Auraptene alleviates inflammatory injury and cell apoptosis in children with pneumonia in vitro
Main Article Content
Keywords
apoptosis, auraptene, inflammation, NF-κB axis, pneumonia
Abstract
Objective: The aim of the present study is to investigate the effects of auraptene on inflammation and apoptosis of pneumonia cell model and uncover the mechanism.
Methods: WI-38 cells were treated with lipopolysaccharide (LPS) to construct a pneumonia model. Cell counting kit-8 assay, enzyme-linked-immunosorbent serologic assay, and quantitative polymerase chain reaction assay were conducted to confirm the effects of auraptene on the viability and inflammation of WI-38 cells. Flow cytometry (FCM) and immunoblot assays were conducted to detect the effects of auraptene on the apoptosis of WI-38 cells. Immunoblot assay was performed to confirm the mechanism.
Results: We found that auraptene stimulated cell viability in WI-38 cells upon LPS treatment. Auraptene also inhibited cellular inflammation. Furthermore, auraptene inhibited cell apoptosis of WI-38 cells upon LPS treatment. Mechanically, auraptene inhibited the nuclear factor kappa B signaling pathway, thereby suppressing the pneumonia.
Conclusion: Auraptene alleviates inflammatory injury and cell apoptosis in pneumonia, thus has the potential to act as a pneumonia drug.
References
1. Sanders NL, Martin IMC, Sharma A, Jones MR, Quinton LJ, Bosmann M, et al. Neutrophil extracellular traps as an exacerbating factor in bacterial pneumonia. Infect and Immun. 2022;90(3):e0049121. https://doi.org/10.1128/iai.00491-21
2. Pulavendran S, Rudd JM, Maram P, Thomas PG, Akhilesh R, Malayer JR, et al. Combination therapy targeting platelet activation and virus replication protects mice against lethal influenza pneumonia. Am J Resp Cell Mol Biol. 2019;61(6):689–701. https://doi.org/10.1165/rcmb.2018-0196OC
3. Zhang J, Zhu Y, Zhou Y, Gao F, Qiu X, Li J, et al. Pediatric adenovirus pneumonia: Clinical practice and current treatment. Front Med. 2023;10:1207568. https://doi.org/10.3389/fmed.2023.1207568
4. Luan Y, Liu H, Luan Y, Yang Y, Yang J, Ren KD. New insight in HDACs: Potential therapeutic targets for the treatment of atherosclerosis. Front Pharmacol. 2022;13:863677. https://doi.org/10.3389/fphar.2022.863677
5. Ghorbani M, Soukhtanloo M, Farrokhi AS, Hassanian SM, Ghorbani F, Afshari AR, et al. Auraptene-induced cytotoxic effects in acute myeloid leukemia cell lines. Med Oncol. 2023;40(8):231. https://doi.org/10.1007/s12032-023-02088-5
6. Goudarzi S, Rassouli FB, Kahrizi D, Paryan S, Mahdifar M, Mehrdad I, et al. Comparing toxicity of galbanic acid, auraptene and umbelliprenin on adult T-cell leukaemia-lymphoma in normoxia and hypoxia. Cell Mol Biol. 2022;68(12):17–20. https://doi.org/10.14715/cmb/2022.68.12.4
7. Kim YH, Lee SY, Kim EY, Kim KH, Koong MK, Lee KA. The antioxidant auraptene improves aged oocyte quality and embryo development in mice. Antioxidants. 2022;12(1). https://doi.org/10.3390/antiox12010087
8. Min JS, Jin YH, Kwon S. Auraptene has antiviral activity against human coronavirus OC43 in MRC-5 cells. Nutrients. 2023;15(13). https://doi.org/10.3390/nu15132960
9. Okuyama S, Minami S, Shimada N, Makihata N, Nakajima M, Furukawa Y. Anti-inflammatory and neuroprotective effects of auraptene, a citrus coumarin, following cerebral global ischemia in mice. Eur J Pharmacol. 2013;699(1–3):118–23. https://doi.org/10.1016/j.ejphar.2012.11.043
