The Effect of the Bioactive Compound Curcumin on Conditions After Ischemic Stroke: A Systematic Review
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Ischemic stroke is a common degenerative disease in Indonesia caused by interrupted or restricted blood supply to part of brain, preventing it from getting oxygen and nutrients. Without sufficient blood supply, brain cells begin to die. Various treatments for ischemic stroke patients have been developed and implemented, but are still ineffective in treating or preventing brain damage. Curcumin is one of the bioactive compounds which mostly found in turmeric which is one of the main spices resource in Indonesia that has many benefits as a medicine. People have been making use of curcumin as a medicine for various diseases, one of which is stroke. Therefore, this systematic review analysed qualitatively the effect of curcumin on the brain condition after ischemic stroke. The method used in this study was a systematic review of 8 databases in the last 10 years, from 2012 to August 2022. Study included was only experimental study on rats. Based on 19 articles gathered, there was a decrement in ROS, COX-2, iNOS, NF-kB, TNF-α, IL-6, Bax, Caspase-9, Caspase-3, ICAM-1, MMP-9, neurological deficit score, and an increment in BCL-2, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in rats receiving curcumin intervention either orally or intravenously. Curcumin affects the ischemic brain in a number of ways, namely as an antioxidant, anti-inflammatory, anti-apoptotic, Blood-Brain-Barrier (BBB) protector, increasing neurogenesis, and reducing neurological deficits. It is concluded that curcumin has an elevating effect in protecting brain condition after an ischemic stroke.
Alcí¢ntara, G. de F. T., Simíµes-Neto, E., da Cruz, G. M. P., Nobre, M. E. P., Neves, K. R. T., de Andrade, G. M., Brito, G. A. de C., & Viana, G. S. de B. (2017). Curcumin reverses neurochemical, histological and immuno-histochemical alterations in the model of global brain ischemia. Journal of Traditional and Complementary Medicine, 7(1), 14–23. https://doi.org/10.1016/j.jtcme.2015.10.001
Altinay, S., Cabalar, M., Isler, C., Yildirim, F., Celik, D. S., Zengi, O., Tas, A., & Gulcubuk, A. (2017). Is chronic curcumin supplementation neuroprotective against ischemia for antioxidant activity, neurological deficit, or neuronal apoptosis in an experimental stroke model? Turkish Neurosurgery, 27(4), 537–545. https://doi.org/10.5137/1019-5149.JTN.17405-16.0
Awad, A. S. (2011). Effect of Combined Treatment With Curcumin and Candesartan on Ischemic Brain Damage in Mice. Journal of Stroke and Cerebrovascular Diseases, 20(6), 541–548. https://doi.org/10.1016/J.JSTROKECEREBROVASDIS.2010.03.008
Bavarsad, K., Barreto, G. E., Hadjzadeh, M. A. R., & Sahebkar, A. (2019). Protective Effects of Curcumin Against Ischemia-Reperfusion Injury in the Nervous System. Molecular Neurobiology, 56(2), 1391–1404. https://doi.org/10.1007/s12035-018-1169-7
Béjot, Y., Daubail, B., & Giroud, M. (2016). Epidemiology of stroke and transient ischemic attacks: Current knowledge and perspectives. Revue Neurologique, 172(1), 59–68. https://doi.org/10.1016/j.neurol.2015.07.013
Briggs, R., Kennelly, S. P., & O'Neill, D. (2016). Drug treatments in Alzheimer's disease. Clinical Medicine, Journal of the Royal College of Physicians of London, 16(3), 247–253. https://doi.org/10.7861/clinmedicine.16-3-247
Cassella, C. R., & Jagoda, A. (2017). Ischemic Stroke: Advances in Diagnosis and Management. Emergency Medicine Clinics of North America, 35(4), 911–930. https://doi.org/10.1016/J.EMC.2017.07.007
Chh-Hung, H., & Ann-Lii, C. (2007). Clinical studies with curcumin. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, 12(579), 471–480. https://pubmed.ncbi.nlm.nih.gov/17569225/
