Skip to main content
Log in

Taraxasterol Inhibits Hyperactivation of Macrophages to Alleviate the Sepsis-induced Inflammatory Response of ARDS Rats

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

To explore the effect and mechanism of taraxasterol on sepsis-induced acute respiratory distress syndrome (ARDS). Twenty-four male SD rats were randomly divided into four groups: the control group, model (lipopolysaccharide, LPS) group, lipopolysaccharide+taraxasterol (LPS + TXL) group, and lipopolysaccharide+ulinastatin (LPS + UTI) group. The model of sepsis-induced ARDS was established by intraperitoneal injection of LPS. The lung water content of the rats in each group was determined by the dry/wet ratio. Pathology of rat lung tissue was observed through H&E staining. Wright staining was applied to count the number of neutrophils, macrophages, and total cells. ELISA was utilized to measure the levels of the inflammatory factors TNF-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid (BALF). Biochemical detection was adopted to check the levels of myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) in lung tissue. Western blotting was performed to check the protein expression of IL-12, iNOS, Arg-1, and Mrc1 in lung tissue. Compared with the LPS group, both taraxasterol and ulinastatin significantly decreased lung tissue water content, improved lung tissue injury, reduced the number of neutrophils, macrophages and total cells, and decreased the level of inflammatory factors. In addition, taraxasterol and ulinastatin also reduced the content of MPO and the expression of IL-12 and iNOS and increased the activity of SOD and CAT as well as the protein expression of Arg-1 and Mrc1. Taraxasterol can suppress macrophage M1 polarization to alleviate the inflammatory response and oxidative stress, thereby treating sepsis-induced ARDS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Bellani, G., Laffey, J. G., Pham, T., Fan, E., Brochard, L., Esteban, A., Gattinoni, L., van Haren, F., Larsson, A., & McAuley, D. F., et al. (2016). Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. Jama, 315(8), 788–800.

    Article  CAS  PubMed  Google Scholar 

  2. Laffey, J. G., Bellani, G., Pham, T., Fan, E., Madotto, F., Bajwa, E. K., Brochard, L., Clarkson, K., Esteban, A., & Gattinoni, L., et al. (2016). Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Medicine, 42(12), 1865–1876.

    Article  CAS  PubMed  Google Scholar 

  3. Schwingshackl, A., & Meduri, G. U. (2016). Rationale for Prolonged Glucocorticoid Use in Pediatric ARDS: What the Adults Can Teach Us. Frontiers Pediatrics, 4, 58.

    Article  Google Scholar 

  4. Bersten, A. D., Edibam, C., Hunt, T., & Moran, J. (2002). Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. American Journal of Respiratory Critical Care Medicine, 165(4), 443–448.

    Article  PubMed  Google Scholar 

  5. Caser, E. B., Zandonade, E., Pereira, E., Gama, A. M., & Barbas, C. S. (2014). Impact of distinct definitions of acute lung injury on its incidence and outcomes in Brazilian ICUs: prospective evaluation of 7,133 patients*. Critical Care Medicine, 42(3), 574–582.

    Article  PubMed  Google Scholar 

  6. Parsons, P. E., Eisner, M. D., Thompson, B. T., Matthay, M. A., Ancukiewicz, M., Bernard, G. R., & Wheeler, A. P. (2005). Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Critical Care Medicine, 33(1), 1–6.

    Article  CAS  PubMed  Google Scholar 

  7. Sheu, C. C., Gong, M. N., Zhai, R., Chen, F., Bajwa, E. K., Clardy, P. F., Gallagher, D. C., Thompson, B. T., & Christiani, D. C. (2010). Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS. Chest, 138(3), 559–567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brower, R. G., Matthay, M. A., Morris, A., Schoenfeld, D., Thompson, B. T., & Wheeler, A. (2000). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The New England Journal of Medicine, 342(18), 1301–1308.

    Article  PubMed  Google Scholar 

  9. Thille, A. W., Contou, D., Fragnoli, C., Córdoba-Izquierdo, A., Boissier, F., & Brun-Buisson, C. (2013). Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors. Critical Care, 17(6), R269.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Antonelli, M., Conti, G., Moro, M. L., Esquinas, A., Gonzalez-Diaz, G., Confalonieri, M., Pelaia, P., Principi, T., Gregoretti, C., & Beltrame, F., et al. (2001). Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study. Intensive Care Medicine, 27(11), 1718–1728.

    Article  CAS  PubMed  Google Scholar 

  11. Lomas-Neira, J., Chung, C. S., Perl, M., Gregory, S., Biffl, W., & Ayala, A. (2006). Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge. Am J Physiol Lung Cell Mol Physiol, 290(1), L51–58.

