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Pachymic Acid Protects Against Bleomycin-Induced Pulmonary Fibrosis by Suppressing Fibrotic, Inflammatory, and Oxidative Stress Pathways in Mice

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Abstract

Pachymic acid (PA), a natural extract from Poria cocos (Schw.) Wolf, possesses anti-inflammatory and anti-oxidative properties. However, it is still unknown whether PA can protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, we investigated the effects of PA in mice administered BLM. Our results showed that PA significantly improved lung damage and pathological manifestations. Additionally, PA reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while increasing the level of IL-10. PA also decreased the levels of hydroxyproline and malondialdehyde, and increased the activities of superoxide dismutase and glutathione peroxidase in lung tissue. Furthermore, PA inhibited the increases in pyrin domain-containing protein 3 (NLRP3), ASC, IL-1β, P20, and TXNIP induced by BLM. In conclusion, our study demonstrated the protective effects of PA against BLM-induced PF in mice by suppressing fibrotic, inflammatory, and oxidative stress pathways.

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Data Availability

All data included in this study are available upon request by contact with the corresponding author.

Abbreviations

PF :

Pulmonary fibrosis

BLM :

Bleomycin

PA :

Pachymic acid

BALF :

Bronchoalveolar lavage fluid

MDA :

Malondialdehyde

GPX :

Glutathione peroxidase

SOD :

Superoxide dismutase

GSH-Px :

Plasma glutathione peroxidase

HYP :

Determination of hydroxyproline

NLRP3 :

Pyrin domain-containing protein 3

References

  1. Tsoyi, K., Chu, S. G., Patino-Jaramillo, N. G., Wilder, J., Villalba, J., Doyle-Eisele, M., McDonald, J., Liu, X., El-Chemaly, S., Perrella, M. A., & Rosas, I. O. (2018). Syndecan-2 attenuates radiation-induced pulmonary fibrosis and inhibits fibroblast activation by regulating PI3K/Akt/ROCK pathway via CD148. American Journal Of Respiratory Cell And Molecular Biology, 58, 208–215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. **e, Y., Jiang, H., Zhang, Q., Mehrotra, S., Abel, P. W., Toews, M. L., Wolff, D. W., Rennard, S., Panettieri, R. A. Jr., Casale, T. B., & Tu, Y. (2016). Upregulation of RGS2: A new mechanism for pirfenidone amelioration of pulmonary fibrosis. Respiratory Research, 17, 103.

  3. Desai, O., Winkler, J., Minasyan, M., & Herzog, E. L. (2018). The role of immune and inflammatory cells in idiopathic pulmonary fibrosis. Front Med (Lausanne), 5, 43.

    Article  PubMed  Google Scholar 

  4. Liu, M. W., Su, M. X., Tang, D. Y., Hao, L., Xun, X. H., & Huang, Y. Q. (2019). Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression. Bmc Pulmonary Medicine, 19, 35.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Suzuki, T., Tada, Y., Gladson, S., Nishimura, R., Shimomura, I., Karasawa, S., Tatsumi, K., & West, J. (2017). Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition. Respiratory Research, 18, 177.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Judge, J. L., & Nagel, D. J. (2018). Prevention and treatment of bleomycin-induced pulmonary fibrosis with the lactate dehydrogenase inhibitor gossypol. PLoS One, 13, e0197936.

  7. Cabrera, S., Maciel, M., Herrera, I., Nava, T., Vergara, F., Gaxiola, M., López-Otín, C., Selman, M., & Pardo, A. (2015). Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis. Autophagy, 11, 670–684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dong, Y., Geng, Y., Li, L., Li, X., Yan, X., Fang, Y., Li, X., Dong, S., Liu, X., Li, X., et al. (2015). Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice. Journal Of Experimental Medicine, 212, 235–252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ma, J., Liu, J., Lu, C. W., & Cai, D. F. (2015). Pachymic acid modified carbon nanoparticles reduced angiogenesis via inhibition of MMP-3. International Journal of Clinical and Experimental Pathology, 8, 5464–5470.

