Artemisinin exerts a protective effect in the MPTP mouse model of Parkinson's disease by inhibiting microglial activation via the TLR4/Myd88/NF-KB pathway

Aims: We performed cell and animal experiments to explore the therapeutic effect of artemisinin on Parkinson's disease (PD) and the TLR4/MyD88 signaling pathway.

Methods: C57 mice were randomly divided into the blank, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and artemisinin-treated groups. Clinical symptoms, the number of dopaminergic (DAergic) neurons in the substantia nigra, and microglial cell activation were compared among the three groups. Subsequently, BV-2 cell activation and TLR4/MyD88 pathway component expression were compared among the blank, MPP⁺ -treated, artemisinin-treated, and TLR4 activator-treated groups.

Results: Behavioral symptoms were improved, the number of DAergic neurons in the substantia nigra of the midbrain was increased, and microglial cell activation was decreased in artemisinin-treated MPTP-induced PD model mice compared with control-treated MPTP-induced PD model mice (p < 0.05). The cell experiments revealed that artemisinin treatment reduced MPP⁺ -induced BV-2 cell activation and inhibited the TLR4/MyD88 signaling pathway. Moreover, the effect of artemisinin on the BV-2 cell model was inhibited by the TLR4 Activator LPS (p < 0.05).

Conclusion: Artemisinin may reduce damage to DAergic neurons in a PD mouse model by decreasing microglial activation through the TLR4-mediated MyD88-dependent signaling pathway. However, this finding cannot explain the relationship between microglia and DAergic neurons.

Parkinson's disease; artemisinin; inflammation; microglia; toll-like receptor 4.