Dissecting the antidepressant effect of troxerutin: modulation of neuroinflammatory and oxidative stress biomarkers in lipopolysaccharide-treated mice

• Abdulrahim HA, Alagbonsi IA, Amuda O, Omeiza NA, Feyitimi ARA, Olayaki LA (2021) Cannabis sativa and/or melatonin do not alter brain lipid but alter oxidative mechanisms in female rats. Journal of Cannabis Research 3(1):1–10

  Article  Google Scholar 

• Adebayo OG, Otene CI, Emmanuel, M. U., Onwuka, F. C., Aduema, W., Ben-Azu, B., Omeiza, N. A., ... & Onasanwo, S. A. (2023). Chronic intermittent oxygen deprivation alters hippocampal cholinergic and glutamatergic system via oxido-inflammatory burden and HIF-1a/Bcl-2 activity in hypothyroid mice: ameliorative role of Ginkgo biloba supplement. Phytomedicine Plus, 3(2):100451

• Akanmu MA, Olowookere TA, Atunwa SA, Ibrahim BO, Lamidi OF, Adams PA, ..., Adeyemo LE (2011) Neuropharmacological effects of Nigerian honey in mice. Afr J Tradit Complement Altern Med 8(3)

• Anisman H, Merali Z (2003) Cytokines, stress and depressive illness: brain-immune interactions. Ann Med 35(1):2–11

  Article  CAS  PubMed  Google Scholar 

• Anjomshoa M, Boroujeni SN, Ghasemi S, Lorigooini Z, Amiri A, Balali-Dehkordi S, Amini-Khoei H (2020) Rutin via increase in the CA3 diameter of the hippocampus exerted antidepressant‐like effect in mouse model of maternal separation stress: possible involvement of NMDA receptors. Behav Neuro 2020(1):4813616

• Batista CRA, Gomes GF, Candelario-Jalil E, Fiebich BL, De Oliveira ACP (2019) Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration. Int J Mol Sci 20(9):2293

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Benasi G, Fava GA, Guidi J (2021) Prodromal symptoms in depression: a systematic review. Psychother Psychosom 90(6):365–372

  Article  PubMed  Google Scholar 

• Ben-Azu B, Adebesin A, Moke GE, Ojiokor VO, Olusegun A, Jarikre TA, ..., Omamogho F (2024) Alcohol exacerbates psychosocial stress-induced neuropsychiatric symptoms: Attenuation by geraniol. Neurochem Int 177:105748

• Bianchi M, Canavesi R, Aprile S, Grosa G, Del Grosso E (2018) Troxerutin, a mixture of O-hydroxyethyl derivatives of the natural flavonoid rutin: chemical stability and analytical aspects. J Pharm Biomed Anal 150:248–257

  Article  CAS  PubMed  Google Scholar 

• Bodnoff SR, Suranyi-Cadotte B, Aitken DH, Quirion R, Meaney MJ (1988) The effects of chronic antidepressant treatment in an animal model of anxiety. Psychopharmacology 95:298–302

  Article  CAS  PubMed  Google Scholar 

• Brent D, Maalouf F (2015) Depressive disorders in childhood and adolescence. Rutter's child and adolescent psychiatry 874–892

• Carabelli B, Delattre AM, Waltrick APF, Araujo G, Suchecki D, Machado RB, ..., Ferraz AC (2020) Fish-oil supplementation decreases Indoleamine-2, 3-Dioxygenase expression and increases hippocampal serotonin levels in the LPS depression model. Behav Brain Res 390:112675

• Caspani G, Kennedy S, Foster JA, Swann J (2019) Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microbial Cell 6(10):454

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Dantzer R, O’connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Eneni AEO, Ben-Azu B, Ajayi AM, Aderibibge AO (2023) Lipopolysaccharide exacerbates ketamine-induced psychotic-like behavior, oxidative stress, and neuroinflammation in mice: ameliorative effect of diosmin. J Mol Neurosci 73(2–3):129–142

  Article  CAS  PubMed  Google Scholar 

• Forbes EE, Dahl RE (2005) Neural systems of positive affect: relevance to understanding child and adolescent depression? Dev Psychopathol 17(3):827–850

  Article  PubMed  PubMed Central  Google Scholar 

• Ge L, Liu L, Liu H, Liu S, Xue H, Wang X, ..., Liu D (2015) Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice. Eur J Pharmacol 768:49–57

• Gerhard DM, Wohleb ES, Duman RS (2016) Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity. Drug Discovery Today 21(3):454–464

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Ghafarimoghadam M, Mashayekh R, Gholami M, Fereydani P, Shelley-Tremblay J, Kandezi N, ... Motaghinejad, M (2022) A review of behavioral methods for the evaluation of cognitive performance in animal models: current techniques and links to human cognition. Physiol Behavior 244:113652

