Şenol, HalilOzgun-Acar, ÖzdenDaǧ, AydanEken, AhmetGuner, HüseyinAykut, Zaliha GamzeSen, Alaattin2025-09-252025-09-2520230163-38641520-6025https://doi.org/10.1021/acs.jnatprod.2c00798https://hdl.handle.net/20.500.12573/4729Multiple 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 MOG<inf>35-55</inf>-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. © 2023 Elsevier B.V., All rights reserved.eninfo:eu-repo/semantics/openAccessFingolimodGamma Interferon Inducible Protein 10Gelatinase BLactate DehydrogenaseLactate Dehydrogenase AProtein Bcl 2Anti-Inflammatory AgentsCytokinesFty 720Antiinflammatory AgentCd4 AntigenCxcl9 ChemokineFingolimodGamma Interferon Inducible Protein 10Gelatinase BGlial Fibrillary Acidic ProteinHla Dr1 AntigenImmunoglobulin Enhancer Binding ProteinInterleukin 17Interleukin 6Lactate DehydrogenaseMessenger RnaMyelinOlean 12En 28 Ol 3Beta PentacosanoateProtein Bcl 2RantesStat ProteinStat3 ProteinTransforming Growth Factor BetaTransforming Growth Factor Beta1TriterpenoidTumor Necrosis FactorUnclassified DrugCytokineAnimal ExperimentAnimal ModelAnimal TissueAntiinflammatory ActivityArticleBrainBrain DevelopmentControlled StudyDrug EfficacyDrug StabilityDrug SynthesisFemaleGene ExpressionHigh Performance Liquid ChromatographyHumanIn Vivo StudyInnate ImmunityLactate Dehydrogenase Blood LevelMass SpectrometryMog-Induced Experimental Autoimmune EncephalomyelitisMouseNonhumanPromoter RegionProtein Blood LevelProtein StructureProton Nuclear Magnetic ResonanceRemyelinizationSymptomTh1 CellTh17 CellThin Layer ChromatographyAnimalC57Bl MouseExperimental Autoimmune EncephalomyelitisInflammationMetabolismAnimalsAnti-Inflammatory AgentsCytokinesEncephalomyelitis, Autoimmune, ExperimentalHumansInflammationMiceMice, Inbred C57BlArticle10.1021/acs.jnatprod.2c007982-s2.0-85146058063