Abstract
Background: Luteolin is a natural flavonoid, and its
neuroprotective and anti-inflammatory effects have been confirmed to
mitigate neurodegeneration. Despite these findings, the underlying
mechanisms responsible for these effects remain unclear. Toll-like
receptor 4 (TLR4) is widely expressed in microglia and plays a pivotal
role in neuroinflammation and neurodegeneration. Here we outline studies
aimed at determining the mechanisms responsible for the neuroprotective
and anti-inflammatory effects of luteolin using a mouse model of
Parkinson’s disease (PD), and specifically focusing on the role of TLR4
in this process.
Methods: The mouse model of PD used in this study was
established through a single injection of LPS. Mice were subsequently
randomly assigned to either the luteolin or vehicle-treated group, then
motor performance and dopaminergic neuronal injury were evaluated. BV2
microglial cells were treated with luteolin or vehicle saline prior to
LPS challenge. mRNA expression of microglial marker IBA-1 and M1/M2
polarization markers, as well as the levels of pro-inflammatory
cytokines in the mesencephalic tissue and BV2 were quantified by RT-PCR
and ELISA, respectively. Apoptosis and cell viability of SH-SY5Y cells
co-cultured with BV2 were examined. TLR4 RNA transcript and protein
abundance in mesencephalic tissue and BV2 cells were detected.
NFkB p65 subunit phosphorylation bothin vivo and in vitro was evaluated by immunoblotting.
Results: Luteolin treatment induced functional improvements and
alleviated dopaminergic neuronal loss in our PD model. Luteolin
inhibited apoptosis and promoted cell survival in SH-SY5Y cells.
Luteolin treatment shifted microglial M1/M2 polarization towards the
anti-inflammatory M2 phenotype both in vivo and in vitro .
Finally, we found that luteolin treatment significantly downregulated
both TLR4 mRNA and protein expression as well as restraining NFkB p65
subunit phosphorylation.
Conclusions: Luteolin promoted dopaminergic neuronal survivalin vivo and in vitro by blocking TLR4-mediated
neuroinflammation.