Neuropharmacological effects of Nigella sativa

Document Type : Review Article

Authors

1 Departments of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

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

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

Abstract

Nigella sativa (NS) (Ranunculaceae family) is generally utilized as a therapeutic plant all over the world. The seeds of the plant have a long history of use in different frameworks of medicines and food. In Islamic literature, it is considered as one of the greatest forms of therapeutics. It has been widely used to treat nervous system diseases such as memory impairment, epilepsy, neurotoxicity, pain, etc. Additionally, this is uncovered that the majority of therapeutic properties of this plant are due to the presence of thymoquinone (TQ) which is a major bioactive component of the essential oil. Pharmacological studies have been done to evaluate the effects of NS on the central nervous system (CNS). The present review is an effort to provide a detailed scientific literature survey about pharmacological activities of the plant on nervous system. Our literature review showed that NS and its components can be considered as promising agents in the treatment of nervous system disorders.

Keywords

Main Subjects

References

Abdel-Daim MM, Ghazy EW. 2015. Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced hepato-renal toxicity in rabbits. Iran J Basic Med Sci, 18: 221.‏
Abdel-Fattah AM, Matsumoto K,  Watanabe, H. 2000. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol, 400: 89-97.
Abdel-Zaher AO, Abdel-Rahman MS, Elwasei FM. 2011. Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: role of nitric oxide and oxidative stress. Neurotoxicology,32: 725-733.
Abel-Salam BK. 2012. Immunomodulatory effects of black seedsand garlic on alloxan-induced diabetes in albino rat. Allergol  Immunopathol (Madr), 40: 336-340.
Adams EH, Breiner S, Cicero TJ, Geller A, Inciardi JA, Schnoll SH, Senay EC, Woody GE. 2006. A comparison of the abuse liability of tramadol, NSAIDs, and hydrocodone in patients with chronic pain. J Pain Symptom Manage, 31: 465-476.
Adewale OO, Brimson  JM, Odunola OA, Gbadegesin MA, Owumi SE, Isidoro C,  Tencomnao T. 2015. The Potential for Plant Derivatives against Acrylamide Neurotoxicity. Phytother Res.
Adnan LHM, Bakar NHA, Mohamad N. 2014. Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy. Iran J Basic Med Sci, 17: 926.‏
Ahmad A, Husain A, Mujeeb M, Khan S A, 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.
Akhondian J, Kianifar H, Raoofziaee M, Moayedpour A, Toosi MB,  Khajedaluee M. 2011. The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res, 93: 39-43.
Akhondian J, Parsa A, Rakhshande H. 2007. The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures. Med Sci Monit, 13: CR555-559.
Akhtar M, Maikiyo AM, Khanam R, Mujeeb M, Aqil M, Najmi AK. 2012 . Ameliorating effects of two extracts of Nigella sativa in middle cerebral artery occluded rat. J Pharm Bioallied Sci, 4: 7075.
Akhtar M, Maikiyo AM, Najmi AK, Khanam R, Mujeeb M, Aqil M. 2013. Neuroprotective effects of chloroform and petroleum ether extracts of Nigella sativa seeds in stroke model of rat. J Pharm Bioallied Sci, 5: 119-125.
Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. 2008. Oral and  intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad, 20: 25-27.
Al-Ghamdi MS. 2001. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol, 76: 45-48.‏
Ali BH, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17: 299-305.‏
Al-Jassir MS. 1992. Chemical composition and microflora of black cumin  (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chem, 45: 239-242.
Al-Majed AA., Al-Omar FA, Nagi MN. 2006. Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharmacol, 543: 40-47.
Al Mofleh IA, Alhaider AA, Mossa JS, Al-Sohaibani MO, Al-Yahya MA, Rafatullah S, Shaik SA. 2008. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J Gastroenterol, 14: 128.‏
Al-Naggar TB, Gomez-Serranillos MP, Carretero ME, Villar AM. 2003. Neuropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol 88: 63-68.
Alhebshi A, Odawara A, Gotoh M,  Suzuki I. 2013. Thymoquinone protects cul-tured hippocampal and human induced pluripotent stem cells-derived neuronsagainst α-synuclein-induced synapse damage. Neurosci Lett, 570: 126-131.
Alhebshi AH, Gotoh M, Suzuki I. 2013. Thymoquinone protects cultured rat primary neurons against amyloid beta-induced neurotoxicity. Biochem Biophys Res Commun, 433: 362-367.
Amin B, Taheri MM, Hosseinzadeh H. 2014. Effects of intraperitoneal thymoquinone on chronic neuropathic pain in rats. Planta Med, 80: 1269-1277.
Ansari AA, Hassan S, Kenne L, Wehler T. 1988. Structural studies on a saponin isolated from Nigella sativa. Phytochemistry, 27: 3977-3979.‏
Anvari M, Seddigh A, Shafei MN, Rakhshandeh H, Talebi AH, Tahani MR, Saeedjalal SM, Hosseini M. 2012. Nigella sativa extract affects conditioned place preference induced by morphine in rats. Anc Sci Life, 32: 82-88.
Ashraf M, Ali Q, Iqbal Z. 2006. Effect of nitrogen application rate on the content and composition of oil, essential oil and minerals in black cumin (Nigella sativa L.) seeds. J Sci Food Agr, 86: 871-876.
Atta MB. 2003. Some characteristics of nigella (Nigella sativa L.) seed cultivated in Egypt and its lipid profile. Food Chem, 83: 63-68.‏
Azizi-Malekabadi H, Pourganji M, Zabihi H, Saeedjalali M, Hosseini M. 2015. Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats. Arq Neuropsiquiatr, 73: 132-139.
Bailey CJ, Day C. 1989. Traditional plant medicines as treatments for diabetes. Diabetes care, 12: 553-564.
Barbee JG. 1998. Mixed symptoms and syndromes of anxiety and depression: diagnostic, prognostic, and etiologic issues. Ann Clin Psychiatry, 10: 15-29.
Bashir MU, Qureshi HJ. 2010. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. J Coll Physicians Surg Pak, 20: 464-467.
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.
Beheshti F, Hosseini M, Vafaee F, Shafei MN, Soukhtanloo M. 2015. Feeding of Nigella sativa during neonatal and juvenile growth improves learning and memory of rats. J Tradit Complement Med. doi:10.1016/j.jtcme.2014.11.039.
 