    PubMed  PubMed Central  Google Scholar 

  10. Cheng, S., Swanson, K., Eliaz, I., McClintick, J. N., Sandusky, G. E., & Sliva, D. (2015). Pachymic acid inhibits growth and induces apoptosis of pancreatic cancer in vitro and in vivo by targeting ER stress. PLoS One, 10, e0122270.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Li, F. F., Yuan, Y., Liu, Y., Wu, Q. Q., Jiao, R., Yang, Z., Zhou, M. Q., & Tang, Q. Z. (2015). Pachymic acid protects H9c2 cardiomyocytes from lipopolysaccharide-induced inflammation and apoptosis by inhibiting the extracellular signal-regulated kinase 1/2 and p38 pathways. Molecular Medicine Reports, 12(2), 2807–2813.

  12. Li, J. Y., Wu, H. X., & Yang, G. (2017). Pachymic acid improves survival and attenuates acute lung injury in septic rats induced by cecal ligation and puncture. European Review for Medical & Pharmacological Sciences, 21, 1904.

  13. Total glycosides of Yu**feng protects. (2015). Against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial–mesenchymal transition. Inflammation Research, 64, 953–961.

    Article  Google Scholar 

  14. Karampitsakos, T., Woolard, T., Bouros, D., & Tzouvelekis, A. (2017). Toll-like receptors in the pathogenesis of pulmonary fibrosis. European Journal of Pharmacology, 808, 35–43

  15. Khazdair, M. R., Boskabady, M. H., & Ghorani, V. (2015). Respiratory effects of sulfur mustard exposure, similarities and differences with asthma and COPD. Inhalation Toxicology, 27(14), 731–744.

  16. Duan, X., Wen, Z., Shen, H., Shen, M., & Chen, G. (2016). Intracerebral hemorrhage, oxidative stress, and antioxidant therapy. Oxidative Medicine and Cellular Longevity, 2016, 1203285.

  17. He, R., Cui, M., Lin, H., Zhao, L., Wang, J., Chen, S., & Shao, Z. (2018). Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells. Life Sciences, 199, 122–130.

    Article  CAS  PubMed  Google Scholar 

  18. Heink, A. E., Parrish, A. N., Thorgaard, G. H., & Carter, P. A. (2013). Oxidative stress among SOD-1 genotypes in rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology, 144–145, 75–82.

    Article  PubMed  Google Scholar 

  19. Zhang, L., Gao, Z., Yu, L., Zhang, B., Wang, J., & Zhou, J. (2018). Nucleotide-binding and oligomerization domain (NOD)-like receptors in teleost fish: Current knowledge and future perspectives. Journal Of Fish Diseases, 41, 1317–1330.

    Article  CAS  PubMed  Google Scholar 

  20. Liu, W., Guo, W. J., Xu, Q., & Sun, Y. (2016). [Advances in mechanisms for NLRP3 inflammasomes regulation]. Yao Xue Xue Bao = Acta Pharmaceutica Sinica, 51, 1505–1512.

    PubMed  Google Scholar 

  21. Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019). The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. International Journal of Molecular Sciences, 20(13), 3328.

  22. Cáceres, F. T., Gaspari, T. A., Samuel, C. S., & Pinar, A. A. (2019). Serelaxin inhibits the profibrotic TGF-β1/IL-1β axis by targeting TLR-4 and the NLRP3 inflammasome in cardiac myofibroblasts. The FASEB Journal, 33, 14717–14733.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Yangpu District, Shanghai, 200433, China

    Shanmei Wang & Hongbin Jiang

  2. Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Yangpu District, Shanghai, 200433, China

    Wei Tan & Li Zhang

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  1. Shanmei Wang
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  2. Wei Tan
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  4. Hongbin Jiang
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Contributions

WSM, TW, and JHB performed the experiments, analyzed the data, and wrote the paper. WSM, ZL, and JHL designed the present study and provided experimental materials. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hongbin Jiang.

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Ethical Approval

All experiments of animals were approved by the Institutional Animal Care and Use Committee of Shanghai Pulmonary Hospital.

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The authors declare no competing interests.

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Wang, S., Tan, W., Zhang, L. et al. Pachymic Acid Protects Against Bleomycin-Induced Pulmonary Fibrosis by Suppressing Fibrotic, Inflammatory, and Oxidative Stress Pathways in Mice. Appl Biochem Biotechnol 196, 3344–3355 (2024). https://doi.org/10.1007/s12010-023-04686-5

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