Synthesis and comprehensive in vivo activity profiling of Olean-12-en-28-ol, 3β-Pentacosanoate in experimental autoimmune encephalomyelitis: A natural remyelinating and anti-inflammatory agent

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buir.contributor.authorAykut, Zeliha Gamze
buir.contributor.orcidAykut, Zeliha Gamze|0000-0003-2184-8628
dc.citation.epage118en_US
dc.citation.issueNumber1en_US
dc.citation.spage103en_US
dc.citation.volumeNumber86en_US
dc.contributor.authorŞenol, H.
dc.contributor.authorOzgun Acar, O.
dc.contributor.authorDağ, A.
dc.contributor.authorEken, A.
dc.contributor.authorGuner, H.
dc.contributor.authorAykut, Zeliha Gamze
dc.contributor.authorTopcu, G.
dc.contributor.authorSen, A.
dc.date.accessioned2023-02-23T15:52:01Z
dc.date.available2023-02-23T15:52:01Z
dc.date.issued2023-01-27
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractMultiple sclerosis (MS) treatment has received much attention, yet there is still no certain cure. We herein investigate the therapeutic effect of olean-12-en-28-ol, 3β-pentacosanoate (OPCA) on a preclinical model of MS. First, OPCA was synthesized semisynthetically and characterized. Then, the mice with MOG35-55-induced experimental autoimmune/allergic encephalomyelitis (EAE) were given OPCA along with a reference drug (FTY720). Biochemical, cellular, and molecular analyses were performed in serum and brain tissues to measure anti-inflammatory and neuroprotective responses. OPCA treatment protected EAE-induced changes in mouse brains maintaining blood-brain barrier integrity and preventing inflammation. Moreover, the protein and mRNA levels of MS-related genes such as HLD-DR1, CCL5, TNF-α, IL6, and TGFB1 were significantly reduced in OPCA-treated mouse brains. Notably, the expression of genes, including PLP, MBP, and MAG, involved in the development and structure of myelin was significantly elevated in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included a substantial reduction in pro-inflammatory cytokines in the serum of treated EAE animals. Lastly, following OPCA treatment, the promoter regions for most inflammatory regulators were hypermethylated. These data support that OPCA is a valuable and appealing candidate for human MS treatment since OPCA not only normalizes the pro- and anti-inflammatory immunological bias but also stimulates remyelination in EAE.en_US
dc.identifier.doi10.1021/acs.jnatprod.2c00798en_US
dc.identifier.eissn1520-6025
dc.identifier.issn0163-3864
dc.identifier.urihttp://hdl.handle.net/11693/111647
dc.language.isoEnglishen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionofhttps://dx.doi.org/10.1021/acs.jnatprod.2c00798en_US
dc.source.titleJournal of Natural Productsen_US
dc.titleSynthesis and comprehensive in vivo activity profiling of Olean-12-en-28-ol, 3β-Pentacosanoate in experimental autoimmune encephalomyelitis: A natural remyelinating and anti-inflammatory agenten_US
dc.typeArticleen_US

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