10. Sekiguchi H, Takabayashi F, Irie K, Murakami A. Auraptene attenuates gastritis via reduction of helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice. J Med Food. 2012;15(7):658–63. https://doi.org/10.1089/jmf.2011.1844
11. Hsia CW, Wu MP, Shen MY, Hsia CH, Chung CL, Sheu JR. Regulation of human platelet activation and prevention of arterial thrombosis in mice by auraptene through inhibition of NF-kappaB pathway. Int J Mol Sci. 2020;21(13). https://doi.org/10.3390/ijms21134810
12. 1. Sanders NL, Martin IMC, Sharma A, Jones MR, Quinton LJ, Bosmann M, et al. Neutrophil extracellular traps as an exacerbating factor in bacterial pneumonia. Infect and Immun. 2022;90(3):e0049121. https://doi.org/10.1128/iai.00491-21
2. Pulavendran S, Rudd JM, Maram P, Thomas PG, Akhilesh R, Malayer JR, et al. Combination therapy targeting platelet activation and virus replication protects mice against lethal influenza pneumonia. Am J Resp Cell Mol Biol. 2019;61(6):689–701. https://doi.org/10.1165/rcmb.2018-0196OC
3. Zhang J, Zhu Y, Zhou Y, Gao F, Qiu X, Li J, et al. Pediatric adenovirus pneumonia: Clinical practice and current treatment. Front Med. 2023;10:1207568. https://doi.org/10.3389/fmed.2023.1207568
4. Luan Y, Liu H, Luan Y, Yang Y, Yang J, Ren KD. New insight in HDACs: Potential therapeutic targets for the treatment of atherosclerosis. Front Pharmacol. 2022;13:863677. https://doi.org/10.3389/fphar.2022.863677
5. Ghorbani M, Soukhtanloo M, Farrokhi AS, Hassanian SM, Ghorbani F, Afshari AR, et al. Auraptene-induced cytotoxic effects in acute myeloid leukemia cell lines. Med Oncol. 2023;40(8):231. https://doi.org/10.1007/s12032-023-02088-5
6. Goudarzi S, Rassouli FB, Kahrizi D, Paryan S, Mahdifar M, Mehrdad I, et al. Comparing toxicity of galbanic acid, auraptene and umbelliprenin on adult T-cell leukaemia-lymphoma in normoxia and hypoxia. Cell Mol Biol. 2022;68(12):17–20. https://doi.org/10.14715/cmb/2022.68.12.4
7. Kim YH, Lee SY, Kim EY, Kim KH, Koong MK, Lee KA. The antioxidant auraptene improves aged oocyte quality and embryo development in mice. Antioxidants. 2022;12(1).
https://doi.org/ 10.3390/antiox12010087
8. Min JS, Jin YH, Kwon S. Auraptene has antiviral activity against human coronavirus OC43 in MRC-5 cells. Nutrients. 2023;15(13). https://doi.org/10.3390/nu15132960
9. Okuyama S, Minami S, Shimada N, Makihata N, Nakajima M, Furukawa Y. Anti-inflammatory and neuroprotective effects of auraptene, a citrus coumarin, following cerebral global ischemia in mice. Eur J Pharmacol. 2013;699(1–3):118–23. https://doi.org/10.1016/j.ejphar.2012.11.043
10. Sekiguchi H, Takabayashi F, Irie K, Murakami A. Auraptene attenuates gastritis via reduction of helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice. J Med Food. 2012;15(7):658–63. https://doi.org/10.1089/jmf.2011.1844
11. Hsia CW, Wu MP, Shen MY, Hsia CH, Chung CL, Sheu JR. Regulation of human platelet activation and prevention of arterial thrombosis in mice by auraptene through inhibition of NF-kappaB pathway. Int J Mol Sci. 2020;21(13). https://doi.org/ 10.3390/ijms21134810
12. Luan Y, Ren KD, Luan Y, Chen X, Yang Y. Mitochondrial dynamics: Pathogenesis and therapeutic targets of vascular diseases. Front Cardiovasc Med. 2021;8:770574. https://doi.org/ 10.3389/fcvm.2021.770574
13. Ghezelayagh TS, Wu ES, Barber EL, Dao MD, Zsiros E, Urban RR, et al. Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: A multi-institution study. Eur J Gynaecol Oncol. 2023;44(1):17–25.
