Research Article
Nigella sativa oil attenuates neuroinflammation and cognitive deficits in a rat model of Alzheimer's disease
Abstract
Purpose: Alzheimer's disease (AD) is a progressive disease, characterized by the progressive deterioration of cognitive functions. Amyloid plaques formed by accumulation of Aβ peptides are typical of the disease. These peptides are known to trigger inflammatory processes and play a role in disease progression. In this study, we aimed to investigate the effects of Nigella sativa oil in the rats with Alzheimer’s disease model made by bilateral intrahippocampal injection of Aβ1-42.
Materials and Methods: Nigella sativa oil was administered to the rats by oral gavage from 7 days before to 10 days after the injection. Passive avoidance and Morris Water Maze were performed. At the end of the experiments, the hippocampus of the sacrificed animals was extracted for biochemical analysis.
Results: Learning and memory decline induced by Aβ1-42 administration is reversed by 1 ml/kg, 2 ml/kg NS oil delivery. The increase in astrocytes and microglia activity in Alzheimer’s disease group was attenuated in all treatment groups except 0.5 ml/kg NS oil group. We found that the increase in proinflammatory cytokine TNF-α and IL-1β levels induced by injecting Aβ in the hippocampus was suppressed in treatment groups.
Conclusion: According to our experimental findings, the positive effects of Nigella sativa oil on impaired learning and memory in Alzheimer's disease development may be due to the suppression of the excessive inflammatory response in the pathology of the disease.
Project Number
Ankara Yıldırım Beyazıt University Scientific Research Projects Unit (Project No: 4992)
References
- Kumar A, Singh A, Ekavali. A review on Alzheimer’s disease pathophysiology and its management: An update. Pharmacol Rep. 2015;67:195–203.
- 2024 Alzheimer’s disease facts and figures. Alzheimers Dement. 2024;20:3708-21.
- Barage SH, Sonawane KD. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease. Neuropeptides. 2015;52:1-18.
- Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma D. Neuroinflammation: the role and consequences. Neurosci Res. 2014;79:1–12.
- Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, et.al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J Neurosci. 2000;20:5709–14.
- Richardson RL, Kim EM, Shephard RA, Gardiner T, Cleary J, O’Hare E. Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Abeta(1-42) injections in the rat. Brain Res. 2002;954:1–10.
- El-far AH, Korshom MA, Mandour AA, El-bessoumy AA, El-sayed YS. Hepatoprotective efficacy of Nigella sativa seeds dietary supplementation against lead acetate-induced oxidative damage in rabbit – Purification and characterization of glutathione peroxidase. Biomed. Pharmacother. 2017;89:711–18.
- Balbaa M, El-Zeftawy M, Ghareeb D, Taha N, Mandour AW. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet. Oxid Med Cell Longev. 2016:2016:2492107.
- Abulfadl Y, El-Maraghy N, Ahmed AE, Nofal S, Abdel-Mottaleb Y, Badary O. Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling. Hum Exp Toxicol. 2018;37:1092–104.
- Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol. 2016;190:372–86.
- 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;148:780–6.
- Gülşen I, Ak H, Çölçimen N, Alp HH, Akyol ME, Demir I, et al. Neuroprotective effects of thymoquinone on the hippocampus in a rat model of traumatic brain injury. World Neurosurg. 2016;86:243–9.
- Hobbenaghi R, Javanbakht J, Sadeghzadeh S, Kheradmand D, Abdi FS, Jaberi MH. 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;337:74–9.
- Paxinos G, Watson C. The rat brain in stereotaxic coordinates - 7th ed. 2013.
- Aquino R, de Concini V, Dhenain M, Lam S, Gosset D, Baquedano L, et al. Intrahippocampal inoculation of Aβ1–42 peptide in rat as a model of Alzheimer’s disease identified microRNA-146a-5p as blood marker with anti-inflammatory function in astrocyte cells. Cells. 2023;12:694.
- Asadbegi M, Yaghmaei P, Salehi I, Komaki A, Ebrahim-Habibi A. Investigation of thymol effect on learning and memory impairment induced by intrahippocampal injection of amyloid beta peptide in high fat diet-fed rats. Metab Brain Dis. 2017;32:827–39.
- Ji ZH, Xu ZQ, Zhao H, Yu XY. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer’s disease. Steroids. 2017;119:31–5.
