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Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats

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Abstract

Inflammation can cause memory impairment. In the present study, the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide (LPS)-challenged rats was evaluated. The animals were grouped and treated: (1) control which received vehicle instead of LPS and carvacrol, (2) LPS (1 mg/kg; i.p. 120 min before behavioral tests), and (3–5) in these groups, 25, 50, or 100 mg/kg of carvacrol (i.p.) was administered 30 min prior to LPS. In a Morris water maze test, compared to LPS group, administration of all three doses of carvacrol shortened the elapsed time and the traveled distance to find the platform, while it prolonged the traveled time in the target area. In a passive avoidance test, administration of all 25, 50, and 100 mg/kg carvacrol significantly increased the latency at the 3 h, 24 h, 48 h, and 72 h after the shock compared to the LPS group. Interleukin (IL)-6, malondialdehyde (MDA), and NO (nitric oxide) metabolites were increased in the brain by LPS injection, while thiol, superoxide dismutase (SOD), and catalase (CAT) were decreased. Pretreatment with carvacrol reduced IL-6, NO metabolites, and MDA, while it improved thiol content, CAT, and SOD. The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress in LPS-challenged rats.

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References

  • Abareshi A, Anaeigoudari A, Norouzi F et al (2016a) Lipopolysaccharide-induced spatial memory and synaptic plasticity impairment is preventable by captopril. Adv Med 2016:7676512

    Article  Google Scholar 

  • Abareshi A, Hosseini M, Beheshti F et al (2016b) The effects of captopril on lipopolysaccharide induced learning and memory impairments and the brain cytokine levels and oxidative damage in rats. Life Sci 167:46–56

    Article  CAS  Google Scholar 

  • Aebi H (1984) [13] catalase in vitro Methods in Enzymology, vol 105. Academic Press, Cambridge, pp 121–126

    Google Scholar 

  • Aeschbach R, Löliger J, Scott B, Murcia A, Butler J, Halliwell B, Aruoma OI (1994) Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol. Food Chem Toxicol 32:31–36

    Article  CAS  Google Scholar 

  • Bargi R, Asgharzadeh F, Beheshti F, Hosseini M, Sadeghnia HR, Khazaei M (2017) The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine 96:173–184

    Article  CAS  Google Scholar 

  • Barrientos RM, Higgins EA, Biedenkapp JC et al (2006) Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging 27:723–732

    Article  Google Scholar 

  • Benveniste EN (1992) Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Phys Cell Phys 263:C1–C16

    Article  CAS  Google Scholar 

  • Chenet AL, Duarte AR, de Almeida FJS, Andrade CMB, de Oliveira MR (2019) Carvacrol depends on Heme Oxygenase-1 (HO-1) to exert antioxidant, anti-inflammatory, and mitochondria-related protection in the human Neuroblastoma SH-SY5Y cells line exposed to hydrogen peroxide. Neurochem Res 44:884–896. https://doi.org/10.1007/s11064-019-02724-5

    Article  CAS  PubMed  Google Scholar 

  • da Silva Lima M, Quintans-Júnior LJ, de Santana WA et al (2013) Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10. Eur J Pharmacol 699:112–117

    Article  Google Scholar 

  • Dati LM, Ulrich H, Real CC, Feng ZP, Sun HS, Britto LR (2017) Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neuroscience 356:176–181. https://doi.org/10.1016/j.neuroscience.2017.05.013

    Article  CAS  PubMed  Google Scholar 

  • Deng W, Lu H, Teng J (2013) Carvacrol attenuates diabetes-associated cognitive deficits in rats. J Mol Neurosci 51:813–819

    Article  CAS  Google Scholar 

  • Ferrero-Miliani L, Nielsen O, Andersen P, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1β generation. Clin Exp Immunol 147:227–235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gilroy DW, Newson J, Sawmynaden P et al (2004) A novel role for phospholipase A2 isoforms in the checkpoint control of acute inflammation. FASEB J 18:489–498

