Artesunate Alleviates Chronic Hyperoxia-induced Bronchopulmonary Dysplasia by Suppressing NF-κB Pathway in Neonatal Mice


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Abstract

Background:Bronchopulmonary dysplasia (BPD) is a chronic lung condition that occurs in premature infants who undergo prolonged mechanical ventilation and oxygen therapy. Existing treatment methods have shown limited efficacy, highlighting the urgent need for new therapeutic strategies. Artesunate (AS) is a compound known for its potential anti-inflammatory properties, and studies have shown its protective effects against acute lung injury. However, its impact on BPD and the underlying mechanisms remain unclear.

Objective:To investigate the effect and underlying mechanism of AS on chronic hyperoxiainduced BPD in neonatal mice.

Method:Full-term C57BL/6J mice were randomly assigned to the Air+lactate Ringer's solution (L/R) group, O2 + L/R group, and O2 + AS group. Analysis was performed using assay methods such as ELISA, RT-qPCR, hematoxylin-eosin staining, and Western blotting.

Results:Compared with the O2+L/R group, the expression of inflammatory factors in the serum, tissue, and BALF of the O2+AS group was significantly reduced, the lung function of the mice was improved, and the inflammatory infiltrates were significantly alleviated. AS inhibited the mRNA expression of inflammatory factors in mice. We found that the expression of nuclear p65 and cytoplasmic p-IκBα in the NF-κB pathway was inhibited after adding AS.

Conclusion:AS ameliorated chronic hyperoxia-induced BPD in neonatal mice probably by inhibiting the expression of NF-κB pathway and inflammatory factors.