    Article  CAS  PubMed  Google Scholar 

  12. Johnston, L. K., Rims, C. R., Gill, S. E., McGuire, J. K., & Manicone, A. M. (2012). Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury. American Journal of Respiratory Cell and Molecular Biology, 47(4), 417–426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Huang, X., Xiu, H., Zhang, S., & Zhang, G. (2018). The Role of Macrophages in the Pathogenesis of ALI/ARDS. Mediators of Inflammation, 2018, 1264913.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Patel, V. J., Biswas Roy, S., Mehta, H. J., Joo, M., & Sadikot, R. T. (2018). Alternative and Natural Therapies for Acute Lung Injury and Acute Respiratory Distress Syndrome. Biomed Research International, 2018, 2476824.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Schütz, K., Carle, R., & Schieber, A. (2006). Taraxacum–a review on its phytochemical and pharmacological profile. Journal of Ethnopharmacology, 107(3), 313–323.

    Article  PubMed  Google Scholar 

  16. You, Y., Yoo, S., Yoon, H. G., Park, J., Lee, Y. H., Kim, S., Oh, K. T., Lee, J., Cho, H. Y., & Jun, W. (2010). In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress. Food and Chemical Toxicology, 48(6), 1632–1637.

    Article  CAS  PubMed  Google Scholar 

  17. Ahmad, V. U., Yasmeen, S., Ali, Z., Khan, M. A., Choudhary, M. I., Akhtar, F., Miana, G. A., & Zahid, M. (2000). Taraxacin, a new guaianolide from Taraxacum wallichii. Journal of Natural Products, 63(7), 1010–1011.

    Article  CAS  PubMed  Google Scholar 

  18. Colle, D., Arantes, L. P., Gubert, P., da Luz, S. C., Athayde, M. L., Teixeira Rocha, J. B., & Soares, F. A. (2012). Antioxidant properties of Taraxacum officinale leaf extract are involved in the protective effect against hepatoxicity induced by acetaminophen in mice. Journal of Medicinal Food, 15(6), 549–556.

    Article  PubMed  Google Scholar 

  19. Xiong, H., Cheng, Y., Zhang, X., & Zhang, X. (2014). Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7 macrophages. Journal of Ethnopharmacology, 155(1), 753–757.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang, X., Xiong, H., Li, H., & Cheng, Y. (2014). Protective effect of taraxasterol against LPS-induced endotoxic shock by modulating inflammatory responses in mice. Immunopharmacology Immunotoxicology, 36(1), 11–16.

    Article  PubMed  Google Scholar 

  21. Baradaran Rahimi, V., Rakhshandeh, H., Raucci, F., Buono, B., Shirazinia, R., Samzadeh Kermani, A., Maione, F., Mascolo, N. & Askari, V. R. (2019). Anti-Inflammatory and Anti-Oxidant Activity of Portulaca oleracea Extract on LPS-Induced Rat Lung Injury. Molecules, 24(1).

  22. He, H., Liu, L., Chen, Q., Liu, A., Cai, S., Yang, Y., Lu, X., & Qiu, H. (2015). Mesenchymal Stem Cells Overexpressing Angiotensin-Converting Enzyme 2 Rescue Lipopolysaccharide-Induced Lung Injury. Cell Transplant, 24(9), 1699–1715.

    Article  PubMed  Google Scholar 

  23. Zhang, X., Chen, J., Xue, M., Tang, Y., Xu, J., Liu, L., Huang, Y., Yang, Y., Qiu, H., & Guo, F. (2019). Overexpressing p130/E2F4 in mesenchymal stem cells facilitates the repair of injured alveolar epithelial cells in LPS-induced ARDS mice. Stem Cell Research and Therapy, 10(1), 74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ruan, G., Tao, B., Wang, D., Li, Y., Wu, J., & Yin, G. (2016). Chinese herbal medicine formula Gu-Ben-Fang-Xiao-Tang attenuates airway inflammation by modulating Th17/Treg balance in an ovalbumin-induced murine asthma model. Experimental and Therapeutic Medicine, 12(3), 1428–1434.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Meduri, G. U., Kohler, G., Headley, S., Tolley, E., Stentz, F., & Postlethwaite, A. (1995). Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest, 108(5), 1303–1314.

    Article  CAS  PubMed  Google Scholar 

  26. Tirunavalli, S. K., Gourishetti, K., Kotipalli, R. S. S., Kuncha, M., Kathirvel, M., Kaur, R., Jerald, M. K., Sistla, R., & Andugulapati, S. B. (2021). Dehydrozingerone ameliorates Lipopolysaccharide induced acute respiratory distress syndrome by inhibiting cytokine storm, oxidative stress via modulating the MAPK/NF-κB pathway. Phytomedicine, 92, 153729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wilson, K. C., & Saukkonen, J. J. (2004). Acute respiratory failure from abused substances. Journal Intensive Care Medicine, 19(4), 183–193.

