WuMei-pill alleviates Parkinson's disease induced by dopamine neuron damage in mice by regulating the gut-brain-microbiome axis

Abstract

Objective

To investigate the protective effects and the ways WuMei-Pill (WMP) work on Parkinson's disease (PD), focusing on its ability to restore the PD-induced gut microbiota imbalance and elucidate the underlying mechanisms.

Methods

This study employed LPS-induced inflammation BV2 cells and a PD mouse model induced by 6-OHDA to explore the treatment of WMP. A series of assessments were performed, encompassing behavioral evaluations, immunohistochemistry, Western blot, and ELISA, to evaluate the neuroprotective effect of WMP on PD. Fecal and brain samples were collected for microbiome and transcriptome analysis.

Results

WMP effectively reverses LPS-induced inflammation in BV2 cells. Based on PD mouse model, WMP treatment elevated neurological motor function (evidenced by reduced pole descent time and increased rotarod performance), increased the number of TH + cells, and brain dopamine levels. Microbiome dysbiosis correlates with exacerbated PD symptoms in the 6-OHDA model. 6-OHDA-induced dopaminergic neuronal damage was connected to an increase in pro-inflammatory bacteria (Bacteroides), bacteria involved in tryptophan metabolism (Azospirillum_sp.47_25 and unclassified Bacteroidia) and cholesterol metabolism, while the number of anti-inflammatory bacteria (Roseburia) was reduced. We also found changes in key brain metabolites, including L-tryptophan and Bambuterol. WMP normalized L-tryptophan levels, a precursor of neurotoxic kynurenine metabolites implicated in PD progression.

Conclusion

Dopaminergic neuron damage-induced microbiome dysbiosis worsen Parkinson's disease symptoms. WMP restores gut microbiota composition by reducing pro-inflammatory Bacteroides and upregulating anti-inflammatory Roseburia, while modulating L-tryptophan metabolism, thereby mitigating dopaminergic neuron loss.