO2 exposure and reduce the number and area of silicotic nodules in the interstitial lung region.
[0009] As a preferred technical solution of the present invention, the rhodioloside is used to inhibit the expression of pulmonary fibrosis-related proteins Collagen 1 and α-SMA, thereby reducing diffuse deposition of collagen fibers in lung tissue.
[0010] As a preferred technical solution of the present invention, the dosage of rhodioloside is 50 mg / kg to 100 mg / kg. At this dosage, the inhibitory effect of rhodioloside on silicosis fibrosis is better than that of tetrandrine at the same dosage.
[0011] As a preferred technical solution of the present invention, the rhodioloside is used to inhibit the transdifferentiation of TGF-β-induced mouse fibroblasts (NIH / 3T3) into myofibroblasts and downregulate the expression levels of Collagen 1 and α-SMA proteins in these cells.
[0012] As a preferred technical solution of the present invention, the preparation method of the rhodioloside is as follows: the rhodioloside raw material is dissolved in sterile water to prepare a mother liquor with a final concentration of 60 mg / mL, which is then dispensed and stored at -20℃.
[0013] A drug to inhibit silicosis fibrosis, wherein the active ingredient of the health product includes rhodioloside, and the content of rhodioloside meets the equivalent dose of 4 mg / kg to 8 mg / kg corresponding to the daily intake dose for humans.
[0014] As a preferred embodiment of the present invention, the health product further includes pharmaceutically acceptable excipients, which are selected from one or more of distilled water, physiological saline, fillers, and disintegrants.
[0015] As a preferred technical solution of the present invention, the rhodioloside is an extract of the traditional Chinese medicine Rhodiola rosea L., and has no obvious liver and kidney toxicity.
[0016] Compared with existing technologies, the beneficial effects of this invention are as follows: This invention confirms that rhodioloside can inhibit the expression levels of Collagen 1 and α-SMA, proteins related to pulmonary fibrosis, in SiO2-exposed mice, reduce the number of diffuse high-density shadows and characteristic silicotic nodules in the interstitial lung fields, and decrease the area of diffuse collagen fiber deposition. Simultaneously, rhodioloside can also inhibit TGF-β-induced expression levels of Collagen 1 and α-SMA in NIH / 3T3 cells, inhibiting fibroblast differentiation into myofibroblasts. Furthermore, research results show that the effect of the same dose of rhodioloside is comparable to, or even superior to, the current first-line clinical drug for alleviating silicosis fibrosis, tetrandrine. These research results demonstrate that rhodioloside can effectively alleviate silicosis fibrosis. Attached Figure Description
[0017] Figure 1 The attached figure shows the effect of rhodioloside provided by the present invention on the CT imaging morphology and degree of lung lesions in silicosis mice.
[0018] Figure 2 The attached figure shows the effects of rhodioloside provided by this invention on liver and kidney function and histopathology in mice.
[0019] Figure 3 The attached figure shows the effect of rhodioloside provided by this invention on the degree of pulmonary fibrosis in silicosis mice.
[0020] Figure 4 The attached figure shows the effect of rhodioloside provided by this invention on the transdifferentiation of mouse fibrotic NIH / 3T3 cells. Detailed Implementation
[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.
[0022] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely illustrates some embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention. It should be noted that, in the absence of conflict, the embodiments and features and technical solutions in the embodiments of the present invention can be combined with each other. It should be noted that similar reference numerals and letters in the following figures indicate similar items; therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.
[0023] Example 1: Application of a drug to inhibit silicosis fibrosis: The application of rhodioloside in the preparation of drugs to alleviate silicosis and pulmonary fibrosis. The application of rhodioloside in the preparation of drugs to inhibit silicosis fibrosis.
[0024] Rhodioloside is used to inhibit pulmonary inflammatory responses caused by exposure to free silica (SiO2) and reduce the number and area of silicotic nodules in the pulmonary interstitial region.
[0025] Rhodioloside is used to inhibit the expression of pulmonary fibrosis-related proteins Collagen 1 and α-SMA, reducing diffuse deposition of collagen fibers in lung tissue.
[0026] The dosage of rhodioloside is 50 mg / kg to 100 mg / kg. At this dosage, rhodioloside is more effective than tetrandrine at the same dosage in inhibiting silicosis fibrosis.
[0027] Rhodioloside was used to inhibit TGF-β-induced transdifferentiation of mouse fibroblasts (NIH / 3T3) into myofibroblasts and downregulated the expression levels of Collagen 1 and α-SMA proteins in these cells.
[0028] The preparation method of rhodioloside is as follows: dissolve the rhodioloside raw material in sterile water to prepare a stock solution with a final concentration of 60 mg / mL, and store it at -20℃ after dispensing.
[0029] A drug to inhibit silicosis fibrosis, the active ingredient of which includes rhodioloside, the content of which meets the equivalent dose of 4 mg / kg to 8 mg / kg for daily human intake.
