Protective Effects and Mechanisms of Luteolin against Acute Respiratory Distress Syndrome: Network Pharmacology and In vivo and In vitro Studies
- 作者: Li Q.1, Chen J.1, Ren Y.1, Yang Z.1, Wang M.1, Zhang W.2, Cao L.2, Sun H.3, Nie S.4, Sun Z.1
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隶属关系:
- Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
- Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School,, Nanjing University
- Department of Intensive Care Unit, Suqian First Hospital
- Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School,, Nanjing University,
- 期: 卷 30, 编号 18 (2024)
- 页面: 1404-1418
- 栏目: Immunology, Inflammation & Allergy
- URL: https://vestnikugrasu.org/1381-6128/article/view/645714
- DOI: https://doi.org/10.2174/0113816128289341240327072531
- ID: 645714
如何引用文章
全文:
详细
Background:Acute Respiratory Distress Syndrome (ARDS) is an acute life-threatening disease, and luteolin has the potential to become a therapeutic agent for ARDS. However, its mechanism of action has not yet been clarified.
Objective:The present study explored the potential effects and mechanisms of luteolin in the treatment of ARDS through network pharmacology analysis and verified them through biological experiments.
Methods:The potential targets of luteolin and ARDS were obtained from online databases. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the underlying molecular mechanisms and to identify hub targets. Molecular docking was used to verify the relationship between luteolin and target proteins. Finally, the effects of luteolin on key signaling pathways and biological processes were verified by in vitro and in vivo experiments.
Results:A total of 146 luteolin- and 496 ARDS-related targets were extracted from public databases. The network pharmacological analysis suggested that luteolin could inhibit ARDS through the following potential therapeutic targets: AKT1, RELA, and NFKBIA. Inflammatory and oxidative stress responses were the main biological processes involved, with the AKT/NF-κB signaling pathway being the key signaling pathway targeted by luteolin for the treatment of ARDS. Molecular docking analysis indicated that luteolin had a good binding affinity to AKT1, RELA, and NFKBIA. The in vitro and in vivo experiments revealed that luteolin could regulate the inflammatory response and oxidative stress in the treatment of ARDS by inhibiting the AKT/NF- κB signaling pathway.
Conclusion:Luteolin could reduce the production of reactive oxygen species and inflammatory factors by inhibiting the AKT/NF-κB signaling pathway, thus reducing apoptosis and attenuating ARDS.
作者简介
Quan Li
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
Email: info@benthamscience.net
Juan Chen
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
Email: info@benthamscience.net
Yi Ren
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
Email: info@benthamscience.net
Zhizhou Yang
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
Email: info@benthamscience.net
Mengmeng Wang
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
Email: info@benthamscience.net
Wei Zhang
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School,, Nanjing University
Email: info@benthamscience.net
Liping Cao
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School,, Nanjing University
Email: info@benthamscience.net
Haijun Sun
Department of Intensive Care Unit, Suqian First Hospital
Email: info@benthamscience.net
Shinan Nie
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School,, Nanjing University,
编辑信件的主要联系方式.
Email: info@benthamscience.net
Zhaorui Sun
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
编辑信件的主要联系方式.