Bielekova B, Martin R. 2004. Development of biomarkers in multiple sclerosis. Brain, 127: 1463-1478.
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.
Biswas D, Guha D. 2007. “Nigella sativa: its role as an anticonvulsant in pentylenetetrazole induced seizures”. Biogenic Amines, 21: 66-76.
Boskabady MH, Keyhanmanesh R, Khamneh S, Ebrahimi MA. 2011a.  The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs. Clinics (Sao Paulo), 66:879-87.
Boskabady MH, Vahedi N, Amery S, Khakzad MR. 2011b. The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs. J Ethnopharmacol, 137:1028-34.
Bourgou S, Ksouri R, Bellila A, Skandrani I, Falleh H, Marzouk B. 2008. Phenolic composition and biological activities of Tunisian Nigella sativa L. shoots and roots. C R Biol, 331: 48-55.‏
Casson RJ, Chidlow G, Ebneter A, Wood JP, Crowston J, Goldberg I. 2012. Translational neuroprotection research in glaucoma: a review of definitions and principles. Clin Experiment Ophthalmol, 40: 350-357.
Chatap VK, Sharma DK, Parial SD, Nangude TD, Khan M. 2006. Nigella sativa Linn: A Golden Seed. Int J Plant Sci , 1: 357-360.
Cheikh-Rouhou S, Besbes S, Lognay G, Blecker C, Deroanne C, Attia H. 2008. Sterol composition of black cumin (Nigella sativa L.) and  Aleppo pine (Pinus halpensis Mill.) seed oils. J Food Comp Anal, 21: 162-168.
Dahri AH, Chandiol AM, Rahoo AA, Memon RA. 2005. Effect of Nigella sativa (kalonji) on serum cholesterol of albino rats. J Ayub Med Coll Abbottabad, 17: 72-74.‏
Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad S. 2015. Thymoquinone and its therapeutic potentials. Pharmacol Res, 95: 138-158.
Denenberg VH. 1969. Open-field bheavior in the rat: what does it mean? Ann N Y Acad Sci, 159: 852-859.
Dickson DW, Feany MB, Yen SH, Mattiace LA, Davies P. 1996. Cytoskeletal pathology in non-Alzheimer degenerative dementia: new lesions in diffuse Lewy body disease, Pick's disease, and corticobasal degeneration. J Neural Transm Suppl, 47: 31-46.
Eddy NB, Leimbach D. 1953. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther, 107: 385-393.
El-Marasy SA, El-Shenawy SM, El-Khatib AS, Shabrawy OA, Kenawy SA. 2012. “Effect of Nigella sativa and wheat germ oils on scopolamine-induced memory impairment in rats”. Bull Fac Pharm Cairo Univ, 50: 81-88.
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.
El Sherbiny DA, Khalifa AE, Attia AS, Eldenshary EES. 2003. Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Pharmacol Biochem Behav, 76: 523-533.
Elmansy RA, Almasry SM. 2013. Morphological and Immunohistochemical Analysis of the Effects of Thymoquinone on the Neurovascular Component of Jejunal Submucosa of Diabetic Rat Model. J Am Sci, 9.
Eltony SA, Elgayar SA. 2014. Histological study on effect of Nigella sativa on aged olfactory system of female albino rat. Rom J Morphol Embryol, 55: 325-334.
Ersahin M, Toklu HZ, Akakin D, Yuksel M, Yegen BC, Sener G. 2011. The effects of Nigella sativa against oxidative injury in a rat model of subarachnoid hemorrhage. Acta Neurochir (Wien), 153: 333-341.
Eun JJ, Ki YL, Seung HK, Sang HS, Young CK. 2008. Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treate dmice. Eur J Pharmacol, 588: 78-84.
Ezz HS, Khadrawy YA, Noor NA. 2011. The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate. Neurochem Res, 36: 2195-2204.
Gella A, Durany N. 2009. Oxidative stress in Alzheimer′s disease. Cell Adh Migr, 3: 88-93.
