Feeding of Nigella sativa during neonatal and juvenile growth improves learning and memory of rats

10.1016/j.jtcme.2014.11.039

Farimah Beheshti；Mahmoud Hosseini；Farzaneh Vafaee；Mohammad Naser Shafei；Mohammad Soukhtanloo

Juvenile ； Learning ； Memory ； Neonatal ； Nigella sativa ； Oxidative stress

Journal of Traditional and Complementary Medicine

6卷2期（2016 / 04 / 01）

146 - 152

英文

The positive roles of antioxidants on brain development and learning and memory have been suggested. Nigella sativa (NS) has been suggested to have antioxidant and neuroprotective effects. This study was done to investigate the effects of feeding by the hydro-alcoholic extract of NS during neonatal and juvenile growth on learning and memory of rats. The pregnant rats were kept in separate cages. After delivery, they were randomly divided into four Groups including: (1) control; (2) NS 100 mg/kg (NS 100); (3) NS 200 mg/kg (NS 200); and (4) NS 400 mg/kg (NS 400). Rats in the control group (Group 1) received normal drinking water, whereas Groups 2, 3, and 4 received the same drinking water supplemented with the hydro-alcoholic extract of NS (100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively) from the 1st day after birth through the first 8 weeks of life. After 8 weeks, 10 male offspring from each group were randomly selected and tested in the Morris water maze (MWM) and passive avoidance (PA) test. Finally, the brains were removed and total thiol groups and malondialdehyde (MDA) concentrations were determined. In the MWM, treatment by 400 mg/kg extract reduced both the time latency and the distance traveled to reach the platform compared to the control group (p ＜ 0.05-p ＜ 0.01). Both 200 mg/kg and 400 mg/kg of the extract increased the time spent in the target quadrant (p ＜ 0.05-p ＜ 0.01). In the PA test, the treatment of the animals by 200 mg/kg and 400 mg/kg of NS extract significantly increased the time latency for entering the dark compartment (p ＜ 0.05-p ＜ 0.001). Pretreatment of the animals with 400 mg/kg of NS extract decreased the MDA concentration in hippocampal tissues whereas it increased the thiol content compared to the control group (p ＜ 0.001). These results allow us to propose that feeding of the rats by the hydro-alcoholic extract of NS during neonatal and juvenile growth has positive effects on learning and memory. The effects might be due to the antioxidant effects.

