The effects of Nigella sativa on sickness behavior induced by lipopolysaccharide in male Wistar rats

Document Type : Original Research Article

Authors

1 Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Physiology, School of Medicine, Jiroft University of medical Sciences, Jiroft, Iran

4 Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Mashhad Technical Faculty, Technical and Vocational University, Mashhad, Iran

6 Department of Physiology School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Objective: Neuroimmune factors contribute on the pathogenesis of sickness behaviors. Nigella sativa (NS) has anti-inflammatory, anti-anxiety and anti-depressive effects. In the present study, the effect of NS hydro-alcoholic extract on sickness behavior induced by lipopolysaccharide (LPS) was investigated.
Materials and Methods: The rats were divided into five groups (n=10 in each): (1) control (saline), (2) LPS (1 mg/kg, administered two hours before behavioral tests), (3-5) LPS-Nigella sativa 100 , 200 and 400 mg/kg (LPS-NS 100, LPS-NS 200 and LPS-NS 400, respectively). Open- field (OF), elevated plus maze (EPM) and forced swimming test (FST) were performed.
Results: In OF, LPS reduced the peripheral crossing, peripheral distance, total crossing and total distance compared to control (pConclusion: The results of the present study showed that the hydro-alcoholic extract of NS reduced the LPS-induced sickness behaviors in rats. Further investigations are required for better understanding the responsible compound (s) and the underlying mechanism(s).