Gholamnezhad Z, Boskabady MH, Hosseini M. 2014. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Altern Med, 14: 437.‏
Gilani A, Jabeen Q, Ullah khan M. 2004. A review of medicinal uses and pharmacological activities of Nigella sativa. Pak J Biol Sci, 7: 441-451.
Gilani AH, Aziz N, Khurram IM, Chaudhary KS, Iqbal A. 2001. Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses. J Pak Med Assoc, 51: 115-120.‏
Gilhotra N, Dhingra D. 2011. Thymoquinone produced antianxietylike effects in mice through modulation of GABA and NO levels. Pharmacol Rep, 63: 660-669.
Goreja WG. 2003. Black seed: Nature’s Miracle Remedy. New York, NY: Amazing Herbs Press.
Grandjean P, Landrigan PJ. 2006. Developmental neurotoxicity of industrial chemicals. Lancet, 368: 2167-2178.
Greene LA, Tischler AS. 1976. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A, 73: 2424-2428.
Guha D, Biswas D, Purkayastha S. 2005. Suppression of penicillin-induced epileptiform activity by Nigella sativa: possible mediation by neurotransmitters. Biogenic Amines, 19: 309-321.
Hajhashemi V, Ghannadi A, Jafarabadi H. 2004. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother Res, 18: 195-199.
Hanafy MSM, Hatem ME. 1991. Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol, 34: 275-278.‏
Hasselmo ME. 2006. The role of acetylcholine in learning and memory. Curr Opin Neurobiol, 16: 710-715.
Hobbenaghi R, Javanbakht J, Sadeghzadeh Sh, Kheradmand D, Abdi FS, Jaberi MH, Mohammadiyan MR, Khadivar F, Mollaei Y. 2014. Neuroprotective effects of Nigella sativa extract on cell death in hippocampal neurons following experimental global cerebral ischemia-reperfusion injury in rats. J Neurol Sci, 337: 74-79.
Hosseini M, Alaei H, Eslamizadeh MJ, Safarzadeh F. 2007. Effect of morphine self-administration on water and food intake in rat. Iran J Basic Med Sci, 169-175.
Hosseini M, Alaei HA, Naderi A, Sharifi MR, Zahed R. 2009. Treadmill exercise reduces self-administration of morphine in male rats. Pathophysiology, 16: 3-7.
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: 219-225.
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, 1-7.
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: 438-444.
Hosseinzadeh H, Parvardeh S. 2004. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine, 11: 56-64.
Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri MT. 2005. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit, 11: BR106-110.
Ishiyama T, Tokuda K, Ishibashi T, Ito A, Toma S, Ohno Y. 2007. Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. Eur J Pharmacol, 572: 160-170.
Ismail M, Yaheya M. 2009. Therapeutic role of prophetic medicine Habbat El Baraka (Nigella sativa L.)-A review. World Appl Sci J, 7: 1203-1208.
Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, Azmi NH, Ghafar SA, Chan KW. 2013. Thymoquinone prevents beta-amyloid neurotoxicity in primary cultured cerebellar granule neurons. Cell Mol Neurobiol, 33: 1159-1169.
Jalali MR, Roghani M. 2009. “The effect of Nigella sativa on learning and memory in male diabetic rats”. Basic Clin Neurosci, 1: 32-34.
Javanbakht J, Hobbenaghi R, Hosseini E, Bahrami AM, Khadivar F, Fathi S, Hassan MA. 2013. Histopathological investigation of neuroprotective effects of Nigella sativa on motor neurons anterior horn spinal cord after sciatic nerve crush in rats. Pathol Biol (Paris), 61: 250-253.
Jukic M, Politeo O, Maksimovic M, Milos M. 2007. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother Res, 21: 259-261.
