PREVENTIVE EFFECT OF NIGELLA SATIVA L. AGAINST CEREBRAL OXIDATIVE ALTERATIONS INDUCED BY A HIGH-FAT, IRON-ENRICHED DIET IN MICE
Abstract
Recent research underscores the pivotal role of oxidative stress in cerebral alterations, prompting investigations into strategies such as the utilization of natural substances derived from medicinal plants, including Nigella sativa L. (NS) for their therapeutic potential. NS is known for its bioactive compounds that play a significant role in disease prevention and treatment. This study employed Fourier Transform Infrared Spectroscopic (FT-IR) analysis to identify functional groups and compounds in NS seed and to examine its preventive effects on cerebral oxidative changes induced by a high-fat diet (HFD) supplemented with iron in NMRI mice. The focus was on lipid oxidation, Ferric Reducing Antioxidant Power (FRAP), thiol groups, catalase activity, and Reduced Glutathione (GSH) levels. Mice were randomly assigned to four experimental groups (six mice per group): control (ST), control + NS seed powder (ST+NSP), high-fat diet with FeCl₃ (HFD/Fe3+), and HFD/Fe3+ + NSP. Following an 11-week experimental period, lipid oxidation, FRAP, thiol groups, and CAT activity were measured in plasma and brain, while GSH levels were assessed exclusively in the brain. NS significantly reduced lipid peroxidation in HFD/Fe3+ mice and restored FRAP, thiol groups, CAT activity, and GSH levels, which were markedly reduced in HFD/Fe3+ mice compared to the ST group. The HFD/Fe3+ regimen increased lipid peroxidation products relative to the ST group. These findings suggest that NSP supplementation mitigates cerebral oxidative stress and enhances antioxidant enzyme activity.
References
Aebi, H. (1984). Catalase in vitro. Methods in Enzymo-logy, 105, 121-126. https://doi.org/10.1016/S0076-6879(84)05016-3
Alu'datt, M. H., Rababah, T., Al‐u'datt, D. A. G., Gammoh, S., Alkandari, S., Allafi, A., Alrosan, M., Kubow, S., & Al‐Rashdan, H. K. (2024). Designing novel industrial and functional foods using the bioactive compounds from Nigella sativa L. (black cumin): Biochemical and biological prospects toward health implications. Journal of Food Science, 89(4), 1865-1893. https://doi.org/10.1111/1750-3841.16981
Balbaa, M., Abdulmalek, S. A., & Khalil, S. (2017). Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs. PLoS One, 12(5), e0172429. https://doi.org/10.1371/journal.pone.0172429
Balbaa, M., El-Zeftawy, M., Ghareeb, D., Taha, N., & Mandour, A. W. (2016). Nigella sativa relieves the altered insulin receptor signaling in streptozotocin-induced diabetic rats fed with a high‐fat diet. Oxidative Medicine and Cellular Longevity, 2016(1), 2492107. https://doi.org/10.1155/2016/2492107
Benzie, I. F., & Strain, J. J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of “anti-oxidant power”: the FRAP assay. Analytical Bio-chemistry, 239(1), 70-76. https://doi.org/10.1006/abio.1996.0292
Berg, D., & Youdim, M. B. (2006). Role of iron in neuro-degenerative disorders. Topics in Magnetic Re-sonance Imaging, 17(1), 5-17. https://doi.org/10.1097/01.rmr.0000245461.90406.ad
Bhullar, K. S., & Rupasinghe, H. V. (2013). Polyphe-nols: multipotent therapeutic agents in neuro-degenerative diseases. Oxidative Medicine and Cel-lular Longevity, 2013(1), 891748. https://doi.org/10.1155/2013/891748
Bonnefont-Rousselot, D. (2014). Obésité et stress oxydant. Obésité, 1(9), 8-13. https://doi.org/10.1007/s11690-013-0408-3
Bruce, S. O., Nwafor, O. I., Omoirri, M. A., Adione, N. M., Onyeka, I. P., & Ezeoru, V. C. (2021). GC-MS, FTIR and antiulcer screening of aqueous seed extract and oil of Nigella sativa in Wistar rats. Journal of Drug Delivery and Thera-peutics, 11(6), 48-60. https://doi.org/10.22270/jddt.v11i6.5036