1. Agar, E,Bosnak, M,Amanvermez, R,Demir, S,Ayyildiz, M,Celik, C(1999).The effect of ethanol on lipid peroxidation and glutathione level in the brain stem of rat.Neuroreport,10,1799-1801.
2. Ali, BH,Blunden, G.(2003).Pharmacological and toxicological properties of Nigella sativa.Phytother Res,17,299-305.
3. Azzubaidi, MS,Saxena, AK,Talib, NA,Ahmed, QU,Dogarai, BB(2012).Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion.Acta Neurobiol Exp.,72,154-165.
4. Barker, DJP,Godfrey, KM,Gluckman, PD,Harding, JE,Owens, JA,Robinson, JS(1993).Fetal nutrition and cardiovascular disease in adult life.Lancet,341,938-941.
5. Ben-Ari, Y(2013).Neuropaediatric and neuroarchaeology: understanding development to correct brain disorders.Acta Paed,102,331-334.
6. Bin Sayeed, MS,Asaduzzaman, M,Morshed, H,Hossain, MM,Kadir, MF,Rahman, MR(2013).The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers.J Ethnopharmacol,148,780-786.
7. Boskabady, MH,Farhadi, J(2008).The possible prophylactic effect of Nigella sativa seed aqueous extract on respiratory symptoms and pulmonary function tests on chemical war victims: a randomized, double-blind, placebo-controlled trial.J Altern Complement Med,14,1137-1144.
8. Boskabady, MH,Javan, H,Sajady, M,Rakhshandeh, H(2007).The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients.Fundam Clin Pharmacol,21,559-566.
9. Boskabady, MH,Keyhanmanesh, R,Saadatloo, MA(2008).Relaxant effects of different fractions from Nigella sativa L. on guinea pig tracheal chains and its possible mechanism(s).Indian J Exp Biol,46,805-810.
10. Boskabady, MH,Mohsenpoor, N,Takaloo, L(2010).Antiasthmatic effect of Nigella sativa in airways of asthmatic patients.Phytomedicine,17,707-713.
11. Boskabady, MH,Shafei, MN,Parsaee, H(2005).Effects of aqueous and macerated extracts from Nigella sativa on guinea pig isolated heart activity.Pharmazie,60,943-948.
12. Boskabady, MH,Shirmohammadi, B,Jandaghi, P,Kiani, S(2004).Possible mechanism(s) for relaxant effect of aqueous and macerated extracts from Nigella sativa on tracheal chains of guinea pig.BMC Pharmacol,4,3.
13. Edgar, JA(1970).Dehydroascorbic acid and cell division.Nature,227,24-26.
14. Ellman, GL.(1959).Tissue sulfhydryl groups.Arch Biochem Biophys,82,70-77.
15. El-Marasy, SA,El-Shenawy, SM,El-Khatib, AS,El-Shabrawy, OA,Kenawy, SA(2010).Effect of Nigella sativa and wheat germ oils on scopolamine-induced memory impairment in rats.Bull FacPharmacy, Cairo Univ,50,81-88.
16. El-Naggar, T,Gomez-Serranillos, MP,Palomino, OM,Arce, C,Carretero, ME(2010).Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro.J Biomed Biotechnol.,2010,398312.
17. Fariss, MW,Zhang, JG(2003).Vitamin E therapy in Parkinson's disease.Toxicology,189,129-146.
18. Gomez-Pinilla, F.(2008).Brain foods: the effects of nutrients on brain function.Nat Rev Neurosci,9,568-578.
19. Gonzalez-Polo, RA,Soler, G,Alvarez, A,Fabregat, I,Fuentes, JM(2003).Vitamin E blocks early events induced by 1-methyl-4-phenylpyridinium (MPPþ) in cerebellar granule cells.J Neurochem,84,305-315.
20. Guerri, C,Montoliu, C,Renau-Piqueras, J(1994).Involvement of free radical mechanism in the toxic effects of alcohol: implications for fetal alcohol syndrome.Free Rad Diagn Med,291-305.
21. Hasselmo, ME(2006).The role of acetylcholine in learning and memory.Curr Opin Neurobiol,16,710-715.
22. Heaton, MB,Mitchell, JJ,Paiva, M(2000).Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy.Alcohol Clin Exp Res.,24,512-518.
23. Hensley, K(2008).Antioxidants in central nervous system diseases: preclinical promise and translational challenges.J Alzheimers Dis.,15,473-493.
24. Hosseini, M,Hadjzadeh, MA,Derakhshan, M(2010).The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.Arch Pharm Res,33,463-468.
25. Hosseini, M,Harandizadeh, F,Niazamand, S,Soukhtanloo, M,Mahmoudabady, M(2013).Antioxidant effect of Achillea wilhelmsii extract on pentylenetetrazole (seizure model)-induced oxidative brain damage in Wistar rats.Indian J Physiol Pharmacol,57,418-424.
26. Hosseini, M,Mohammadpour, T,Karami, R,Rajaei, Z,Sadeghnia, HR,Soukhtanloo, M(2014).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
27. Hosseini, M,Pourganji, M,Khodabandehloo, F,Soukhtanloo, M,Zabihi, H(2012).Protective effect of L-arginine against oxidative damage as a possible mechanism of its beneficial properties on spatial learning in ovariectomized rats.Basic Clin Neurosci,3,36-44.
28. 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.
29. Ismail, M,Al-Naqeep, G,Chan, KW(2010).Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats.Free Radic Biol Med.,48,664-672.
30. Ismail, N,Ismail, M,Mazlan, M(2013).Thymoquinone prevents beta-amyloid neurotoxicity in primary cultured cerebellar granule neurons.Cell Mol Neurobiol,33,1159-1169.
31. Jalali, MR,Roghani, M(2009).The effect of Nigella sativa on learning and memory in male diabetic rats.Basic Clin Neurosci,1,32-34.
