Protective effects of quercetin on traumatic brain injury-induced inflammation and oxidative stress in cortex through activating Nrf2/HO-1 pathway

  • Jianqiang Song Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, China
  • Guoliang Du Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, China
  • Haiyun Wu Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, China
Keywords: Quercetin, traumatic brain injury, neuroinflammation, oxidative stress

Abstract

Background: Traumatic brain injury (TBI) has been a serious public health issue. Clinically, there is an urgent need for agents to ameliorate the neuroinflammation and oxidative stress induced by TBI. Our previous research has demonstrated that quercetin could protect the neurological function. However, the detailed mechanism underlying this process remains poorly understood. This research was designed to investigate the mechanisms of quercetin to protect the cortical neurons.

Methods: A modified weight-drop device was used for the TBI model. 5, 20, or 50 mg/kg quercetin was injected intraperitoneally to rats at 0.5, 12, and 24 h post-TBI. Rats were sacrificed 3 days post-injury, and their cerebral cortex was obtained from the injured side. The rats were randomly assigned into three groups of equal number: TBI and quercetin group, TBI group, and Sham group. The brain water content was calculated to estimate the brain damage induced by TBI. Immunohistochemical and Western blot assays were utilized to investigate the neurobehavioral status. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction were performed to evaluate the inflammatory responses. The cortical oxidative stress was measured by estimating the activities of malondialdehyde, superoxide dismutase, catalase, and glutathione-Px. Western blot was utilized to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1).

Results: Quercetin attenuated the brain edema and microgliosis in TBI rats. Quercetin treatment attenuated cortical inflammatory responses and oxidative stress induced by TBI insults. Quercetin treatment activated the cortical Nrf2/HO-1 pathway in TBI rats.

Conclusions: Quercetin ameliorated the TBI-induced neuroinflammation and oxidative stress in the cortex through activating the Nrf2/HO-1 pathway.

Downloads

Download data is not yet available.

References

Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury: an overview of epidemiology, pathophysiology, and medical management. Med Clin North Am 2020; 104(2): 213–38. doi: 10.1016/j.mcna.2019.11.001

Sulhan S, Lyon KA, Shapiro LA, Huang JH. Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: pathophysiology and potential therapeutic targets. J Neurosci Res 2020; 98(1): 19–28. doi: 10.1002/jnr.24331

Pavlovic D, Pekic S, Stojanovic M, Popovic V. Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary 2019; 22(3): 270–82. doi: 10.1007/s11102-019-00957-9

Hiebert JB, Shen Q, Thimmesch AR, Pierce JD. Traumatic brain injury and mitochondrial dysfunction. Am J Med Sci 2015; 350(2): 132–8. doi: 10.1097/MAJ.0000000000000506

Kempuraj D, Ahmed ME, Selvakumar GP, Thangavel R, Raikwar SP, Zaheer SA, et al. Mast cell activation, neuroinflammation, and tight junction protein derangement in acute traumatic brain injury. Mediators Inflamm 2020; 2020: 4243953. doi: 10.1155/2020/4243953

Jiang Z, Tang M. Inflammatory events drive neural stem cell migration by elevating stromal-derived factor 1 alpha. STEMedicine 2020; 1(3): e59. doi: 10.37175/stemedicine.v1i3.59

Takada S, Sakakima H, Matsuyama T, Otsuka S, Nakanishi K, Norimatsu K, et al. Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation. J Neuroinflammation 2020; 17(1): 40. doi: 10.1186/s12974-020-1709-8

Sharma R, Kambhampati SP, Zhang Z, Sharma A, Chen S, Duh EI, et al. Dendrimer mediated targeted delivery of sinomenine for the treatment of acute neuroinflammation in traumatic brain injury. J Control Release 2020; 323: 361–75. doi: 10.1016/j.jconrel.2020.04.036

D’Andrea G. Quercetin: a flavonol with multifaceted therapeutic applications? Fitoterapia 2015; 106: 256–71. doi: 10.1016/j.fitote.2015.09.018

Rauf A, Imran M, Khan IA, Ur-Rehman M, Gilani SA, Mehmood Z, et al. Anticancer potential of quercetin: a comprehensive review. Phytother Res 2018; 32(11): 2109–30. doi: 10.1002/ptr.6155

Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and its anti-allergic immune response. Molecules 2016; 21(5): 623. doi: 10.3390/molecules21050623

Eid HM, Haddad PS. The antidiabetic potential of quercetin: underlying mechanisms. Curr Med Chem 2017; 24(4): 355–64. doi: 10.2174/0929867323666160909153707

Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules 2019; 24(6): 1123. doi: 10.3390/molecules24061123

Belviranli M, Okudan N. Well-known antioxidants and newcomers in sport nutrition: coenzyme Q10, quercetin, resveratrol, pterostilbene, pycnogenol and astaxanthin. In: Lamprecht M, ed. Antioxidants in Sport Nutrition. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 5.

