{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:45:50Z","timestamp":1791902750969,"version":"4.3.4"},"reference-count":110,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Fund Projects","award":["IFPDP-44\u201322"],"award-info":[{"award-number":["IFPDP-44\u201322"]}]},{"name":"Ministry of Education and Deanship of Scientific Research (DSR), King Abdulaziz University (KAU), Jeddah, Saudi Arabia","award":["IFPDP-44\u201322"],"award-info":[{"award-number":["IFPDP-44\u201322"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS include inflammatory demyelination, axonal injury, white matter degeneration, and the development of CNS lesions that result in severe neuronal degeneration. Several studies suggested downregulation of nuclear factor erythroid-2-related factor-2 (Nrf2)\/Heme oxygenase-1 (HO-1) signaling is a causative factor for MS pathogenesis. Acetyl-11-keto-\u03b2-boswellic acid (AKBA) is an active pentacyclictriterpenoid obtained from Boswellia serrata, possessing antioxidant and anti-inflammatory properties. The present study explores the protective potential of AKBA on behavioral, molecular, neurochemical, and gross pathological abnormalitiesandhistopathological alterations by H&amp;E and LFB staining techniques in an experimental model of multiple sclerosis, emphasizing the increase inNrf2\/HO-1 levels in the brain. Moreover, we also examine the effect of AKBA on the intensity of myelin basic protein (MBP) in CSF and rat brain homogenate. Specific apoptotic markers (Bcl-2, Bax, andcaspase-3) were also estimated in rat brain homogenate. Neuro behavioralabnormalities in rats were examined using an actophotometer, rotarod test, beam crossing task (BCT),and Morris water maze (MWM). AKBA 50 mg\/kg and 100 mg\/kg were given orally from day 8 to 35 to alleviate MS symptoms in the EB-injected rats. Furthermore, cellular, molecular, neurotransmitter, neuroinflammatory cytokine, and oxidative stress markers in rat whole brain homogenate, blood plasma, and cerebral spinal fluid were investigated. This study shows that AKBA upregulates the level of antioxidant proteins such as Nrf2 and HO-1 in the rat brain. AKBA restores altered neurochemical levels, potentially preventing gross pathological abnormalities during MS progression.<\/jats:p>","DOI":"10.3390\/genes13081324","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T21:20:59Z","timestamp":1658784059000},"page":"1324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Nrf2\/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2018-8402","authenticated-orcid":false,"given":"Shubham","family":"Upadhayay","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-835X","authenticated-orcid":false,"given":"Sidharth","family":"Mehan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-8581","authenticated-orcid":false,"given":"Aradhana","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranshul","family":"Sethi","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Suri","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-3279","authenticated-orcid":false,"given":"Ayat","family":"Zawawi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6619-0287","authenticated-orcid":false,"given":"Majed N.","family":"Almashjary","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Animal House Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-415X","authenticated-orcid":false,"given":"Shams","family":"Tabrez","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s11011-021-00691-x","article-title":"Guggulsterone ameliorates ethidium bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain","volume":"36","author":"Kumar","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-86191-5","article-title":"Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis","volume":"11","author":"Oveland","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/1570163817666200207100903","article-title":"Neuroprotective Methodologies in the Treatment of Multiple Sclerosis Current Status of Clinical and Pre-clinical Findings","volume":"18","author":"Mehan","year":"2021","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1007\/s12640-021-00401-6","article-title":"Understanding Abnormal c-JNK\/p38MAPK Signaling Overactivation Involved in the Progression of Multiple Sclerosis: Possible Therapeutic Targets and Impact on Neurodegenerative Diseases","volume":"39","author":"Singh","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/NHH.0000000000000666","article-title":"Multiple Sclerosis: An update for home healthcare clinicians","volume":"36","author":"Capriotti","year":"2018","journal-title":"Home Healthc. Now"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.3389\/fimmu.2018.03116","article-title":"Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis","volume":"9","author":"Lassmann","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_7","first-page":"S2","article-title":"Multiple sclerosis immunology: The healthy immune system vs the MS immune system","volume":"74","author":"Kasper","year":"2009","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00401-017-1744-4","article-title":"Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients","volume":"134","author":"Michels","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/jnr.24224","article-title":"Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis","volume":"96","author":"Bjelobaba","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Miller, R.H., Fyffe-Maricich, S., and Caprariello, A.C. (2017). Animal models for the study of multiple sclerosis. Animal Models for the Study of Human Disease, Academic Press.","DOI":"10.1016\/B978-0-12-809468-6.00037-1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s13105-018-00660-6","article-title":"LINGO-1 siRNA nanoparticles promote central remyelination in ethidium bromide-induced demyelination in rats","volume":"75","author":"Youssef","year":"2019","journal-title":"J. Physiol. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.2174\/1871530321666210309112234","article-title":"Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review of SIRTUIN Activators as Potential Immunomodulators and their Influences on other Dysfunctions","volume":"21","author":"Sharma","year":"2021","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_13","first-page":"63","article-title":"Focal Injection of Ethidium Bromide as a Simple Model to Study Cognitive Deficit and Its Improvement","volume":"7","author":"Goudarzvand","year":"2016","journal-title":"Basic Clin. Neurosci. J."},{"key":"ref_14","unstructured":"Silva, B.A., and Ferrari, C.C. (2016). Animal Experimental Models for Understanding and Treating Multiple Sclerosis, SMGE Books."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100051","DOI":"10.1016\/j.phyplu.2021.100051","article-title":"Neuroprotection by solanesol against ethidium bromide-induced multiple sclerosis-like neurobehavioral, molecular, and neurochemical alterations in experimental rats","volume":"1","author":"Sharma","year":"2021","journal-title":"Phytomedicine Plus"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100139","DOI":"10.1016\/j.phyplu.2021.100139","article-title":"Inhibition of c-JNK\/p38MAPK signaling pathway by Apigenin prevents neurobehavioral and neurochemical defects in ethidium bromide-induced experimental model of multiple sclerosis in rats: Evidence from CSF, blood plasma and brain samples","volume":"1","author":"Singh","year":"2021","journal-title":"Phytomedicine Plus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41467-017-00932-7","article-title":"Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder","volume":"8","author":"Huppke","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"172973","DOI":"10.1016\/j.ejphar.2020.172973","article-title":"Targeting Keap1\/Nrf2\/ARE signaling pathway in multiple sclerosis","volume":"873","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.3389\/fimmu.2020.01467","article-title":"Naturally Derived Heme-Oxygenase 1 Inducers and Their Therapeutic Application to Immune-Mediated Diseases","volume":"11","author":"Funes","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100019","DOI":"10.1016\/j.dscb.2021.100019","article-title":"Targeting Nrf2\/HO-1 anti-oxidant signaling pathway in the progression of multiple sclerosis and influences on neurological dysfunctions","volume":"3","author":"Upadhayay","year":"2021","journal-title":"Brain Disord."},{"key":"ref_21","first-page":"1503","article-title":"Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis","volume":"22","author":"Larabee","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/toxsci\/kfp274","article-title":"The Absence of the Pro-antioxidant Transcription Factor Nrf2 Exacerbates Experimental Autoimmune Encephalomyelitis","volume":"114","author":"Johnson","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_23","first-page":"630","article-title":"Targeting abnormal Nrf2\/HO-1 signaling in amyotrophic lateral sclerosis: Current Insights on drug targets and influences on neurological disorders","volume":"21","author":"Minj","year":"2021","journal-title":"Curr. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1093\/hmg\/ddx361","article-title":"Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of Alzheimer\u2019s disease","volume":"26","author":"Branca","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","first-page":"4179","article-title":"Overexpression of miR-153 promotes oxidative stress in MPP+-induced PD model by negatively regulating the Nrf2\/HO-1 signaling pathway","volume":"11","author":"Zhu","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.freeradbiomed.2020.10.022","article-title":"NRF2 activation by reversible KEAP1 binding induces the antioxidant response in primary neurons and astrocytes of a Huntington\u2019s disease mouse model","volume":"162","author":"Moretti","year":"2021","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1159\/000481840","article-title":"\u03b1-Lipoic acid promotes neurological recovery after ischemic stroke by activating the Nrf2\/HO-1 pathway to attenuate oxidative damage","volume":"43","author":"Lv","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1161\/STROKEAHA.107.486506","article-title":"Transcription Factor Nrf2 Protects the Brain From Damage Produced by Intracerebral Hemorrhage","volume":"38","author":"Zhao","year":"2007","journal-title":"Stroke"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.2147\/DDDT.S172612","article-title":"Design and development of Nrf2 modulators for cancer chemoprevention