POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR

Authors

  • S. A. Tsiumpala VASYL STEFANYK PRECARPATHIAN NATIONAL UNIVERSITY, IVANO-FRANKIVSK
  • K. M. Starchevska VASYL STEFANYK PRECARPATHIAN NATIONAL UNIVERSITY, IVANO-FRANKIVSK
  • V. I. Lushchak VASYL STEFANYK PRECARPATHIAN NATIONAL UNIVERSITY, IVANO-FRANKIVSK I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY RESEARCH AND DEVELOPMENT UNIVERSITY, IVANO-FRANKIVSK

DOI:

https://doi.org/10.11603/mcch.2410-681X.2021.i2.12048

Keywords:

neuroprotector, sulforaphane, neuroinflammation, neurodegenerative diseases

Abstract

Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed.

The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation.

Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.

References

Vanduchova, A., Anzenbacher, P., & Anzen­bacherova, E. (2019). Isothiocyanate from broccoli, sulforaphane, and its properties. Journal of Medicinal Food, 22 (2), 121-126. Retrieved from: https://doi.org/10.1089/jmf.2018.0024.

Halkier, B.A., & Gershenzon, J. (2006). Biology and biochemistry of glucosinolates. Annual Review of Plant Biology, 57, 303-333. Retrieved from: https://doi.org/10.1146/annurev.arplant.57.032905.105228.

Juge, N., Mithen, R.F., & Traka, M. (2007). Molecular basis for chemoprevention by sulforaphane: A comprehensive review. Cellular and Molecular Life Sciences, 64 (9), 1105-1127. Retrieved from: https://doi.org/10.1007/s00018-007-6484-5.

Fischer, R., & Maier, O. (2015). Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF. Oxidative Medicine and Cellular Longevity, 2015, 610813. Retrieved from: https://doi.org/10.1155/2015/610813.

Song, H., Sieurin, J., Wirdefeldt, K., Pedersen, N.L., Almqvist, C., Larsson, H., Valdimarsdóttir, U.A., & Fang, F. (2020). Association of stress-related disorders with subsequent neurodegenerative diseases. JAMA Neuro­logy, 77 (6), 700-709. Retrieved from: https://doi.org/ 10.1001/jamaneurol.2020.0117.

He, J., Zhu, G., Wang, G., & Zhang, F. (2020). Oxidative stress and neuroinflammation potentiate each other to promote progression of dopamine neurode­generation. Oxidative Medicine and Cellular Longevity, 2020, 6137521. Retrieved from: https://doi.org/10.1155/ 2020/6137521.

Blach-Olszewska, Z., & Leszek, J. (2007). Me­chanisms of over-activated innate immune system regu­lation in autoimmune and neurodegenerative disor­ders. Neuropsychiatric Disease and Treatment, 3 (3), 365-372.

Garaschuk, O., Semchyshyn, H.M., & Lushchak, V.I. (2018). Healthy brain aging: Interplay between reactive species, inflammation and energy supply. Ageing Re­search Reviews, 43, 26-45. Retrieved from: https://doi.org/10.1016/j.arr.2018.02.003.

Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454 (7203), 428-435. Retrieved from: https://doi.org/10.1038/nature07201.

Buendia, I., Michalska, P., Navarro, E., Ga­mei­ro, I., Egea, J., & León, R. (2016). Nrf2-ARE pathway: An emerging target against oxidative stress and neuro­inflammation in neurodegenerative diseases. Pharma­cology and Therapeutics, 157, 84-104. Retrieved from: https://doi.org/10.1016/j.pharmthera.2015.11.003.

Solleiro-Villavicencio, H., & Rivas-Arancibia, S. (2018). Effect of chronic oxidative stress on neuro­in­flammatory response mediated by CD4+T cells in neuro­degenerative diseases. Frontiers in Cellular Neuro­science, 12, 114. Retrieved from: https://doi.org/10.3389/fncel.2018.00114.

