Coptisine attenuates sepsis lung injury by suppressing LPS-induced lung epithelial cell inflammation and apoptosis

Main Article Content

Junjun Huang
Ke Ren
Lili Huang


apoptosis, coptisine, inflammation, lung injury, sepsis


Objective: This study aimed to investigate the functioning and mechanism of coptisine in acute lung injury (ALI).

Methods: Murine Lung Epithelial 12 (MLE-12) cells were stimulated with lipopolysaccharide (LPS) to construct an in vitro pulmonary injury model to study the functioning of coptisine in sepsis-induced ALI. The viability of MLE-12 cells was assessed by the cell counting kit-8 assay. The cytokine release of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-1β was measured by enzyme-linked-immunosorbent serologic assay. The relative expression levels of TNF-α, IL-6, and IL-1β mRNA were examined by reverse transcription-quantitative polymerase chain reaction. The cell apoptosis of MLE-12 cells was determined by Annexin V/propidium iodide staining and analyzed by flow cytometry. The expressions of apoptosis-related proteins Bax and cleaved Caspase-3 were observed by Western blot analysis. The activation of nuclear factor kappa B (NF-κB) signaling pathway was discovered by the determination of phospho-p65, p65, phospho-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and IκBα through Western blot analysis.

Results: Coptisine treatment could significantly restore decrease in MLE-12 cell viability caused by LPS stimulation. The release of TNF-α, IL-6, and IL-1β was significantly inhibited by coptisine treatment. Coptisine treatment inhibited MLE-12 cell apoptosis induced by LPS, and also inhibited the expression levels of Bax and cleaved Caspase-3. Coptisine treatment along with LPS stimulation, significantly reduced the protein level of phospho-IκBα, increased the level of IκBα, and reduced phospho-p65–p65 ratio.

Conclusion: These results indicated that coptisine attenuated sepsis lung injury by suppressing lung epithelial cell inflammation and apoptosis through NF-κB pathway. Therefore, coptisine may have potential to treat sepsis-induced ALI.

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1. Jarczak D, Kluge S, Nierhaus A. Sepsis-pathophysiology and therapeutic concepts. Front Med (Lausanne). 2021;8:628302. 10.3389/fmed.2021.628302

2. Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20(21): 5376. 10.3390/ijms20215376

3. Gong H, Chen Y, Chen M, Li J, Zhang H, Yan S, et al. Advanced development and mechanism of sepsis-related acute respiratory distress syndrome. Front Med (Lausanne). 2022;9:1043859. 10.3389/fmed.2022.1043859

4. Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14(2):121–37. 10.1038/nrneph.2017.165

5. Dolmatova EV, Wang K, Mandavilli R, Griendling KK. The effects of sepsis on endothelium and clinical implications. Cardiovasc Res. 2021;117(1):60–73. 10.1093/cvr/cvaa070

6. Cusack R, Bos LD, Povoa P, Martin-Loeches I. Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: A narrative review. Front Med (Lausanne). 2023;10:1203827. 10.3389/fmed.2023.1203827

7. Naffaa M, Makhoul BF, Tobia A, Kaplan M, Aronson D, Saliba W, et al. Interleukin-6 at discharge predicts all-cause mortality in patients with sepsis. Am J Emerg Med. 2013;31(9):1361–4. 10.1016/j.ajem.2013.06.011

8. Georgescu AM, Banescu C, Azamfirei R, Hutanu A, Moldovan V, Badea I, et al. Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression. BMC Infect Dis. 2020;20(1):221. 10.1186/s12879-020-4910-6

9. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023. 10.1038/sigtrans.2017.23

10. Iacobazzi D, Convertini P, Todisco S, Santarsiero A, Iacobazzi V, Infantino V. New insights into NF-κB signaling in innate immunity: Focus on immunometabolic crosstalks. Biology (Basel). 2023;12(6): 776. 10.3390/biology12060776

11. Yu H, Lin L, Zhang Z, Zhang H, Hu H. Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct Target Ther. 2020;5(1):209. 10.1038/s41392-020-00312-6

12. Jeucken KCM, van Rooijen CCN, Kan YY, Kocken LA, Jongejan A, van Steen ACI, et al. Differential contribution of NF-κB signaling pathways to CD4(+) memory T cell induced activation of endothelial cells. Front Immunol. 2022;13:860327. 10.3389/fimmu.2022.860327

13. 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 Health Eng. 2021;2021:5657284. 10.1155/2021/5657284

14. Jin LY, Li CF, Zhu GF, Wu CT, Wang J, Yan SF. Effect of siRNA against NF-κB on sepsis-induced acute lung injury in a mouse model. Mol Med Rep. 2014;10(2):631–7. 10.3892/mmr.2014.2299