and therapy: A review","volume":"12","author":"Sova","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Panieri, E., Buha, A., Telkoparan-Akillilar, P., Cevik, D., Kouretas, D., Veskoukis, A., Skaperda, Z., Tsatsakis, A., Wallace, D., and Suzen, S. (2020). Potential Applications of NRF2 Modulators in Cancer Therapy. Antioxidants, 9.","DOI":"10.3390\/antiox9030193"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111610","DOI":"10.1016\/j.ecoenv.2020.111610","article-title":"Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of Nrf2 pathway","volume":"208","author":"Fang","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1111\/jcmm.16504","article-title":"Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2 through epigenetic modification","volume":"25","author":"Su","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eaba3613","DOI":"10.1126\/scitranslmed.aba3613","article-title":"Activation of NRF2 ameliorates oxidative stress and cystogenesis in autosomal dominant polycystic kidney disease","volume":"12","author":"Lu","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"780","DOI":"10.2337\/db15-0564","article-title":"An Essential Role of NRF2 in Diabetic Wound Healing","volume":"65","author":"Long","year":"2016","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1177\/1352458517690617","article-title":"Evidence of activation of the Nrf2 pathway in multiple sclerosis patients treated with delayed-release dimethyl fumarate in the Phase 3 DEFINE and CONFIRM studies","volume":"23","author":"Gopal","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1007\/s11064-021-03366-2","article-title":"Nrf2\/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated Neuroprotection in Methyl Mercury-Induced Experimental Model of ALS","volume":"46","author":"Minj","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101206","DOI":"10.1016\/j.arr.2020.101206","article-title":"Nrf2: A dark horse in Alzheimer\u2019s disease treatment","volume":"64","author":"Osama","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/ars.2015.6549","article-title":"Repurposing the NRF2 Activator Dimethyl Fumarate as Therapy Against Synucleinopathy in Parkinson\u2019s Disease. Antioxid","volume":"25","author":"Scannevin","year":"2016","journal-title":"Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/jnc.12647","article-title":"Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington\u2019s disease","volume":"129","author":"Liu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1097\/WNR.0000000000001542","article-title":"Protocatechuic acid attenuates brain edema and blood-brain barrier disruption after intracerebral hemorrhage in mice by promoting Nrf2\/HO-1 pathway","volume":"31","author":"Xi","year":"2020","journal-title":"NeuroReport"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/jcb.29413","article-title":"3-Acetyl-11-keto-\u03b2-boswellic acid attenuated oxidative glutamate toxicity in neuron-like cell lines by apoptosis inhibition","volume":"121","author":"Rajabian","year":"2020","journal-title":"J Cell Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Al-Harrasi, A., Rehman, N.U., Khan, A.L., Al-Broumi, M., Al-Amri, I., Hussain, J., Hussain, H., and Csuk, R. (2018). Chemical, molecular and structural studies of Boswellia species: \u03b2-Boswellic Aldehyde and 3-epi-11\u03b2-Dihydroxy BA as precursors in biosynthesis of boswellic acids. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198666"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5798","DOI":"10.1007\/s12035-017-0801-2","article-title":"Role of 3-Acetyl-11-Keto-Beta-Boswellic Acid in Counteracting LPS-Induced Neuroinflammation via Modulation of miRNA-155","volume":"55","author":"Sayed","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Conti, S., Vexler, A., Edry-Botzer, L., Kalich-Philosoph, L., Corn, B.W., Shtraus, N., Meir, Y., Hagoel, L., Shtabsky, A., and Marmor, S. (2018). Combined acetyl-11-keto-\u03b2-boswellic acid and radiation treatment inhibited glioblastoma tumor cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198627"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000452744","article-title":"Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-\u03b2-Boswellic Acid in Skin Keratinocytes","volume":"30","author":"Yang","year":"2017","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.3892\/ijmm.2016.2571","article-title":"Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-\u03b2-boswellic acid in combination on isoproterenol-induced myocardial injury in rats","volume":"37","author":"Chen","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.4049\/jimmunol.176.5.3127","article-title":"Acetyl-11-keto-\u03b2-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-\u03baB and NF-\u03baB-regulated gene expression","volume":"176","author":"Takada","year":"2006","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.freeradbiomed.2020.02.022","article-title":"Acetyl-11-keto-\u03b2-boswellic acid ameliorates cognitive deficits and reduces amyloid-\u03b2 levels in APPswe\/PS1dE9 mice through antioxidant and anti-inflammatory pathways","volume":"150","author":"Wei","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","first-page":"281","article-title":"Effects of Boswellia serrata