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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Review Article

Potential role of Nigella Sativa and its Constituent (Thymoquinone) in Ischemic Stroke

Author(s): Shakiba Azami and Fatemeh Forouzanfar*

Volume 24, Issue 3, 2024

Published on: 27 April, 2023

Page: [327 - 334] Pages: 8

DOI: 10.2174/1566524023666230410101724

Price: $65

Abstract

Ischemic stroke is one of the major causes of global mortality, which puts great demands on health systems and social welfare. Ischemic stroke is a complex pathological process involving a series of mechanisms such as ROS accumulation, Ca2+ overload, inflammation, and apoptosis. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients has led scientists to find new treatments. The use of herbal medicine, as an alternative or complementary therapy, is increasing worldwide. For centuries, our ancestors had known the remedial nature of Nigella sativa (Family Ranunculaceae) and used it in various ways, either as medicine or as food. Nowadays, N. sativa is generally utilized as a therapeutic plant all over the world. Most of the therapeutic properties of this plant are attributed to the presence of thymoquinone which is the major biological component of the essential oil. The present review describes the pharmacotherapeutic potential of N. sativa in ischemic stroke that has been carried out by various researchers. Existing literature highlights the protective effects of N. sativa as well as thymoquinone in ischemia stroke via different mechanisms including anti-oxidative stress, anti-inflammation, anti-apoptosis, neuroprotective, and vascular protective effects. These properties make N. sativa and thymoquinone promising candidates for developing potential agents for the prevention and treatment of ischemic stroke.

