Advanced Search

Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 6: 1236 - 1246

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240626.004

Research Articles

Bufei Huoxue capsule (补肺活血胶囊) alleviates silicosis by inhibiting the activation of nucleotide-like receptor containing pyrin domain 3 inflammasome and macrophages polarization based on network pharmacology

  • Wenlu HANG ,
  • Lin WANG ,
  • Yun BO ,
  • Shurun ZUO ,
  • Songquan WANG ,
  • Haiquan LI ,
  • Chunlu BU ,
  • Jie ZHAO ,
  • Xianmei ZHOU
Expand
  • 1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China
    2 Medical College of Anhui University of Science and Technology, Anhui 232001, China
    3 School of Mechatronic Engineering, Jiangsu Normal University, Xuzhou 221000, China
    4 Department of Respiratory Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210023, China

Received date: 2023-11-11

  Accepted date: 2024-03-08

  Online published: 2024-06-26

Supported by

Jiangsu Natural Science Foundation Youth Program: Regulation of Alveolar Macrophage Pyroptosis based on (Never in Mitosis Gene A)-Related Kinase 7 /Nucleotide-like Receptor Containing Pyrin Domain 3 Inflammasome to Explore the Mechanism of Bufei Huoxue Capsule on Pulmonary Fibrosis in Silicosis(BK20220236);Key Research and Development Project of Xuzhou City: Evaluation of Pyroptosis Induced by Nucleotide-like Receptor Containing Pyrin Domain 3 Inflammasome Activation in Pneumoconiosis Patients by Bronchoalveolar Lavage Fluid Ion Assay Combined with High-Resolution Computed Tomography Quantitative Analysis(KC22212);Youth Medical Science and Technology Innovation Project of Xuzhou Municipal Health Commission and Development Fund of Affiliated Hospital of Xuzhou Medical University: Study on the Regulation of Various Cytokines and the Effect of c-Jun Activation Domain-Binding Protein 1 on Immune Response in Lung Cancer(XWKYHT20210565);Youth Medical Science and Technology Innovation Project of Xuzhou Municipal Health Commission and Development Fund of Affiliated Hospital of Xuzhou Medical University: Study on the Regulation of Various Cytokines and the Effect of c-Jun Activation Domain-Binding Protein 1 on Immune Response in Lung Cancer(XYFY2020051)

Fold

Abstract

OBJECTIVE: To predict the targets of Bufei Huoxue capsule (补肺活血胶囊, BFHX) using network pharmacology analysis and to explore its effects and functional targets in a silicotic rat model.

METHODS: The drug and disease targets were correlated through network pharmacology analysis to explore the targets and signaling pathways of BFHX affecting silicosis. NR8383 cells were cultured to verify the core genes and pathways. A rat model of silicosis was established to verify whether the mechanism behind SiO2-caused pulmonary fibrosis was alleviated by BFHX (0.82 g/kg) and how it affected key targets and pathways.

RESULTS: Overlapping BFHX and silicotic gene targets produced 159 interactive targets, and 55 were screened by network topology analysis. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses suggested that BFHX could affect silicosis through the nucleotide-like receptor containing pyrin domain 3 (NLRP3) inflammasome. In NR8383 cells, the expression of core genes related to the NLRP3 inflammasome could be inhibited by BFHX treatment. BFHX reduced the degree of alveolitis and collagen deposition, attenuating pulmonary fibrosis in SiO2-induced rat model. Pulmonary macrophage pyroptosis after SiO2 exposure was observed under transmission electron microscopy. BFHX alleviated the morphological characteristics of pyroptosis. BFHX also reduced the expression of NLRP3, caspase-1, interleukin-1 beta (IL-1β), IL-18, IL-6, and tumor necrosis factor-alpha in lung tissues of silicotic rat model. BFHX affected the K ion content in bronchoalveolar lavage fluid when assessed by energy dispersive spectrometer testing. The expression of CD68+ and CD206+ were also reduced after BFHX intervention.