Kanter M. 2008. Nigella sativa and derived thymoquinone prevents hippocampal neurodegeneration after chronic toluene exposure in rats. Neurochem Res, 33: 579-588.
Kanter M, Coskun O, Budancamanak M. 2005. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol, 11: 6684-6688.
Kapoor S. 2009. Emerging clinical and therapeutic applications of Nigella sativa in gastroenterology. World J Gastroenterol,
15:2170-1.
Karami M, Zarrindast MR. 2011. Place Aversion by Morphine in Offspring Born of Female Morphine Administered Wistar Rats. Iran j pharm res, 10: 577.
Keyhanmanesh R, Gholamnezhad Z, Boskabady MH.2014a.The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms and clinical applications. Iran J Basic Med Sci, 17:939-49.
Keyhanmanesh R, Nazemiyeh H, Mazouchian H, Bagheri Asl MM, Karimi Shoar M, Alipour MR, Boskabady MH. 2014b. Nigella sativa Pretreatment in Guinea Pigs Exposed to Cigarette Smoke Modulates In Vitro Tracheal Responsiveness. Iran Red Crescent Med J, 16.
Khan MAU, Ashfaq MK, Zuberi, HS, Mahmood MS, Gilani AH. 2003. The in vivo antifungal activity of the aqueous xtract from Nigella sativa seeds. Phytother Res, 17:183-186.
Khare CP. 2004. Encyclopedia of Indian medicinal plants. NewYork: Springes-Verlag Berlin Heidelberg.
Khoddami A, Ghazali HM, Yassoralipour A, Ramakrishnan Y, Ganjloo A. 2011. Physicochemical characteristics of nigella seed (Nigella sativa L.) oil as affected by different extraction methods. J Am Oil Chem Soc, 88: 533-540.
Liu MY, Wang S, Yao WF, Zhang ZJ, Zhong X, Sha L, He M, Zheng ZH, Wei MJ. 2014. Memantine improves spatial learning and memory impairments by regulating NGF signaling in APP/PS1 transgenic mice. Neuroscience, 273: 141-151.
Malenka RC, Nestler EJ, Hyman SE. 2009. Reinforcement and Addictive Disorders. In A. Sydor & R. Y. Brown (Eds.), Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed., pp. 364-375. New York: McGraw-Hill Medical.
Ming H, Chen R, Wang J, Ju J, Sun L, Zhang G. 2014. [Role of hippocampal neuronal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia]. Zhonghua Jie He He Hu Xi Xi Ji Bing Za Zhi, 37: 893-897.
Mohamed A, Waris HM, Ramadan H, Quereshi M, Kalra J. 2009. Amelioration of chronic relapsing experimental autoimmune encephalomyelitis (cr-eae) using thymoquinone. Biomed Sci Instrum, 45: 274-279.
Morikawa T, Xu F, Kashima Y, Matsuda H, Ninomiya K, Oshikawa M. (2004. Noveldolabellane-type diterpene alkaloids with lipidmetabolism promoting activities from the seeds of Nigella sativa. Org Lett, 6: 869-872.
Mousavi G, Mohajeri D. 2014. Effect of ground black seeds (Nigella sativa L.) on renal tubular cell apoptosis induced by ischemia/reperfusion injury in the rats. Iran J Basic Med Sci, 17: 1032.‏
Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. 2010. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cell Mol. Neurobiol, 30: 591-598.
Nabeshima T. 1993. Behavioral aspects of cholinergic transmission: role of basal forebrain cholinergic system in learning and memory. Prog Brain Res, 98: 405-411.
Nickavar B, Mojab F, Javidnia K, Amoli MA. 2003. Chemical composition  of the fixed and volatile oils of Nigella sativa L. from Iran. Z  Naturforsch C, 58: 629-631.
Paarakh PM. 2010. Nigella sativa Linn.–A comprehensive review. Indian J Nat Prod Resour, 1: 409-429.
Pellow  S, Chopin P, File SE, Briley M. 1985. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods, 14: 149-167.