About the authors

Wenbo Weng

, Yuyao Health Training School

Email: info@benthamscience.net

Xiaoying Wang

Department of Pediatrics, Jiande First People's Hospital

Email: info@benthamscience.net

Yifei Cui

Department of Pharmacy, Children's Hospital of Zhejiang University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Pierro, M.; Thebaud, B.; Soll, R. Mesenchymal stem cells for the prevention and treatment of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst. Rev., 2017, 11, CD011932. doi: 10.1002/14651858.CD011932.pub2
  2. Gilfillan, M.; Bhandari, A.; Bhandari, V. Diagnosis and management of bronchopulmonary dysplasia. BMJ, 2021, 375, n1974. doi: 10.1136/bmj.n1974 PMID: 34670756
  3. Gough, A.; Linden, M.; Spence, D.; Patterson, C.C.; Halliday, H.L.; McGarvey, L.P.A. Impaired lung function and health status in adult survivors of bronchopulmonary dysplasia. Eur. Respir. J., 2014, 43(3), 808-816. doi: 10.1183/09031936.00039513 PMID: 23900988
  4. McGlynn, J.R.; Aoyama, B.C.; Martin, A.; Collaco, J.M.; McGrath-Morrow, S.A. Outpatient respiratory outcomes in children with BPD on supplemental oxygen. Pediatr. Pulmonol., 2023, 58(5), 1535-1541. doi: 10.1002/ppul.26356
  5. Omar, S.A.; Abdul-Hafez, A.; Ibrahim, S.; Pillai, N.; Abdulmageed, M.; Thiruvenkataramani, R.P. Stem-cell therapy for Bronchopulmonary Dysplasia (BPD) in newborns. Cells, 2022, 11(8), 1275. doi: 10.3390/cells11081275
  6. Sinclair, K.; Yerkovich, S.T.; Chambers, D.C. Mesenchymal stem cells and the lung. Respirology, 2013, 18(3), 397-411. doi: 10.1111/resp.12050 PMID: 23316733
  7. Lesage, F.; Jimenez, J.; Toelen, J.; Deprest, J. Preclinical evaluation of cell-based strategies to prevent or treat bronchopulmonary dysplasia in animal models: A systematic review. J. Matern. Fetal Neonatal Med., 2018, 31(7), 958-966. doi: 10.1080/14767058.2017.1301927 PMID: 28277906
  8. Nold, M.F.; Mangan, N.E.; Rudloff, I.; Cho, S.X.; Shariatian, N.; Samarasinghe, T.D. Interleukin-1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia. Proc. Natl. Acad. Sci., 2013, 110(35), 14384-14389. doi: 10.1073/pnas.1306859110
  9. Jobe, A. Mechanisms of lung injury and bronchopulmonary dysplasia. Am. J. Perinatol., 2016, 33(11), 1076-1078. doi: 10.1055/s-0036-1586107 PMID: 27603539
  10. Hsiao, C.C.; Chang, J.C.; Tsao, L.Y.; Yang, R.C.; Chen, H.N.; Lee, C.H.; Lin, C.Y.; Tsai, Y.G. Correlates of elevated interleukin-6 and 8-Hydroxy-2′-Deoxyguanosine levels in tracheal aspirates from very low birth weight infants who develop bronchopulmonary dysplasia. Pediatr. Neonatol., 2017, 58(1), 63-69. doi: 10.1016/j.pedneo.2016.01.004 PMID: 27321203
  11. Tian, X.Y.; Zhang, X.D.; Li, Q.L.; Shen, Y.; Zheng, J. Biological markers in cord blood for prediction of bronchopulmonary dysplasia in premature infants. Clin. Exp. Obstet. Gynecol., 2014, 41(3), 313-318. doi: 10.12891/ceog16292014 PMID: 24992784
  12. Jiang, W.; Li, B.; Zheng, X.; Liu, X.; Cen, Y.; Li, J.; Pan, X.; Cao, H.; Zheng, J.; Zhou, H. Artesunate in combination with oxacillin protect sepsis model mice challenged with lethal live methicillin-resistant Staphylococcus aureus (MRSA) via its inhibition on proinflammatory cytokines release and enhancement on antibacterial activity of oxacillin. Int. Immunopharmacol., 2011, 11(8), 1065-1073. doi: 10.1016/j.intimp.2011.02.028 PMID: 21396483
  13. Meng, L.; Li, L.; Lu, S.; Li, K.; Su, Z.; Wang, Y.; Fan, X.; Li, X.; Zhao, G. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways. Mol. Immunol., 2018, 94, 7-17. doi: 10.1016/j.molimm.2017.12.008 PMID: 29241031
  14. Wang, Z.; Wang, Q.; He, T.; Li, W.; Liu, Y.; Fan, Y.; Wang, Y.; Wang, Q.; Chen, J. The combination of artesunate and carboplatin exerts a synergistic anti‐tumour effect on non‐small cell lung cancer. Clin. Exp. Pharmacol. Physiol., 2020, 47(6), 1083-1091. doi: 10.1111/1440-1681.13287 PMID: 32072678
  15. Roussel, C.; Caumes, E.; Thellier, M.; Ndour, P.A.; Buffet, P.A.; Jauréguiberry, S. Artesunate to treat severe malaria in travellers: Review of efficacy and safety and practical implications. J. Travel Med., 2017, 24(2) doi: 10.1093/jtm/taw093 PMID: 28395097
  16. Wang, R.Y.; Li, H.W.; Zhang, Q.; Lin, J.T. Effect of artesunate on airway responsiveness and airway inflammation in asthmatic mice. Zhonghua Yi Xue Za Zhi, 2019, 99(32), 2536-2541. doi: 10.3760/cma.j.issn.0376-2491.2019.32.014 PMID: 31484283