• Ghanaatfar F, Ghanaatfar A, Isapour P, Farokhi N, Bozorgniahosseini S, Javadi M, ..., Motaghinejad M (2023) Is lithium neuroprotective? An updated mechanistic illustrated review. Fundam Clin Pharmacol 37(1):4–30

• Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126(1):131–138

  Article  CAS  PubMed  Google Scholar 

• Han H, Zhang J, Chen Y, Shen M, Yan E, Wei C, ..., Wang T (2020) Dietary taurine supplementation attenuates lipopolysaccharide-induced inflammatory responses and oxidative stress of broiler chickens at an early age. J Anim Sci 98(10):skaa311

• Hasin DS, Sarvet AL, Meyers JL, Saha TD, Ruan WJ, Stohl M, Grant BF (2018) Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiat 75(4):336–346

  Article  Google Scholar 

• Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, ..., Godbout JP (2008) Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation 5(1):1–14

• Hritcu L, Ionita R, Postu PA, Gupta GK, Turkez H, Lima TC, ..., de Sousa DP (2017) Antidepressant flavonoids and their relationship with oxidative stress. Oxid Med Cell Longev 2017(1):5762172

• Ilçe F, Gök G, Pandir D (2019) Acute effects of lipopolysaccharide (LPS) in kidney of rats and preventive role of vitamin E and sodium selenite. Hum Exp Toxicol 38(5):547–560

  Article  PubMed  Google Scholar 

• Ingram S, Mengozzi M, Heikal L, Mullen L, Ghezzi P (2019) Inflammation-induced reactive nitrogen species cause proteasomal degradation of dimeric peroxiredoxin-1 in a mouse macrophage cell line. Free Radical Res 53(8):875–881

  Article  CAS  Google Scholar 

• Isibor H, Ajayi AM, Ben-Azu B, Omeiza NA, Ademola AP, Umukoro S (2022) D-ribose-L-cysteine reduces oxidative stress and inflammatory cytokines to mitigate liver damage, and memory decline induced by copper sulfate in mice. J Trace Elem Med Biol 73:127001

  Article  CAS  PubMed  Google Scholar 

• Jamali-Raeufy N, Kardgar S, Baluchnejadmojarad T, Roghani M, Goudarzi M (2019) Troxerutin exerts neuroprotection against lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting SIRT1/SIRT3 signaling pathway. Metab Brain Dis 34:1505–1513

  Article  CAS  PubMed  Google Scholar 

• Jamali-Raeufy N, Alizadeh F, Mehrabi Z, Mehrabi S, Goudarzi M (2021) Acetyl-L-carnitine confers neuroprotection against lipopolysaccharide (LPS)-induced neuroinflammation by targeting TLR4/NFκB, autophagy, inflammation and oxidative stress. Metab Brain Dis 36:1391–1401

  Article  CAS  PubMed  Google Scholar 

• Jang S, Johnson RW (2010) Can consuming flavonoids restore old microglia to their youthful state? Nutr Rev 68(12):719–728

  Article  PubMed  Google Scholar 

• Jazvinšćak Jembrek M, Oršolić N, Karlović D, Peitl V (2023) Flavonols in action: targeting oxidative stress and neuroinflammation in major depressive disorder. Int J Mol Sci 24(8):6888

  Article  PubMed  PubMed Central  Google Scholar 

• Jeon SW, Kim YK (2016) Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? World Journal of Psychiatry 6(3):283

  Article  PubMed  PubMed Central  Google Scholar 

• Karthika C, Najda A, Klepacka J, Zehravi M, Akter R, Akhtar MF, ..., Rahman MH (2022) Involvement of resveratrol against brain cancer: a combination strategy with a pharmaceutical approach. Molecules 27(14):4663

• Kaster MP, Gadotti VM, Calixto JB, Santos AR, Rodrigues ALS (2012) Depressive-like behavior induced by tumor necrosis factor-α in mice. Neuropharmacology 62(1):419–426

  Article  CAS  PubMed  Google Scholar 

• Kaur G, Tirkey N, Chopra K (2006a) Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity. Toxicology 226(2–3):152–160

  Article  CAS  PubMed  Google Scholar 

• Kaur G, Tirkey N, Bharrhan S, Chanana V, Rishi P, Chopra K (2006b) Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents. Clin Exp Immunol 145(2):313–321

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Lasselin J, Schedlowski M, Karshikoff B, Engler H, Lekander M, Konsman JP (2020) Comparison of bacterial lipopolysaccharide-induced sickness behavior in rodents and humans: relevance for symptoms of anxiety and depression. Neurosci Biobehav Rev 115:15–24

  Article  CAS  PubMed  Google Scholar 

• Li Y, Du Y, Yang J, Xiu Z, Yang N, Zhang J, ..., Shi H (2018) Narirutin produces antidepressant-like effects in a chronic unpredictable mild stress mouse model. Neuroreport 29(15):1264–1268