[0030] The drug also includes pharmaceutically acceptable excipients, which are selected from one or more of distilled water, physiological saline, fillers, and disintegrants.
[0031] Rhodioloside is an extract of the traditional Chinese medicine Rhodiola rosea L., and it has no obvious liver or kidney toxicity.
[0032] Experimental Example: This invention discloses experimental evidence of the application of rhodioloside in the preparation of silicosis and pulmonary fibrosis.
[0033] In the following examples, each treatment was repeated three times or more. All data are expressed as mean ± standard deviation, and all data were analyzed using one-way ANOVA with SPSS software. P <0.05 indicates a significant difference. P >0.05 indicates that the difference is not significant.
[0034] Experimental materials not mentioned in the examples are all conventional or commercially available experimental materials, and experimental steps not mentioned are conventional experimental steps, which will not be described in detail here.
[0035] In this invention, animal experiments have confirmed that rhodioloside plays an important role in alleviating silicosis and fibrosis. The experimental methods and results are as follows: 1. Experimental Materials 1.1 Experimental Subjects 1.1.1 Inbred line C57BL / 6 male mice 1.1.2 Mouse embryonic fibroblasts NIH / 3T3 1.2 Medicines and Reagents: 60 mg / mL rhodioloside solution, 200 mg / mL SiO2, distilled water, physiological saline, 70% ethanol, RIPA lysis buffer, protein loading buffer, pre-stained protein marker, and DAPI mounting medium.
[0036] 1.3 Main Instruments and Equipment: High-speed refrigerated centrifuges; -80℃ ultra-low temperature freezers; micropipettes; low-speed centrifuges; electrically heated constant temperature water baths; electronic balances; mixers; inverted optical microscopes; NEMO® Micro CT.
[0037] 2 Experimental Methods 2.1.1 Animal grouping: The groups for SiO2 exposure and rhodioloside intervention were: control group (Unt), silicosis model group (SiO2), silicosis model group with 50 mg / kg rhodioloside intervention (SAL 50 + SiO2), silicosis model group with 100 mg / kg rhodioloside intervention (SAL 100 + SiO2), and silicosis model group with 50 mg / kg tetrandrine intervention (Tet 50 + SiO2).
[0038] 2.1.2 Grouping of fibroblasts: NIH / 3T3 cells were divided into a control group (Con), a TGF-β treatment group (10 ng / mL), a SAL (50 μM) + TGF-β (10 ng / mL) combined treatment group, and a SAL (100 μM) + TGF-β (10 ng / mL) combined treatment group. The treatment time was 2 h of SAL pretreatment followed by 24 h of TGF-β co-treatment.
[0039] 2.2 Statistical Analysis Statistical analysis of the experimental data was performed using Graphpad Prism 10, and the results are expressed as mean ± standard deviation. Independent samples were used. t The test performs a comparison between two groups, while for multiple normally distributed data, a one-way ANOVA is performed to... P <0.05 indicates a statistically significant difference.
[0040] 3 Experimental Results 3.1 Rhodioloside alleviates lung inflammation and fibrosis in silicosis mice Small animal CT in vivo imaging was used to monitor changes in lung structure; histopathological techniques were used to analyze the morphology of mouse lung tissue. Results are as follows: Figure 1 As shown, after 56 days of SiO2 exposure, diffuse high-density shadows appeared in the lung fields of silicosis model mice, with lesions clustered around the bronchovascular bundles. Compared with the silicosis model group, the lesion volume in the lung tissue of mice treated with 50 and 100 mg / kg rhodioloside was smaller, and the 50 mg / kg rhodioloside group showed a better alleviating effect than the tetrandrine group. P <0.05).
[0041] Pathological findings of mouse lungs stained with hematoxylin and eosin (HE) are as follows: Figure 1 As shown, SiO2 exposure increased the number of characteristic silicotic nodules in the lung interstitial region of mice, mainly composed of dense collagen fibers, with obvious hyaline degeneration in the central area and abundant macrophage and lymphocyte infiltration around them. Compared with silicotic nodules in the lungs of mice treated with 50 and 100 mg / kg rhodioloside, the area of silicotic nodules in the lungs of mice was significantly reduced, and the degree of fibrosis in the core area of the nodules was significantly reduced, showing looser collagen fiber arrangement and reduced inflammatory cell infiltration, with more intact alveolar structure.
[0042] VG and Masson staining results showed that, compared with the lungs of healthy mice, collagen fibers in the lung tissue of silicosis mice were diffusely deposited in the lung interstitium. P <0.05). Compared with silicosis model mice, the area of collagen deposition in the lungs of mice treated with 50 and 100 mg / kg rhodioloside was significantly reduced. P<0.05). The above results suggest that rhodioloside intervention can effectively inhibit lung inflammation and excessive collagen deposition in SiO2-exposed mice, and alleviate the progression of silicosis fibrosis.
