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
posted on 2023-01-04, 17:05authored byHalil Senol, Ozden Ozgun-Acar, Aydan Dağ, Ahmet Eken, Hüseyin Guner, Zaliha Gamze Aykut, Gulacti Topcu, Alaattin Sen
Multiple 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.