Email: info@benthamscience.net
参考
- Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet 2021; 398(10300): 622-37. doi: 10.1016/S0140-6736(21)00439-6 PMID: 34217425
- Huppert L, Matthay M, Ware L. Pathogenesis of acute respiratory distress syndrome. Semin Respir Crit Care Med 2019; 40(1): 031-9. doi: 10.1055/s-0039-1683996 PMID: 31060086
- He YQ, Zhou CC, Yu LY, et al. Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms. Pharmacol Res 2021; 163: 105224. doi: 10.1016/j.phrs.2020.105224 PMID: 33007416
- Liu B, Yu H, Baiyun R, et al. Protective effects of dietary luteolin against mercuric chloride-induced lung injury in mice: Involvement of AKT/Nrf2 and NF-κB pathways. Food Chem Toxicol 2018; 113: 296-302. doi: 10.1016/j.fct.2018.02.003 PMID: 29421646
- Rungsung S, Singh TU, Rabha DJ, et al. Luteolin attenuates acute lung injury in experimental mouse model of sepsis. Cytokine 2018; 110: 333-43. doi: 10.1016/j.cyto.2018.03.042 PMID: 29655568
- Xiong J, Wang K, Yuan C, et al. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects. Int J Mol Med 2017; 39(1): 113-25. doi: 10.3892/ijmm.2016.2809 PMID: 27878246
- He D, Huang J, Zhang Z, et al. A network pharmacology-based strategy for predicting active ingr-edients and potential targets of liuwei dihuang pill-in treating type 2 diabetes mellitus. Drug Des Devel Ther 2019; 13: 3989-4005. doi: 10.2147/DDDT.S216644 PMID: 31819371
- Liu L, Du B, Zhang H, et al. A network pharmacology approach to explore the mechanisms of Erxian decoction in polycystic ovary syndrome. Chin Med 2018; 13(1): 46. doi: 10.1186/s13020-018-0201-1 PMID: 30181771
- Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019; 10(1): 1523. doi: 10.1038/s41467-019-09234-6 PMID: 30944313
- Obaidullah AJ, Alanazi MM, Alsaif NA, et al. Deeper insights on Cnesmone javanica blume leaves extract: Chemical profiles, Biological attributes, network pharmacology and molecular docking. Plants 2021; 10(4): 728. doi: 10.3390/plants10040728 PMID: 33917986
- Yang L, Liu S, Han S, et al. The HDL from septic-ARDS patients with composition changes exacerbates pulmonary endothelial dysfunction and acute lung injury induced by cecal ligation and puncture (CLP) in mice. Respir Res 2020; 21(1): 293. doi: 10.1186/s12931-020-01553-3 PMID: 33148285
- Wang C, Yuan J, Du J. Resveratrol alleviates acute lung injury through regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in a cecal ligation and puncture model. Eur J Pharmacol 2021; 913: 174643. doi: 10.1016/j.ejphar.2021.174643 PMID: 34808102
- Bringué J, Guillamat-Prats R, Martinez M, et al. Methotrexate ameliorates systemic inflammation and septic associated-lung damage in a cecal ligation and puncture septic rat model. Int J Mol Sci 2021; 22(17): 9612. doi: 10.3390/ijms22179612 PMID: 34502521
- Li R, Zhao Y, Zhang X, Yang L, Zou X. NLRC3 participates in inhibiting the pulmonary inflammatory response of sepsis-induced acute lung injury. Immunol Invest 2023; 52(5): 567-82. doi: 10.1080/08820139.2023.2206445 PMID: 37139806
- Xie K, Chai Y, Lin S, Xu F, Wang C. Luteolin regulates the differentiation of regulatory T cells and activates IL-10-dependent macrophage polarization against acute lung injury. J Immunol Res 2021; 2021: 1-12. doi: 10.1155/2021/8883962 PMID: 33532509
- Ding Q, Zhu W, Diao Y, et al. Elucidation of the mechanism of action of ginseng against acute lung injury/acute respiratory distress syndrome by a network pharmacology-based strategy. Front Pharmacol 2021; 11: 611794. doi: 10.3389/fphar.2020.611794 PMID: 33746744
- Ullah HMA, Elfadl AK, Park S, et al. Nogoa is critical for pro-inflammatory gene regulation in myocytes and macrophages. Cells 2021; 10(2): 282. doi: 10.3390/cells10020282 PMID: 33572505
- Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016; 315(8): 788-800. doi: 10.1001/jama.2016.0291 PMID: 26903337
- Banavasi H, Nguyen P, Osman H, Soubani AO. Management of ards - what works and what does not. Am J Med Sci 2021; 362(1): 13-23. doi: 10.1016/j.amjms.2020.12.019 PMID: 34090669
- Li YC, Yeh CH, Yang ML, Kuan YH. Luteolin suppresses inflammatory mediator expression by blocking the akt/NFκB pathway in acute lung injury induced by lipopolysaccharide in mice. Evid Based Complement Alternat Med 2012; 2012: 1-8. doi: 10.1155/2012/383608 PMID: 22203870