Liu W, Zhang M, Feng J, Fan A, Zhou Y, Xu Y. The influence of quercetin on maternal immunity, oxidative stress, and inflammation in mice with exposure of fine particulate matter during gestation. Int J Environ Res Public Health 2017; 14(6): 592. doi: 10.3390/ijerph14060592

Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients 2016; 8(3): 167. doi: 10.3390/nu8030167

Spagnuolo C, Moccia S, Russo GL. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 2018; 153: 105–15. doi: 10.1016/j.ejmech.2017.09.001

Juurlink BH, Paterson PG. Review of oxidative stress in brain and spinal cord injury: suggestions for pharmacological and nutritional management strategies. J Spinal Cord Med 1998; 21(4): 309–34. doi: 10.1080/10790268.1998.11719540

Bala A, Panditharadyula SS. Role of nuclear factor erythroid 2-related factor 2 (NRF-2) mediated antioxidant response on the synergistic antitumor effect of L-arginine and 5-fluro uracil (5FU) in breast adenocarcinoma. Curr Pharm Des 2019; 25(14): 1643–52. doi: 10.2174/1381612825666190705205155

Ahmed SM, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 2017; 1863(2): 585–97. doi: 10.1016/j.bbadis.2016.11.005

Agca CA, Tuzcu M, Hayirli A, Sahin K. Taurine ameliorates neuropathy via regulating NF-kappaB and Nrf2/HO-1 signaling cascades in diabetic rats. Food Chem Toxicol 2014; 71: 116–21. doi: 10.1016/j.fct.2014.05.023

Du G, Zhao Z, Chen Y, Li Z, Tian Y, Liu Z, et al. Quercetin protects rat cortical neurons against traumatic brain injury. Mol Med Rep 2018; 17(6): 7859–65. doi: 10.3892/mmr.2018.8801

Chen X, Pan Z, Fang Z, Lin W, Wu S, Yang F, et al. Omega-3 polyunsaturated fatty acid attenuates traumatic brain injury-induced neuronal apoptosis by inducing autophagy through the upregulation of SIRT1-mediated deacetylation of Beclin-1. J Neuroinflammation 2018; 15(1): 310. doi: 10.1186/s12974-018-1345-8

Stocchetti N, Taccone FS, Citerio G, Pepe PE, Le Roux PD, Oddo M, et al. Neuroprotection in acute brain injury: an up-to-date review. Crit Care 2015; 19: 186. doi: 10.1186/s13054-015-0887-8

Roozenbeek B, Maas AI, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 2013; 9(4): 231–6. doi: 10.1038/nrneurol.2013.22

DeKosky ST, Asken BM. Injury cascades in TBI-related neurodegeneration. Brain Inj 2017; 31(9): 1177–82. doi: 10.1080/02699052.2017.1312528

Pearn ML, Niesman IR, Egawa J, Sawada A, Almenar-Queralt A, Shah SB, et al. Pathophysiology associated with traumatic brain injury: current treatments and potential novel therapeutics. Cell Mol Neurobiol 2017; 37(4): 571–85. doi: 10.1007/s10571-016-0400-1

Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, et al. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn 2018; 18(2): 165–80. doi: 10.1080/14737159.2018.1428089

Loane DJ, Kumar A. Microglia in the TBI brain: the good, the bad, and the dysregulated. Exp Neurol 2016; 275(Pt 3): 316–27. doi: 10.1016/j.expneurol.2015.08.018

Dinet V, Petry KG, Badaut J. Brain-immune interactions and neuroinflammation after traumatic brain injury. Front Neurosci 2019; 13: 1178. doi: 10.3389/fnins.2019.01178

Yang H, Yang T, Heng C, Zhou Y, Jiang Z, Qian X, et al. Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice. Phytother Res 2019; 33(12): 3140–52. doi: 10.1002/ptr.6486

Roslan J, Giribabu N, Karim K, Salleh N. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats. Biomed Pharmacother 2017; 86: 570–82. doi: 10.1016/j.biopha.2016.12.044

Luo M, Tian R, Yang Z, Peng YY, Lu N. Quercetin suppressed NADPH oxidase-derived oxidative stress via heme oxygenase-1 induction in macrophages. Arch Biochem Biophys 2019; 671: 69–76. doi: 10.1016/j.abb.2019.06.007

Published
2023-12-13
How to Cite
SongJ., DuG., & WuH. (2023). Protective effects of quercetin on traumatic brain injury-induced inflammation and oxidative stress in cortex through activating Nrf2/HO-1 pathway. STEMedicine, 5(1), e189. https://doi.org/10.37175/stemedicine.v5i1.189
Section
Research articles