32. Javanbakht, J,Hobbenaghi, R,Hosseini, E(2013).Histopathological investigation of neuroprotective effects of Nigella sativa on motor neurons anterior horn spinal cord after sciatic nerve crush in rats.Pathol Biol,61,250-253.
33. Kanter, M(2008).Nigella sativa and derived thymoquinone prevents hippocampal neurodegeneration after chronic toluene exposure in rats.Neurochem Res,33,579-588.
34. Kanter, M,Coskun, O,Uysal, H(2006).The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage.Arch Toxicol,80,217-224.
35. Khodabandehloo, F,Hosseini, M,Rajaei, Z,Soukhtanloo, M,Farrokhi, E,Rezaeipour, M(2013).Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats.Arq Neuropsiquiatr,71,313-319.
36. Knickmeyer, RC,Gouttard, S,Kang, C(2008).A structural MRI study of human brain development from birth to 2 years.J Neurosci,28,12176-12182.
37. Koudinov, A,Kezlya, E,Koudinova, N,Berezov, T(2009).Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions.J Alzheimers Dis,18,381-400.
38. Langen, M,Leemans, A,Johnston, P(2012).Fronto-striatal circuitry and inhibitory control in autism: findings from diffusion tensor imaging tractography.Cortex,48,183-193.
39. Lucas, A(1998).Programming by early nutrition: an experimental approach.J Nutr,128,401S-406S.
40. Lucas, A(1994).Role of nutritional programming in determining adult morbidity.Arch Dis Child,71,288-290.
41. Mansour, MA,Ginawi, OT,El-Hadiyah, T,El-Khatib, AS,Al-Shabanah, OA,Al-Sawaf, HA(2001).Effects of volatile oil constituents of Nigella sativa on carbon tetrachloride-induced hepatotoxicity in mice: evidence for antioxidant effects of thymoquinone.Res Commun Mol Pathol Pharmacol,110,239-251.
42. Martin, A,Prior, R,Shukitt-Hale, B,Cao, G,Joseph, JA(2000).Effect of fruits, vegetables, or vitamin E-rich diet on vitamins E and C distribution in peripheral and brain tissues: implications for brain function.J Gerontol A Biol Sci Med Sci.,55,B144-B151.
43. Millen, JW,Woollam, DH,Lamming, GE(1954).Congenital hydrocephalus due to experimental hypovitaminosis A.Lancet,267,679-683.
44. Miller, RR, Jr,Olson, BM,Rorick, N,Wittingen, AL,Bullock, M(2003).Embryonic exposure to exogenous alpha- and gamma-tocopherol partially attenuates ethanol-induced changes in brain morphology and brain membrane fatty acid composition.Nutr Neurosci,6,201-212.
45. Mitchell, JJ,Paiva, M,Heaton, MB(1999).Vitamin E and beta-carotene protect against ethanol combined with ischemia in an embryonic rat hippocampal culture model of fetal alcohol syndrome.Neurosci Lett.,263,189-192.
46. Naseer, MI,Lee, HY,Kim, MO(2010).Neuroprotective effect of vitamin C against the ethanol and nicotine modulation of GABA(B) receptor and PKA-alpha expression in prenatal rat brain.Synapse,64,467-477.
47. Nash, CM,Ibram, F,Dringenberg, HC,Reynolds, JN,Brien, JF(2007).Effects of maternal administration of vitamins C and E on ethanol neurobehavioral teratogenicity in the guinea pig.Alcohol,41,577-586.
48. Perumal, AS,Gopal, VB,Tordzro, WK,Cooper, TB,Cadet, JL(1992).Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain.Brain Res Bull,29,699-701.
49. Post, A,Rucker, M,Ohl, F(2002).Mechanisms underlying the protective potential of alpha-tocopherol (vitamin E) against haloperidol-associated neurotoxicity.Neuropsychopharmacology,26,397-407.
50. 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.
51. Radad, K,Hassanein, K,Al-Shraim, M,Moldzio, R,Rausch, WD(2014).Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.Exp Toxicol Pathol,66,13-17.
52. Saffarzadeh, F,Eslamizade, MJ,Nemati Karimooy, HA,Hadjzadeh, MA,Khazaei, M,Hosseini, M(2010).The effect of L-arginine on Morris water maze tasks of ovariectomized rats.Acta Physiol Hung,97,216-223.
53. Salem, ML(2005).Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.Int Immunopharmacol,5,1749-1770.
54. Sandhu, KS,Rana, AC(2013).Evaluation of anti-Parkinson's activity of Nigella sativa (kalonji) seeds in chlorpromazine induced experimental animal model.Int J Pharm Pharm Sci.,5
55. Siler-Marsiglio, KI,Shaw, G,Heaton, MB(2004).Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar granule cells.J Neurobiol,59,261-271.
56. Smith, CD,Carney, JM,Tatsumo, T,Stadtman, ER,Floyd, RA,Markesbery, WR(1992).Protein oxidation in aging brain.Ann N Y Acad Sci,663,110-119.
57. Ullah, I,Ullah, N,Naseer, MI,Lee, HY,Kim, MO(2012).Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons.BMC Neurosci,13,11.
58. Winick, M,Noble, A(1966).Cellular response in rats during malnutrition at various ages.J Nutr,9,300-306.
59. Yaman, I,Balikci, E(2010).Protective effects of Nigella sativa against gentamicin-induced nephrotoxicity in rats.Exp Toxicol Pathol,62,183-190.
60. Zandi, PP,Anthony, JC,Khachaturian, AS(2004).Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.Arch Neurol,61,82-88.