15. Gong Y, Wang J. Monotropein alleviates sepsis-elicited acute lung injury via the NF-κB pathway. J Pharm Pharmacol. 2023:rgad051. 10.1093/jpp/rgad051

16. Song Y, Wu Q, Jiang H, Hu A, Xu L, Tan C, et al. The effect of shionone on sepsis-induced acute lung injury by the ECM1/STAT5/NF-κB pathway. Front Pharmacol. 2021;12:764247. 10.3389/fphar.2021.764247

17. Wang X, Xu T, Jin J, Ting Gao MM, Wan B, Gong M, et al. Topotecan reduces sepsis-induced acute lung injury and decreases the inflammatory response via the inhibition of the NF-κB signaling pathway. Pulm Circ. 2022;12(2):e12070. 10.1002/pul2.12070

18. Mathur N, Mehdi SF, Anipindi M, Aziz M, Khan SA, Kondakindi H, et al. Ghrelin as an anti-sepsis peptide: Review. Front Immunol. 2020;11:610363. 10.3389/fimmu.2020.610363

19. Wu J, Luo Y, Deng D, Su S, Li S, Xiang L, et al. Coptisine from Coptis chinensis exerts diverse beneficial properties: A concise review. J Cell Mol Med. 2019;23(12):7946–60. 10.1111/jcmm.14725

20. Lan Y, Wang H, Wu J, Meng X. Cytokine storm-calming property of the isoquinoline alkaloids in Coptis chinensis Franch. Front Pharmacol. 2022;13:973587. 10.3389/fphar.2022.973587

21. Li MY, Zhang ZH, Wang Z, Zuo HX, Wang JY, Xing Y, et al. Convallatoxin protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB signaling through activation of PPARγ. Pharmacol Res. 2019;147:104355. 10.1016/j.phrs.2019.104355

22. Jo HG, Park C, Lee H, Kim GY, Keum YS, Hyun JW, et al. Inhibition of oxidative stress-induced cytotoxicity by coptisine in V79-4 Chinese hamster lung fibroblasts through the induction of Nrf-2-mediated HO-1 expression. Genes Genomics. 2021;43(1):17–31. 10.1007/s13258-020-01018-3

23. Chen HB, Luo CD, Liang JL, Zhang ZB, Lin GS, Wu JZ, et al. Anti-inflammatory activity of coptisine free base in mice through inhibition of NF-κB and MAPK signaling pathways. Eur J Pharmacol. 2017;811:222–31. 10.1016/j.ejphar.2017.06.027

24. Zhou K, Hu L, Liao W, Yin D, Rui F. Coptisine prevented IL-β-induced expression of inflammatory mediators in chondrocytes. Inflammation. 2016;39(4):1558–65. 10.1007/s10753-016-0391-6

25. Sebag SC, Bastarache JA, Ware LB. Mechanical stretch inhibits lipopolysaccharide-induced keratinocyte-derived chemokine and tissue factor expression while increasing procoagulant activity in murine lung epithelial cells. J Biol Chem. 2013;288(11):7875–84. 10.1074/jbc.M112.403220

26. Long Y, Wang G, Li K, Zhang Z, Zhang P, Zhang J, et al. Oxidative stress and NF-κB signaling are involved in LPS-induced pulmonary dysplasia in chick embryos. Cell Cycle. 2018;17(14):1757–71. 10.1080/15384101.2018.1496743

27. Kalyan M, Tousif AH, Sonali S, Vichitra C, Sunanda T, Praveenraj SS, et al. Role of endogenous lipopolysaccharides in neurological disorders. Cells. 2022;11(24): 4038. 10.3390/cells11244038

28. Ranjit S, Kissoon N. Challenges and solutions in translating sepsis guidelines into practice in resource-limited settings. Transl Ped. 2021;10(10):2646–65. 10.21037/tp-20-310

29. Zhang J, Zheng Y, Wang Y, Wang J, Sang A, Song X, et al. YAP1 alleviates sepsis-induced acute lung injury via inhibiting ferritinophagy-mediated ferroptosis. Front Immunol. 2022;13:884362. 10.3389/fimmu.2022.884362

30. Millar MW, Fazal F, Rahman A. Therapeutic targeting of NF-κB in acute lung injury: A double-edged sword. Cells. 2022;11(20): 3317. 10.3390/cells11203317

31. Wu Y, Guo X, Peng Y, Fang Z, Zhang X. Roles and molecular mechanisms of physical exercise in sepsis treatment. Front Physiol. 2022;13:879430. 10.3389/fphys.2022.879430

32. Scheffer DDL, Latini A. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165823. 10.1016/j.bbadis.2020.165823