- Chen J-H, Ke K-F, Lu J-H, Qiu Y-H, Peng Y-P. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1–42–induced Alzheimer’s disease model rats. PLoS One. 2015;10:e0116549.
- Tomita T. Aberrant proteolytic processing and therapeutic strategies in Alzheimer disease. Adv Biol Regul. 2017;64:33–8.
- Kozlov S, Afonin A, Evsyukov I, Bondarenko A. Alzheimer’s disease: As it was in the beginning. Rev Neurosci. 2017;28:825–43.
- Soodi M, Saeidnia S, Sharifzadeh M, Hajimehdipoor H, Dashti A, Sepand MR, et al. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer’s disease. Metab Brain Dis. 2016;31:395-04.
- Kiasalari Z, Heydarifard R, Khalili M, Afshin-Majd S, Baluchnejadmojarad T, Zahedi E,et al. Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer’s disease: an exploration of underlying mechanisms. Psychopharmacology (Berl). 2017;234:1841–52.
- Sastre M, Klockgether T, Heneka MT. Contribution of inflammatory processes to Alzheimer’s disease: molecular mechanisms. Int J Dev Neurosci. 2006;24:167–76.
- Cai Z, Hussain MD, Yan LJ. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. Int J Neurosci. 2014;124:307–21.
- Shaftel SS, Kyrkanides S, Olschowka JA, Miller JNH, Johnson RE, O’Banion MK. Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest. 2007;117:1595–604.
- Mandrekar-Colucci S, Landreth GE. Microglia and inflammation in Alzheimer’s disease. CNS Neurol Disord Drug Targets. 2010;9:156–67.
- Chen JH, Ke KF, Lu JH, Qiu YH, Peng YP. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer’s disease model rats. PLoS One. 2015;10:e0116549.
- Lu BL, Li J, Zhou J, Li WW, Wu HF. Tanshinone IIA decreases the levels of inflammation induced by Aβ1-42 in brain tissues of Alzheimer’s disease model rats. Neuroreport. 2016;27:883–93.
- Prokop S, Miller KR, Heppner FL. Microglia actions in Alzheimer’s disease. Acta Neuropathol. 2013;126:461–77.
- Combs CK, Karlo JC, Kao SC, Landreth GE. beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci. 2001;21:1179–88.
- Shi X, Zheng Z, Li J, Xiao Z, Qi W, Zhang A, et al. Curcumin inhibits Aβ-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways. Neurosci Lett. 2015;594:105–10.
- Morales I, Guzmán-Martínez L, Cerda-Troncoso C, Farías GA, Maccioni RB. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci. 2014;8:112.
- Verkhratsky A, Olabarria M, Noristani HN, Yeh CY, Rodriguez JJ. Astrocytes in Alzheimer’s disease. Neurotherapeutics. 2010;7:399–412.
- Duan MH, Wang LN, Jiang YH, Pei YY, Guan DD, Qiu ZD. Angelica sinensis reduced Aβ-induced memory impairment in rats. J Drug Target. 2016;24(4):340-7.
- Smits HA, Rijsmus A, Van Loon JH, Wat JWY, Verhoef J, Boven LA, et al. Amyloid-β-induced chemokine production in primary human macrophages and astrocytes. J Neuroimmunol. 2002;127:160–8.
- Alam MF, Khan G, Safhi MM, Alshahrani S, Siddiqui R, Sivagurunathan Moni S, et al. Thymoquinone ameliorates doxorubicin-induced cardiotoxicity in swiss albino mice by modulating oxidative damage and cellular inflammation. Cardiol Res Pract. 2018;2018: 1483041.
- Abdelghany AK, El-Nahass E-S, Ibrahim MA, El-Kashlan AkramM, Emeash HH, Khalil F. Neuroprotective role of medicinal plant extracts evaluated in a scopolamine-induced rat model of Alzheimer’s disease. Biomarkers. 2022;27:773–83
Nigella sativa yağı, Alzheimer hastalığı rat modelinde nöroenflamasyonu ve bilişsel bozuklukları hafifletir
Abstract
Amaç: Alzheimer hastalığı (AH) bilişsel işlevlerin giderek bozulması ile karakterize ilerleyici bir hastalıktır. Aβ peptidlerinin birikimiyle oluşan amiloid plaklar hastalığın tipik özelliğidir. Bu peptitlerin inflamatuar süreçleri tetiklediği ve hastalığın ilerlemesinde rol oynadığı bilinmektedir. Bu çalışmada, bilateral intrahipokampal Aβ1-42 enjeksiyonu ile Alzheimer hastalığı modeli oluşturulan sıçanlarda Nigella sativa yağının etkilerini araştırmayı amaçladık.