Dang, Q. B., Lapergue, B., Tran-dinh, A., Diallo, D., Moreno, J., Mazighi, M., Romero, I. A., Weksler, B., Michel, J., Amarenco, P., & Meilhac, O. (2013). High-density lipoproteins limit neutrophil-induced damage to the blood – brain barrier in vitro. August 2012, 575–582. https://doi.org/10.1038/jcbfm.2012.206
Daniel, B. J., Balla, J., & Bereczki, D. (2018). Heme Oxygenase-1: Clinical Relevance in Ischemic Stroke. Current Pharmaceutical Design, 24(20), 2229. https://doi.org/10.2174/1381612824666180717101104
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999). Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences, 22(9), 391–397. https://doi.org/10.1016/S0166-2236(99)01401-0
Feigin, V. L., Norrving, B., & Mensah, G. A. (2017). Global Burden of Stroke. Circulation Research, 120(3), 439–448. https://doi.org/10.1161/CIRCRESAHA.116.308413
Funk, J. L., Frye, J. B., Davis-Gorman, G., Spera, A. L., Bernas, M. J., Witte, M. H., Weinand, M. E., Timmermann, B. N., Mcdonagh, P. F., & Ritter, L. (2013). Curcuminoids Limit Neutrophil-Mediated Reperfusion Injury in Experimental Stroke by Targeting the Endothelium. Microcirculation, 20(6), 544–554. https://doi.org/10.1111/MICC.12054
Gaire, B. P. rasa., Moon, S. K., & Kim, H. (2014). Scutellaria baicalensis in stroke management: nature's blessing in traditional Eastern medicine. Chinese Journal of Integrative Medicine, 20(9), 712–720. https://doi.org/10.1007/s11655-014-1347-9
Godínez-Rubí, M., Rojas-Mayorquín, A. E., & Ortuño-Sahagún, D. (2013). Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction. Oxidative Medicine and Cellular Longevity, 2013. https://doi.org/10.1155/2013/297357
Goozee, K. G., Shah, T. M., Sohrabi, H. R., Rainey-Smith, S. R., Brown, B., Verdile, G., & Martins, R. N. (2016). Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease. British Journal of Nutrition, 115(3), 449–465. https://doi.org/10.1017/S0007114515004687
Hagl, S., Kocher, A., Schiborr, C., Kolesova, N., Frank, J., & Eckert, G. P. (2015). Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice - Impact on bioavailability. Neurochemistry International, 89, 234–242. https://doi.org/10.1016/j.neuint.2015.07.026
He, R., Jiang, Y., Shi, Y., Liang, J., & Zhao, L. (2020). Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis. Materials Science and Engineering C, 117(August), 111314. https://doi.org/10.1016/j.msec.2020.111314
Hussein, Y. A., Al-sarraf, A. M., & Alfalluji, W. L. (2020). Modulation of oxidative stress, inflammatory and apoptotic response by curcumin against cerebral ischemia reperfusion injury in a mouse model. Interdisciplinary Neurosurgery: Advanced Techniques and Case Management, 21(April), 100741. https://doi.org/10.1016/j.inat.2020.100741
Jia, G., Tan, B., Ma, J., Zhang, L., Jin, X., & Li, C. (2017). Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke. BioMed Research International, 1–9. https://doi.org/10.1155/2017/6597401
Jia, J.-M., Chowdary, P. D., Gao, X., Ci, B., Li, W., Mulgaonkar, A., Plautz, E. J., Hassan, G., Kumar, A., Stowe, A. M., Yang, S.-H., Zhou, W., Sun, X., Cui, B., & Ge, W.-P. (n.d.). Control of cerebral ischemia with magnetic nanoparticles. https://doi.org/10.1038/nmeth.4105
Jiang, X., Andjelkovic, A. V., Zhu, L., Yang, T., Bennett, M. V. L., Chen, J., Keep, R. F., & Shi, Y. (2018). Blood-brain barrier dysfunction and recovery after ischemic stroke. Progress in Neurobiology, 163–164, 144–171. https://doi.org/10.1016/J.PNEUROBIO.2017.10.001
Joshi, G., & Johnson, J. A. (2012). The Nrf2-ARE pathway: a valuable therapeutic target for the treatment of neurodegenerative diseases. Recent Patents on CNS Drug Discovery, 7(3), 218–229. https://doi.org/10.2174/157488912803252023
