Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cells
Main Article Content
Keywords
dihydrokaempferol, infantile pneumonia, SIRT1, inflammation injury, lipopolysaccharide
Abstract
Background: Globally, pneumonia has been associated as a primary cause of mortality in children aged less than 5 years. Dihydrokaempferol (DHK) has been proposed for being correlated with the process of various diseases. Nevertheless, whether DHK has a role in the progression of infantile pneumonia remains unclear. This study aimed at exploring whether DHK was involved in the progression of infantile pneumonia.
Methods: Human fibroblast cells WI-38 were treated with lipopolysaccharide (LPS). The viability of WI-38 cells was measured via Cell counting kit-8. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed the protein levels of IL-1β, IL-6, TNF-α, Bax, and cleaved-caspase 3. Flow cytometry was applied for exploring the apoptosis of WI-38 cells. The concentrations of IL-1β, IL-6, and TNF-α were assessed via enzyme-linked-immunosorbent serologic assay.
Results: DHK modulated the viability of WI-38 cells in infantile pneumonia. Furthermore, we identified that DHK treatment inversely changed LPS induction-mediated elevation on the levels of inflammation biomarkers. Besides, DHK counteracted LPS-induced production of reactive oxygen species (ROS) in WI-38 cells. DHK also decreased LPS-induced elevation of WI-38 cells apoptosis and mediated the levels of apoptosis-associated indexes. Moreover, modulating sirtuin-1 (SIRT1) protein level was lowered by the induction of LPS, and was reversed by DHK treatment. In addition, DHK counteracted LPS induction-mediated elevation of p-p65 and phosphorylated inhibitor of nuclear factor kappa-B kinase subunit alpha (p-IκBα) protein levels.
Conclusion: DHK alleviated LPS-induced WI-38 cells inflammation injury in infantile pneumonia through SIRT1/NF-κB pathway. The results shed light on the implications of DHK on the prevention and treatment of infantile pneumonia.
References
2. Yang A, Chen C, Hu Y, Zheng G, Chen P, Xie Z et al. Application of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) in diagnosing pneumonia of children. Microbiol Spectr. 2022;10(5):e0148822. 10.1128/spectrum.01488-22
3. Chinese Preventive Medicine Association; Vaccine and Immunology Branch of the Chinese Preventive Medicine Association. Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version). Zhonghua Liu Xing Bing Xue Za Zhi. 2020;54(12):1315–63. 10.3760/cma.j.cn112338-20201111-01322
4. Haesuk Jung, Youngho Seo, Seung Baik Han, Ji Hye Kim, Areum Durey. Risk factors of methicillin-resistant Staphylococcus aureus bacteremic pneumonia in the emergency department. Signa Vitae. 2022;18(5):103–9. https://www.signavitae.com/articles/10.22514/sv.2022.003
5. Wang J, Xu ZH, Lu J. Hospitalization costs for children with pneumonia in Shanghai, China from 2019 to 2020. Hum Vaccin Immunother 2022;18(5):2081459. 10.1080/21645515.2022.2081459
6. Yadav KK Awasthi S. Childhood pneumonia: What's unchanged, and what's new? Indian J Pediatr. 2023;90(7):693–9. 10.1007/s12098-023-04628-3
7. Braune A, Gütschow M, Blaut M. An NADH-dependent reductase from eubacterium ramulus catalyzes the stereospecific heteroring cleavage of flavanones and flavanonols. Appl Environ Microbiol. 2019;85(19):e01233–19. 10.1128/AEM.01233-19
8. Lee JW, Kim NH, Kim JY, Park JH, Shin SY, Kwon YS et al. Aromadendrin inhibits lipopolysaccharide-induced nuclear translocation of NF-κB and phosphorylation of JNK in RAW 264.7 macrophage cells. Biomol Ther (Seoul). 2013;21(3):216–21. 10.4062/biomolther.2013.023
9. Cui S, Cui Y, Li Y, Zhang Y, Wang H, Qin W et al. Inhibition of cardiac hypertrophy by aromadendrin through down-regulating NFAT and MAPKs pathways. Biochem Biophys Res Commun. 2018;506(4):805–11. 10.1016/j.bbrc.2018.10.143
10. Alam F, Mohammadin K, Shafique Z, Amjad ST, Asad MHHB. Citrus flavonoids as potential therapeutic agents: A review. Phytother Res. 2022;36(4):1417–41. 10.1002/ptr.7261
11. Liang X, Hu C, Liu C, Yu K, Zhang J, Jia Y. Dihydrokaempferol (DHK) ameliorates severe acute pancreatitis (SAP) via Keap1/Nrf2 pathway. Life Sci. 2020;261:118340. 10.1016/j.lfs.2020.118340
12. Huang H, Wei S, Wu X, Zhang M, Zhou B, Huang D et al. Dihydrokaempferol attenuates CCl(4)-induced hepatic fibrosis by inhibiting PARP-1 to affect multiple downstream pathways and cytokines. Toxicol Appl Pharmacol. 2023;464:116438. 10.1016/j.taap.2023.116438
