Decursin alleviates LPS-induced lung epithelial cell injury by inhibiting NF-κB pathway activation

Main Article Content

Jiangfeng Zhu
Xiaoping Dong

Keywords

acute lung injury (ALI), decursin, oxidative stress, pneumonia, NF-κB pathway

Abstract

Objective: To reveal the possible effects of decursin on viability, oxidative stress, and inflammatory response in lipopolysaccharide (LPS)-treated human bronchial epithelial cells-2B (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) cells, and revealed the potential mechanisms.


Methods: LPS was used to induce acute lung injury (ALI) in normal human lung epithelial cells, including BEAS-2B and HPAEC cells. Cell viability and apoptosis in response to LPS and decursin in BEAS-2B and HPAEC cells were, respectively, evaluated by MTT colorimetric and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The oxidative stress and inflammatory response in LPS-treated BEAS-2B and HPAEC cells were detected by enzyme-linked-immunosorbent serologic assay. In addition, the role of decursin in nuclear-factor-kappa B (NF-κB) activation was analyzed by immunoblot and immunofluorescence assays.


Results: Our data revealed that decursin could alleviate the viability of LPS-induced BEAS-2B and HPAEC cells. Decursin could also reduce LPS-induced oxidative stress in BEAS-2B and HPAEC cells. In addition, it could reduce LPS-induced inflammation in BEAS-2B and HPAEC cells. Mechanically, decursin suppressed the activation of NF-κB pathway.


Conclusion: Decursin suppressed NF-κB pathway, and therefore alleviated ALI.

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References

1. Song J, Chen D, Pan Y, Shi X, Liu Q, Lu X, et al. Discovery of a novel MyD88 inhibitor M20 and its protection against sepsis-mediated acute lung injury. Front Pharmacol. 2021;12:775117. 10.3389/fphar.2021.775117

2. Jin A, Zhao Y, Yuan Y, Ma S, Chen J, Yang X, et al. Single treatment of vitamin D3 aAmeliorates LPS-induced acute lung injury through changing lung rodentibacter abundance. Mol Nut Food Res. 2021;66(3):e2100952. 10.1002/mnfr.202100952

3. Engeroff P, Belbezier A, Monsel A, Klatzmann D. Anakinra reduces lung inflammation in experimental acute lung injury. Immun Inflamm Dis. 2022;10(2):123–9. 10.1002/iid3.548.

4. Chen X, Sun Z, Zhang H, Wang L. Correlation of impaired NF-kB activation in sepsis-induced acute lung injury (ALI) in diabetic rats. J Healthc Eng. 2021;2021:5657284. 10.1155/2021/5657284

5. Yang L, Zhao L, Zhang H, Chen P. Up-regulation of TUG1 can regulate miR-494/PDK4 axis to inhibit LPS-induced acute lung injury caused by sepsis. Am J Transl Res. 2021;13(11):12375–85. PMid: 34956459;

6. Kim J, Yun M, Kim EO, Jung DB, Won G, Kim B, et al. Decursin enhances TRAIL-induced apoptosis through oxidative stress-mediated endoplasmic reticulum stress signalling in non-small cell lung cancers. Br J Pharmacol. 2016;173(6):1033–44. 10.1111/bph.13408

7. Kim BS, Seo H, Kim HJ, Bae SM, Son HN, Lee YJ, et al. Decursin from Angelica gigas nakai inhibits B16F10 melanoma growth through induction of apoptosis. J Med Food. 2015;18(10):1121–7. 10.1089/jmf.2014.3397

8. Choi HS, Cho SG, Kim MK, Kim MS, Moon SH, Kim IH, et al. Decursin in Angelica gigas Nakai (AGN) enhances doxorubicin chemosensitivity in NCI/ADR-RES ovarian cancer cells via inhibition of P-glycoprotein expression. Phytother Res (PTR). 2016;30(12):2020–6. 10.1002/ptr.5708

9. Lee TK, Kang IJ, Sim H, Lee JC, Ahn JH, Kim DW, et al. Therapeutic effects of decursin and Angelica gigas nakai root extract in gerbil brain after transient ischemia via protecting BBB leakage and astrocyte endfeet damage. Molecules. 2021;26(8):2161. 10.3390/molecules26082161