- Heron-Milhavet L, Khouya N, Fernandez A, Lamb NJ. Akt1 and Akt2: Differentiating the aktion. Histol Histopathol 2011; 26(5): 651-62. doi: 10.14670/HH-26.651 PMID: 21432781
- Kan X, Liu B, Guo W, et al. Myricetin relieves LPS-induced mastitis by inhibiting inflammatory response and repairing the blood milk barrier. J Cell Physiol 2019; 234(9): 16252-62. doi: 10.1002/jcp.28288 PMID: 30746687
- Guo W, Liu B, Hu G, et al. Vanillin protects the bloodmilk barrier and inhibits the inflammatory response in LPS-induced mastitis in mice. Toxicol Appl Pharmacol 2019; 365: 9-18. doi: 10.1016/j.taap.2018.12.022 PMID: 30610879
- Wang WY, Chen Y, Su X, et al. Resistin-like molecule-α causes lung injury in rats with acute pancreatitis by activating the PI-3K/Akt-NF-κB pathway and promoting inflammatory cytokine release. Curr Mol Med 2016; 16(7): 677-87. doi: 10.2174/1566524016666160802145700 PMID: 27492801
- Zhao M, Li C, Shen F, Wang M, Jia N, Wang C. Naringenin ameliorates LPS-induced acute lung injury through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/Akt pathway. Exp Ther Med 2017; 14(3): 2228-34. doi: 10.3892/etm.2017.4772 PMID: 28962147
- Ho YC, Lee SS, Yang ML, et al. Zerumbone reduced the inflammatory response of acute lung injury in endotoxin-treated mice via Akt-NFκB pathway. Chem Biol Interact 2017; 271: 9-14. doi: 10.1016/j.cbi.2017.04.017 PMID: 28442377
- Cui H, Zhang Q. Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway. J Anesth 2021; 35(3): 394-404. doi: 10.1007/s00540-021-02909-9 PMID: 33821300
- Kan X, Chen Y, Huang B, 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. doi: 10.1631/jzus.B2000583 PMID: 34783223
- Kellner M, Noonepalle S, Lu Q, Srivastava A, Zemskov E, Black SM. Ros signaling in the pathogenesis of acute lung injury (ali) and acute respiratory distress syndrome (ards). Adv Exp Med Biol 2017; 967: 105-37. doi: 10.1007/978-3-319-63245-2_8 PMID: 29047084
- Pooladanda V, Thatikonda S, Bale S, et al. Nimbolide protects against endotoxin-induced acute respiratory distress syndrome by inhibiting TNF-α mediated NF-κB and HDAC-3 nuclear translocation. Cell Death Dis 2019; 10(2): 81. doi: 10.1038/s41419-018-1247-9 PMID: 30692512
- Reiss LK, Schuppert A, Uhlig S. Inflammatory processes during acute respiratory distress syndrome: A complex system. Curr Opin Crit Care 2018; 24(1): 1-9. doi: 10.1097/MCC.0000000000000472 PMID: 29176329
- Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med 2017; 377(6): 562-72. doi: 10.1056/NEJMra1608077 PMID: 28792873
- Dolinay T, Kim YS, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med 2012; 185(11): 1225-34. doi: 10.1164/rccm.201201-0003OC PMID: 22461369
- Chang HY, Chen YC, Lin JG, et al. Asatone prevents acute lung injury by reducing expressions of NF-κB, MaPK and inflammatory cytokines. Am J Chin Med 2018; 46(3): 651-71. doi: 10.1142/S0192415X18500349 PMID: 29595073
- Sugiura R, Satoh R, Takasaki T. Erk: A double-edged sword in cancer. Erk-dependent apoptosis as a potential therapeutic strategy for cancer. Cells 2021; 10(10): 2509. doi: 10.3390/cells10102509 PMID: 34685488
- Zhu S, Song W, Sun Y, Zhou Y, Kong F. MiR-342 attenuates lipopolysaccharide-induced acute lung injury via inhibiting MAPK1 expression. Clin Exp Pharmacol Physiol 2020; 47(8): 1448-54. doi: 10.1111/1440-1681.13315 PMID: 32248545
- Xie M, Cheng B, Ding Y, Wang C, Chen J. Correlations of IL-17 and NF-κB gene polymorphisms with susceptibility and prognosis in acute respiratory distress syndrome in a chinese population. Biosci Rep 2019; 39(2): BSR20181987. doi: 10.1042/BSR20181987 PMID: 30655311
- Zhang H, Wang Z, Liu R, et al. Reactive oxygen species stimulated pulmonary epithelial cells mediate the alveolar recruitment of FasL+ killer B cells in LPS-induced acute lung injuries. J Leukoc Biol 2018; 104(6): 1187-98. doi: 10.1002/JLB.3A0218-075R PMID: 30295956
- Fu C, Dai X, Yang Y, Lin M, Cai Y, Cai S. Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats. Mol Med Rep 2017; 15(1): 131-8. doi: 10.3892/mmr.2016.6012 PMID: 27959438
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