Kaempferol and Isorhamnetin alleviate Lipopolysaccharide-Induced Anxiety and Depression-Like Behavioral in Balb/C Mice

PDF
Published: Jul 9, 2023
Updated: 2023-07-09
Versions:
2023-07-09 (2)
DOI: https://doi.org/10.12681/jhvms.30232
Keywords:
Anxiety Depression Oxidative Stress Mice Kaempferol
M Ekici
Sivas Cumhuriyet University, Faculty of Veterinary Medicine, Department of Veterinary Physiology, Sivas
https://orcid.org/0000-0002-2163-6214
H Güngör
Sivas Cumhuriyet University, Faculty of Veterinary Medicine, Department of Veterinary Pharmacology and Toxicology, Sivas
https://orcid.org/0000-0002-2163-6214
DG Mert
Ankara City Hospital, Department of Psychiatry, Ankara
https://orcid.org/0000-0003-0925-339X
Abstract

The etiology of anxiety and depression is linked to inflammation and oxidative stress. Isorhamnetin and Kaempferol are strong antioxidants with antiinflammatory and neuroprotective properties. This study, it was aimed to investigate the effect of Kaempferol and Isorhamnetin in Lipopolysaccharide (LPS)-induced anxiety and depression model in mice. Thirty Balb/C mice were divided into six groups of five mice each weighing 25-35 gr. Kaempferol (50 mg/kg and 100 mg/kg) and Isorhamnetin (30 mg/kg and 60 mg/kg) were given orally to the treatment group, and the vehicle was given to the control and LPS groups for fourteen days, followed by intraperitoneal (0.83 mg/kg) LPS injection (control group excluding) on the fifteenth day. Kaempferol and Isorhamnetin ameliorated LPS-induced anxiety evaluated by open field test, light/dark test, and elevated plus maze test, and LPS-induced depression evaluated by forced swimming test and tail suspension test. Kaempferol and Isorhamnetin alleviated LPS-induced increased oxidative stress in the prefrontal cortex and hippocampus by decreasing MDA and total oxidant status (TOS) levels and increased total antioxidant status (TAS) levels. In addition, it was observed that Kaempferol and Isorhamnetin regulated the increase in prefrontal and hippocampal inflammation caused by LPS by decreasing TNF-α, IL-1β, and IL-6 levels. Most importantly, LPS reduced prefrontal and hippocampal brain-derived neurotrophic factor (BDNF) levels, but the treatment groups reversed it. These results show the possible therapeutic potential of Kaempferol and Isorhamnetin, along with the importance of oxidative stress, inflammation, and BDNF in the etiopathogenesis of anxiety and depression.

Article Details
  • Section
  • Research Articles
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with this journal agree to the following terms:

· Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution Non-Commercial License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

· Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g. post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

· Authors are permitted and encouraged to post their work online (preferably in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.