Kementrian Kesehatan. (2018). Hasil Utama Riset Kesehata Dasar (RISKESDAS) (Vol. 44, Issue 8). https://doi.org/10.1088/1751-8113/44/8/085201
Lan, C., Chen, X., Zhang, Y., Wang, W., Wang, W. E., Liu, Y., Cai, Y., Ren, H., Zheng, S., Zhou, L., & Zeng, C. (2018). Curcumin prevents strokes in stroke-prone spontaneously hypertensive rats by improving vascular endothelial function. BMC Cardiovascular Disorders, 18(1), 1–10. https://doi.org/10.1186/s12872-018-0768-6
Lapchak, P. A. (2010). A critical assessment of edaravone acute ischemic stroke efficacy trials: Is edaravone an effective neuroprotective therapy? Expert Opinion on Pharmacotherapy, 11(10), 1753–1763. https://doi.org/10.1517/14656566.2010.493558
Lapchak, P. A., & Araujo, D. M. (2007). Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opinion on Emerging Drugs, 12(1), 97–112. https://doi.org/10.1517/14728214.12.1.97
Li, W., Suwanwela, N. C., & Patumraj, S. (2016). Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvascular Research, 106, 117–127. https://doi.org/10.1016/j.mvr.2015.12.008
Li, W., Suwanwela, N. C., & Patumraj, S. (2017). Curcumin prevents Reperfusion injury following ischemic stroke in rats via inhibition of NF-κB, ICAM-1, MMP-9 and caspase-3 expression. Molecular Medicine Reports, 16(4), 4710–4720. https://doi.org/10.3892/mmr.2017.7205
Li, Y., Li, J., Li, S., Li, Y., Wang, X., Liu, B., Fu, Q., & Ma, S. (2015). Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicology and Applied Pharmacology, 286(1), 53–63. https://doi.org/10.1016/j.taap.2015.03.010
Liu, S., Cao, Y., Qu, M., Zhang, Z., Feng, L., Ye, Z., Xiao, M., Hou, S. T., Zheng, R., & Han, Z. (2016). Curcumin protects against stroke and increases level of Notch intracellular domain. Neurological Research, 38(6), 553–559. https://doi.org/10.1080/01616412.2016.1187804
Liu, W., Yuan, J., Zhu, H., Zhang, X., Li, L., Liao, X., Wen, Z., Chen, Y., Feng, H., & Lin, J. (2016). Curcumin reduces brain-infiltrating T lymphocytes after intracerebral hemorrhage in mice. Neuroscience Letters, 620, 74–82. https://doi.org/10.1016/j.neulet.2016.03.047
Liu, Z., Ran, Y., Huang, S., Wen, S., Zhang, W., Liu, X., Ji, Z., Geng, X., Ji, X., Du, H., Leak, R. K., & Hu, X. (2017). Curcumin protects against ischemic stroke by titrating microglia/macrophage polarization. Frontiers in Aging Neuroscience, 9(JUL), 1–10. https://doi.org/10.3389/fnagi.2017.00233
Luo, S., & Rubinsztein, D. C. (2013). BCL2L11/BIM: A novel molecular link between autophagy and apoptosis. Autophagy, 9(1), 104–105. https://doi.org/10.4161/auto.22399
Manca, M. L., Castangia, I., Zaru, M., Nácher, A., Valenti, D., Ferní ndez-Busquets, X., Fadda, A. M., & Manconi, M. (2015). Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring. Biomaterials, 71, 100–109. https://doi.org/10.1016/j.biomaterials.2015.08.034
Marler, J. (1995). Tissue Plasminogen Activator for Acute Ischemic Stroke. Journal of Medicine. http://www.nejm.org/doi/pdf/10.1056/NEJM199512143332401
Miao, Y., Zhao, S., Gao, Y., Wang, R., Wu, Q., Wu, H., & Luo, T. (2016). Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling. Brain Research Bulletin, 121, 9–15. https://doi.org/10.1016/j.brainresbull.2015.11.019
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010). The science of stroke: Mechanisms in search of treatments. Neuron, 67(2), 181–198. https://doi.org/10.1016/j.neuron.2010.07.002
Mukherjee, A., Sarkar, S., Jana, S., Swarnakar, S., & Das, N. (2019). Neuro-protective role of nanocapsulated curcumin against cerebral ischemia-reperfusion induced oxidative injury. Brain Research, 1704(September 2018), 164–173. https://doi.org/10.1016/j.brainres.2018.10.016
Oh, J., Lee, J., Piao, C., Jeong, J. H., & Lee, M. (2019). A self-assembled DNA-nanoparticle with a targeting peptide for hypoxia-inducible gene therapy of ischemic stroke. Biomaterials Science, 7(5), 2174–2190. https://doi.org/10.1039/c8bm01621f
