Akademik Veri Yönetim Sistemi
International Multidisciplinary Symposium on Drug Research and Development - DRD 2023, İzmir, Türkiye, 4 - 06 Mayıs 2023, ss.344
Microglia are primary immune cells residing in the central nervous system.The play key roles
in homeostasis, inflammatory responses and tissue repair in brain. Microglial activation is
closely associated with neuroinflammation which plays an important role in the
neurodegenerative diseases [1,2]. Mitogen activated protein kinases (MAPKs) and IκB
signaling pathways are involved in the production of inflammatory cytokines. Activation of
microglia results in the induction of these intracellular signalling pathways leading to changes
of genes that are related to inflammation. Flavonoids are naturally occurring polyphenolic
compounds that are known to have neuroprotective effects. Casticin is an active component
of Vitex agnus-castus. It is a polymethylflavone which has been shown to have anticancer and
antioxidant activities [3-5]. In the present study, we investigated the effect of casticin on the
lipopolysaccharide (LPS)-activated activation of p38 MAPK and IκB pathways in microglial cells
in vitro. N9 mouse microglial cells were used in the study. The cells were treated with 0.1, 0.5
and 1 μM of casticin for 24 h and the viability of cells was determined using WST-1 assay. N9
cells were pretreated with 0.1 and 0.5 μM of casticin for 1 h and then incubated with 1 μg/mL
of LPS for 4, 8 and 24h. LPS-induced phosphorylation levels of p38 MAPK and of IκB-α were
analyzed by Western blotting. The viability of cells incubated with 0.1 and 0.5 μM of casticin
did not show significant differences compared to untreated cells, whereas 1 μM of casticin
decreased cell viability to 89.3% at 24 h. Phosphorylation of p38 MAPK and of IκB-α were
induced after LPS incubation at 2, 4 and 8 h compared to control cells. Casticin decreased LPSinduced phosphorylation of p38 MAPK at concentrations of 0.1 and 0.5 μM at 4 h and at the
concentration of 0.5 μM at 8 h. Casticin also inhibited LPS-induced phosphorylation of IκB-α
at concentrations of 0.1 and 0.5 μM at 4 h. Our results demonstrate that casticin could
regulate inflammation by inhibiting phosphorylation of p38 MAPK and IκB-α in a time- and
dose-depent manner. These findings suggest a neuroprotective effect and promising
therapeutic potential of casticin for neuroinflammation.