Cascella, M., Bimonte, S., Barbieri, A., Del Vecchio, V., Muzio, M. R., Vitale, A., Benincasa, G., Ferriello, A. B., Azzariti, A, Arra, C., & Cuomo, A. (2018). Dissecting the potential roles of Nigella sativa and its constituent thymoquinone on the prevention and on the progression of Alzheimer's Disease. Fron-tiers in Aging Neuroscience, 10, 16. https://doi.org/10.3389/fnagi.2018.00016
Chen, W. J., Kung, G. P., & Gnana-Prakasam, J. P. (2022). Role of iron in aging related diseases. Antioxidants, 11(5), 865. https://doi.org/10.3390/antiox11050865
Chen, X., Guo, C., & Kong, J. (2012). Oxidative stress in neurodegenerative diseases. Neural Regeneration Research, 7(5), 376-385. https://doi.org/10.3969/j.issn.1673-5374.2012.05.009
Chianese, R., Coccurello, R., Viggiano, A., Scafuro, M., Fiore, M., Coppola, G., Operto, F. F., Fasano, S., Laye, S., Pierantoni, R., & Meccariello, R. (2018). Impact of dietary fats on brain functions. Current Neuropharmacology, 16(7), 1059-1085. https://doi.org/10.2174/1570159X15666171017102547
(CEC) Council of the European Communities. (1986). Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official Journal of the European Communities, L358/1. https://op.europa.eu/publication-detail/-/publication/cc3a8ccb-5a30-4b6e-8da8-b13348caeb0c
Chung, A. P. Y., Gurtu, S., Chakravarthi, S., Moorthy, M., & Palanisamy, U. D. (2018). Geraniin protects high-fat diet-induced oxidative stress in Sprague Dawley rats. Frontiers in Nutrition, 5, 17. https://doi.org/10.3389/fnut.2018.00017
Custers, E. M. E, & Kiliaan, A. J. (2022). Dietary lipids from body to brain. Progress in Lipid Research, 85, 101144. https://doi.org/10.1016/j.plipres.2021.101144
Desai, S. D., Saheb, S. H., Das, K. K., & Haseena, S. (2015). Effect of Nigella sativa seed powder on MDA and SOD levels in sterptozotocine induced diabetes albino rats. Journal of Pharmaceutical Sciences and Research, 7(4), 206.
Dong, J., Liang, Q., Niu, Y., Jiang, S., Zhou, L. I., Wang, J., Ma, C., & Kang, W. (2020). Effects of Nigella sativa seed polysaccharides on type 2 diabetic mice and gut microbiota. International Journal of Bio-logical Macromolecules, 159, 725-738. https://doi.org/10.1016/j.ijbiomac.2020.05.042
Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70-77. https://doi.org/10.1016/0003-9861(59)90090-6
European Union. (2010). Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union, L276/33. https://eur-lex.europa.eu/eli/dir/2010/63/oj/eng
Gaeta, A., & Hider, R. C. (2005). The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. British Journal of Pharmacology, 146(8), 1041-1059. https://doi.org/10.1038/sj.bjp.0706416
Gholamnezhad, Z., Keyhanmanesh, R., & Boskabady, M. H. (2015). Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella sativa for its preventive and bronchodilatory effects on ob-structive respiratory diseases: A review of basic and clinical evidence. Journal of Functional Foods, 17, 910-927. https://doi.org/10.1016/j.jff.2015.06.032
Gil-Cardoso, K., Ginés, I., Pinent, M., Ardévol, A., Terra, X., & Blay, M. (2017). A cafeteria diet triggers intestinal inflammation and oxidative stress in obese rats. British Journal of Nutrition, 117(2), 218-229. https://doi.org/10.1017/S0007114516004608
Grabska-Kobyłecka, I., Szpakowski, P., Król, A., Książek-Winiarek, D., Kobyłecki, A., Głąbiński, A., & Nowak, D. (2023). Polyphenols and their impact on the prevention of neurodegenerative diseases and development. Nutrients, 15(15), 3454. https://doi.org/10.3390/nu15153454
Hininger-Favier, I., Osman, M., Roussel, A. M., Intes, L., & Montanari, B. (2016). Positive effects of an oral supplementation by Glisodin, a gliadin-combined SOD-rich melon extract, in an animal model of die-tary-induced oxidative stress. Phytothérapie, 14(1), 29-34. https://doi.org/10.1007/s10298-015-0928-4
Hosseinian, S., Roshan, N. M., Khazaei, M., Shahraki, S., Mohebbati, R., & Rad, A. K. (2018). Reno-protective effect of Nigella sativa against cisplatin-induced nephrotoxicity and oxidative stress in rat. Saudi Journal of Kidney Diseases and Transplantation, 29(1), 19-29. https://doi.org/10.4103/1319-2442.225208.