CONCLUSION: NOD-like receptor signaling is vital for BFHX’s effects on silicosis. It exerts anti-pulmonary fibrosis effects by inhibiting pulmonary macrophage pyroptosis and polarization through NLRP3 inflammasome activation.

Key words： silicosis; pulmonary fibrosis; NLR proteins; inflammasomes; pyroptosis; Bufei Huoxue capsule

Cite this article

Wenlu HANG , Lin WANG , Yun BO , Shurun ZUO , Songquan WANG , Haiquan LI , Chunlu BU , Jie ZHAO , Xianmei ZHOU . Bufei Huoxue capsule (补肺活血胶囊) alleviates silicosis by inhibiting the activation of nucleotide-like receptor containing pyrin domain 3 inflammasome and macrophages polarization based on network pharmacology[J]. Journal of Traditional Chinese Medicine, 2024 , 44(6) : 1236 -1246 . DOI: 10.19852/j.cnki.jtcm.20240626.004

References

1. Leso V, Fontana L, Romano R, Gervetti P, Iavicoli I. Artificial stone associated silicosis: a systematic review. Int J Environ Res Public Health 2019; 16: 568.
2. Harris DA, Willis J, Tomann M. A new era of coal workers' pneumoconiosis: decades in mines may not be required. Lancet 2020; 395: e82.
3. Fubini B, Hubbard A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic Biol Med 2003; 34: 1507-16.
4. Liu S, Chen D, Li X, et al. Fullerene nanoparticles: a promising candidate for the alleviation of silicosis-associated pulmonary inflammation. Nanoscale 2020; 12: 17470-9.
5. Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol 2021; 18: 2114-27.
6. Campden RI, Zhang Y. The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation. Arch Biochem Biophys 2019; 670: 32-42.
7. Luna-Gomes T, Santana PT, Coutinho-Silva R. Silica-induced inflammasome activation in macrophages: role of ATP and P2X7 receptor. Immunobiology 2015; 220: 1101-6.
8. Li X, Yan X, Wang Y, et al. NLRP3 inflammasome inhibition attenuates silica-induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells. Exp Cell Res 2018; 362: 489-97.
9. Tan S, Chen S. The mechanism and effect of autophagy, apoptosis, and pyroptosis on the Progression of Silicosis. Int J Mol Sci 2021; 22: 8110.
10. Jing Y, Zhang H, Cai Z, et al. Bufei Huoxue capsule attenuates PM2.5-induced pulmonary inflammation in mice. Evid Based Complement Alternat Med 2017; 2017: 1575793.
11. Hang WL, Li WJ, Shao Q, et al. Exploring the therapeutic effect of Bufei Huoxue capsule on patients with pneumoconiosis of Qi deficiency and blood stasis syndrome based on network pharmacology and clinical research. Zhong Cao Yao 2023; 45: 3819-25.
12. Gong XW, Cui KW, Huang YM, et al. Effects of Bufei Huoxue capsule on quality of life, respiratory function and oxidative stress in patients with stageⅡ pneumoconiosis. Jian Yan Yi Xue Yu Lin Chuang 2022; 19: 2628-31.
13. Hang WL, Zhao J, Li YJ, Wang L, Li HQ. Experimental study on the effect of Si and P ion content in SiO2 exposure environment on the degree of pulmonary fibrosis. Indian J Pathol Microbiol 2021; 64: 644-50.
14. Schniering J, Guo L, Brunner M, et al. Evaluation of (99m)Tc-rhAnnexin V-128 SPECT/CT as a diagnostic tool for early stages of interstitial lung disease associated with systemic sclerosis. Arthritis Res Ther 2018; 20: 183.
15. Wang L, Hauenstein AV. The NLRP3 inflammasome: Mechanism of action, role in disease and therapies. Mol Aspects Med 2020; 76: 100889.
16. Li T, Yang X, Xu H, Liu H. Early identification, accurate diagnosis, and treatment of Silicosis. Can Respir J 2022; 2022: 3769134.