Downloads
Download data is not yet available.
References
Bouayed J, Rammal, H, Soulimani, R (2009) Oxidative stress and anxiety: relationship and cellular pathways. Oxid Med Cell Longev 2(2):
–67.
Brenes GA (2007) Anxiety, depression, and quality of life in primary care
patients. Prim Care Companion J Clin Psychiatry9(6): 437–443.
Brunoni AR, Lopes M, Fregni F (2008) A systematic review and meta-analysis of clinical studies on major depression and BDNF levels:
implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 11(8):1169–1180.
Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal
steroids in the dentate gyrus. Neuroscience 61(2): 203–209.
Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth
M, Yang C, McEwen BS, Hempstead BL, Lee FS (2006) Genetic
variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314(5796): 140–143.
Cheng X, Yang YL, Yang H, Wang YH, Du GH (2018) Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice
via inhibiting HMGB1 release and down-regulating TLR4/MyD88
pathway. Int Immunopharmacol 56: 29–35.
Chi G, Zhong W, Liu Y, Lu G, Lü H, Wang D, Sun F (2016) Isorhamnetin
protects mice from lipopolysaccharide-induced acute lung injury via
the inhibition of inflammatory responses. Inflamm Res 65(1): 33–41.
Gao W, Wang W, Peng Y, Deng Z (2019) Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory
cytokines and up-regulation of AKT/β-catenin cascade. Metab Brain
Dis 34(2): 485–494.
Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS (1992)
Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci 12(9): 3642–3650.
Grases G, Colom MA, Fernandez RA, Costa-Bauzá A, Grases F (2014)
Evidence of higher oxidative status in depression and anxiety. Oxid
Med Cell Longev 2014: 430216.
Hannestad J, DellaGioia N, Bloch M (2011) The effect of antidepressant
medication treatment on serum levels of inflammatory cytokines: a
meta-analysis. Neuropsychopharmacology 36(12): 2452–2459.
Hussein RM, Mohamed WR, Omar HA (2018) A neuroprotective role of
kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway. Pestic Biochem
Physiol 152: 29–37.
Jamali-Raeufy N, Baluchnejadmojarad T, Roghani M, Keimasi S, Goudarzi M (2019) Isorhamnetin exerts neuroprotective effects in STZ-induced diabetic rats via attenuation of oxidative stress, inflammation
and apoptosis. J Chem Neuroanat 102: 101709.
Jangra A, Lukhi MM, Sulakhiya K, Baruah CC, Lahkar M (2014) Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice. Eur J Pharmacol 740:
–345.
Kalueff AV, Avgustinovich DF, Kudryavtseva NN, Murphy DL (2006)
BDNF in anxiety and depression. Science312(5780);1598–1599.
Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM
(2002) Decreased serum brain-derived neurotrophic factor levels in
major depressed patients. Psychiatry Res 109(2); 143–148.
Ko YH, Kim SK, Lee SY, Jang CG (2020) Flavonoids as therapeutic candidates for emotional disorders such as anxiety and depression. Arch
Pharm Res 43(11); 1128–1143.
Lin YL, Wang S (2014) Prenatal lipopolysaccharide exposure increases
depression-like behaviors and reduces hippocampal neurogenesis in
adult rats. Behav Brain Res 259; 24–34.
Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, Cui R (2017) The Role
of Neural Plasticity in Depression: From Hippocampus to Prefrontal
Cortex. Neural Plast2017; 6871089.
McEwen BS,Morrison JH (2013) The brain on stress: vulnerability and
plasticity of the prefrontal cortex over the life course. Neuron79(1);
–29.
McEwen BS, Nasca C, Gray JD (2016) Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex. Neuropsychopharmacology : Official Publication of the American College of
Neuropsychopharmacology 41(1); 3–23.
Mesfin M, Asres K, Shibeshi W (2014) Evaluation of anxiolytic activity
of the essential oil of the aerial part of Foeniculum vulgare Miller in
mice. BMC Complement Altern Med14; 310.
Mormède C, Palin K, Kelley KW, Castanon N, Dantzer R (2004) Conditioned taste aversion with lipopolysaccharide and peptidoglycan does
not activate cytokine gene expression in the spleen and hypothalamus of mice. Brain Behav Immun18(2); 186–200.
O’Connor JC, Lawson MA, André C, Moreau M, Lestage J, Castanon N,
Kelley KW, Dantzer R (2009) Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 14(5); 511–522.
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal
tissues by thiobarbituric acid reaction. Anal Biochem 95(2); 351–358.
Parrella E, Del Gallo F, Porrini V, Gussago C, Benarese M, Fabene PF,
Pizzi M (2022) Age-Dependent Neuropsychiatric Symptoms in the
NF-κB/c-Rel Knockout Mouse Model of Parkinson’s Disease. Front
Behav Neurosci 11(16); 831664.
Peng J, Liu Y, Umpierre AD, Xie M, Tian DS, Richardson JR, Wu LJ
(2019) Microglial P2Y12 receptor regulates ventral hippocampal
CA1 neuronal excitability and innate fear in mice. Mol Brain 12(1);
Rammal H, Bouayed J, Younos C, Soulimani R (2008) Evidence that oxidative stress is linked to anxiety-related behaviour in mice. Brain
Behav Immun 22(8); 1156–1159.
Sah SP, Tirkey N, KuhadA, Chopra K (2011) Effect of quercetin on lipopolysaccharide induced-sickness behavior and oxidative stress in
rats. Indian J Pharmacol 43(2); 192–196.
Saki K, Bahmani M,Rafieian-Kopaei M (2014) The effect of most important medicinal plants on two importnt psychiatric disorders (anxiety
and depression)-a review. Asian Pac J Trop Med 7S1; S34-42.
Satomura E, Baba H, Nakano Y, Maeshima H, Suzuki T, Arai H (2011)
Correlations between brain-derived neurotrophic factor and clinical
symptoms in medicated patients with major depression. J Affect Disord 135(1–3); 332–335.
Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C,
Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in
depressed patients with or without antidepressants. Biol Psychiatry
(1); 70–75.
Steimer T (2002) The biology of fear- and anxiety-related behaviors. Dialogues Clin Neurosci 4(3); 231–249.
Sulakhiya K, Keshavlal GP, Bezbaruah BB, Dwivedi S, Gurjar SS, Munde
N, Jangra A, Lahkar M, Gogoi R (2016) Lipopolysaccharide induced
anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin. Neurosci Lett 611; 106–111.
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.
Xu SL, Choi RCY, Zhu KY, Leung K-W, Guo AJY, Bi D, Xu H, Lau
DTW, Dong TTX, Tsim KWK (2012) Isorhamnetin, A Flavonol
Aglycone from Ginkgo biloba L., Induces Neuronal Differentiation
of Cultured PC12 Cells: Potentiating the Effect of Nerve Growth Factor. Evid Based Complement Alternat Med 2012; 278273.
Zhang L-M, Yao J-Z, Li Y, Li K, ChenH-X, Zhang Y.-Z,Li Y-F (2012)
Anxiolytic effects of flavonoids in animal models of posttraumatic
stress disorder. Evid Based Complement Alternat Med 2012; 623753.
Zhao JJ, Song JQ, Pan SY, Wang K (2016) Treatment with Isorhamnetin
Protects the Brain Against Ischemic Injury in Mice. Neurochem Res
(8); 1939–1948.
Most read articles by the same author(s)