Gereç ve Yöntemler: Nigella sativa yağı sıçanlara enjeksiyondan 7 gün öncesinden 10 gün sonrasına kadar oral gavaj yoluyla uygulandı. Pasif kaçınma ve Morris Su Labirenti deneyleri yapıldı. Deneylerin sonunda, sakrifiye edilen hayvanların hipokampüsleri biyokimyasal analiz için çıkarıldı.
Bulgular: Aβ1-42 uygulaması ile indüklenen öğrenme ve hafıza gerilemesi 1 ml/kg, 2 ml/kg NS yağı uygulaması ile tersine çevrilmiştir. Alzheimer hastalığı grubunda astrosit ve mikroglia aktivitesindeki artış, 0,5 ml/kg NS yağı grubu hariç tüm tedavi gruplarında zayıflamıştır. Hipokampüste Aβ enjeksiyonu ile indüklenen proinflamatuar sitokin TNF-α ve IL-1β seviyelerindeki artışın tedavi gruplarında baskılandığını bulduk.
Sonuç: Deneysel bulgularımıza göre, Nigella sativa yağının Alzheimer hastalığı gelişiminde bozulmuş öğrenme ve hafıza üzerindeki olumlu etkileri, hastalığın patolojisindeki aşırı inflamatuar cevabın baskılanmasına bağlı olabilir.
Project Number
Ankara Yıldırım Beyazıt University Scientific Research Projects Unit (Project No: 4992)
References
- Kumar A, Singh A, Ekavali. A review on Alzheimer’s disease pathophysiology and its management: An update. Pharmacol Rep. 2015;67:195–203.
- 2024 Alzheimer’s disease facts and figures. Alzheimers Dement. 2024;20:3708-21.
- Barage SH, Sonawane KD. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease. Neuropeptides. 2015;52:1-18.
- Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma D. Neuroinflammation: the role and consequences. Neurosci Res. 2014;79:1–12.
- Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, et.al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J Neurosci. 2000;20:5709–14.
- Richardson RL, Kim EM, Shephard RA, Gardiner T, Cleary J, O’Hare E. Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Abeta(1-42) injections in the rat. Brain Res. 2002;954:1–10.
- El-far AH, Korshom MA, Mandour AA, El-bessoumy AA, El-sayed YS. Hepatoprotective efficacy of Nigella sativa seeds dietary supplementation against lead acetate-induced oxidative damage in rabbit – Purification and characterization of glutathione peroxidase. Biomed. Pharmacother. 2017;89:711–18.
- Balbaa M, El-Zeftawy M, Ghareeb D, Taha N, Mandour AW. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet. Oxid Med Cell Longev. 2016:2016:2492107.
- Abulfadl Y, El-Maraghy N, Ahmed AE, Nofal S, Abdel-Mottaleb Y, Badary O. Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling. Hum Exp Toxicol. 2018;37:1092–104.
- Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol. 2016;190:372–86.
- 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;148:780–6.
- Gülşen I, Ak H, Çölçimen N, Alp HH, Akyol ME, Demir I, et al. Neuroprotective effects of thymoquinone on the hippocampus in a rat model of traumatic brain injury. World Neurosurg. 2016;86:243–9.
- Hobbenaghi R, Javanbakht J, Sadeghzadeh S, Kheradmand D, Abdi FS, Jaberi MH. 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;337:74–9.
- Paxinos G, Watson C. The rat brain in stereotaxic coordinates - 7th ed. 2013.
- Aquino R, de Concini V, Dhenain M, Lam S, Gosset D, Baquedano L, et al. Intrahippocampal inoculation of Aβ1–42 peptide in rat as a model of Alzheimer’s disease identified microRNA-146a-5p as blood marker with anti-inflammatory function in astrocyte cells. Cells. 2023;12:694.
- Asadbegi M, Yaghmaei P, Salehi I, Komaki A, Ebrahim-Habibi A. Investigation of thymol effect on learning and memory impairment induced by intrahippocampal injection of amyloid beta peptide in high fat diet-fed rats. Metab Brain Dis. 2017;32:827–39.
