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.