Akademik Veri Yönetim Sistemi
Chemistry & Biodiversity, cilt.0, sa.0, ss.1-31, 2025 (SCI-Expanded)
This study was conducted to investigate the mechanism of the potential
and anti-inflammatory properties of nitrogen-substituted oleanolic acid
derivatives that can be used to treat neuroinflammatory diseases.
Nitrogen-containing oleanolic acid derivatives have been evaluated for
their anti-neuroinflammatory effects in vitro in neuronal and monocytic
cell lines at nontoxic doses, and the production of cytokines (TNF-α,
IL-6 and IL-17), the inflammatory enzyme induced nitric oxide synthase
(iNOS) and NF-κB signalling under LPS-stimulated conditions, and the
expression of genes associated with Alzheimer's disease have been
assessed. In addition, molecular docking and molecular dynamics
simulation assessments are conducted in silico. Key protein markers of
neurodegenerative diseases, especially Alzheimer's disease and
neuroinflammation, TAU protein levels, and microglial activation, as
well as ionised calcium-binding adaptor protein-1 (IBA1) levels, were
significantly reduced with the addition of oleanolic acid derivatives.
LPS-induced NF-κB luciferase reporter activity and iNOS activity were
significantly inhibited, approaching the levels in uninduced controls.
The mRNA expression of proinflammatory cytokines critical for
neuroinflammation, such as TNF-α, NF-κB, IL-6 and IL-17, was reduced
twofold to sevenfold. Furthermore, the molecular docking and MD
simulation analyses revealed potential interactions with the TNF-α and
NF-κB proteins. These findings underscore the potential of oleanolic
acid derivatives, particularly compound 16, as candidates for
further development as therapeutic agents for neurodegenerative diseases
associated with chronic inflammation.