    Article  CAS  Google Scholar 

  • González H, Elgueta D, Montoya A, Pacheco R (2014) Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J Neuroimmunol 274:1–13

    Article  Google Scholar 

  • Haddadi H, Rajaei Z, Alaei H, Shahidani S (2018) Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson's disease. Arq Neuropsiquiatr 76:71–77

    Article  Google Scholar 

  • Hamzehloei L, Rezvani ME, Rajaei Z (2019) Effects of carvacrol and physical exercise on motor and memory impairments associated with Parkinson's disease. Arq Neuropsiquiatr 77:493–500

    Article  Google Scholar 

  • Karkabounas S, Kostoula O, Daskalou T, Veltsistas P, Karamouzis M, Zelovitis I, Metsios A, Lekkas P, Evangelou AM, Kotsis N, Skoufos I (2006) Anticarcinogenic and antiplatelet effects of carvacrol. Exp Oncol 28:121–125

    CAS  PubMed  Google Scholar 

  • Khalil A, Kovac S, Morris G, Walker MC (2017) Carvacrol after status epilepticus (SE) prevents recurrent SE, early seizures, cell death, and cognitive decline. Epilepsia 58:263–273

    Article  CAS  Google Scholar 

  • Khazdair MR, Boskabady MH (2019) The effect of carvacrol on inflammatory mediators and respiratory symptoms in veterans exposed to sulfur mustard, a randomized, placebo-controlled trial. Respir Med 150:21–29. https://doi.org/10.1016/j.rmed.2019.01.020

    Article  PubMed  Google Scholar 

  • Khazdair MR, Anaeigoudari A, Hashemzehi M, Mohebbati R (2019) Neuroprotective potency of some spice herbs, a literature review. J Tradit Complement Med 9:98–105. https://doi.org/10.1016/j.jtcme.2018.01.002

    Article  PubMed  Google Scholar 

  • Kianmehr M, Rezaei A, Boskabady MH (2016) Effect of carvacrol on various cytokines genes expression in splenocytes of asthmatic mice. Iran J Basic Med Sci 19:402–410

    PubMed  PubMed Central  Google Scholar 

  • Landa P, Kokoska L, Pribylova M, Vanek T, Marsik P (2009) In vitro anti-inflammatory activity of carvacrol: inhibitory effect on COX-2 catalyzed prostaglandin E 2 biosynthesisb. Arch Pharm Res 32:75–78

    Article  CAS  Google Scholar 

  • Lee JW, Lee YK, Yuk DY et al (2008) Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflammation 5:37

    Article  Google Scholar 

  • Madesh M, Balasubramanian K (1998) Microtiter plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J Biochem Biophys 35:184–188

    CAS  PubMed  Google Scholar 

  • McGeer P, Itagaki S, Boyes B et al (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38:1285–1285

    Article  CAS  Google Scholar 

  • Mehri S, Abnous K, Khooei A et al (2015) Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran J Basic Med Sci 18:902

    PubMed  PubMed Central  Google Scholar 

  • Nakagawa Y, Chiba K (2014) Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases. Pharmaceuticals 7:1028–1048

    Article  CAS  Google Scholar 

  • Paik YH, Schwabe RF, Bataller R, Russo MP, Jobin C, Brenner DA (2003) Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 37:1043–1055

    Article  CAS  Google Scholar 

  • Papandreou MA, Tsachaki M, Efthimiopoulos S, Cordopatis P, Lamari FN, Margarity M (2011) Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behav Brain Res 219:197–204

    Article  CAS  Google Scholar 

  • Pohl F, Kong Thoo Lin P (2018) The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: in vitro, In Vivo and Clinical Trials. Molecules 23. https://doi.org/10.3390/molecules23123283

