Neuroprotective Effects of <i>Paeonia lactiflora</i> Through the Regulation of Gut <i>Dubosiella</i> in an MPTP-Induced Parkinson’s Disease Mouse Model

Emerging evidence suggests that changes in the composition of the gut microbiota may play an important role in the pathogenesis of Parkinson's disease (PD). <i>Paeonia lactiflora</i> Pall., a traditional Chinese medicinal herb belonging to the genus <i>Paeonia</i>, is commonly used in Chinese medicinal practice for the treatment of PD. However, the specific mechanisms of its action remain poorly understood. This study aimed to further determine the neuroprotective properties of <i>Paeonia lactiflora</i> Pall. water extract (PWE) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and to investigate its potential implications for the pathogenesis of PD. A PD mouse model was established via the intraperitoneal administration of MPTP, followed by the assessment of motor function using behavioral tests. Western blotting and histopathological analysis were used to measure the levels of dopaminergic (DAergic) neurodegeneration-related factors in the midbrain (containing the substantia nigra (SN)) and striatum. 16S rRNA gene sequencing and metabolomic analysis were applied to identify differences in the gut microbiota and metabolites, respectively. Our results indicate that PWE effectively protects against MPTP-induced motor deficits, loss of DAergic neurons, blood-brain barrier (BBB) damage, and neuroinflammation in PD. The protective effects of PWE against PD are mediated through modulation of the gut microbiota, specifically by an increase in the abundance of the genus <i>Dubosiella</i>. In this study, we selected <i>D. newyorkensis</i> as a representative strain of the genus, and determined its therapeutic effects in an MPTP-induced PD mouse model. Our preliminary findings suggest that the neuroprotective effects of <i>D. newyorkensis</i> may be related to the production of serum indoleacetic acid.