Verminoside attenuates inflammatory responses in microglial cells and exerts neuroprotective effects in a mouse model of Parkinson's disease

Background: Neuroinflammation plays a critical role in the pathogenesis and progression of Parkinson's disease. Verminoside (VMS) is a natural iridoid exhibiting anti-inflammatory properties. We aimed to investigate the effects of VMS on neuroinflammation and neuronal death in lipopolysaccharide (LPS)-treated BV2 microglial cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse models.

Methods: The production of inflammatory mediators, including nitric oxide, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, were measured by Griess assay, ELISA, or Real-Time PCR. The protein levels of IκBα and nuclear factor kappa B (NF-κB) were determined by western blot. Cell viability and apoptotic rate were assessed using a cell viability assay and flow cytometry, respectively. Immunofluorescence was employed to label Iba-1-positive microglia and tyrosine hydroxylase-positive dopaminergic neurons. In addition, the motor function of mice was evaluated using the rotarod and traction tests.

Results: Our results demonstrated that VMS effectively suppressed the upregulation of inflammatory mediators induced by LPS in BV2 cells. VMS also inhibited the nuclear translocation of NF-κB and eliminated NF-κB activity. Moreover, VMS mitigated the toxicity of conditioned media from LPS-treated BV2 cells. In MPTP-treated mice, VMS decreased the number of Iba-1-positive microglia, reduced the production of inflammatory mediators, preserved tyrosine hydroxylase-positive dopaminergic neurons, and ameliorated motor deficits.

Conclusion: In summary, VMS prevents dopaminergic neuron degeneration and alleviates behavioral impairments by suppressing NF-κB-mediated neuroinflammation, highlighting its potential as a therapeutic drug for Parkinson's disease.

Parkinson’s disease; microglia; neuroinflammation; nuclear factor-κB; verminoside.