[0043] 3.2 Detection of hepatotoxicity and nephrotoxicity of rhodioloside in mice Experimental studies showed that rhodioloside had no significant toxic effects on the liver and kidneys of mice. Histopathological examination of the liver and kidney tissues of mice at oral doses of 50 and 100 mg / kg revealed no obvious abnormalities such as cellular edema, degeneration, necrosis, or inflammatory cell infiltration observed in HE staining; Masson staining also showed no increased collagen fiber deposition or tissue fibrosis. These results suggest that under the experimental conditions, rhodioloside did not damage the structure of mouse liver and kidney tissues and has good safety.
[0044] 3.3 Rhodioloside inhibits the expression of pulmonary fibrosis-related proteins in silicosis mice. The protein expression levels of the fibrinogens Collagen 1 and α-SMA were detected using immunofluorescence. The results are as follows: Figure 2 As shown, the expression of fibrotic proteins Collagen 1 and α-SMA in the lungs of silicosis mice was significantly increased ( P <0.05. Rhodioloside at 50 and 100 mg / kg inhibited the expression of Collagen 1 and α-SMA, proteins involved in pulmonary fibrosis, in SiO2-exposed mice. P <0.05, and the inhibitory effect of 50 mg / kg rhodioloside was better than that of the tetrandrine group ( P <0.05). This further confirms that rhodioloside can alleviate pulmonary fibrosis, and its effect at the same dose is superior to that of tetrandrine.
[0045] 3.4 Rhodioloside alleviates the transdifferentiation of mouse NIH / 3T3 fibroblasts into myofibroblasts Protein expression levels were detected using immunofluorescence. Results are as follows: Figure 3 As shown, TGF-β exposure significantly increased the expression levels of Collagen 1 and α-SMA proteins in NIH / 3T3 cells (P<0.05), indicating the successful establishment of a fibroblast transdifferentiation model into myofibroblasts. The results also showed that 50 and 100 μM rhodioloside could downregulate the expression levels of Collagen 1 and α-SMA proteins in TGF-β exposure NIH / 3T3 cells (P<0.05). P <0.05), indicating that rhodioloside can alleviate the transdifferentiation of fibroblasts into myofibroblasts.
[0046] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.
[0047] The above embodiments are only used to illustrate the present invention and are not intended to limit the technical solutions described herein. Although the present invention has been described in detail with reference to the above embodiments, the present invention is not limited to the specific embodiments described above. Therefore, any modifications or equivalent substitutions to the present invention, as well as all technical solutions and improvements that do not depart from the spirit and scope of the invention, are covered within the scope of the claims of the present invention.
Claims
1. Use of a drug that suppresses fibrosis of silicosis, characterized in that, Application of rhodioloside in the preparation of drugs to relieve silicosis and pulmonary fibrosis.
2. The application of a drug for inhibiting silicosis fibrosis according to claim 1, characterized in that, Application of rhodioloside in the preparation of drugs to inhibit silicosis fibrosis.
3. The application of a drug for inhibiting silicosis fibrosis according to claim 2, characterized in that, Rhodioloside is used to inhibit pulmonary inflammatory responses caused by exposure to free silica (SiO2) and reduce the number and area of silicotic nodules in the pulmonary interstitial region.
4. The application of a drug for inhibiting silicosis fibrosis according to claim 1, characterized in that, The rhodioloside is used to inhibit the expression of pulmonary fibrosis-related proteins Collagen 1 and α-SMA, and reduce diffuse deposition of collagen fibers in lung tissue.
5. The application of a drug for inhibiting silicosis fibrosis according to claim 1, characterized in that, The dosage of rhodioloside is 50 mg / kg to 100 mg / kg. At this dosage, rhodioloside has a better inhibitory effect on silicosis fibrosis than tetrandrine at the same dosage.
6. The application of a drug for inhibiting silicosis fibrosis according to claim 2, characterized in that, The rhodioloside was used to inhibit TGF-β-induced transdifferentiation of mouse fibroblasts (NIH / 3T3) into myofibroblasts and to downregulate the expression levels of Collagen 1 and α-SMA proteins in these cells.
7. The application of a drug for inhibiting silicosis fibrosis according to claim 1, characterized in that, The preparation method of the rhodioloside is as follows: the rhodioloside raw material is dissolved in sterile water to prepare a stock solution with a final concentration of 60 mg / mL, which is then dispensed and stored at -20℃.
8. A drug for inhibiting silicosis fibrosis, characterized in that, The active ingredient of the drug includes rhodioloside, and the content of rhodioloside meets the equivalent dose of 4 mg / kg to 8 mg / kg corresponding to the daily intake dose for humans.
9. The medicament according to claim 8, characterized in that, The drug also includes pharmaceutically acceptable excipients selected from one or more of distilled water, physiological saline, fillers, and disintegrants.
10. The application of a drug for inhibiting silicosis fibrosis according to any one of claims 1 to 9, characterized in that, The rhodioloside mentioned is an extract of the traditional Chinese medicine Rhodiola rosea L., and has no obvious liver and kidney toxicity.