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Luteolin blocks dopaminergic neuron degeneration and shifts microglial M1/M2 polarization by inhibiting Toll like receptor 4
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  • Luo yan,
  • Yangzhi Xie,
  • Liang Chen,
  • Jiacheng Chen
Luo yan
University of South China Affiliated Nanhua Hospital

Corresponding Author:[email protected]

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Yangzhi Xie
University of South China Affiliated Nanhua Hospital
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Liang Chen
University of South China Affiliated Nanhua Hospital
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Jiacheng Chen
University of South China Affiliated Nanhua Hospital
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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 both in 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 survival in vivo and in vitro by blocking TLR4-mediated neuroinflammation.
06 Jun 2023Submitted to Immunity, Inflammation and Disease
08 Jun 2023Assigned to Editor
08 Jun 2023Submission Checks Completed
08 Jun 2023Review(s) Completed, Editorial Evaluation Pending
19 Jun 2023Reviewer(s) Assigned
29 Aug 2023Editorial Decision: Revise Major