• Malhi GS, Mann JJ (2018) Course and prognosis. Lancet 392(10161):2299–2312

  Article  PubMed  Google Scholar 

• Malik AAK, Ahmad W, Younas F, Badshah H, Alharazy S, Rehman SU, ..., Ullah I (2023) Pretreatment with troxerutin protects/improves neurological deficits in a mouse model of traumatic brain injury. Heliyon 9(7)

• Maria Michel T, Pulschen D, Thome J (2012) The role of oxidative stress in depressive disorders. Curr Pharm Des 18(36):5890–5899

  Article  Google Scholar 

• Masood MI, Schäfer KH, Naseem M, Weyland M, Meiser P (2020) Troxerutin flavonoid has neuroprotective properties and increases neurite outgrowth and migration of neural stem cells from the subventricular zone. PLoS ONE 15(8):e0237025

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Matsuura M (2013) Structural modifications of bacterial lipopolysaccharide that facilitate gram-negative bacteria evasion of host innate immunity. Front Immunol 4:109

  Article  PubMed  PubMed Central  Google Scholar 

• Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175

  Article  CAS  PubMed  Google Scholar 

• Mokhtari-Zaer A, Norouzi F, Askari VR, Khazdair MR, Roshan NM, Boskabady M, ..., Boskabady MH (2020) The protective effect of Nigella sativa extract on lung inflammation and oxidative stress induced by lipopolysaccharide in rats. J Ethnopharmacol 253:112653

• Montoya T, Sánchez-Hidalgo M, Castejón ML, Rosillo MÁ, González-Benjumea A, Alarcón-de-la-Lastra C (2021) Dietary oleocanthal supplementation prevents inflammation and oxidative stress in collagen-induced arthritis in mice. Antioxidants 10(5):650

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582(1):67–78

• Motaghinejad M, Motevalian M, Falak R, Heidari M, Sharzad M, Kalantari E (2016) Neuroprotective effects of various doses of topiramate against methylphenidate-induced oxidative stress and inflammation in isolated rat amygdala: the possible role of CREB/BDNF signaling pathway. J Neural Transm 123:1463–1477

  Article  CAS  PubMed  Google Scholar 

• Noworyta-Sokołowska K, Górska A, Gołembiowska K (2013) LPS-induced oxidative stress and inflammatory reaction in the rat striatum. Pharmacol Rep 65(4):863–869

  Article  PubMed  Google Scholar 

• Ohgi Y, Futamura T, Kikuchi T, Hashimoto K (2013) Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav 103(4):853–859

  Article  CAS  PubMed  Google Scholar 

• Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

  Article  CAS  PubMed  Google Scholar 

• Omeiza NA, Abdulrahim HA, Alagbonsi AI, Ezurike PU, Soluoku TK, Isiabor H, Alli-oluwafuyi AA (2021) Melatonin salvages lead-induced neuro-cognitive shutdown, anxiety, and depressive-like symptoms via oxido-inflammatory and cholinergic mechanisms. Brain and Behavior 11(8):e2227

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Omeiza NA, Bakre AG, Abdulrahim HA, Isibor H, Ezurike PU, Sowunmi AA, ..., Aderibigbe AO (2022) Pretreatment with Carpolobia lutea ethanol extract prevents schizophrenia-like behavior in mice models of psychosis. J Ethnopharmacol 295:115432

• Omeiza NA, Bakre A, Ben-Azu B, Sowunmi AA, Abdulrahim HA, Chimezie J, ..., Aderibigbe AO (2023) Mechanisms underpinning Carpolobia lutea G. Don ethanol extract’s neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia. J Ethnopharmacol 301:115767

• Oredeko OM, Omeiza NA, Ben-Azu B, Ogiogio HA, Falade J, Aderibigbe AO, Gbotosho GO (2023) Anthocleista vogelii (Planch) stem bark ethanol extract prevents inflammatory and pain phenotypes in experimental rodent models by modulating oxido-inflammatory mediators. Phytomedicine plus 3(3):100475

  Article  Google Scholar 

• Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD (2020) Inflammatory markers in depression: a meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain Behav Immun 87:901–909

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. Journal of Nutritional Science 5:e47

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Porsolt RD, Bertin A, Jalfre MJAIP (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229(2):327–336

  CAS  PubMed  Google Scholar 

• Prestwood TR, Asgariroozbehani R, Wu S, Agarwal SM, Logan RW, Ballon JS, ..., Freyberg Z (2021) Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia. Behav Brain Res 402:113101

• Roumestan C, Michel A, Bichon F, Portet K, Detoc M, Henriquet C, ..., Mathieu M (2007) Anti-inflammatory properties of desipramine and fluoxetine. Respir Res 8:1–11

• Salzano S, Checconi P, Hanschmann EM, Lillig CH, Bowler LD, Chan P, ..., Ghezzi P (2014) Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proc Natl Acad Sci 111(33):12157–12162.