Ismail, M., Al-Naqeep, G., & Chan, K. W. (2010). Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats. Free Radical Biology and Medicine, 48(5), 664-672. https://doi.org/10.1016/j.freeradbiomed.2009.12.002
Jarmakiewicz-Czaja, S., Zielińska, M., Helma, K., Sokal, A., & Filip, R. (2023). Effect of Nigella sativa on selected gastrointestinal diseases. Current Issues in Molecular Biology, 45(4), 3016-3034. https://doi.org/10.3390/cimb45040198
Javidi, S., Razavi, B. M., & Hosseinzadeh, H. (2016). A review of neuropharmacology effects of Nigella sativa and its main component, thymoqui-none. Phytotherapy Research, 30(8), 1219-1229. https://doi.org/10.1002/ptr.5634
Juurlink, B. H., & Paterson, P. G. (1998). Review of oxidative stress in brain and spinal cord injury: suggestions for pharmacological and nutritional management strategies. The Journal of Spinal Cord Medicine, 21(4), 309-334. https://doi.org/10.1080/10790268.1998.11719540
Kanter, M., Coskun, O., Kalayc, M., Buyukbas, S., & Cagavi, F. (2006). Neuroprotective effects of Ni-gella sativa on experimental spinal cord injury in rats. Human & Experimental Toxicology, 25(3), 127-133. https://doi.org/10.1191/0960327106ht608oa
Kehili, N., Saka, S., & Aouacheri, O. (2018). L’effet phytoprotecteur de la nigelle (Nigella sativa) contre la toxicité induite par le cadmium chez les rats. Phytothérapie, 16(4), 194. https://doi.org/10.3166/phyto-2018-0053
Leong, X. F., Rais Mustafa, M., & Jaarin, K. (2013). Nigella sativa and its protective role in oxidative stress and hypertension. Evidence‐Based Comple-mentary and Alternative Medicine, 2013(1), 120732. https://doi.org/10.1155/2013/120732
Mamun, M. A. A., Faruk, M., Rahman, M. M., Nahar, K., Kabir, F., Alam, M. A., & Subhan, N. (2019). High carbohydrate high fat diet induced hepatic steatosis and dyslipidemia were ameliorated by Psidium guajava leaf powder supplementation in rats. Evi-dence‐Based Complementary and Alternative Medi-cine, 2019(1), 1897237. https://doi.org/10.1155/2019/1897237
Mehri, S., Shahi, M., Razavi, B. M., Hassani, F. V., & Hosseinzadeh, H. (2014). Neuroprotective effect of thymoquinone in acrylamide-induced neurotoxicity in Wistar rats. Iranian Journal of Basic Medical Sciences, 17(12), 1007.
Melo, H. M., Santos, L. E., & Ferreira, S. T. (2019). Diet-derived fatty acids, brain inflammation, and mental health. Frontiers in Neuroscience, 13, 265. https://doi.org/10.3389/fnins.2019.00265
Meral, I., Yener, Z., Kahraman, T., & Mert, N. (2001). Effect of Nigella sativa on glucose concentration, lipid peroxidation, anti‐oxidant defence system and liver damage in experimentally‐induced diabetic rabbits. Journal of Veterinary Medicine Series A, 48(10), 593-599. https://doi.org/10.1046/j.1439-0442.2001.00393.x
Meziti, A., Meziti, H., Boudiaf, K., Mustapha, B., & Bouriche, H. (2012). Polyphenolic profile and anti-oxidant activities of Nigella sativa seed extracts in vitro and in vivo. International Journal of Bio-technology and Bioengineering, 6(4), 109-117.
Nivetha, K., & Prasanna, G. (2016). GC-MS and FT-IR analysis of Nigella sativa L. seeds. International Journal of Advanced Research in Biological Sciences, 3(6), 45-54. http://www.ijarbs.com/pdfcopy/june2016/ijarbs7
Rasoli, M. S., Khalili, M., Mohammadi, R., Soleimani, A., Kohzadi, R., Ilkhanipour, M., Heidari, R., & Gol-kari, S. (2018). The chemical composition of Nigella sativa L. and its extract effects on lipid peroxidation levels, total antioxidant capacity and catalase activity of the liver and kidney in rats under stress. Gene, Cell and Tissue, 5(1), e61323. https://doi.org/10.5812/gct.61323
Ré, D. B., Nafia, I., Nieoullon, A., Le Goff, L. K., & Had-Aissouni, L. (2005). Stress oxydatif cérébral : les astrocytes sont-ils vulnérables aux faibles concen-trations intracellulaires de glutamate ? Implications sur la survie neuronale. Annales Françaises d'Anesthésie et de Réanimation, 24(5), 502-509. https://doi.org/10.1016/j.annfar.2005.03.004
Salama, R. H., Abd-El-Hameed, N. A., Abd-El-Ghaffar, S. K., Mohammed, Z. T., & Ghandour, N. (2011). Nephroprotective effect of Nigella sativa and Matricaria chamomilla in cisplatin induced renal injury—supportive treatments in cisplatin nephron-toxicity. International Journal of Clinical Medi-cine, 2(03), 185-195. https://doi.org/10.4236/ijcm.2011.23031
Tavakkoli, A., & Hosseinzadeh, H. (2020). Nigella sativa L. and thymoquinone as neuroprotective antioxi-dants. In C.R. Martin and V.R. Preedy (Eds.) Oxi-dative stress and dietary antioxidants in neuro-logical diseases (pp. 325-341). Academic Press. https://doi.org/10.1016/B978-0-12-817780-8.00021-9
Yagi, K. (1976). A simple fluorometric assay for lipo-peroxide in blood plasma. Biochemical Medicine, 15(2), 212-216. https://doi.org/10.1016/0006-2944(76)90049-1
Yarjanli, Z., Ghaedi, K., Esmaeili, A., Rahgozar, S., & Zarrabi, A. (2017). Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation. BMC Neuroscience, 18, 1-12. https://doi.org/10.1186/s12868-017-0369-9 1
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