Protective effect of luteolin on acute lung injury induced by extracorporeal circulation and its mechanism_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LING Yunfei , LI Tiange , CAO Rong ,  QIAN Yongjun

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding author：

QIAN Yongjun, Email: qianyongjun@scu.edu.cn

Keywords：

Extracorporeal circulation; acute lung injury; luteolin; nuclear factor kappa B; IκB kinase

DOI：

10.7507/1007-4848.202104025

Video：

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Objective To investigate the protective effect of atomized inhalation of nano-luteolin preparation on acute lung injury caused by extracorporeal circulation, and to explore the anti-inflammatory mechanism of luteolin, so as to provide study basis for clinical application.Methods Thirty male SD rats aged 5-6 weeks and weighting 160-190 g, were randomly divided into a preoperative baseline (BL) group, arteriovenous partial diversion (ECC) group, luteolin atomization pretreatment for 1 h group, 2 h group, and 3 h group by random number method, with 6 rats in each group. In the BL group, lung tissue samples were collected directly without any treatment. The ECC group received mechanical ventilation, and the whole body was heparinized after the jugular arteriovenous intubation. The flow was transferred for 30 minutes, followed by observation for 60 minutes, then lung tissue samples were collected. Subjects in the 1 h, 2 h and 3 h groups were placed in a small animal atomizer 1 h, 2 h and 3 h before flow transfer respectively, and the subsequent operation was the same as that in the ECC group. The inflammatory level of lung tissue was detected to evaluate the degree of pathological injury of lung tissue. Western blotting (WB) was used to detect the contents of p65, IKKα, IKKβ and IKKγ in the cytoplasm of lung tissue samples of each group.Results Compared with the ECC group, the levels of IL-6 and TNF-α in lung tissues and the degree of pathological injury in the 1 h, 2 h and 3 h groups decreased, and the difference between the 3 h group and the ECC group was statistically different (P<0.05). WB results showed that compared with the ECC group, the levels of p65 in lung tissue of the 1 h, 2 h and 3 h groups decreased; the levels of IKKβ in the lung tissue increased in the 1 h, 2 h and 3 h groups, and the difference of the 3 h group was statistically different from the ECC group (P<0.05).Conclusion Luteolin has a protective effect on acute lung injury induced by ECC, and atomization 3 h in advance has the best protective effect on lung. The mechanism plays a protective role in ECC-induced acute lung injury, may be through inhibition of IKKβ phosphorylation, thereby inhibiting the classical NF-κB signaling pathway.

Citation： LING Yunfei, LI Tiange, CAO Rong, QIAN Yongjun. Protective effect of luteolin on acute lung injury induced by extracorporeal circulation and its mechanism. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(8): 1181-1187. doi: 10.7507/1007-4848.202104025 Copy