Lushchak, V.I. (2014). Free radicals, reactive oxygen species, oxidative stress and its classification. Chemico-Biological Interactions, 224 (October), 164-175. Retrieved from: https://doi.org/10.1016/j.cbi.2014.10.016.

Dan Dunn, J., Alvarez, L.A.J., Zhang, X., & Sol­dati, T. (2015). Reactive oxygen species and mitochondria: A nexus of cellular homeostasis. Redox Biology, 6, 472-485. Retrieved from: https://doi.org/10.1016/j.redox. 2015.09.005.

Banks, W.A., & Erickson, M.A. (2010). The blood-brain barrier and immune function and dysfunction. Neurobiology of Disease, 37 (1), 26-32. Retrieved from: https://doi.org/10.1016/j.nbd.2009.07.031.

Ray, D., & Yung, R. (2018). Immune senescence, epigenetics and autoimmunity. Clinical Immunology, 196 (March), 59-63. Retrieved from: https://doi.org/10.1016/j.clim.2018.04.002.

Lenz, K.M., & Nelson, L.H. (2018). Microglia and beyond: innate immune cells as regulators of brain development and behavioral function. Frontiers in Immu­nology, 9, 698. Retrieved from: https://doi.org/10.3389/fimmu.2018.00698.

Myhre, C.L., Thygesen, C., Villadsen, B., Vollerup, J., Ilkjær, L., Krohn, K.T., Grebing, M., Zhao, S., Khan, A.M., Dissing-Olesen, L., Jensen, M.S., Bab­cock, A. A., & Finsen, B. (2019). Microglia express insulin-like growth factor-1 in the hippocampus of aged APPswe/PS1ΔE9 transgenic mice. Frontiers in Cellular Neuro­science, 13 (July), 1-17. Retrieved from: https://doi.org/ 10.3389/fncel.2019.00308.

Parkhurst, C.N., Yang, G., Ninan, I., Savas, J.N., Yates, J.R.3rd, Lafaille, J.J., Hempstead, B.L., Littman, D.R., & Gan, W.-B. (2013). Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell, 155 (7), 1596-1609. Retrieved from: https://doi.org/10.1016/j.cell.2013.11.030.

Diaz-Aparicio, I., Paris, I., Sierra-Torre, V., Plaza-Zabala, A., Rodríguez-Iglesias, N., Márquez-Ropero, M., Beccari, S., et al. (2020). Microglia actively remodel adult hippocampal neurogenesis through the phagocytosis secretome. Journal of Neuroscience, 40 (7), 1453-1482. Retrieved from: https://doi.org/10.1523/JNEUROSCI. 0993-19.2019.

’t Hart, B.A., & den Dunnen, W.F. (2013). Com­mentary on special issue: CNS diseases and the immune system. Journal of Neuroimmune Pharmacology: The Official Journal of the Society on NeuroImmune Pharma­cology, 8 (4), 757-759. Retrieved from: https://doi.org/10.1007/s11481-013-9486-0.

’t Hart, B.A., Hintzen, R.Q., & Laman, J D. (2009). Multiple sclerosis - a response-to-damage model. Trends in Molecular Medicine, 15 (6), 235-244. Retrieved from: https://doi.org/10.1016/j.molmed.2009.04.001.

Male, D. (2014). Adaptive immune responses in the CNS. In neuroinflammation and CNS disorders (pp. 37–57). John Wiley & Sons, Ltd. Retrieved from: https://doi.org/10.1002/9781118406557.ch3.

Santín-Márquez, R., Alarcón-Aguilar, A., López-Diazguerrero, N.E., Chondrogianni, N., & Königsberg, M. (2019). Sulforaphane – role in aging and neurodegeneration. GeroScience, 41 (5), 655-670. Retrieved from: https://doi.org/10.1007/s11357-019-00061-7.

Schain, M., & Kreisl, W.C. (2017). Neuroin­flam­mation in neurodegenerative disorders – a review. Current Neurology and Neuroscience Reports, 17 (3). Retrieved from: https://doi.org/10.1007/s11910-017-0733-2.