• Samuels BA, Hen R (2011) Novelty-suppressed feeding in the mouse. Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests II:107–121

  Article  Google Scholar 

• Sangaran PG, Ibrahim ZA, Chik Z, Mohamed Z, Ahmadiani A (2021) LPS preconditioning attenuates apoptosis mechanism by inhibiting NF-κB and caspase-3 activity: TLR4 pre-activation in the signaling pathway of LPS-induced neuroprotection. Mol Neurobiol 58:2407–2422

  Article  CAS  PubMed  Google Scholar 

• Sellmeijer J (2016) The ACC is a critical hub for neuropathic pain-induced depression (Doctoral dissertation, University_of_Basel)

• Sharpley CF, Bitsika V (2013) Differences in neurobiological pathways of four “clinical content” subtypes of depression. Behav Brain Res 256:368–376

  Article  PubMed  Google Scholar 

• Stepanichev M, Manolova A, Peregud D, Onufriev M, Freiman S, Aniol V, ..., Gulyaeva N (2018) Specific activity features in the forced swim test: brain neurotrophins and development of stress-induced depressive-like behavior in rats. Neurosci. 375:49–61

• Stone TW, Williams RO (2023) Tryptophan metabolism as a ‘reflex’ feature of neuroimmune communication: sensor and effector functions for the indoleamine‐2, 3‐dioxygenase kynurenine pathway. J Neurochem

• Strawbridge R, Arnone D, Danese A, Papadopoulos A, Vives AH, Cleare AJ (2015) Inflammation and clinical response to treatment in depression: a meta-analysis. Eur Neuropsychopharmacol 25(10):1532–1543

  Article  CAS  PubMed  Google Scholar 

• Sulakhiya K, Kumar P, Jangra A, Dwivedi S, Hazarika NK, Baruah CC, Lahkar M (2014) Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice. Eur J Pharmacol 744:124–131

  Article  CAS  PubMed  Google Scholar 

• Sun E, Motolani A, Campos L, Lu T (2022) The pivotal role of NF-KB in the pathogenesis and therapeutics of Alzheimer’s disease. Int J Mol Sci 23(16):8972

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Thomas NS, George K, Selvam AAA (2019) Anticancer mechanism of troxerutin via targeting Nrf2 and NF-κB signalling pathways in hepatocarcinoma cell line. Toxicol in Vitro 54:317–329

  Article  CAS  PubMed  Google Scholar 

• Venkataramana S, Lourenssen S, Miller KG, Blennerhassett MG (2015) Early inflammatory damage to intestinal neurons occurs via inducible nitric oxide synthase. Neurobiol Dis 75:40–52

  Article  CAS  PubMed  Google Scholar 

• Wang T, Wang J, Sun T, Li Y (2021) Amelioration of Juglanin against LPS-induced activation of NLRP3 inflammasome in chondrocytes mediated by SIRT1. Inflammation 44:1119–1129

  Article  PubMed  Google Scholar 

• Wang T, Sun X, Qin W, Zhang X, Wu L, Li Y, ..., Cong H (2019) From inflammatory reactions to neurotransmitter changes: implications for understanding the neurobehavioral changes in mice chronically infected with Toxoplasma gondii. Behav Brain Res 359:737–748

• Wei X, Zhang L, Zhang R, Koci M, Si D, Ahmad B, ..., Zhang M (2020) A novel cecropin-LL37 hybrid peptide protects mice against EHEC infection-mediated changes in gut microbiota, intestinal inflammation, and impairment of mucosal barrier functions. Front Immunol 11:1361

• Wu S, Pan L, Liao H, Yao W, Shen N, Chen C, ..., Ge M (2020) High-fat diet increased NADPH-oxidase-related oxidative stress and aggravated LPS-induced intestine injury. Life Sci 253:117539

• Yankelevitch-Yahav R, Franko M, Huly A, Doron R (2015) The forced swim test as a model of depressive-like behavior. JoVE (journal of Visualized Experiments) 97:e52587

  Google Scholar 

• Yu Y, Li Y, Qi K, Xu W, Wei Y (2022) Rosmarinic acid relieves LPS-induced sickness and depressive-like behaviors in mice by activating the BDNF/Nrf2 signaling and autophagy pathway. Behav Brain Res 433:114006

  Article  CAS  PubMed  Google Scholar 

• Zhang G, Stackman RW Jr (2015) The role of serotonin 5-HT2A receptors in memory and cognition. Front Pharmacol 6:225

  Article  PubMed  PubMed Central  Google Scholar 

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