resin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson\u2019s disease","volume":"9","author":"Doaee","year":"2019","journal-title":"Avicenna J. Phytomed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1007\/s12035-014-8929-9","article-title":"Post treatment with 11-keto-\u03b2-boswellic acid ameliorates cerebral ischemia\u2013reperfusion injury: Nrf2\/HO-1 pathway as a potential mechanism","volume":"52","author":"Ding","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"155107","DOI":"10.1016\/j.cyto.2020.155107","article-title":"The effects of acetyl-11-keto-\u03b2-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats","volume":"131","author":"Marefati","year":"2020","journal-title":"Cytokine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"116887","DOI":"10.1016\/j.lfs.2019.116887","article-title":"Acetyl-11-keto-\u03b2-boswellic acid regulates the repair of rat sciatic nerve injury by promoting the proliferation of Schwann cells","volume":"254","author":"Jiang","year":"2020","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104516","DOI":"10.1016\/j.neuint.2019.104516","article-title":"Neuroprotective natural products against experimental autoimmune encephalomyelitis: A review","volume":"129","author":"Mohtashami","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/eji.201343629","article-title":"Boswellic acids reduce T h17 differentiation via blockade of IL-1\u03b2-mediated IRAK 1 signaling","volume":"44","author":"Verse","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7002","DOI":"10.1038\/srep07002","article-title":"Neuroprotection by acetyl-11-keto-\u03b2-boswellic acid, in ischemic brain injury involves the Nrf2\/HO-1 defense pathway","volume":"4","author":"Ding","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/978-1-4939-9072-6_21","article-title":"Toxin-based models to investigate demyelination and remyelination Oligodendrocytes","volume":"1936","author":"McMurran","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.1016\/j.sjbs.2021.07.010","article-title":"Neuroprotective efficacy of 4-Hydroxyisoleucine in experimentally induced intracerebral hemorrhage","volume":"28","author":"Siddiqui","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.toxrep.2022.04.023","article-title":"Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats","volume":"9","author":"Sahu","year":"2022","journal-title":"Toxicol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"601","DOI":"10.2174\/1567205017666201007120112","article-title":"Investigation of Low Dose Cabazitaxel Potential as Microtubule Stabilizer in Experimental Model of Alzheimer\u2019s Disease: Restoring Neuronal Cytoskeleton","volume":"17","author":"Duggal","year":"2020","journal-title":"Curr. Alzheimer Res."},{"key":"ref_60","first-page":"212","article-title":"Effect of Mitogen Activated Protein Kinase Inhibitor in Animal Model of Alzheimer\u2019s Diseases","volume":"2","author":"Mehan","year":"2011","journal-title":"Int. J. Pharma Prof. Res."},{"key":"ref_61","first-page":"121","article-title":"Neuroprotective potential of Mangosteen in 3-nitropropionic acid induced Huntington\u2019s disease like behavioral and biochemical alterations in rats","volume":"10","author":"Khera","year":"2018","journal-title":"Pharmaspire"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Alam, M.M., Minj, E., Yadav, K.R., and Mehan, S. (2021). Neuroprotective Potential of Adenyl Cyclase\/cAMP\/CREB and Mitochondrial CoQ10 Activator in Amyotrophic Lateral Sclerosis Rats. Curr. Bioa. Com., 17.","DOI":"10.2174\/1573407216999200723113054"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"46","DOI":"10.12680\/balneo.2017.141","article-title":"Different blood collection methods from rats: A review","volume":"8","author":"Kumar","year":"2017","journal-title":"Balneo Res. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S603","DOI":"10.33549\/physiolres.933220","article-title":"Signs of Myelin Impairment in Cerebrospinal Fluid After Osmotic Opening of the Blood-Brain Barrier in Rats","volume":"64","author":"Kozler","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1021\/pr201244t","article-title":"Profiling and Identification of Cerebrospinal Fluid Proteins in a Rat EAE Model of Multiple Sclerosis","volume":"11","author":"Rosenling","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00702-015-1479-0","article-title":"CSF Nrf2 and HSPA8 in Parkinson\u2019s disease patients with and without LRRK2 gene mutations","volume":"123","author":"Loeffler","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1212\/WNL.54.6.1297","article-title":"Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD","volume":"54","author":"Schipper","year":"2000","journal-title":"Neurology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1177\/09603271211013456","article-title":"Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism","volume":"40","author":"Rahi","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Song, J., Jiao, Y., Zhang, T., Zhang, Y., Huang, X., Li, H., and Wu, H. (2015). Longitudinal Changes in Plasma Caspase-1 and Caspase-3 during the First 2 Years of HIV-1 Infection in CD4Low and CD4High Patient Groups. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121011"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tiwari, A., Khera, R., Rahi, S., Mehan, S., Makeen, H., Khormi, Y., Rehman, M., and Khan, A. (2021). Neuroprotective Effect of \u03b1-Mangostin in Ameliorating Propionic Acid-Induced Experimental Model of Autism in Wistar Rats. Brain Sci., 11.","DOI":"10.3390\/brainsci11030288"},{"key":"ref_71","first-page":"1790","article-title":"Correlation of the expression of inflammatory factors with expression of apoptosis-related genes Bax and Bcl-2, in burned rats","volume":"17","author":"Wang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.toxrep.2019.10.019","article-title":"Neuroprotective potential of solanesol in intracerebroventricular propionic acid induced experimental model of autism: Insights from behavioral and biochemical evidence","volume":"6","author":"Sharma","year":"2019","journal-title":"Toxicol. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Khera, R., Mehan, S., Bhalla, S., Kumar, S., Alshammari, A., Alharbi, M., and Sadhu, S.S. (2022). Guggulsterone Mediated JAK\/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism. Molecules, 27.","DOI":"10.3390\/molecules27030889"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ibror.2020.03.001","article-title":"Neuroprotective potential of solanesol in a combined model of intracerebral and intraventricular hemorrhage in rats [IBRO rep]","volume":"8","author":"Rajdev","year":"2020","journal-title":"IBRO Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/09603271221084276","article-title":"Protective effects of apigenin on methylmercury-induced behavioral\/neurochemical abnormalities and neurotoxicity in rats","volume":"41","author":"Yadav","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"309","DOI":"10.4103\/ijp.IJP_11_18","article-title":"Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington\u2019s disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction","volume":"50","author":"Mehan","year":"2018","journal-title":"Indian J. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s11011-022-01026-0","article-title":"PI3K\/AKT\/mTOR signalling inhibitor chrysophanol ameliorates neurobehavioural and neurochemical defects in propionic acid-induced experimental model of autism in adult rats","volume":"37","author":"Sharma","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1515\/tnsci-2021-0006","article-title":"Pelargonidin ameliorates MCAO-induced cerebral ischemia\/reperfusion injury in rats by the action on the Nrf2\/HO-1 pathway","volume":"12","author":"Fu","year":"2021","journal-title":"Transl. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Gupta, R., Mehan, S., Sethi, P., Prajapati, A., Alshammari, A., Alharbi, M., Al-Mazroua, H.A., and Narula, A.S. (2022). Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder. Brain Sci., 12.","DOI":"10.3390\/brainsci12030342"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"192","DOI":"10.5567\/pharmacologia.2015.192.212","article-title":"Precautionary Ellagic Acid Treatment Ameliorates Chronically Administered Scopolamine Induced Alzheimer\u2019s Type Memory and Cognitive Dysfunctions in Rats","volume":"6","author":"Mehan","year":"2015","journal-title":"Pharmacologia"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1515\/tnsci-2018-0026","article-title":"Benificial effect of stachydrine on the traumatic brain injury induced neurodegeneration by attenuating the expressions of Akt\/mTOR\/PI3K and TLR4\/NF\u03ba-B pathway","volume":"9","author":"Yu","year":"2018","journal-title":"Transl. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejphar.2009.08.027","article-title":"Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine\u2014A PDE1 inhibitor","volume":"620","author":"Deshmukh","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4103\/1673-5374.200812","article-title":"Adenyl cyclase activator forskolin protects against Huntington\u2019s disease-like neurodegenerative disorders","volume":"12","author":"Mehan","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.4103\/1673-5374.270316","article-title":"Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats","volume":"15","author":"Mehan","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_85","first-page":"68","article-title":"Neuroprotection of brain permeable Forskolin ameliorates behavioral, biochemical and histopathological alterations in rat model of intracerebral hemorrhage","volume":"10","author":"Dudi","year":"2018","journal-title":"Pharmaspire"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"72881","DOI":"10.1039\/C5RA13160J","article-title":"Experimental evidence for the potential of lycopene in the management of scopolamine induced amnesia","volume":"5","author":"Bala","year":"2015","journal-title":"RSC Adv."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40478-018-0510-8","article-title":"Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945","volume":"6","author":"Beckmann","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S1474-4422(18)30245-X","article-title":"Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: A retrospective study","volume":"17","author":"Trapp","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/nan.12405","article-title":"Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex","volume":"44","author":"Carassiti","year":"2017","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Shandilya, A., Mehan, S., Kumar, S., Sethi, P., Narula, A.S., Alshammari, A., Alharbi, M., and Alasmari, A.F. (2022). Activation of IGF-1\/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity. Molecules, 27.","DOI":"10.3390\/molecules27123878"},{"key":"ref_91","unstructured":"Carleton, H.M., Drury, R.A., and Wallington, E.A. (1980). Carleton\u2019s Histological Technique, Oxford University Press."