Houghton, C.A. (2019). Sulforaphane: Its “coming of age” as a clinically relevant nutraceutical in the pre­vention and treatment of chronic disease. Oxidative Medicine and Cellular Longevity. Retrieved from: https://doi.org/10.1155/2019/2716870.

Lushchak, V.I. (2021). Interplay between bio­energetics and oxidative stress at normal brain aging. Aging as a result of increasing disbalance in the system oxidative stress-energy provision. Pflügers Archiv – European Journal of Physiology. Retrieved from: https://doi.org/10.1007/s00424-021-02531-4.

Brasier, A.R. (2006). The NF-kappaB regulatory network. Cardiovascular Toxicology, 6 (2), 111-130. Re­trieved from: https://doi.org/10.1385/ct:6:2:111.

Gilmore, T.D. (2006). Introduction to NF-κB: Players, pathways, perspectives. Oncogene, 25 (51), 6680-6684. Retrieved from: https://doi.org/10.1038/sj.onc.1209954.

Hayden, M.S., & Ghosh, S. (2011). NF-κB in immunobiology. Cell Research, 21 (2), 223-244. Retrieved from: https://doi.org/10.1038/cr.2011.13.

Yu, L., Mohamed, A.J., Simonson, O.E., Var­gas, L., Blomberg, K.E.M., Björkstrand, B., Arteaga, H.J., Nore, B.F., & Smith, C.I.E. (2008). Proteasome-dependent autoregulation of Bruton tyrosine kinase (Btk) promoter via NF-kappaB. Blood, 111 (9), 4617-4626. Retrieved from: https://doi.org/10.1182/blood-2007-10-121137.

Giridharan, S., & Srinivasan, M. (2018). Me­chanisms of NF-κB p65 and strategies for therapeutic manipulation. Journal of Inflammation Research, 11, 407-419. Retrieved from: https://doi.org/10.2147/JIR.S140188.

Chen, J., & Chen, Z.J. (2013). Regulation of NF κB by ubiquitination. Current Opinion in Immunology, 25 (1), 4-12. Retrieved from: https://doi.org/10.1016/j.coi.2012.12.005.

Bonizzi, G., & Karin, M. (2004). The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends in Immunology, 25 (6), 280-288. Retrieved from: https://doi.org/10.1016/j.it.2004.03.008.

Mobeen, A., & Ramachandran, S. (2020). Modeling the post-translational modifications and its effects in the NF-κB pathway. BioRxiv. Retrieved from: https://doi.org/10.1101/2020.02.13.947010.

Lipinski, M., Del Blanco, B., & Barco, A. (2019). CBP/p300 in brain development and plasticity: disen­tangling the KAT’s cradle. Current Opinion in Neurobiology, 59, 1-8. Retrieved from: https://doi.org/10.1016/j.conb.2019.01.023.

Hayden, M.S., & Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell, 132 (3), 344-362. Retrieved from: https://doi.org/10.1016/j.cell.2008.01.020.

Basak, S., Shih, V.F.-S., & Hoffmann, A. (2008). Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system. Molecular and Cellular Biology, 28 (10), 3139-3150. Retrieved from: https://doi.org/10.1128/MCB.01469-07.

Assar, M. El, Angulo, J., & Rodríguez-Mañas, L. (2016). Diabetes and ageing-induced vascular inflam­mation. Journal of Physiology, 594 (8), 2125-2146. Re­trieved from: https://doi.org/10.1113/JP270841.

de Figueiredo, S., Binda, N., Nogueira-Macha­do, J., Vieira-Filho, S., & Caligiorne, R. (2015). The antioxidant properties of organosulfur compounds (sul­foraphane). Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 9 (1), 24-39. Retrieved from: https://doi.org/10.2174/1872214809666150505164138.

Kansanen, E., Kuosmanen, S. M., Leinonen, H., & Levonenn, A.L. (2013). The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biology, 1 (1), 45-49. Retrieved from: https://doi.org/10.1016/j.redox.2012.10.001.