13. Zhang J, Hu C, Li X, Liang L, Zhang M, Chen B et al. Protective effect of dihydrokaempferol on acetaminophen-induced liver injury by activating the SIRT1 pathway. Am J Chin Med. 2021;49(3):705–18. 10.1142/S0192415X21500324
14. B K RK, Shrestha S, Adhikari S, Maharjan S et al. Pneumonia among children admitted to the department of medicine in a tertiary care centre: A descriptive cross-sectional study. JNMA J Nepal Med Assoc. 2022;60(253):785–8. 10.31729/jnma.7859
15. Laimoud M, Abdel-moaty M, Elshobary M, Mohamed T, Ahmed W. Predictors of non-invasive ventilation failure in adult patients with cardiac dysfunction presenting with community-acquired pneumonia: An Egyptian multicenter prospective study. Signa Vitae. 2023;19(3):121–31. https://www.signavitae.com/articles/10.22514/sv.2022.078
16. Yang M, Yan Y, Yin X, Wang BY, Dong BR. Chest physiotherapy for pneumonia in adults. Coch Database Syst Rev. 2013;2(2):Cd006338. 10.1002/14651858.CD006338.pub3
17. Bogusławski S, Strzelak A, Gajko K, Peradzyńska J, Popielska J, Marczyńska M et al. The outcomes of COVID-19 pneumonia in children-clinical, radiographic, and pulmonary function assessment. Pediatr Pulmonol. 2023;58(4):1042–50. 10.1002/ppul.26291
18. Udina C, Ars J, Morandi A, Vilaró J, Cáceres C, Inzitari M. Rehabilitation in adult post-COVID-19 patients in post-acute care with therapeutic exercise. J Frailty Aging. 2021;10(3):297–300. 10.14283/jfa.2021.1
19. Zhang J, Wang CH, Liu XJ, Cheng SF, Han LH, Lv CL. Efficacy and safety analysis of dopamine combined with creatine phosphate sodium in the treatment of infantile pneumonia combined with heart failure. J Biol Regul Homeost Agents. 2020;34(6):2103–8. 10.23812/20-300-L
20. Bai D, Han A, Cong S. The effect of down-regulation of CCL5 on lipopolysaccharide-induced WI-38 fibroblast injury: A potential role for infantile pneumonia. Iran J Basic Med Sci. 2018;21(5):449–54. 10.22038/IJBMS.2018.27165.6640
21. Yao YQ, Wang ZW, Ding YX, Yu Y, Jiang WX, Liu XH et al. Effect of Zhifei mixture combined Western drugs on symptoms and signs of children with mycoplasma pneumonia. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014;34(5):522–5. PMid: 24941836.
22. Wu M, Zhang J, Gu R, Dai F, Yang D, Zheng Y et al. The role of Sirtuin 1 in the pathophysiology of polycystic ovary syndrome. Eur J Med Res. 2022;27(1):158. 10.1186/s40001-022-00746-4
23. Karnewar S, Pulipaka S, Katta S, Panuganti D, Neeli PK, Thennati R et al. Mitochondria-targeted esculetin mitigates atherosclerosis in the setting of aging via the modulation of SIRT1-mediated vascular cell senescence and mitochondrial function in Apoe(-/-) mice. Atherosclerosis. 2022;356:28–40. 10.1016/j.atherosclerosis.2022.07.012
24. Liu H, Xu S, Wang C, Deng Y, Xu B, Yang T et al. The beneficial role of sirtuin 1 in preventive or therapeutic options of neurodegenerative diseases. Neuroscience. 2022;504:79–92. 10.1016/j.neuroscience.2022.09.021
25. Fangma Y, Wan H, Shao C, Jin L, He Y. Research progress on the role of sirtuin 1 in cerebral ischemia. Cell Mol Neurobiol. 2023;43(5):1769–83. 10.1007/s10571-022-01288-3
26. Van Le TN, Zoungrana LI, Wang H, Fatmi MK, Ren D, Krause-Hauch M et al. Sirtuin 1 aggravates hypertrophic heart failure caused by pressure overload via shifting energy metabolism. Biochem Biophys Res Commun. 2022;637:170–80. 10.1016/j.bbrc.2022.11.014
27. Zeng Y, Fang Z, Lai J, Wu Z, Lin W, Yao H et al. Activation of sirtuin-1 by pinocembrin treatment contributes to reduced early brain injury after subarachnoid hemorrhage. Oxid Med Cell Longev. 2022;2022:2242833. 10.1155/2022/2242833
28. Fujita Y, Yamashita T. Sirtuins in neuroendocrine regulation and neurological diseases. Front Neurosci. 2018;12:778. 10.3389/fnins.2018.00778
29. Qian Y, Xin Z, Lv Y, Wang Z, Zuo L, Huang X et al. Asiatic acid suppresses neuroinflammation in BV2 microglia via modulation of the Sirt1/NF-κB signaling pathway. Food Funct. 2018;9(2):1048–57. 10.1039/C7FO01442B
30. Song X, Cao W, Wang Z, Li F, Xiao J, Zeng Q et al. Nicotinamide n-oxide attenuates HSV-1-induced microglial inflammation through sirtuin-1/NF-κB signaling. Int J Mol Sci. 2022;23(24):16085. 10.3390/ijms232416085
31. Stark RJ, Koch SR, Stothers CL, Pourquoi A, Lamb CK, Miller MR et al. Loss of sirtuin 1 (SIRT1) potentiates endothelial dysfunction via impaired glycolysis during infectious challenge. Clin Transl Med. 2022;12(9):e1054. 10.1002/ctm2.1054
32. Kim JK, Silwal P, Jo EK. Sirtuin 1 in host defense during Infection. Cells. 2022;11(18):2921. 10.3390/cells11182921
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