Park, J. Y., Sohn, H. Y., Koh, Y. H., & Jo, C. (2021). Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351. Scientific Reports, 11(1), 1–12. https://doi.org/10.1038/s41598-021-87225-8
Patel, P., Yavagal, D., & Khandelwal, P. (2020). Hyperacute Management of Ischemic Strokes: JACC Focus Seminar. Journal of the American College of Cardiology, 75(15), 1844–1856. https://doi.org/10.1016/j.jacc.2020.03.006
Peng, Y., Ao, M., Dong, B., Jiang, Y., Yu, L., Chen, Z., Hu, C., & Xu, R. (2021). Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures. Drug Design, Development and Therapy, 15, 4503–4525. https://doi.org/10.2147/DDDT.S327378
Pluta, R., & UÅ‚amek-KozioÅ‚, M. (2021). Genes Associated with Alzheimer's Disease in Post-Ischemic Brain Neurodegeneration. Cerebral Ischemia, 31–44. https://doi.org/10.36255/EXONPUBLICATIONS.CEREBRALISCHEMIA.2021.GENES
Pluta, R., UÅ‚amek-KozioÅ‚, M., Januszewski, S., & Czuczwar, S. J. (2019). Amyloid pathology in the brain after ischemia. Folia Neuropathologica, 57(3), 220–226. https://doi.org/10.5114/FN.2019.88450
Ran, Y., Su, W., Gao, F., Ding, Z., Yang, S., Ye, L., Chen, X., Tian, G., Xi, J., & Liu, Z. (2021). Curcumin Ameliorates White Matter Injury after Ischemic Stroke by Inhibiting Microglia/Macrophage Pyroptosis through NF-κ B Suppression and NLRP3 Inflammasome Inhibition. Oxidative Medicine and Cellular Longevity, 2021. https://doi.org/10.1155/2021/1552127
Rusek, M., & Czuczwar, S. J. (2021). The Role of Curcumin in Post-Ischemic Brain. Cerebral Ischemia, 149–164. https://doi.org/10.36255/exonpublications.cerebralischemia.2021.curcumin
Sarmah, D., Kaur, H., Saraf, J., Vats, K., Pravalika, K., Wanve, M., Kalia, K., Borah, A., Kumar, A., Wang, X., Yavagal, D. R., Dave, K. R., & Bhattacharya, P. (2019). Mitochondrial Dysfunction in Stroke: Implications of Stem Cell Therapy. Translational Stroke Research, 10(2), 121–136. https://doi.org/10.1007/s12975-018-0642-y
Scholpa, N. E., & Schnellmann, R. G. (2017). Mitochondrial-based therapeutics for the treatment of spinal cord injury: Mitochondrial biogenesis as a potential pharmacological target. Journal of Pharmacology and Experimental Therapeutics, 363(3), 303–313. https://doi.org/10.1124/jpet.117.244806
Sekerdag, E., Solaroglu, I., & Gursoy-Ozdemir, Y. (2018). Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options. Current Neuropharmacology, 16(9), 1396–1415. https://doi.org/10.2174/1570159X16666180302115544
Shah, F. A., Gim, S. A., Sung, J. H., Jeon, S. J., Kim, M. O., & Koh, P. O. (2016). Identification of proteins regulated by curcumin in cerebral ischemia. Journal of Surgical Research, 201(1), 141–148. https://doi.org/10.1016/j.jss.2015.10.025
Shi, J., Yu, W., Xu, L., Yin, N., Liu, W., Zhang, K., Liu, J., & Zhang, Z. (2020). Bioinspired Nanosponge for Salvaging Ischemic Stroke via Free Radical Scavenging and Self-Adapted Oxygen Regulating. Nano Letters, 20(1), 780–789. https://doi.org/10.1021/acs.nanolett.9b04974
Subedi, L., & Gaire, B. P. (2021). Neuroprotective Effects of Curcumin in Cerebral Ischemia: Cellular and Molecular Mechanisms. ACS Chemical Neuroscience, 12(14), 2562–2572. https://doi.org/10.1021/acschemneuro.1c00153
Sun, G., Miao, Z., Ye, Y., Zhao, P., Fan, L., Bao, Z., Tu, Y., Li, C., Chao, H., Xu, X., & Ji, J. (2020). Curcumin alleviates neuroinflammation, enhances hippocampal neurogenesis, and improves spatial memory after traumatic brain injury. Brain Research Bulletin, 162(April), 84–93. https://doi.org/10.1016/j.brainresbull.2020.05.009