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e01213","DOI":"10.1016\/j.heliyon.2019.e01213","article-title":"Moderating effects of crocin on some stress oxidative markers in rat brain following demyelination with ethidium bromide","volume":"5","author":"Fathimoghadam","year":"2019","journal-title":"Heliyon"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ijdevneu.2007.02.005","article-title":"Cyclosporine A inhibits acetylcholinesterase activity in rats experimentally demyelinated with ethidium bromide","volume":"25","author":"Mazzanti","year":"2007","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.lfs.2014.03.033","article-title":"Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide","volume":"103","author":"Beckmann","year":"2014","journal-title":"Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"878030","DOI":"10.1155\/2012\/878030","article-title":"Nrf2\/ARE signaling pathway: Key mediator in oxidative stress and potential therapeutic target in ALS","volume":"2012","author":"Petri","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/acn3.553","article-title":"The NRF2 pathway as potential biomarker for dimethyl fumarate treatment in multiple sclerosis","volume":"5","author":"Hammer","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1365-2990.2008.00986.x","article-title":"Abundant extracellular myelin in the meninges of patients with multiple sclerosis","volume":"35","author":"Kooi","year":"2009","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1074\/mcp.M200050-MCP200","article-title":"Multiple Sclerosis: An important role for post-translational modifications of myelin basic protein in pathogenesis","volume":"2","author":"Kim","year":"2003","journal-title":"Mol. Cell. Proteom."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s10571-015-0279-2","article-title":"Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect","volume":"36","author":"Salem","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1177\/135245859800400306","article-title":"Myelin basic protein in CSF as indicator of disease activity in multiple sclerosis","volume":"4","author":"Lamers","year":"1998","journal-title":"Mult. Scler."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/ana.410080104","article-title":"A diagnostic index of active demyelination: Myelin basic protein in cerebrospinal fluid","volume":"8","author":"Cohen","year":"1980","journal-title":"Ann. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.celrep.2016.06.008","article-title":"Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases","volume":"16","author":"Weil","year":"2016","journal-title":"Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1007\/s11064-016-1920-2","article-title":"Myelin Basic Protein Citrullination in Multiple Sclerosis: A Potential Therapeutic Target for the Pathology","volume":"41","author":"Yang","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2013.08.011","article-title":"Downregulation of Nrf2\/HO-1 pathway and activation of JNK\/c-Jun pathway are involved in homocysteic acid-induced cytotoxicity in HT-22 cells","volume":"223","author":"Tan","year":"2013","journal-title":"Toxicol Lett."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Call, C.L., De Biase, L.M., and Bergles, D.E. (2020). Neuron\u2013glial interactions and neurotransmitter signaling to cells of the oligodendrocyte lineage. Patterning Cell Type Specif. Dev. CNS PNS, 891\u2013918.","DOI":"10.1016\/B978-0-12-814405-3.00036-9"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1002\/glia.22674","article-title":"Neurotransmitter signaling in white matter","volume":"62","author":"Butt","year":"2014","journal-title":"Glia"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2\/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/brain\/awq386","article-title":"Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway","volume":"134","author":"Linker","year":"2011","journal-title":"Brain"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1093\/brain\/awp335","article-title":"High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis","volume":"133","author":"Schmierer","year":"2010","journal-title":"Brain"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1136\/jnnp-2014-307712","article-title":"Multiple sclerosis deep grey matter: The relation between demyelination, neurodegeneration, inflammation and iron","volume":"85","author":"Haider","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1324\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:56:16Z","timestamp":1760140576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,25]]},"references-count":110,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["genes13081324"],"URL":"https:\/\/doi.org\/10.3390\/genes13081324","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,25]]}}}