    Article  Google Scholar 

  28. Mégarbane, B., & Chevillard, L. (2013). The large spectrum of pulmonary complications following illicit drug use: features and mechanisms. Chemico Biological Interactions, 206(3), 444–451.

    Article  PubMed  Google Scholar 

  29. Reutershan, J., & Ley, K. (2004). Bench-to-bedside review: acute respiratory distress syndrome - how neutrophils migrate into the lung. Criticial Care, 8(6), 453–461.

    Article  Google Scholar 

  30. Sang, R., Yu, Y., Ge, B., Xu, L., Wang, Z., & Zhang, X. (2019). Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs/NF-κB and Bax/Bc1-2 signalling pathways. Artificial Cells Nanomedicine Biotechnology, 47(1), 3929–3937.

    Article  CAS  PubMed  Google Scholar 

  31. Chen, J., Wu, W., Zhang, M., & Chen, C. (2019). Taraxasterol suppresses inflammation in IL-1β-induced rheumatoid arthritis fibroblast-like synoviocytes and rheumatoid arthritis progression in mice. International Immunopharmacology, 70, 274–283.

    Article  CAS  PubMed  Google Scholar 

  32. Xueshibojie, L., Duo, Y., & Tiejun, W. (2016). Taraxasterol inhibits cigarette smoke-induced lung inflammation by inhibiting reactive oxygen species-induced TLR4 trafficking to lipid rafts. European Journal of Pharmacology, 789, 301–307.

    Article  PubMed  Google Scholar 

  33. Williams, G. W., Berg, N. K., Reskallah, A., Yuan, X., & Eltzschig, H. K. (2021). Acute Respiratory Distress Syndrome. Anesthesiology, 134(2), 270–282.

    Article  CAS  PubMed  Google Scholar 

  34. Grommes, J., & Soehnlein, O. (2011). Contribution of neutrophils to acute lung injury. Molecular Medicine, 17(3–4), 293–307.

    Article  CAS  PubMed  Google Scholar 

  35. Aisiku, I. P., Yamal, J. M., Doshi, P., Benoit, J. S., Gopinath, S., Goodman, J. C., & Robertson, C. S. (2016). Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury. Critical Care, 20, 288.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ndengele, M. M., Muscoli, C., Wang, Z. Q., Doyle, T. M., Matuschak, G. M., & Salvemini, D. (2005). Superoxide potentiates NF-kappaB activation and modulates endotoxin-induced cytokine production in alveolar macrophages. Shock, 23(2), 186–193.

    Article  CAS  PubMed  Google Scholar 

  37. Milligan, S. A., Hoeffel, J. M., Goldstein, I. M., & Flick, M. R. (1988). Effect of catalase on endotoxin-induced acute lung injury in unanesthetized sheep. The American Review of Respiratory Disease, 137(2), 420–428.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang, X., Xiong, H., & Liu, L. (2012). Effects of taraxasterol on inflammatory responses in lipopolysaccharide-induced RAW 264.7 macrophages. Journal of Ethnopharmacology, 141(1), 206–211.

    Article  CAS  PubMed  Google Scholar 

  39. Yang, X., Pan, Y., Xu, X., Tong, T., Yu, S., Zhao, Y., Lin, L., Liu, J., Zhang, D., & Li, C. (2018). Sialidase Deficiency in Porphyromonas gingivalis Increases IL-12 Secretion in Stimulated Macrophages Through Regulation of CR3, IncRNA GAS5 and miR-21. Frontiers in Cellular and Infection Microbiology, 8, 100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Balasubbramanian, D., Goodlett, B. L., & Mitchell, B. M. (2019). Is IL-12 pro-inflammatory or anti-inflammatory? Depends on the blood pressure. Cardiovascular Research, 115(6), 998–999.

    Article  CAS  PubMed  Google Scholar 

  41. Chen, X., Shan, Q., Jiang, L., Zhu, B., & Xi, X. (2013). Quantitative proteomic analysis by iTRAQ for identification of candidate biomarkers in plasma from acute respiratory distress syndrome patients. Biochemical and Biophysics Research Communications, 441(1), 1–6.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

C.B. and B.L.J. carried out the experiments. R.W. and S.H. drafted the manuscript. Y.W. and X.Z. were responsible for data integrity and analysis. C.B. and X.Z. designed the study and reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Xiangyang Zhao.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bu, C., Wang, R., Wang, Y. et al. Taraxasterol Inhibits Hyperactivation of Macrophages to Alleviate the Sepsis-induced Inflammatory Response of ARDS Rats. Cell Biochem Biophys 80, 763–770 (2022). https://doi.org/10.1007/s12013-022-01092-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-022-01092-2

Keywords

Navigation