Tiwari, S. K., Agarwal, S., Seth, B., Yadav, A., Nair, S., Bhatnagar, P., Karmakar, M., Kumari, M., Chauhan, L. K. S., Patel, D. K., Srivastava, V., Singh, D., Gupta, S. K., Tripathi, A., Chaturvedi, R. K., & Gupta, K. C. (2014). Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer's disease model via canonical Wnt/β-catenin pathway. ACS Nano, 8(1), 76–103. https://doi.org/10.1021/nn405077y
UÅ‚amek-KozioÅ‚, M., Czuczwar, S. J., Januszewski, S., & Pluta, R. (2020). Substantiation for the use of curcumin during the development of neurodegeneration after brain ischemia. International Journal of Molecular Sciences, 21(2), 1–17. https://doi.org/10.3390/ijms21020517
Uzdensky, A. B. (2019). Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins. Apoptosis, 24(9–10), 687–702. https://doi.org/10.1007/s10495-019-01556-6
Wang, L., Zhang, B., Yang, X., Guo, S., Waterhouse, G. I. N., Song, G., Guan, S., Liu, A., Cheng, L., & Zhou, S. (2023). Targeted alleviation of ischemic stroke reperfusion via atorvastatin-ferritin Gd-layered double hydroxide. Bioactive Materials, 20, 126–136. https://doi.org/10.1016/J.BIOACTMAT.2022.05.012
Wang, S., Ye, Q., Tu, J., Zhang, M., & Ji, B. (2017). Curcumin protects against hypertension aggravated retinal ischemia/reperfusion in a rat stroke model. Clinical and Experimental Hypertension, 39(8), 711–717. https://doi.org/10.1080/10641963.2017.1313854
Wang, Y., Luo, J., & Li, S. Y. (2019). Nano-Curcumin Simultaneously Protects the Blood-Brain Barrier and Reduces M1 Microglial Activation during Cerebral Ischemia-Reperfusion Injury. ACS Applied Materials and Interfaces, 11(4), 3763–3770. https://doi.org/10.1021/ACSAMI.8B20594/SUPPL_FILE/AM8B20594_SI_001.PDF
WHO. (2011). Stroke, Cerebrovascular accident. http://www.emro.who.int/health-topics/stroke-cerebrovascular-accident/index.html
WHO. (2020a). Definition of Stroke. https://www.publichealth.com.ng/world-health-organization-who-definition-of-stroke/
WHO. (2020b). Definition of Stroke. https://www.publichealth.com.ng/world-health-organization-who-definition-of-stroke/
Wicha, P., Tocharus, J., Janyou, A., Jittiwat, J., & Chaichompoo, W. (2020). Hexahydrocurcumin alleviated blood – brain barrier dysfunction in cerebral ischemia / reperfusion rats. Pharmacological Reports, 72(3), 659–671. https://doi.org/10.1007/s43440-019-00050-9
Wu, S., Guo, T., Qi, W., Li, Y., Gu, J., Liu, C., Sha, Y., Yang, B., Hu, S., & Zong, X. (2021). Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood"‘brain barrier. Experimental and Therapeutic Medicine, 22(1), 5–12. https://doi.org/10.3892/etm.2021.10215
Xie, C. J., Gu, A. P., Cai, J., Wu, Y., & Chen, R. C. (2018). Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke. Brain and Behavior, 8(2), 1–12. https://doi.org/10.1002/brb3.921
Yang, C., Zhang, X., Fan, H., & Liu, Y. (2009). Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Research, 1282, 133–141. https://doi.org/10.1016/J.BRAINRES.2009.05.009
Yang, X., Song, D., Chen, L., Xiao, H., Ma, X., Jiang, Q., & Cheng, O. (2020). Curcumin promotes neurogenesis of hippocampal dentate gyrus via Wnt/β-catenin signal pathway following cerebral ischemia in mice. Brain Research, 1751(May 2020), 147197. https://doi.org/10.1016/j.brainres.2020.147197
Zhang, Y., Yan, Y., Cao, Y., Yang, Y., Zhao, Q., Jing, R., Hu, J., & Bao, J. (2017). Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats. Life Sciences, 183, 45–49. https://doi.org/10.1016/j.lfs.2017.06.023
Zhao, J., Yu, S., Zheng, W., Feng, G., Luo, G., Wang, L., & Zhao, Y. (2010). Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. Neurochemical Research, 35(3), 374–379. https://doi.org/10.1007/s11064-009-0065-y
Zhou, J., Wu, N., & Lin, L. (2020). Curcumin suppresses apoptosis and inflammation in hypoxia/reperfusion-exposed neurons via Wnt signaling pathway. Medical Science Monitor, 26, 1–7. https://doi.org/10.12659/MSM.920445
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