- Ji ZH, Xu ZQ, Zhao H, Yu XY. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer’s disease. Steroids. 2017;119:31–5.
- Chen J-H, Ke K-F, Lu J-H, Qiu Y-H, Peng Y-P. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1–42–induced Alzheimer’s disease model rats. PLoS One. 2015;10:e0116549.
- Tomita T. Aberrant proteolytic processing and therapeutic strategies in Alzheimer disease. Adv Biol Regul. 2017;64:33–8.
- Kozlov S, Afonin A, Evsyukov I, Bondarenko A. Alzheimer’s disease: As it was in the beginning. Rev Neurosci. 2017;28:825–43.
- Soodi M, Saeidnia S, Sharifzadeh M, Hajimehdipoor H, Dashti A, Sepand MR, et al. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer’s disease. Metab Brain Dis. 2016;31:395-04.
- Kiasalari Z, Heydarifard R, Khalili M, Afshin-Majd S, Baluchnejadmojarad T, Zahedi E,et al. Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer’s disease: an exploration of underlying mechanisms. Psychopharmacology (Berl). 2017;234:1841–52.
- Sastre M, Klockgether T, Heneka MT. Contribution of inflammatory processes to Alzheimer’s disease: molecular mechanisms. Int J Dev Neurosci. 2006;24:167–76.
- Cai Z, Hussain MD, Yan LJ. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. Int J Neurosci. 2014;124:307–21.
- Shaftel SS, Kyrkanides S, Olschowka JA, Miller JNH, Johnson RE, O’Banion MK. Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest. 2007;117:1595–604.
- Mandrekar-Colucci S, Landreth GE. Microglia and inflammation in Alzheimer’s disease. CNS Neurol Disord Drug Targets. 2010;9:156–67.
- Chen JH, Ke KF, Lu JH, Qiu YH, Peng YP. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer’s disease model rats. PLoS One. 2015;10:e0116549.
- Lu BL, Li J, Zhou J, Li WW, Wu HF. Tanshinone IIA decreases the levels of inflammation induced by Aβ1-42 in brain tissues of Alzheimer’s disease model rats. Neuroreport. 2016;27:883–93.
- Prokop S, Miller KR, Heppner FL. Microglia actions in Alzheimer’s disease. Acta Neuropathol. 2013;126:461–77.
- Combs CK, Karlo JC, Kao SC, Landreth GE. beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci. 2001;21:1179–88.
- Shi X, Zheng Z, Li J, Xiao Z, Qi W, Zhang A, et al. Curcumin inhibits Aβ-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways. Neurosci Lett. 2015;594:105–10.
- Morales I, Guzmán-Martínez L, Cerda-Troncoso C, Farías GA, Maccioni RB. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci. 2014;8:112.
- Verkhratsky A, Olabarria M, Noristani HN, Yeh CY, Rodriguez JJ. Astrocytes in Alzheimer’s disease. Neurotherapeutics. 2010;7:399–412.
- Duan MH, Wang LN, Jiang YH, Pei YY, Guan DD, Qiu ZD. Angelica sinensis reduced Aβ-induced memory impairment in rats. J Drug Target. 2016;24(4):340-7.
- Smits HA, Rijsmus A, Van Loon JH, Wat JWY, Verhoef J, Boven LA, et al. Amyloid-β-induced chemokine production in primary human macrophages and astrocytes. J Neuroimmunol. 2002;127:160–8.
- Alam MF, Khan G, Safhi MM, Alshahrani S, Siddiqui R, Sivagurunathan Moni S, et al. Thymoquinone ameliorates doxorubicin-induced cardiotoxicity in swiss albino mice by modulating oxidative damage and cellular inflammation. Cardiol Res Pract. 2018;2018: 1483041.
- Abdelghany AK, El-Nahass E-S, Ibrahim MA, El-Kashlan AkramM, Emeash HH, Khalil F. Neuroprotective role of medicinal plant extracts evaluated in a scopolamine-induced rat model of Alzheimer’s disease. Biomarkers. 2022;27:773–83
There are 37 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences (Other) |
| Journal Section | Research |
| Authors | |
| Project Number | Ankara Yıldırım Beyazıt University Scientific Research Projects Unit (Project No: 4992) |
| Publication Date | June 30, 2025 |
| Submission Date | November 27, 2024 |
| Acceptance Date | May 15, 2025 |
| Published in Issue | Year 2025 Volume: 50 Issue: 2 |
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