Baicalein Attenuates Neuroinflammation by Inhibiting NLRP3/Caspase-1/GSDMD Pathway in MPTP-Induced Mice Model of Parkinson's Disease

Background: Inflammasome-induced neuroinflammation is a major pathogenic mechanism underlying the degeneration of nigral dopaminergic neurons in Parkinson's disease (PD). Baicalein is a flavonoid isolated from the traditional Chinese medicinal herbal Scutellaria baicalensis Georgi with known anti-inflammatory and neuroprotective efficacy in models of neurodegenerative diseases, including PD. However, its effects on inflammasome-induced neuroinflammation during PD remain unclear. Methods: We used N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like pathology in mice. Behavioral assessments including the pole test, rotarod test, and open field test were conducted to evaluate the effects of baicalein on MPTP-induced motor dysfunction. The efficacies of baicalein against MPTP-induced dopaminergic neuron loss and glial cell activation in the substantia nigra compact were examined by immunohistochemistry, effects on proinflammatory cytokines by quantitative real-time PCR and enzyme-linked immunosorbent assay, and effects on inflammasome pathway activation by immunoblotting and flow cytometry. Results: Administration of baicalein reversed MPTP-induced motor dysfunction, loss of dopaminergic neurons, and proinflammatory cytokine elevation. Baicalein also inhibited NLRP3 and caspase-1 activation and suppressed gasdermin D-dependent pyroptosis. Additionally, baicalein inhibited the activation and proliferation of disease-associated proinflammatory microglia. Conclusions: These findings suggest that baicalein can reverse MPTP-induced neuroinflammation in mice by suppressing NLRP3/caspase-1/gasdermin D pathway. Our study provides potential insight into the use of baicalein in PD therapy.