Keywords

Main Subjects

References

Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
Ali BH, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. [Review]. Phytother Res, 17: 299-305.
Azizi-Malekabadi H, Hosseini M, Pourganji M, Zabihi H, Saeedjalali M, Anaeigoudari A. 2015a. Deletion of ovarian hormones induces a sickness behavior in rats comparable to the effect of lipopolysaccharide. Neurol Res Int,  627642.
Azizi-Malekabadi H, Pourganji  M, Zabihi H, Saeedjalali M, Hosseini M. 2015 b. Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats. Arq Neuropsiquiatr, 73: 132-139.
Beheshti F, Hosseini M, Shafei MN, Soukhtanloo M, Ghasemi S, Vafaee F, Zarepoor L. 2014. The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. Nutr Neurosci, DOI: http://dx.doi.org/10.1179/1476830514Y.0000000144.
Burton MD, Sparkman NL, Johnson RW. 2011. Inhibition of interleukin-6 trans-signaling in the brain facilitates recovery from lipopolysaccharide-induced sickness behavior. J Neuroinflammation, 8: 54.
Chourbaji S, Urani A, Inta I, Sanchis-Segura C, Brandwein C, Zink M, Schwaninger M, Gass P. 2006. IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis, 23: 587-594.
Contreras CM, Rodriguez-Landa Jf, Fau - Gutierrez-Garcia  AG, Gutierrez-Garcia Ag, Fau - Bernal-Morales B, Bernal-Morales B. 2001. The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat. J Psychopharmacol, 15:231-6.
Coppen AJ, Doogan DP. 1988. Serotonin and its place in the pathogenesis of depression. J Clin Psychiatry, 49:4-11.
Dantzer  R, O’Connor  JC, Lawson MA, Kelley KW. 2011. Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology, 36: 426-436.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham  L, Reim  E K, Lanctôt  KL. 2010. A meta-analysis of cytokines in major depression. Biol Psychiatry, 67: 446-457.
Dunn AJ.2000. Cytokine activation of the HPA axis. Ann N Y Acad Sci, 917: 608-617.
Dunn AJ. 2006. Effects of cytokines and infections on brain neurochemistry. Clin Neurosci Res, 6: 52-68.
Dunn A  J, Wang  J, Ando T. 1999. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol, 1999;461:117-27.
El Gazzar MA. 2007. Thymoquinone suppressses in vitro production of IL-5 and IL-13 by mast cells in response to lipopolysaccharide stimulation. Inflamm Res, 56: 345-351.
el Tahir  KE, Ashour MM, al-Harbi MM. 1993. The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action. Gen Pharmacol, 24: 1115-1122.
 Entok  E, Ustuner MC, Ozbayer C, Tekin N, Akyuz F, Yangi B, Kurt H, Degirmenci I Gunes HV. 2014. Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation. Mol Biol Rep, 41: 2827-2834.
Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B. 2002. Microglial activation‐mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem, 81: 1285-1297.
Gilhotra N, Dhingra D. 2011. Thymoquinone produced antianxiety-like effects in mice through modulation of GABA and NO levels. Pharmacol Rep, 63: 660-669.
Hajhashemi V, Ghannadi A, Jafarabadi H. 2004. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. [Research Support, Non-U.S. Gov't]. Phytother Res, 18: 195-199.
Helal GK. 2010. Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pak J Pharm Sci, 23: 131-137.
Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Sadeghnia HR, Soukhtanloo M. 2015. Effects of the hydro-alcoholic extract of Nigella Sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med, 21:438-44.
Hosseini M, Zakeri S, Khoshdast S, Yousefian FT, Rastegar M, Vafaee F, Kahdouee S, Ghorbani F, Rakhshandeh H, Kazemi SA. 2012. The effects of Nigella sativa hydro-alcoholic extract and thymoquinone on lipopolysaccharide-induced depression like behavior in rats. J Pharm Bioallied Sci, 4: 219.
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. 2007. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine, 14: 621-627.
 Houghton PJ, Zarka R, de las Heras B, Hoult JR. 1995. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med, 61: 33-36.
Howren MB, Lamkin DM, Suls J. 2009. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med., 71: 171-186.
Hritcu L, Gorgan LD. 2014. Intranigral lipopolysaccharide induced anxiety and depression by altered BDNF mRNA expression in rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry, 51: 126-132.
Janssen DG, Caniato RN, Verster JC, Baune BT. 2010. A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Hum Psychopharmacol, 25: 201-215.
Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A, Lichius JJ, Kiesewetter H. 2003. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. [Clinical Trial Randomized Controlled Trial]. Phytother Res, 17: 1209-1214.
Kang A, Hao H, Zheng X, Liang Y, Xie Y, Xie T, Dai C, Zhao Q, Wu X, Xie L. 2011. Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy. J Neuroinflammation, 8:100.
Lawson MA, Parrott JM, McCusker RH, Dantzer R, Kelley KW, O’Connor JC. 2013. Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2, 3-dioxygenase-dependent depression-like behaviors. J Neuroinflammation, 10: 87.
Layé S, Gheusi G, Cremona S, Combe C, Kelley K, Dantzer R, Parnet P. 2000. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol Regul Integr Comp Physiol, 279: R93-R98.
Leonard BE. 2001. The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry, 25: 767-780.
Ma XC, Jiang D, Jiang WH, Wang F, Jia M, Wu J, Hashimoto K, Dang YH, Gao CG. 2011. Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress. [Research Support, Non-U.S. Gov't]. PLoS One, 6: e20955.
Maes M, Berk M, Goehler L, Song C, Anderson G, Gałecki P, Leonard B. 2012. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med, 10: 66.
 Maes M, Kubera M, Obuchowiczwa E, Goehler L, Brzeszcz J. 2011. Depression’s multiple comorbidities explained by (neuro) inflammatory and oxidative & nitrosative stress pathways. Neuroendocrinol Lett, 32: 7-24.
Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M. 2009. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis, 24: 27-53.
 Mahgoub AA. 2003. Thymoquinone protects against experimental colitis in rats. Toxicol Lett, 143: 133-143.
 Maier SF, Watkins LR. 1995. Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res, 695: 279-282.
 Miller AH. 2010. Depression and immunity: a role for T cells? Brain Behav Immun, 24: 1-8.
 