« Previous Next »
[1]
Gorelick PB. The global burden of stroke: Persistent and disabling. Lancet Neurol 2019; 18(5): 417-8.
[http://dx.doi.org/10.1016/S1474-4422(19)30030-4] [PMID: 30871943]
[2]
Johnson CO, Nguyen M, Roth GA, et al. Global, regional, and national burden of stroke, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18(5): 439-58.
[http://dx.doi.org/10.1016/S1474-4422(19)30034-1] [PMID: 30871944]
[3]
Forouzanfar F, Shojapour M, Asgharzade S, Amini E. Causes and consequences of MicroRNA dysregulation following cerebral ischemia-reperfusion injury. CNS Neurol Disord Drug Targets 2019; 18(3): 212-21.
[http://dx.doi.org/10.2174/1871527318666190204104629] [PMID: 30714533]
[4]
Kyu HH, Abate D, Abate KH, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392(10159): 1859-922.
[http://dx.doi.org/10.1016/S0140-6736(18)32335-3] [PMID: 30415748]
[5]
Katan M, Luft A. Global burden of stroke. Semin Neurol 2018; 38(2): 208-11.
[6]
Venketasubramanian N, Yoon BW, Pandian J, Navarro JC. Stroke epidemiology in south, east, and south-east asia: A review. J Stroke 2017; 19(3): 286-94.
[http://dx.doi.org/10.5853/jos.2017.00234] [PMID: 29037005]
[7]
Lin HW, Lee RC, Lee MHH, et al. Cerebral ischemia and neuroregeneration. Neural Regen Res 2018; 13(3): 373-85.
[http://dx.doi.org/10.4103/1673-5374.228711] [PMID: 29623912]
[8]
Ojaghihaghighi S, Vahdati SS, Mikaeilpour A, Ramouz A. Comparison of neurological clinical manifestation in patients with hemorrhagic and ischemic stroke. World J Emerg Med 2017; 8(1): 34-8.
[http://dx.doi.org/10.5847/wjem.j.1920-8642.2017.01.006] [PMID: 28123618]
[9]
Peña I, Borlongan C, Shen G, Davis W. Strategies to extend thrombolytic time window for ischemic stroke treatment: An unmet clinical need. J Stroke 2017; 19(1): 50-60.
[http://dx.doi.org/10.5853/jos.2016.01515] [PMID: 28178410]
[10]
Asgharzade S, Talaei A, Farkhondeh T, Forouzanfar F. Combining growth factor and stem cell therapy for stroke rehabilitation, a review. Curr Drug Targets 2020; 21(8): 781-91.
[http://dx.doi.org/10.2174/1389450121666200107100747] [PMID: 31914912]
[11]
Li W, Huang R, Shetty RA, et al. Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model. Neurobiol Dis 2013; 59: 18-25.
[http://dx.doi.org/10.1016/j.nbd.2013.06.014] [PMID: 23845275]
[12]
Gaire BP. Herbal medicine in ischemic stroke: Challenges and prospective. Chin J Integr Med 2018; 24(4): 243-6.
[http://dx.doi.org/10.1007/s11655-018-2828-2] [PMID: 29696521]
[13]
Asgharzade S, Khorrami MB, Forouzanfar F. Neuroprotective effect of herniarin following transient focal cerebral ischemia in rats. Metab Brain Dis 2021; 36(8): 2505-10.
[http://dx.doi.org/10.1007/s11011-021-00841-1] [PMID: 34519909]
[14]
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017; 38(7): 1167-86.
[http://dx.doi.org/10.1007/s10072-017-2938-1] [PMID: 28417216]
[15]
Yang Q, Huang Q, Hu Z, Tang X. Potential neuroprotective treatment of stroke: Targeting excitotoxicity, oxidative stress, and inflammation. Front Neurosci 2019; 13: 1036.
[http://dx.doi.org/10.3389/fnins.2019.01036] [PMID: 31611768]
[16]
He Z, Ning N, Zhou Q, Khoshnam SE, Farzaneh M. Mitochondria as a therapeutic target for ischemic stroke. Free Radic Biol Med 2020; 146: 45-58.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.11.005] [PMID: 31704373]
[17]
Li P, Stetler RA, Leak RK, Shi Y, Li Y, Yu W, et al. Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery. Neuropharmacology, 2018; 134(Pt B): 208-17.
[18]
Elsayed Azab A. A Adwas A, Ibrahim Elsayed AS, A Adwas A, Ibrahim Elsayed AS, Quwaydir FA. Oxidative stress and antioxidant mechanisms in human body. J Appl Biotech & Bioeng 2019; 6(1): 43-7.
[http://dx.doi.org/10.15406/jabb.2019.06.00173]
[19]
Zhang SR, Phan TG, Sobey CG. Targeting the immune system for ischemic stroke. Trends Pharmacol Sci 2021; 42(2): 96-105.
[http://dx.doi.org/10.1016/j.tips.2020.11.010] [PMID: 33341247]
[20]
Wang X, Xuan W, Zhu ZY, et al. The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke. CNS Neurosci Ther 2018; 24(12): 1100-14.
[http://dx.doi.org/10.1111/cns.13077] [PMID: 30350341]
[21]
Ali B, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Wiley Online Library 2003; 17(4): 299-305.
[http://dx.doi.org/10.1002/ptr.1309]
[22]
Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed 2013; 3(5): 337-52.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1] [PMID: 23646296]
[23]
Oskouei Z, Akaberi M, Hosseinzadeh H. A glance at black cumin (Nigella sativa) and its active constituent, thymoquinone, in ischemia: A review. Iran J Basic Med Sci 2018; 21(12): 1200-9.
[PMID: 30627362]
[24]
Javidi S, Razavi BM, Hosseinzadeh H. A review of neuropharmacology effects of Nigella sativa and its main component, thymoquinone. Phytother Res 2016; 30(8): 1219-29.
[http://dx.doi.org/10.1002/ptr.5634] [PMID: 27169925]
[25]
Bin Sayeed MS, Asaduzzaman M, Morshed H, Hossain MM, Kadir MF, Rahman MR. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol 2013; 148(3): 780-6.
[http://dx.doi.org/10.1016/j.jep.2013.05.004] [PMID: 23707331]
[26]
Sahak MKA, Kabir N, Abbas G, Draman S, Hashim NH, Hasan Adli DS. The role of Nigella sativa and its active constituents in learning and memory. Evid Based Complement Alternat Med 2016; 2016: 6075679.
[27]
Bin Sayeed MS, Shams T, Fahim Hossain S, et al. Nigella sativa L. seeds modulate mood, anxiety and cognition in healthy adolescent males. J Ethnopharmacol 2014; 152(1): 156-62.
[http://dx.doi.org/10.1016/j.jep.2013.12.050] [PMID: 24412554]
[28]
Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int Immunopharmacol 2015; 28(1): 295-304.
[http://dx.doi.org/10.1016/j.intimp.2015.06.023] [PMID: 26117430]
[29]
Forouzanfar F, Bazzaz BSF, Hosseinzadeh H. Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects. Iran J Basic Med Sci 2014; 17(12): 929-38.
[PMID: 25859296]
[30]
Khan A, Vaibhav K, Javed H, et al. Attenuation of Aβ-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress. Mol Cell Biochem 2012; 369(1-2): 55-65.
[http://dx.doi.org/10.1007/s11010-012-1368-x] [PMID: 22752387]
[31]
Hossen MJ, Yang WS, Kim D, Aravinthan A, Kim JH, Cho JY. Thymoquinone: An IRAK1 inhibitor with in vivoand in vitro anti-inflammatory activities. Sci Rep 2017; 7(1): 42995.
[http://dx.doi.org/10.1038/srep42995] [PMID: 28216638]
[32]
Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol 2005; 5(13-14): 1749-70.
[http://dx.doi.org/10.1016/j.intimp.2005.06.008] [PMID: 16275613]
[33]
Jakaria M, Cho DY, Ezazul Haque M, et al. Neuropharmacological potential and delivery prospects of thymoquinone for neurological disorders. Oxid Med Cell Longev 2018; 2018: 1-17.
[http://dx.doi.org/10.1155/2018/1209801] [PMID: 29743967]
[34]
Farkhondeh T, Samarghandian S, Shahri AMP, Samini F. The neuroprotective effects of thymoquinone: A review. Dose Response 2018; 16(2)
[http://dx.doi.org/10.1177/1559325818761455] [PMID: 29662431]
[35]
Hussein El-Tahir KE-D, Bakeet DM. The black seed Nigella sativa Linnaeus-A mine for multi cures: A plea for urgent clinical evaluation of its volatile oil. J Taibah Univ Med Sci 2006; 1(1): 1-19.
[http://dx.doi.org/10.1016/S1658-3612(06)70003-8]
[36]
Piras A, Rosa A, Marongiu B, et al. Chemical composition and in vitro bioactivity of the volatile and fixed oils of Nigella sativa L. extracted by supercritical carbon dioxide. Ind Crops Prod 2013; 46: 317-23.
[http://dx.doi.org/10.1016/j.indcrop.2013.02.013]
[37]
Ahmad MF, Ahmad FA, Ashraf SA, et al. An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties. J Herb Med 2021; 25: 100404.
[http://dx.doi.org/10.1016/j.hermed.2020.100404] [PMID: 32983848]
[38]
Soleimannejad K, Rahmani A, Hatefi M, Khataminia M, Hafezi Ahmadi MR, Asadollahi K. effects of Nigella sativa extract on markers of cerebral angiogenesis after global ischemia of brain in rats. J Stroke Cerebrovasc Dis 2017; 26(7): 1514-20.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.02.040] [PMID: 28396188]
[39]
Ismail YM, Abd El Latif EA, Sanad RA, Abdallah OM. Protective effect of Nigella sativa against cerebral ischemia and sodium valproate-induced hepatotoxicity. Benha Med J 2015; 32(1): 41.
[http://dx.doi.org/10.4103/1110-208X.170558]
[40]
Hobbenaghi R, Javanbakht J, Sadeghzadeh S, et al. Neuroprotective effects of Nigella sativa extract on cell death in hippocampal neurons following experimental global cerebral ischemia-reperfusion injury in rats. J Neurol Sci 2014; 337(1-2): 74-9.
[http://dx.doi.org/10.1016/j.jns.2013.11.019] [PMID: 24314720]
[41]
Tian F, Liu R, Fan C, et al. Effects of thymoquinone on small-molecule metabolites in a rat model of cerebral ischemia reperfusion injury assessed using maldi-msi. Metabolites 2020; 10(1): 27.