17. Almberg KS, Friedman LS, Rose CS, Go LHT, Cohen RA. Progression of coal workers' pneumoconiosis absent further exposure. Occup Environ Med 2020; 77: 748-51.
18. Wang M, Zhang Z, Liu J, et al. Gefitinib and fostamatinib target EGFR and SYK to attenuate silicosis: a multi-omics study with drug exploration. Signal Transduct Target Ther 2022; 7: 157.
19. Hang WL, Wu Q, Li W, Bo Y, Zhou XM. Effect of silicon dioxide exposure on airway surface microenvironment and NEK7/NLPR3 inflammasome in rats. Yu Fang Yi Xue 2023; 35: 180-4.
20. Lam M, Mansell A, Tate MD. Another one fights the dust: targeting the NLRP3 inflammasome for the treatment of silicosis. Am J Respir Cell Mol Biol 2022; 66: 601-11.
21. Peng Z, Duan M, Zhao K, Tang Y, Liang F. RAB20 deficiency promotes the development of silicosis via NLRP3 inflammasome. Front Immunol 2022; 13: 967299.
22. Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 2008; 320: 674-7.
23. Song MY, Wang JX, Sun YL, et al. Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages. Acta Pharmacol Sin 2022; 43: 1274-84.
24. Phan THG, Paliogiannis P, Nasrallah GK, et al. Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis. Cell Mol Life Sci 2021; 78: 2031-57.
25. Bing P, Zhou W, Tan S. Study on the mechanism of astragalus polysaccharide in treating pulmonary fibrosis based on "Drug-Target-Pathway" network. Front Pharmacol 2022; 13: 865065.
26. Li Y, Qin W, Liang Q, et al. Bufei Huoxue capsule alleviates bleomycin-induced pulmonary fibrosis in mice via TGF-β1/Smad2/3 signaling. J Ethnopharmacol 2023; 316: 116733.
27. Tian LY, Cao GQ, Liu GT. Efficacy of Bufei Huoxue capsules in the treatment of silicosis. Guangdong Yi Xue 2014; 35:1778-9.
28. Wei X, Xie F, Zhou X, et al. Role of pyroptosis in inflammation and cancer. Cell Mol Immunol 2022; 19: 971-92.
29. Zhao Y, Hao C, Bao L, et al. Silica particles disorganize the polarization of pulmonary macrophages in mice. Ecotoxicol Environ Saf 2020; 193: 110364.
30. Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 2016; 44: 450-62.
31. Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 2015; 265: 130-42.
32. Nawaz A, Bilal M, Fujisaka S, et al. Depletion of CD206(+) M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration. Nat Commun 2022; 13: 7058.
33. Wang J, Xu L, Xiang Z, et al. Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206(+) M2-like macrophage polarization. Cell Death Dis 2020; 11: 136.
34. Fan M, Xiao H, Song D, et al. A novel N-Arylpyridone compound alleviates the inflammatory and fibrotic reaction of silicosis by inhibiting the ASK1-p 38 pathway and regulating macrophage polarization. Front Pharmacol 2022; 13: 848435.
35. Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol 2014; 14: 81-93.
36. Barbieri PG, Somigliana A, Carradori G. Severe silicosis due to diatomaceous earth in dental alginate: a necropsy study. Med Lav 2020; 111: 222-31.
37. Drinkall S, Lawrence CB, Ossola B, et al. The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation. Glia 2022; 70: 1301-16.
38. Duan WX, Ye LS, Du H, Liu C, Duan Y, Mao LC. Analysis of the detection of metals and metalloids in the bronchoalveolar lavage fluid for the etiological diagnosis value of pneumoconiosis. Zhong Hua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2021; 39: 844-8.
39. Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci 2019; 20: 3328.
Options
Outlines

/

〈 〉