Mohamed A, Afridi DM, Garani O, Tucci M. 2005. Thymoquinone inhibits the activation of NF-kappaB in the brain and spinal cord of experimental autoimmune encephalomyelitis. Biomed Sci Instrum, 41: 388-393.
 Neamati A, Chaman F, Hosseini M, Boskabady MH. 2014. The effects of Valeriana officinalis L. hydro-alcoholic extract on depression like behavior in ovalbumin sensitized rats. J Pharm Bioallied Sci, 6: 97-103.
Perveen T, Haider S, Kanwal S, Haleem DJ. 2009. Repeated administration of Nigella sativa decreases 5-HT turnover and produces anxiolytic effects in rats. Pak J Pharm Sci, 22: 139-144.
Petit-Demouliere B, Chenu F Fau - Bourin M, Bourin M.2005. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl). 177:245-55.
 Piser TM. 2010. Linking the cytokine and neurocircuitry hypotheses of depression: a translational framework for discovery and development of novel anti-depressants. Brain Behav Immun, 24: 515-524.
Pourbakhsh H, Taghiabadi E, Abnous K, Hariri AT, Hosseini SM, Hosseinzadeh H. 2014. Effect of Nigella sativa fixed oil on ethanol toxicity in rats. Iran J Basic Med Sci, 17: 1020-1031.
Pourganji M, Hosseini M, Soukhtanloo M, Zabihi H, Hadjzadeh MA. 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.
 
Quan N, Sundar SK, Weiss JM. 1994. Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide. J Neuroimmunol, 49: 125-134.
 Raison CL, Capuron L, Miller AH. 2006. Cytokines sing the blues: inflammation and the pathogenesis of depression.
 Trends Immunol, 27: 24-31.
Sharp LK, Lipsky MS. 2002. Screening for depression across the lifespan. Am Fam Physician, 66: 1001-1008.
Swamy SM, Tan BK. 2000. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. [Research Support, Non-U.S. Gov't]. J Ethnopharmacol, 70: 1-7.
 Swiergiel AH, Dunn AJ. 2007. Effects of interleukin-1β and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests. Pharmacol Biochem Behav, 86: 651-659.
 Szentirmai É, Krueger JM. 2014. Sickness behaviour after lipopolysaccharide treatment in ghrelin deficient mice. Brain Behav Immun, 36: 200-206.
 Takao T, Culp SG, De Souza EB. 1993. Reciprocal modulation of interleukin-1 beta (IL-1 beta) and IL-1 receptors by lipopolysaccharide (endotoxin) treatment in the mouse brain-endocrine-immune axis. Endocrinology, 132: 1497-1504.
Taksande BG, Chopde CT, Umekar MJ, Kotagale NR. 2015. Agmatine attenuates lipopolysaccharide induced anorexia and sickness behavior in rats. Pharmacol Biochem Behav, 132: 108-114.
Tekeoglu I, Dogan A, EdizL, Budancamanak M, Demirel A. 2007. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res, 21: 895-897.
 
Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. 2012. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact, 197: 40-46.
 Vafaee F, Hosseini M, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, Seghatoleslam M, Mousavi SM, Amani A , Shafei MN. 2015. The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats. Iran J Pharm Res, 14: 547-557.
 Vaillancourt F, Silva P, Shi Q, Fahmi H, Fernandes JC, Benderdour M. 2011. Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis. [Research Support, Non-U.S. Gov't]. J Cell Biochem, 112: 107-117.
Wang Y, Gao H, Zhang W, Fang L. 2015. Thymoquinone inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells. Int Immunopharmacol, 26: 169-173.
Worthen DR, Ghosheh OA, Crooks PA. 1998. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. [Research Support, Non-U.S. Gov't]. Anticancer Res, 18: 1527-1532.
 
 
Avicenna Journal of Phytomedicine
Volume 6, Issue 1 - Serial Number 1
January and February 2016
Pages 104-116

Files

Share

How to cite

Statistics