[http://dx.doi.org/10.3390/metabo10010027] [PMID: 31936061]
[42]
Fan C, Tian F, Zhao X, et al. The effect of thymoquinone on the characteristics of the brain extracellular space in transient middle cerebral artery occlusion rats. Biol Pharm Bull 2020; 43(9): 1306-14.
[http://dx.doi.org/10.1248/bpb.b19-00991] [PMID: 32879204]
[43]
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine 2007; 14(9): 621-7.
[http://dx.doi.org/10.1016/j.phymed.2006.12.005] [PMID: 17291733]
[44]
Al-Majed AA, Al-Omar FA, Nagi MN. Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharmacol 2006; 543(1-3): 40-7.
[http://dx.doi.org/10.1016/j.ejphar.2006.05.046] [PMID: 16828080]
[45]
Xiao XY, Zhu YX, Bu JY, Li GW, Zhou JH, Zhou SP. Evaluation of neuroprotective effect of thymoquinone nanoformulation in the rodent cerebral ischemia-reperfusion model. Biomed Res Int 2016; 2016: 2571060.
[http://dx.doi.org/10.1155/2016/2571060]
[46]
Ahmad N, Ahmad R, Alam MA, Samim M, Iqbal Z, Ahmad FJ. Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia. Int J Biol Macromol 2016; 88: 320-32.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.03.019] [PMID: 26976069]
[47]
Alinejad B, Ghorbani A, Sadeghnia HR. Effects of combinations of curcumin, linalool, rutin, safranal, and thymoquinone on glucose/serum deprivation-induced cell death. Avicenna J Phytomed 2013; 3(4): 321-8.
[PMID: 25050289]
[48]
Babazadeh B, Sadeghnia HR, Safarpour Kapurchal E, Parsaee H, Nasri S, Tayarani-Najaran Z. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells. Avicenna J Phytomed 2012; 2(3): 125-32.
[PMID: 25050241]
[49]
Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cell Mol Neurobiol 2010; 30(4): 591-8.
[http://dx.doi.org/10.1007/s10571-009-9484-1] [PMID: 20054635]
[50]
Sinning C, Westermann D, Clemmensen P. Oxidative stress in ischemia and reperfusion: Current concepts, novel ideas and future perspectives. Biomarkers Med 2017; 11(11): 11031-40.
[http://dx.doi.org/10.2217/bmm-2017-0110] [PMID: 29039206]
[51]
Zhao H, Han Z, Ji X, Luo Y. Epigenetic regulation of oxidative stress in ischemic stroke. Aging Dis 2016; 7(3): 295-306.
[http://dx.doi.org/10.14336/AD.2015.1009] [PMID: 27330844]
[52]
Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke 2009; 4(6): 461-70.
[http://dx.doi.org/10.1111/j.1747-4949.2009.00387.x] [PMID: 19930058]
[53]
Shadman J, Sadeghian N, Moradi A, Bohlooli S, Panahpour H. Magnesium sulfate protects blood–brain barrier integrity and reduces brain edema after acute ischemic stroke in rats. Metab Brain Dis 2019; 34(4): 1221-9.
[http://dx.doi.org/10.1007/s11011-019-00419-y] [PMID: 31037556]
[54]
Babar ZU, Azad AK, Wan Sulaiman WMA, Uddin J, Labu ZK. Neuroprotective properties of Nigella sativa (L.) seeds extract in sprague dawley rats models. Dhaka Univ J Pharm Sci 2018; 17(1): 113-21.
[http://dx.doi.org/10.3329/dujps.v17i1.37127]
[55]
Ma Y, Zechariah A, Qu Y, Hermann DM. Effects of vascular endothelial growth factor in ischemic stroke. J Neurosci Res 2012; 90(10): 1873-82.
[http://dx.doi.org/10.1002/jnr.23088] [PMID: 22714747]
[56]
Pawluk H, Woźniak A, Grześk G, et al. The role of selected pro-inflammatory cytokines in pathogenesis of ischemic stroke. Clin Interv Aging 2020; 15: 469-84.
[http://dx.doi.org/10.2147/CIA.S233909] [PMID: 32273689]
[57]
Jin R, Liu L, Zhang S, Nanda A, Li G. Role of inflammation and its mediators in acute ischemic stroke. J Cardiovasc Transl Res 2013; 6(5): 834-51.
[http://dx.doi.org/10.1007/s12265-013-9508-6] [PMID: 24006091]
[58]
Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: Role of inflammatory cells. J Leukoc Biol 2010; 87(5): 779-89.
[http://dx.doi.org/10.1189/jlb.1109766] [PMID: 20130219]
[59]
Hussien NI, Elawady MA, Elmaghrabi MM, Muhammad MH. Impact of thymoquinone on memory deficit-associated with global cerebral ischemia-reperfusion injury in rats; possible role of PPAR-. Am J Biomed Sci 2020; 12(1): 77-90.
[http://dx.doi.org/10.5099/aj200100077]
[60]
Pop RM, Sabin O, Suciu Ș, et al. Nigella sativa’s anti-inflammatory and antioxidative effects in experimental inflammation. Antioxidants 2020; 9(10): 921.
[http://dx.doi.org/10.3390/antiox9100921] [PMID: 32993150]

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