Tonelli, C., Chio, I.I.C., & Tuveson, D.A. (2018). Transcriptional regulation by Nrf2. Antioxidants & Redox Signaling, 29 (17), 1727-1745. Retrieved from: https://doi.org/10.1089/ars.2017.7342.

Bryan, H.K., Olayanju, A., Goldring, C.E., & Park, B.K. (2013). The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochemical Pharmacology, 85 (6), 705-717. Retrieved from: https://doi.org/10.1016/j.bcp.2012.11.016.

Johnson, J.A., Johnson, D.A., Kraft, A.D., Calkins, M.J., Jakel, R.J., Vargas, M.R., & Chen, P.C. (2008). The Nrf2-ARE pathway: An indicator and mo­dulator of oxidative stress in neurodegeneration. Annals of the New York Academy of Sciences, 1147, 61-69. Retrieved from: https://doi.org/10.1196/annals.1427.036.

Sun, Z., Wu, T., Zhao, F., Lau, A., Birch, C.M., & Zhang, D.D. (2011). KPNA6 (Importin {alpha}7)-mediated nuclear import of Keap1 represses the Nrf2-dependent antioxidant response. Molecular and Cellular Biology, 31 (9), 1800-1811. Retrieved from: https://doi.org/10.1128/MCB.05036-11.

Kang, M.-I., Kobayashi, A., Wakabayashi, N., Kim, S.-G., & Yamamoto, M. (2004). Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. Proceedings of the National Academy of Sciences of the United States of America, 101 (7), 2046-2051. Retrieved from: https://doi.org/10.1073/pnas.0308347100.

Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004). Oxidative stress sensor keap1 functions as an adaptor for cul3-based e3 ligase to regulate proteasomal de­gradation of nrf2. Molecular and Cellular Biology, 24 (16), 7130-7139. Retrieved from: https://doi.org/10.1128/mcb.24.16.7130-7139.2004.

Dinkova-Kostova, A.T., Holtzclaw, W.D., Cole, R.N., Itoh, K., Wakabayashi, N., Katoh, Y., Yama­moto, M., & Talalay, P. (2002). Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against car­cinogens and oxidants. Proceedings of the National Academy of Sciences of the United States of America, 99 (18), 11908-11913. Retrieved from: https://doi.org/10.1073/pnas.172398899.

Holland, R., Hawkins, A.E., Eggler, A.L., Mese­car, A.D., Fabris, D., & Fishbein, J.C. (2008). Prospective type 1 and type 2 disulfides of Keap1 protein. Chemical Research in Toxicology, 21 (10), 2051-2060. Retrieved from: https://doi.org/10.1021/tx800226m.

Holland, R., & Fishbein, J.C. (2010). Chemistry of the cysteine sensors in Kelch-like ECH-associated protein 1. Antioxidants & Redox Signaling, 13 (11), 1749-1761. Retrieved from: https://doi.org/10.1089/ars.2010. 3273.

Taguchi, K., Motohashi, H., & Yamamoto, M. (2011). Molecular mechanisms of the Keap1-Nrf2 path­way in stress response and cancer evolution. Genes to Cells, 16 (2), 123-140. Retrieved from: https://doi.org/10.1111/j.1365-2443.2010.01473.x.

Katsuoka, F., & Yamamoto, M. (2016). Small Maf proteins (MafF, MafG, MafK): History, structure and function. Gene, 586 (2), 197-205. Retrieved from: https://doi.org/10.1016/j.gene.2016.03.058.

He, J., Zhu, G., Wang, G., & Zhang, F. (2020). Oxidative stress and neuroinflammation potentiate each other to promote progression of dopamine neurode­generation. Oxidative Medicine and Cellular Longevity, 2020, 6137521. Retrieved from: https://doi.org/10.1155/ 2020/6137521.

Uddin, M.S., Mamun, A.Al, Jakaria, M., Than­gapandiyan, S., Ahmad, J., Rahman, M.A., Mathew, B., Abdel-Daim, M.M., & Aleya, L. (2020). Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders. Science of the Total Environment, 707, 135624. Retrieved from: https://doi.org/10.1016/j.scitotenv.2019.135624.