14. Sayama Y, Okamoto M, Saito M, Tamaki R, Saito-Obata M, Quicho RFN, et al. Lack of zoonotic coronavirus species detected among children hospitalized with pneumonia in the Philippines. Clin Infect Dis. 2023. https://doi.org/10.1093/cid/ciad430
15. Guz D, McNeil R, Buchrits S, Goshen S, Gafter-Gvili A, Avni T. Ceftriaxone 1 g versus 2 g per day, for the treatment of community-acquired pneumonia: a retrospective cohort study. internal and emergency medicine. 2023. https://doi.org/10.1007/s11739-023-03372-y
16. Song S, Xu Y. A retrospective study of the clinical characteristics of 9 children with pulmonary embolism associated with mycoplasma pneumoniae pneumonia. BMC Pediat. 2023;23(1):370. https://doi.org/10.1186/s12887-023-04188-7
17. Gao X, Fu T, Wang C, Ning C, Kong Y, Liu Z, et al. Computational discovery and experimental verification of farnesoid X receptor agonist auraptene to protect against cholestatic liver injury. Biochem Pharmacol. 2017;146:127–38. https://doi.org/10.1016/j.bcp.2017.09.016
18. La VD, Zhao L, Epifano F, Genovese S, Grenier D. Anti-inflammatory and wound healing potential of citrus auraptene. J Med Food. 2013;16(10):961–4. https://doi.org/10.1089/jmf.2013.0029
19. Takahashi N, Senda M, Lin S, Goto T, Yano M, Sasaki T, et al. Auraptene regulates gene expression involved in lipid metabolism through PPAR alpha activation in diabetic obese mice. Mol Nutrit Food Res. 2011;55(12):1791–7. https://doi.org/10.1002/mnfr.201100401
20. Ni Ww, Zhang Qm, Zhang X, Li Y, Yu Ss, Wu Hy, et al. Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model. Allergol Immunopathol. 2020;48(2):149–57. https://doi.org/10.1016/j.aller.2019.06.002
21. Li J, Yan W, Ren F, Sang H. Tectorigenin inhibits inflammation in keratinocytes by inhibition of NLRP3 inflammasome regulated by the TLR4/NF-kappaB pathway. Allergol Immunopathol (Madr). 2023;51(2):82–9. https://doi.org/10.15586/aei.v51i2.780
22. Pandey P, Al Rumaih Z, Kels MJT, Ng E, Kc R, Malley R, et al. Therapeutic targeting of inflammation and virus simultaneously ameliorates influenza pneumonia and protects from morbidity and mortality. Viruses. 2023;15(2). https://doi.org/10.3390/v15020318
23. Wang Y, Jian S, Li W, Zhao L, Ye G, Shi F, et al. Epigallocatechin-3-gallate ameliorates liver injury secondary to pseudomonas aeruginosa pneumonia. Int Immunopharmacol. 2022;112:109239. https://doi.org/10.1016/j.intimp.2022.109239
2. Pulavendran S, Rudd JM, Maram P, Thomas PG, Akhilesh R, Malayer JR, et al. Combination therapy targeting platelet activation and virus replication protects mice against lethal influenza pneumonia. Am J Resp Cell Mol Biol. 2019;61(6):689–701. https://doi.org/10.1165/rcmb.2018-0196OC
3. Zhang J, Zhu Y, Zhou Y, Gao F, Qiu X, Li J, et al. Pediatric adenovirus pneumonia: Clinical practice and current treatment. Front Med. 2023;10:1207568. https://doi.org/10.3389/fmed.2023.1207568
4. Luan Y, Liu H, Luan Y, Yang Y, Yang J, Ren KD. New insight in HDACs: Potential therapeutic targets for the treatment of atherosclerosis. Front Pharmacol. 2022;13:863677. https://doi.org/10.3389/fphar.2022.863677
5. Ghorbani M, Soukhtanloo M, Farrokhi AS, Hassanian SM, Ghorbani F, Afshari AR, et al. Auraptene-induced cytotoxic effects in acute myeloid leukemia cell lines. Med Oncol. 2023;40(8):231. https://doi.org/10.1007/s12032-023-02088-5
6. Goudarzi S, Rassouli FB, Kahrizi D, Paryan S, Mahdifar M, Mehrdad I, et al. Comparing toxicity of galbanic acid, auraptene and umbelliprenin on adult T-cell leukaemia-lymphoma in normoxia and hypoxia. Cell Mol Biol. 2022;68(12):17–20. https://doi.org/10.14715/cmb/2022.68.12.4
7. Kim YH, Lee SY, Kim EY, Kim KH, Koong MK, Lee KA. The antioxidant auraptene improves aged oocyte quality and embryo development in mice. Antioxidants. 2022;12(1). https://doi.org/10.3390/antiox12010087