1.	沈嘉渝, 张尔永, 胡佳. 体外循环急性肺损伤与肺保护策略的研究进展. 中国胸心血管外科临床杂志, 2019, 26(2): 186-191.
2.	Salameh A, Greimann W, Vollroth M, et al. Lung protection in cardio-pulmonary bypass. J Physiol Pharmacol, 2017, 68(1): 99-116.
3.	Liu YS, Yang Q, Li S, et al. Luteolin attenuates angiotensin Ⅱ-induced renal damage in apolipoprotein E-deficient mice. Mol Med Rep, 2021, 23(2): 157.
4.	Ashrafizadeh M, Ahmadi Z, Farkhondeh T, et al. Autophagy regulation using luteolin: New insight into its anti-tumor activity. Cancer Cell Int, 2020, 20(1): 537.
5.	Liu CW, Lin HW, Yang DJ, et al. Luteolin inhibits viral-induced inflammatory response in RAW264.7 cells via suppression of STAT1/3 dependent NF-κB and activation of HO-1. Free Radic Biol Med, 2016, 95: 180-189.
6.	Liu X, Meng J. Luteolin alleviates LPS-induced bronchopneumonia injury in vitro and in vivo by down-regulating microRNA-132 expression. Biomed Pharmacother, 2018, 106: 1641-1649.
7.	Park EJ, Kim YM, Kim HJ, et al. Luteolin activates ERK1/2- and Ca 2+-dependent HO-1 induction that reduces LPS-induced HMGB1, iNOS/NO, and COX-2 expression in RAW264.7 cells and mitigates acute lung injury of endotoxin mice. Inflamm Res, 2018, 67(5): 445-453.
8.	Lin LC, Pai YF, Tsai TH. Isolation of luteolin and luteolin-7-O-glucoside from dendranthema morifolium ramat tzvel and their pharmacokinetics in rats. J Agric Food Chem, 2015, 63(35): 7700-7706.
9.	Li LP, Wu XD, Chen ZJ, et al. Interspecies difference of luteolin and apigenin after oral administration of Chrysanthemum morifolium extract and prediction of human pharmacokinetics. Pharmazie, 2013, 68(3): 195-200.
10.	Cheruvu HS, Yadav NK, Valicherla GR, et al. LC-MS/MS method for the simultaneous quantification of luteolin, wedelolactone and apigenin in mice plasma using hansen solubility parameters for liquid-liquid extraction: Application to pharmacokinetics of Eclipta alba chloroform fraction. J Chromatogr B Analyt Technol Biomed Life Sci, 2018, 1081-1082: 76-86.
11.	Nie Y, Wang Z, Chai G, et al. Dehydrocostus lactone suppresses LPS-induced acute lung injury and macrophage activation through NF-κB signaling pathway mediated by p38 MAPK and Akt. Molecules, 2019, 24(8): 1510.
12.	Chen Y, Guo S, Jiang K, et al. Glycitin alleviates lipopolysaccharide-induced acute lung injury via inhibiting NF-κB and MAPKs pathway activation in mice. Int Immunopharmacol, 2019, 75: 105749.
13.	Zhang H, Chen S, Zeng M, et al. Apelin-13 administration protects against LPS-induced acute lung injury by inhibiting NF-κB pathway and NLRP3 inflammasome activation. Cell Physiol Biochem, 2018, 49(5): 1918-1932.
14.	Li W, Zhao R, Wang X, et al. Nobiletin-ameliorated lipopolysaccharide-induced inflammation in acute lung injury by suppression of NF-κB pathway in vivo and vitro. Inflammation, 2018, 41(3): 996-1007.
15.	Zhu H, Wang Y, Sun J, et al. Tomentosin inhibits lipopolysaccharide-induced acute lung injury and inflammatory response by suppression of the NF-κB pathway in a mouse model of sepsis. J Environ Pathol Toxicol Oncol, 2020, 39(4): 291-298.
16.	Chen Q, Lu X, Zhang X. Noncanonical NF-κB signaling pathway in liver diseases. J Clin Transl Hepatol, 2021, 9(1): 81-89.
17.	Zhang R, Guo N, Yan G, et al. Ginkgolide C attenuates lipopolysaccharide-induced acute lung injury by inhibiting inflammation via regulating the CD40/NF-κB signaling pathway. Int J Mol Med, 2021, 47(4): 62.
18.	Mitchell JP, Carmody RJ. NF-κB and the transcriptional control of inflammation. Int Rev Cell Mol Biol, 2018, 335: 41-84.
19.	Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: Coming of age. Nat Rev Immunol, 2018, 18(5): 309-324.
20.	Ko HJ, Jo YH, Patnaik BB, et al. IKKγ/NEMO is required to confer antimicrobial innate immune responses in the yellow mealworm, Tenebrio molitor. Int J Mol Sci, 2020, 21(18): 6734.
21.	Fu J, Huang D, Yuan F, et al. TRAF-interacting protein with forkhead-associated domain (TIFA) transduces DNA damage-induced activation of NF-κB. J Biol Chem, 2018, 293(19): 7268-7280.
22.	Nighot M, Rawat M, Al-Sadi R, et al. Lipopolysaccharide-induced increase in intestinal permeability is mediated by TAK-1 activation of IKK and MLCK/MYLK gene. Am J Pathol, 2019, 189(4): 797-812.
23.	Chen B, Li C, Yao J, et al. Zebrafish NIK mediates IFN induction by regulating activation of IRF3 and NF-κB. J Immunol, 2020, 204(7): 1881-1891.