Wu, Q.J., Yang, Y., Vogtmann, E., Wang, J., Han, L.H., Li, H.L., & Xiang, Y.B. (2013). Cruciferous vegetables intake and the risk of colorectal cancer: a meta-analysis of observational studies. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 24 (4), 1079-1087. Retrieved from: https://doi.org/10.1093/annonc/mds601.

Abbaoui, B., Lucas, C.R., Riedl, K.M., Clinton, S.K., & Mortazavi, A. (2018). Cruciferous vegetables, isothio­cyanates, and bladder cancer prevention. Molecular Nutrition & Food Research, 62 (18), e1800079. Retrieved from: https://doi.org/10.1002/mnfr.201800079.

McNaughton, S.A., & Marks, G.C. (2003). Development of a food composition database for the estimation of dietary intakes of glucosinolates, the bio­logically active constituents of cruciferous vegetables. British Journal of Nutrition, 90 (3), 687-697. Retrieved from: https://doi.org/10.1079/bjn2003917.

Liang, H., Yuan, Q.P., Dong, H.R., & Liu, Y.M. (2006). Determination of sulforaphane in broccoli and cabbage by high-performance liquid chromatography. Journal of Food Composition and Analysis, 19 (5), 473-476. Retrieved from: https://doi.org/10.1016/j.jfca. 2005.11.005.

Han, D., & Row, K.H. (2011). Separation and purification of sulforaphane from broccoli by solid phase extraction. International Journal of Molecular Sciences, 12 (3), 1854-1861. Retrieved from: https://doi.org/10.3390/ijms12031854.

Hafezian, S.M., Azizi, S.N., Biparva, P., & Bekhradnia, A. (2019). High-efficiency purification of sulforaphane from the broccoli extract by nanostructured SBA-15 silica using solid-phase extraction method. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1108 (December 2018), 1-10. Retrieved from: https://doi.org/10.1016/j.jchromb.2019.01.007.

Shirai, Y., Fujita, Y., Hashimoto, R., Ohi, K., Yamamori, H., Yasuda, Y., Ishima, T., Suganuma, H., Ushida, Y., Takeda, M., & Hashimoto, K. (2015). Dietary intake of sulforaphane-rich broccoli sprout extracts during juvenile and adolescence can prevent phencyclidine-induced cognitive deficits at adulthood. PLoS ONE, 10 (6), 1-22. Retrieved from: https://doi.org/10.1371/journal.pone.0127244.

Dwivedi, S., Rajasekar, N., Hanif, K., Nath, C., & Shukla, R. (2016). Sulforaphane ameliorates okadaic acid-induced memory impairment in rats by activating the Nrf2/HO-1 antioxidant pathway. Molecular Neurobiology, 53 (8), 5310-5323. Retrieved from: https://doi.org/10.1007/s12035-015-9451-4.

Sunkaria, A., Bhardwaj, S., Yadav, A., Halder, A., & Sandhir, R. (2018). Sulforaphane attenuates postnatal proteasome inhibition and improves spatial learning in adult mice. Journal of Nutritional Biochemistry, 51, 69-79. Retrieved from: https://doi.org/10.1016/j.jnutbio.2017. 09.016.

Shati, A.A., & Elsaid, F.G. (2019). Hepatotoxic effect of subacute vincristine administration activates necrosis and intrinsic apoptosis in rats: protective roles of broccoli and Indian mustard. Archives of Physiology and Biochemistry, 125 (1), 1-11. Retrieved from: https://doi.org/10.1080/13813455.2018.1427765.

Published

2021-08-04

How to Cite

Tsiumpala, . S. A., Starchevska, K. M., & Lushchak, V. I. (2021). POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR. Medical and Clinical Chemistry, (2), 125–136. https://doi.org/10.11603/mcch.2410-681X.2021.i2.12048

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