8. Min JS, Jin YH, Kwon S. Auraptene has antiviral activity against human coronavirus OC43 in MRC-5 cells. Nutrients. 2023;15(13). https://doi.org/10.3390/nu15132960
9. Okuyama S, Minami S, Shimada N, Makihata N, Nakajima M, Furukawa Y. Anti-inflammatory and neuroprotective effects of auraptene, a citrus coumarin, following cerebral global ischemia in mice. Eur J Pharmacol. 2013;699(1–3):118–23. https://doi.org/10.1016/j.ejphar.2012.11.043
10. Sekiguchi H, Takabayashi F, Irie K, Murakami A. Auraptene attenuates gastritis via reduction of helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice. J Med Food. 2012;15(7):658–63. https://doi.org/10.1089/jmf.2011.1844
11. Hsia CW, Wu MP, Shen MY, Hsia CH, Chung CL, Sheu JR. Regulation of human platelet activation and prevention of arterial thrombosis in mice by auraptene through inhibition of NF-kappaB pathway. Int J Mol Sci. 2020;21(13). https://doi.org/10.3390/ijms21134810
12. 1. Sanders NL, Martin IMC, Sharma A, Jones MR, Quinton LJ, Bosmann M, et al. Neutrophil extracellular traps as an exacerbating factor in bacterial pneumonia. Infect and Immun. 2022;90(3):e0049121. https://doi.org/10.1128/iai.00491-21
2. Pulavendran S, Rudd JM, Maram P, Thomas PG, Akhilesh R, Malayer JR, et al. Combination therapy targeting platelet activation and virus replication protects mice against lethal influenza pneumonia. Am J Resp Cell Mol Biol. 2019;61(6):689–701. https://doi.org/10.1165/rcmb.2018-0196OC
3. Zhang J, Zhu Y, Zhou Y, Gao F, Qiu X, Li J, et al. Pediatric adenovirus pneumonia: Clinical practice and current treatment. Front Med. 2023;10:1207568. https://doi.org/10.3389/fmed.2023.1207568
4. Luan Y, Liu H, Luan Y, Yang Y, Yang J, Ren KD. New insight in HDACs: Potential therapeutic targets for the treatment of atherosclerosis. Front Pharmacol. 2022;13:863677. https://doi.org/10.3389/fphar.2022.863677
5. Ghorbani M, Soukhtanloo M, Farrokhi AS, Hassanian SM, Ghorbani F, Afshari AR, et al. Auraptene-induced cytotoxic effects in acute myeloid leukemia cell lines. Med Oncol. 2023;40(8):231. https://doi.org/10.1007/s12032-023-02088-5
6. Goudarzi S, Rassouli FB, Kahrizi D, Paryan S, Mahdifar M, Mehrdad I, et al. Comparing toxicity of galbanic acid, auraptene and umbelliprenin on adult T-cell leukaemia-lymphoma in normoxia and hypoxia. Cell Mol Biol. 2022;68(12):17–20. https://doi.org/10.14715/cmb/2022.68.12.4
7. Kim YH, Lee SY, Kim EY, Kim KH, Koong MK, Lee KA. The antioxidant auraptene improves aged oocyte quality and embryo development in mice. Antioxidants. 2022;12(1).
https://doi.org/ 10.3390/antiox12010087
8. Min JS, Jin YH, Kwon S. Auraptene has antiviral activity against human coronavirus OC43 in MRC-5 cells. Nutrients. 2023;15(13). https://doi.org/10.3390/nu15132960
9. Okuyama S, Minami S, Shimada N, Makihata N, Nakajima M, Furukawa Y. Anti-inflammatory and neuroprotective effects of auraptene, a citrus coumarin, following cerebral global ischemia in mice. Eur J Pharmacol. 2013;699(1–3):118–23. https://doi.org/10.1016/j.ejphar.2012.11.043
10. Sekiguchi H, Takabayashi F, Irie K, Murakami A. Auraptene attenuates gastritis via reduction of helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice. J Med Food. 2012;15(7):658–63. https://doi.org/10.1089/jmf.2011.1844
11. Hsia CW, Wu MP, Shen MY, Hsia CH, Chung CL, Sheu JR. Regulation of human platelet activation and prevention of arterial thrombosis in mice by auraptene through inhibition of NF-kappaB pathway. Int J Mol Sci. 2020;21(13). https://doi.org/ 10.3390/ijms21134810
12. Luan Y, Ren KD, Luan Y, Chen X, Yang Y. Mitochondrial dynamics: Pathogenesis and therapeutic targets of vascular diseases. Front Cardiovasc Med. 2021;8:770574. https://doi.org/ 10.3389/fcvm.2021.770574
13. Ghezelayagh TS, Wu ES, Barber EL, Dao MD, Zsiros E, Urban RR, et al. Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: A multi-institution study. Eur J Gynaecol Oncol. 2023;44(1):17–25.
