Polyphyllin I alleviates lipopolysaccharide-induced inflammation reduces pyroptosis in BEAS-2B and HPAEC cells by inhibiting NF-κB signaling

Main Article Content

Fangli Mao
Aiping Wu

Keywords

Polyphyllin I, lipopolysaccharide, oxidative stress, inflammation, pyroptosis, pneumonia, NF-κB

Abstract

Polyphyllin I is an active steroidal saponin isolated from Paris polyphylla with anti-cancer and anti-inflammatory properties. The present study investigates the role of polyphyllin I in acute lung injury. Firstly, the human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were stimulated with increasing concentrations of lipopolysaccharide at 2, 5, and 10 μg/mL. The treatment with lipopolysaccharide reduced the cell viabilities of BEAS-2B and HPAEC, downregulated superoxide dismutase (SOD) and glutathione (GSH), and up-regulated myeloperoxidase (MPO) and malondialdehyde (MDA). Moreover, the levels of TNF-α, IL-1β, and IL-6 were also up-regulated in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Secondly, the lipopolysaccharide-treated cells were then incubated with different concentrations of polyphyllin I. Incubation with polyphyllin I enhanced the cell viabilities of lipopolysaccharide--treated BEAS-2B/HPAEC, up-regulated levels of SOD and GSH, and reduced MPO and MDA. Moreover, polyphyllin I reduced TNF-α, IL-1β, and IL-6 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Thirdly, the up-regulation of GSDMD-N, pro-caspase-1, and cleaved caspase-1 proteins in lipopolysaccharide-treated BEAS-2B/HPAEC cells were decreased by polyphyllin I. Polyphyllin I increased the protein expression of GSDMD-D in the lipopolysaccharide-treated BEAS-2B/HPAEC cells, and inhibited the translocation of GSDMD from cytoplasm to plasma membrane. Lastly, polyphyllin I reduced the expression of p-p65 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. The over-expression of p65 counteracted with the inhibitory effects of polyphyllin I on oxidative stress and inflammation in lipopolysaccharide-treated BEAS-2B. In conclusion, polyphyllin I repressed the lipopolysaccharide-induced oxidative stress and inflammation in BEAS-2B and HPAEC, and reduced pyroptosis through inhibition of NF-κB signaling.

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References

1. Ragaller M, Richter T. Acute lung injury and acute respiratory distress syndrome. J Emerg Trauma Shock. 2010;3(1):43–51. 10.4103/0974-2700.58663

2. Hotchkiss RS, Colston E, Yende S, Angus DC, Moldawer LL, Crouser ED, et al. Immune checkpoint inhibition in sepsis: a Phase 1b randomized, placebo-controlled, single ascending dose study of anti-PD-L1 (BMS-936559). Critical care medicine. 2019;47(5):632. 10.1097/CCM.0000000000003685

3. Sazonov V, Abylkassov R, Tobylbayeva Z, Saparov A, Mironova O, Poddighe D. Case Series: Efficacy and Safety of Hemoadsorption With HA-330 Adsorber in Septic Pediatric Patients With Cancer. Frontiers in Pediatrics. 2021;9. 10.3389/fped.2021.672260

4. Kojicic M, Li G, Hanson AC, Lee K-M, Thakur L, Vedre J, et al. Risk factors for the development of acute lung injury in patients with infectious pneumonia. Critical Care. 2012;16(2):R46. 10.1186/cc11247

5. Herrero R, Sanchez G, Lorente JA. New insights into the mechanisms of pulmonary edema in acute lung injury. Ann Transl Med. 2018;6(2):32. 10.21037/atm.2017.12.18

6. Hai Zhong LH, Xiang Li, Chunjing Wang, Xu Wu. Anti-inflammatory Role of Trilobatin on Lipopolysaccharide-induced Acute Lung Injury through Activation of AMPK/GSK3β-Nrf2 Pathway. Signa Vitae. 2020;16(2):160–6.

7. Metz C, Sibbald WJ. Anti-inflammatory Therapy for Acute Lung Injury: A Review of Animal and Clinical Studies. CHEST. 1991;100(4):1110–9. 10.1378/chest.100.4.1110

8. Brooks D, Barr LC, Wiscombe S, McAuley DF, Simpson AJ, Rostron AJ. Human lipopolysaccharide models provide mechanistic and therapeutic insights into systemic and pulmonary inflammation. European Respiratory Journal. 2020;56(1):1901298. 10.1183/13993003.01298-2019

9. Rittirsch D, Flierl MA, Day DE, Nadeau BA, McGuire SR, Hoesel LM, et al. Acute lung injury induced by lipopolysaccharide is independent of complement activation. J Immunol. 2008;180(11):7664–72. 10.4049/jimmunol.180.11.7664

10. Liu T-Y, Zhao L-L, Chen S-B, Hou B-C, Huang J, Hong X, et al. Polygonatum sibiricum polysaccharides prevent LPS-induced acute lung injury by inhibiting inflammation via the TLR4/Myd88/NF-κB pathway. Exp Ther Med. 2020;20(4):3733–9. 10.3892/etm.2020.9097