  17. Xie, B.; Li, S.; Bai, W.; Li, Z.; Lou, F. Artesunate alleviates hyperoxia-induced lung injury in neonatal mice by inhibiting NLRP3 inflammasome activation. Evid. Based Complement. Alternat. Med., 2023, 2023, 7603943. doi: 10.1155/2023/7603943
  18. Liu, Y.; Dang, W.; Zhang, S.; Wang, L.; Zhang, X. Artesunate attenuates inflammatory injury and inhibits the NF-kappaB pathway in a mouse model of cerebral ischemia. J. Int. Med. Res., 2021, 49(11), 3000605211053549. doi: 10.1177/03000605211053549
  19. Chen, S.; Wu, Q.; Zhong, D.; Li, C.; Du, L. Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-kappaB pathway. Respir. Res., 2020, 21(1), 140. doi: 10.1186/s12931-020-01403-2
  20. Zhang, E.; Wang, J.; Chen, Q.; Wang, Z.; Li, D.; Jiang, N.; Ju, X. Artesunate ameliorates sepsis-induced acute lung injury by activating the mTOR/AKT/PI3K axis. Gene, 2020, 759, 144969. doi: 10.1016/j.gene.2020.144969 PMID: 32712064
  21. Deng, S.; Zhang, H.; Han, W.; Guo, C.; Deng, C. Transforming growth Factor-β-Neutralizing antibodies improve alveolarization in the oxygen-exposed newborn mouse lung. J. Interferon Cytokine Res., 2019, 39(2), 106-116. doi: 10.1089/jir.2018.0080 PMID: 30657417
  22. Zeng, X.Z.; Zhang, Y.Y.; Yang, Q.; Wang, S.; Zou, B.H.; Tan, Y.H. Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCgamma1-Ca(2+)-NFATc1 signaling pathway. Acta Pharmacol. Sin., 2020, 41(2), 229-236. doi: 10.1038/s41401-019-0289-6
  23. Kumar, V.L.; Verma, S.; Das, P. Artesunate suppresses inflammation and oxidative stress in a rat model of colorectal cancer. Drug Dev. Res., 2019, 80(8), 1089-1097. doi: 10.1002/ddr.21590 PMID: 31471932
  24. Feng, F.B.; Qiu, H.Y. RETRACTED: Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis. Biomed. Pharmacother., 2018, 102, 1209-1220. doi: 10.1016/j.biopha.2018.03.142 PMID: 29710540
  25. Liu, Z.; Zhang, J.; Li, S.; Jiang, J. Artesunate inhibits renal ischemia reperfusion-stimulated lung inflammation in rats by activating HO-1 pathway. Inflammation, 2018, 41(1), 114-121. doi: 10.1007/s10753-017-0669-3 PMID: 28921399
  26. Zhou, Z.; Hou, J.; Li, Q. Artesunate attenuates traumatic brain injury-induced impairments in rats. Transl. Neurosci., 2020, 11(1), 309-318. doi: 10.1515/tnsci-2020-0136
  27. Speer, C.P. Inflammation and bronchopulmonary dysplasia. Semin. Neonatol., 2003, 8(1), 29-38. doi: 10.1016/S1084-2756(02)00190-2 PMID: 12667828
  28. Li, K.; Zhang, F.; Wei, L.; Han, Z.; Liu, X.; Pan, Y.; Guo, C.; Han, W. Recombinant human Elafin ameliorates chronic hyperoxia-induced lung injury by inhibiting nuclear factor-Kappa B signaling in neonatal mice. J. Interferon Cytokine Res., 2020, 40(6), 320-330. doi: 10.1089/jir.2019.0241 PMID: 32460595
  29. Russell, D.W.; Gaggar, A.; Solomon, G.M. Neutrophil fates in bronchiectasis and alpha-1 antitrypsin deficiency. Ann. Am. Thorac. Soc., 2016, 13(Suppl. 2), S123-S129. doi: 10.1513/AnnalsATS.201512-805KV PMID: 27115946
  30. Zhang, T.; Wang, J.; Wang, S.; Ma, C. Timosaponin B-II inhibits lipopolysaccharide-induced acute lung toxicity via TLR/NF-κB pathway. Toxicol. Mech. Methods, 2015, 25(9), 665-671. doi: 10.3109/15376516.2015.1045652 PMID: 26540118
  31. Notarte, K.I.R.; Quimque, M.T.J.; Macaranas, I.T.; Khan, A.; Pastrana, A.M.; Villaflores, O.B. Attenuation of lipopolysaccharide-induced inflammatory responses through inhibition of the NF-kappaB pathway and the increased NRF2 level by a flavonol-enriched n-butanol fraction from Uvaria alba. ACS Omega., 2023, 8(6), 5377-5392. doi: 10.1021/acsomega.2c06451
  32. Ali, S.; Hirschfeld, A.F.; Mayer, M.L.; Fortuno, E.S., III; Corbett, N.; Kaplan, M.; Wang, S.; Schneiderman, J.; Fjell, C.D.; Yan, J.; Akhabir, L.; Aminuddin, F.; Marr, N.; Lacaze-Masmonteil, T.; Hegele, R.G.; Becker, A.; Chan-Yeung, M.; Hancock, R.E.W.; Kollmann, T.R.; Daley, D.; Sandford, A.J.; Lavoie, P.M.; Turvey, S.E. Functional genetic variation in NFKBIA and susceptibility to childhood asthma, bronchiolitis, and bronchopulmonary dysplasia. J. Immunol., 2013, 190(8), 3949-3958. doi: 10.4049/jimmunol.1201015 PMID: 23487427
  33. Liu, D.; Wang, Y.; Li, L.; Zhao, H.; Li, L.; Liu, Y. Celecoxib protects hyperoxia-induced lung injury via NF-kappaB and AQP1. Front Pediatr., 2019, 7, 228. doi: 10.3389/fped.2019.00228
  34. Wang, X.H.; Jia, H.L.; Deng, L.; Huang, W.M. Astragalus polysaccharides mediated preventive effects on bronchopulmonary dysplasia in rats. Pediatr. Res., 2014, 76(4), 347-354. doi: 10.1038/pr.2014.107 PMID: 25029259

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