10. Kim S, Lee SI, Kim N, Joo M, Lee KH, Lee MW, et al. Decursin inhibits cell growth and autophagic flux in gastric cancer via suppression of cathepsin C. Am J Cancer Res. 2021;11(4):1304–20. PMid: 33948359;

11. 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. Biomed Pharmacother. 2021;139:111577. 10.1016/j.biopha.2021.111577

12. Keshvari M, Rahmati M, Mirnasouri R, Chehelcheraghi F. Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-Induced diabetic rats. J Ethnopharmacol. 2020;256:112801. 10.1016/j.jep.2020.112801

13. Song YR, Jang B, Lee SM, Bae SJ, Bak SB, Kim YW. Angelica gigas NAKAI and its active compound, decursin, inhibit cellular injury as an antioxidant by the regulation of AMP-activated protein kinase and YAP signaling. Molecules. 2022;27(6):1858. 10.3390/molecules27061858

14. Son DB, Choi W, Kim M, Go EJ, Jeong D, Park CK, et al. Decursin alleviates mechanical allodynia in a paclitaxel--induced neuropathic pain mouse model. Cells. 2021;10(3):547. 10.3390/cells10030547

15. Wu L, Cheng Y, Peng S, Zhang W, Zhang C. Sphingosine kinase 1 plays an important role in atorvastatin-mediated anti--inflammatory effect against acute lung injury. Mediators Inflamm. 2021;2021:9247285. 10.1155/2021/9247285

16. Techarang T, Jariyapong P, Viriyavejakul P, Punsawad C. High mobility group box-1 (HMGB-1) and its receptors in the pathogenesis of malaria-associated acute lung injury/acute respiratory distress syndrome in a mouse model. Heliyon. 2021; 7(12):e08589. 10.1016/j.heliyon.2021.e08589.

17. Tang L, Song D, Qi R, Zhu B, Wang X. Roles of pulmonary telocytes in airway epithelia to benefit experimental acute lung injury through production of telocyte-driven mediators and exosomes. Cell Biol Toxicol. 2022;1–15. 10.1007/s10565-021-09670-5. Online ahead of print.

18. Park IS, Kim B, Han Y, Yang H, Cho U, Kim SI, et al. Decursin and decursinol angelate suppress adipogenesis through activation of beta-catenin signaling pathway in human visceral adipose-derived stem cells. Nutrients. 2019;12(1):13. 10.3390/nu12010013

19. Oh JM, Lee HS, Baek SC, Lee JP, Jeong GS, Paik MJ, et al. Antidepressant-like activities of hispidol and decursin in mice and analysis of neurotransmitter monoamines. Neurochem Res. 2020;45(8):1930–40. 10.1007/s11064-020-03057-4

20. Lee W, Sim H, Choi YJ, Seo JY, Yun MY, Song GY, et al. The decursin analog, CYJ-27, suppresses inflammation via the downregulation of NF-kappaB and STAT-1. J Med Food. 2021;24(8):852–9. 10.1089/jmf.2021.K.0027

21. Lee TK, Kim B, Kim DW, Ahn JH, Sim H, Lee JC, et al. Effects of decursin and angelica gigas nakai root extract on hair growth in mouse dorsal skin via regulating inflammatory cytokines. Molecules. 2020;25(16):3697. 10.3390/molecules25163697

22. Lee SH, Lee JH, Kim EJ, Kim WJ, Suk K, Kim JH, et al. A novel derivative of decursin, CSL-32, blocks migration and production of inflammatory mediators and modulates PI3K and NF-kappaB activities in HT1080 cells. Cell Biol Int. 2012;36(7):683–8. 10.1042/CBI20110257

23. Yang L, Zhang X, Lv X, Yu H. Intensity modulated radiotherapy and brachytherapy for a cervical cancer after renal transplantation. Eur J Gynaecol Oncol. 2017;38(1):162–5. PMid: 29767890.

24. Jerez-Lillo N, Álvarez BL, Gutiérrez JM, Figueroa-Zúñiga JI, Leiva V. A statistical analysis for the epidemiological surveillance of COVID-19 in Chile. Signa Vitae. 2022;18(2):19–30. 10.22514/sv.2021.130