11. Zhang Y, He H, Zhang B, Chen Q, Yao S, Gui P. Amelioration of Lipopolysaccharide-Induced Acute Lung Injury in Rats by Na-H Exchanger-1 Inhibitor Amiloride Is Associated with Reversal of ERK Mitogen-Activated Protein Kinase. BioMed Research International. 2018;2018:3560234. 10.1155/2018/3560234

12. Rahmati M, Keshvari M, Mirnasouri R, Chehelcheraghi F. Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats. Biomedicine & Pharmacotherapy. 2021;139:111577. 10.1016/j.biopha.2021.111577

13. Rodriguez-Ramiro I, Vauzour D, Minihane A. Polyphenols and non-alcoholic fatty liver disease: impact and mechanisms. Proceedings of the Nutrition Society. 2016;75(1):47–60. 10.1017/S0029665115004218

14. Liu X, Sun Z, Deng J, Liu J, Ma K, Si Y, et al. Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer. Int J Oncol. 2018;53(3):1279–88. 10.3892/ijo.2018.4464

15. Tian Y, Gong G-Y, Ma L-L, Wang Z-Q, Song D, Fang M-Y. Anti-cancer effects of Polyphyllin I: An update in 5 years. Chem Biol Interact. 2020;316:108936. 10.1016/j.cbi.2019.108936

16. Han W, Hou G, Liu L. Polyphyllin I (PPI) increased the sensitivity of hepatocellular carcinoma HepG2 cells to chemotherapy. Int J Clin Exp Med. 2015;8(11):20664–9.

17. Yang S, Jiang Y, Yu X, Zhu L, Wang L, Mao J, et al. Polyphyllin I Inhibits Propionibacterium acnes-Induced IL-8 Secretion in HaCaT Cells by Downregulating the CD36/NOX1/ROS/NLRP3/IL-1β Pathway. Evidence-Based Complementary and Alternative Medicine. 2021;2021:1–11. 10.1155/2021/8455709

18. Huang R, Shu J, Dai X, Liu Y, Yu F, Shi G. The protective effect of polyphyllin I on myocardial ischemia/reperfusion injury in rats. Ann Transl Med. 2020;8(10):644.10.21037/atm-20-3371

19. Negi J, Bisht V, Bhandari A, Vp B, Negi P, Singh N. Paris polyphylla: Chemical and Biological Prospectives. Anti-cancer agents in medicinal chemistry. 2014;14:833–9. 10.2174/1871520614666140611101040

20. Zhu T, Wu W, Yang S, Li D, Sun D, He L. Polyphyllin I Inhibits Propionibacterium acnes-Induced Inflammation In Vitro. Inflammation. 2019;42(1):35–44. 10.1007/s10753-018-0870-z

21. Wang Q, Zhou X, Zhao Y, Xiao J, Lu Y, Shi Q, et al. Polyphyllin I Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response in Macrophages Through the NF-κB Pathway. Front Immunol. 2018;9:2091.10.3389/fimmu.2018.02091

22. Liu P, Feng Y, Li H, Chen X, Wang G, Xu S, et al. Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis. Cell Mol Biol Lett. 2020;25:10. 10.1186/s11658-020-00205-0

23. Huang C-Y, Deng J-S, Huang W-C, Jiang W-P, Huang G-J. Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Hispolon in Mice, Through Regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 Pathways, and Suppressing Oxidative Stress-Mediated ER Stress-Induced Apoptosis and Autophagy. Nutrients. 2020;12(6):1742. 10.3390/nu12061742

24. Ward PA. Oxidative stress: acute and progressive lung injury. Annals of the New York Academy of Sciences. 2010;1203(1):53. 10.1111/j.1749-6632.2010.05552.x

25. Chow C-W, Herrera Abreu MT, Suzuki T, Downey G. Oxidative Stress and Acute Lung Injury. American journal of respiratory cell and molecular biology. 2003;29:427–31. 10.1165/rcmb.F278

26. Liu B, He R, Zhang L, Hao B, Jiang W, Wang W, et al. Inflammatory Caspases Drive Pyroptosis in Acute Lung Injury. Frontiers in Pharmacology. 2021;12. 10.3389/fphar.2021.631256

27. Burdette BE, Esparza AN, Zhu H, Wang S. Gasdermin D in pyroptosis. Acta Pharm Sin B. 2021;11(9):2768–82. 10.1016/j.apsb.2021.02.006

28. Wu D, Pan P, Su X, Zhang L, Qin Q, Tan H, et al. Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice. Shock. 2016;46(3):329–38. 10.1097/SHK.0000000000000595

29. Kan X, Chen Y, Huang B, Fu S, Guo W, Ran X, et al. Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway. J Zhejiang Univ Sci B. 2021;22(11):929–40. 10.1631/jzus.B2000583

30. Li N, Song Y, Zhao W, Han T, Lin S, Ramirez O, et al. Small interfering RNA targeting NF-κB attenuates lipopolysaccharide-induced acute lung injury in rats. BMC Physiol. 2016;16(1):7. 10.1186/s12899-016-0027-y