1. 沈嘉渝, 张尔永, 胡佳. 体外循环急性肺损伤与肺保护策略的研究进展. 中国胸心血管外科临床杂志, 2019, 26(2): 186-191.
2. Salameh A, Greimann W, Vollroth M, et al. Lung protection in cardio-pulmonary bypass. J Physiol Pharmacol, 2017, 68(1): 99-116.
3. Liu YS, Yang Q, Li S, et al. Luteolin attenuates angiotensin Ⅱ-induced renal damage in apolipoprotein E-deficient mice. Mol Med Rep, 2021, 23(2): 157.
4. Ashrafizadeh M, Ahmadi Z, Farkhondeh T, et al. Autophagy regulation using luteolin: New insight into its anti-tumor activity. Cancer Cell Int, 2020, 20(1): 537.
5. Liu CW, Lin HW, Yang DJ, et al. Luteolin inhibits viral-induced inflammatory response in RAW264.7 cells via suppression of STAT1/3 dependent NF-κB and activation of HO-1. Free Radic Biol Med, 2016, 95: 180-189.
6. Liu X, Meng J. Luteolin alleviates LPS-induced bronchopneumonia injury in vitro and in vivo by down-regulating microRNA-132 expression. Biomed Pharmacother, 2018, 106: 1641-1649.
7. Park EJ, Kim YM, Kim HJ, et al. Luteolin activates ERK1/2- and Ca 2+-dependent HO-1 induction that reduces LPS-induced HMGB1, iNOS/NO, and COX-2 expression in RAW264.7 cells and mitigates acute lung injury of endotoxin mice. Inflamm Res, 2018, 67(5): 445-453.
8. Lin LC, Pai YF, Tsai TH. Isolation of luteolin and luteolin-7-O-glucoside from dendranthema morifolium ramat tzvel and their pharmacokinetics in rats. J Agric Food Chem, 2015, 63(35): 7700-7706.
9. Li LP, Wu XD, Chen ZJ, et al. Interspecies difference of luteolin and apigenin after oral administration of Chrysanthemum morifolium extract and prediction of human pharmacokinetics. Pharmazie, 2013, 68(3): 195-200.
10. Cheruvu HS, Yadav NK, Valicherla GR, et al. LC-MS/MS method for the simultaneous quantification of luteolin, wedelolactone and apigenin in mice plasma using hansen solubility parameters for liquid-liquid extraction: Application to pharmacokinetics of Eclipta alba chloroform fraction. J Chromatogr B Analyt Technol Biomed Life Sci, 2018, 1081-1082: 76-86.
11. Nie Y, Wang Z, Chai G, et al. Dehydrocostus lactone suppresses LPS-induced acute lung injury and macrophage activation through NF-κB signaling pathway mediated by p38 MAPK and Akt. Molecules, 2019, 24(8): 1510.
12. Chen Y, Guo S, Jiang K, et al. Glycitin alleviates lipopolysaccharide-induced acute lung injury via inhibiting NF-κB and MAPKs pathway activation in mice. Int Immunopharmacol, 2019, 75: 105749.
13. Zhang H, Chen S, Zeng M, et al. Apelin-13 administration protects against LPS-induced acute lung injury by inhibiting NF-κB pathway and NLRP3 inflammasome activation. Cell Physiol Biochem, 2018, 49(5): 1918-1932.
14. Li W, Zhao R, Wang X, et al. Nobiletin-ameliorated lipopolysaccharide-induced inflammation in acute lung injury by suppression of NF-κB pathway in vivo and vitro. Inflammation, 2018, 41(3): 996-1007.
15. Zhu H, Wang Y, Sun J, et al. Tomentosin inhibits lipopolysaccharide-induced acute lung injury and inflammatory response by suppression of the NF-κB pathway in a mouse model of sepsis. J Environ Pathol Toxicol Oncol, 2020, 39(4): 291-298.
16. Chen Q, Lu X, Zhang X. Noncanonical NF-κB signaling pathway in liver diseases. J Clin Transl Hepatol, 2021, 9(1): 81-89.
17. Zhang R, Guo N, Yan G, et al. Ginkgolide C attenuates lipopolysaccharide-induced acute lung injury by inhibiting inflammation via regulating the CD40/NF-κB signaling pathway. Int J Mol Med, 2021, 47(4): 62.
18. Mitchell JP, Carmody RJ. NF-κB and the transcriptional control of inflammation. Int Rev Cell Mol Biol, 2018, 335: 41-84.
19. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: Coming of age. Nat Rev Immunol, 2018, 18(5): 309-324.
20. Ko HJ, Jo YH, Patnaik BB, et al. IKKγ/NEMO is required to confer antimicrobial innate immune responses in the yellow mealworm, Tenebrio molitor. Int J Mol Sci, 2020, 21(18): 6734.
21. Fu J, Huang D, Yuan F, et al. TRAF-interacting protein with forkhead-associated domain (TIFA) transduces DNA damage-induced activation of NF-κB. J Biol Chem, 2018, 293(19): 7268-7280.
22. Nighot M, Rawat M, Al-Sadi R, et al. Lipopolysaccharide-induced increase in intestinal permeability is mediated by TAK-1 activation of IKK and MLCK/MYLK gene. Am J Pathol, 2019, 189(4): 797-812.
23. Chen B, Li C, Yao J, et al. Zebrafish NIK mediates IFN induction by regulating activation of IRF3 and NF-κB. J Immunol, 2020, 204(7): 1881-1891.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Protective effect of luteolin on acute lung injury induced by extracorporeal circulation and its mechanism

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