Perveen T, Abdullah A, Haider S, Sonia B, Munawar AS, Haleem DJ. 2008. Long-term administration of Nigella sativa effects nociceotion and improves learning and memory in rats. Pak J Biochem Mol Biol, 41: 141-143.
Perveen T, Haider S, Kanwal S, Haleem DJ. 2009. Repeated administration of Nigella sativa decreases 5-HTturnover and produces anxiolytic effects in rats. Pak J Pharm Sci, 22: 139-144.
Petit-Demouliere B, Chenu F, Bourin M. 2005. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology, 177: 245-255.
Pourbakhsh H, Taghiabadi E, Abnou, 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.‏
Radad K, Moldzio R, Taha M, Rausch WD. 2009. Thymoquinone protects dopaminergic neurons against MPP+ and rotenone. Phytother Res, 23: 696-700.
Rajsekhar S, Kuldeep B. 2011. Pharmacognosy and pharmacology of Nigella sativa- A review. Int Res J Pharm, 2: 36-39.
Randhawa MA, Alghamdi MS. 2011. Anticancer activity of Nigella sativa (black seed)- a review. Am J Chin Med, 39: 1075-1091.‏
Razavi BM, Hosseinzadeh H. 2014. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest, 37: 1031-1040.‏
Rogers J, Webster S, Lue LF, Brachova L, Civin WH, Emmerling M, Shivers B, Walker D, McGeer P. 1996. Inflammation and Alzheimer′s disease pathogenesis. Neurobiol Aging, 17: 681-686.
Sahak MK, Mohamed AM, Hashim NH, Hasan Adli DS. 2013. Nigella sativa Oil Enhances the Spatial Working Memory Performance of Rats on a Radial Arm Maze. Evid Based Complement Alternat Med, 2013: 180598.
Sangi S, Ahmed SP, Channa MA, Ashfaq M, Mastoi SM. 2008. A new and novel treatment of opioid dependence: Nigella sativa 500 mg. J Ayub Med Coll Abbottabad, 20: 118-124.
Sedaghat R, Roghani M, Khalili M. 2014. Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res, 13: 227-234.
Sharma NK, Ahirwar D, Jhade D, Gupta S. 2009. Medicinal and phamacological potential of nigella sativa: a review. Ethnobotanical Leaflets, 2009: 11.
Sharp LK, Lipsky MS. 2002. Screening for depression across the lifespan: a review of measures for use in primary care settings. Am Fam Physician, 66:1001-8.
Sharrif M. 2011. Nigella sativa Traditional Usages (BlackSeed). Adv Environ Biol, 5: 5-16.
Shrivastava RM, Agrawal RC, Parveen ZJ. 2011. A review on therapeutic applications of Nigella sativa. J Chem Chem Sci, 1: 241-248.
Spillantini MG, Schmidt ML, Lee VMY, Trojanowski JQ, Jakes R, Goedert M. 1997. α-Synuclein in Lewy bodies. Nature, 388: 839-840.
Türkdoğan MK, Ağaoğlu Z, Yener Z, Sekeroğlu R, Akkan HA, Avci ME. 2001. The role of antioxidant vitamins (C and E), selenium and Nigella sativa in the prevention of liver fibrosis and cirrhosis in rabbits: new hopes. DTW. Dtsch Tierarztl Wochenschr, 108: 71-73.
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.
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.‏
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature protocols, 1: 848-858.
Warrier PK, Nambiar VPK. 2004. Indian medicinal plants-a  compendium of 500 species. Orient Longman Pvt Ltd, 139-142.
Yarnell E, Abascal K. 2011. Nigella sativa: holy herb of the middle East. Altern Compl Therap, 17: 99-105.
Yassin MM. 2005. Prophylactic Efficacy of Crushed Garlic Lobes, BlackSeed or Olive Oils on Cholinesterase Activity in Central Nervous System Parts and Serum of Lead In toxicated Rabbits. Turk J Biol, 29: 173-180.
 
Avicenna Journal of Phytomedicine
Volume 6, Issue 1 - Serial Number 1
January and February 2016
Pages 124-141

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