14. Sayama Y, Okamoto M, Saito M, Tamaki R, Saito-Obata M, Quicho RFN, et al. Lack of zoonotic coronavirus species detected among children hospitalized with pneumonia in the Philippines. Clin Infect Dis. 2023. https://doi.org/10.1093/cid/ciad430
15. Guz D, McNeil R, Buchrits S, Goshen S, Gafter-Gvili A, Avni T. Ceftriaxone 1 g versus 2 g per day, for the treatment of community-acquired pneumonia: a retrospective cohort study. internal and emergency medicine. 2023. https://doi.org/10.1007/s11739-023-03372-y
16. Song S, Xu Y. A retrospective study of the clinical characteristics of 9 children with pulmonary embolism associated with mycoplasma pneumoniae pneumonia. BMC Pediat. 2023;23(1):370. https://doi.org/10.1186/s12887-023-04188-7
17. Gao X, Fu T, Wang C, Ning C, Kong Y, Liu Z, et al. Computational discovery and experimental verification of farnesoid X receptor agonist auraptene to protect against cholestatic liver injury. Biochem Pharmacol. 2017;146:127–38. https://doi.org/10.1016/j.bcp.2017.09.016
18. La VD, Zhao L, Epifano F, Genovese S, Grenier D. Anti-inflammatory and wound healing potential of citrus auraptene. J Med Food. 2013;16(10):961–4. https://doi.org/10.1089/jmf.2013.0029
19. Takahashi N, Senda M, Lin S, Goto T, Yano M, Sasaki T, et al. Auraptene regulates gene expression involved in lipid metabolism through PPAR alpha activation in diabetic obese mice. Mol Nutrit Food Res. 2011;55(12):1791–7. https://doi.org/10.1002/mnfr.201100401
20. Ni Ww, Zhang Qm, Zhang X, Li Y, Yu Ss, Wu Hy, et al. Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model. Allergol Immunopathol. 2020;48(2):149–57. https://doi.org/10.1016/j.aller.2019.06.002
21. Li J, Yan W, Ren F, Sang H. Tectorigenin inhibits inflammation in keratinocytes by inhibition of NLRP3 inflammasome regulated by the TLR4/NF-kappaB pathway. Allergol Immunopathol (Madr). 2023;51(2):82–9. https://doi.org/10.15586/aei.v51i2.780
22. Pandey P, Al Rumaih Z, Kels MJT, Ng E, Kc R, Malley R, et al. Therapeutic targeting of inflammation and virus simultaneously ameliorates influenza pneumonia and protects from morbidity and mortality. Viruses. 2023;15(2). https://doi.org/10.3390/v15020318
23. Wang Y, Jian S, Li W, Zhao L, Ye G, Shi F, et al. Epigallocatechin-3-gallate ameliorates liver injury secondary to pseudomonas aeruginosa pneumonia. Int Immunopharmacol. 2022;112:109239. https://doi.org/10.1016/j.intimp.2022.109239
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Nov 1, 2023
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Wang, Y., Yuan, S., Tan, W., Zhou, Y., Liao, R., & Su, W. (2023). Auraptene alleviates inflammatory injury and cell apoptosis in children with pneumonia in vitro. Allergologia Et Immunopathologia, 51(6), 54-59. https://doi.org/10.15586/aei.v51i6.974
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How to Cite
Wang, Y., Yuan, S., Tan, W., Zhou, Y., Liao, R., & Su, W. (2023). Auraptene alleviates inflammatory injury and cell apoptosis in children with pneumonia in vitro. Allergologia Et Immunopathologia, 51(6), 54-59. https://doi.org/10.15586/aei.v51i6.974