    Article  Google Scholar 

  • Pourganji M, Hosseini M, Soukhtanloo M et al (2014) Protective role of endogenous ovarian hormones against learning and memory impairments and brain tissues oxidative damage induced by lipopolysaccharide. Iran Red Crescent Med J 16:e13954

    Article  Google Scholar 

  • Richardson JS (1993) Free radicals in the genesis of Alzheimer's disease a. Ann N Y Acad Sci 695:73–76

    Article  CAS  Google Scholar 

  • Sadegh M, Sakhaie MH (2018) Carvacrol mitigates proconvulsive effects of lipopolysaccharide, possibly through the hippocampal cyclooxygenase-2 inhibition. Metab Brain Dis 33:2045–2050. https://doi.org/10.1007/s11011-018-0314-3

    Article  CAS  PubMed  Google Scholar 

  • Saito T, Saido TC (2018) Neuroinflammation in mouse models of Alzheimer's disease. Clin Exp Neuroimmunol 9:211–218. https://doi.org/10.1111/cen3.12475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salmani H, Hosseini M, Beheshti F, Baghcheghi Y, Sadeghnia HR, Soukhtanloo M, Shafei MN, Khazaei M (2018) Angiotensin receptor blocker, losartan ameliorates neuroinflammation and behavioral consequences of lipopolysaccharide injection. Life Sci 203:161–170. https://doi.org/10.1016/j.lfs.2018.04.033

    Article  CAS  PubMed  Google Scholar 

  • Samarghandian S, Farkhondeh T, Samini F et al (2016) Protective effects of carvacrol against oxidative stress induced by chronic stress in rat’s brain, liver, and kidney. Biochem Res Int 2016:2645237

    Article  Google Scholar 

  • Sharifi-Rad M, Varoni EM, Iriti M, Martorell M, Setzer WN, del Mar Contreras M, Salehi B, Soltani-Nejad A, Rajabi S, Tajbakhsh M, Sharifi-Rad J (2018) Carvacrol and human health: a comprehensive review. Phytother Res 32:1675–1687

    Article  CAS  Google Scholar 

  • Vegeto E, Bonincontro C, Pollio G, Sala A, Viappiani S, Nardi F, Brusadelli A, Viviani B, Ciana P, Maggi A (2001) Estrogen prevents the lipopolysaccharide-induced inflammatory response in microglia. J Neurosci 21:1809–1818

    Article  CAS  Google Scholar 

  • Wang P, Luo Q, Qiao H, Ding H, Cao Y, Yu J, Liu R, Zhang Q, Zhu H, Qu L (2017) The Neuroprotective effects of Carvacrol on ethanol-induced hippocampal neurons impairment via the Antioxidative and Antiapoptotic pathways. Oxidative Med Cell Longev 2017:4079425. https://doi.org/10.1155/2017/4079425

    Article  CAS  Google Scholar 

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Acknowledgments

The results described in this article were part of a MSc. thesis (Zahra Hakimi).

Funding

The Vice Chancellor for Research and Technology of Mashhad University of Medical Sciences financially supported this work (970981).

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Authors and Affiliations

  1. Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Zhara Hakimi, Narges Marefati, Mohammad Naser Shafei & Mahmoud Hosseini

  2. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Salmani, Zohre Arab & Zahra Gholamnezhad

  3. Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    Farimah Beheshti

  4. Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    Farimah Beheshti

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  1. Zhara Hakimi
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  2. Hossein Salmani
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  3. Narges Marefati
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  4. Zohre Arab
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  5. Zahra Gholamnezhad
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  6. Farimah Beheshti
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  7. Mohammad Naser Shafei
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  8. Mahmoud Hosseini
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Correspondence to Mahmoud Hosseini.

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Hakimi, Z., Salmani, H., Marefati, N. et al. Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats. Neurotox Res 37, 965–976 (2020). https://doi.org/10.1007/s12640-019-00144-5

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  • DOI: https://doi.org/10.1007/s12640-019-00144-5

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