Differential gut microbiota modulation associated with anti-Parkinsonian effects of

Introduction: Methods: OJ samples were collected from two major producing regions (Sichuan and Zhejiang) and prepared using two extraction methods (water and ethanol). Chemical profiles were characterized by UHPLC-Q-TOF-MS. Anti-Parkinsonian effects were evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice through behavioral tests (pole, rotarod, open-field, gait, and Morris water maze), biochemical analyses (tyrosine hydroxylase, α-synuclein, and inflammatory markers), and histological examinations. Gut microbiota composition was analyzed via 16S rRNA gene sequencing to identify modulation patterns associated with health outcomes. Results: Chemical profiling revealed substantial compositional differences among extracts depending on geographical origin and extraction method. All OJ extracts significantly ameliorated MPTP-induced motor deficits, anxiety-like behaviors, dopaminergic neuron loss, and neuroinflammation, indicating broadly comparable anti-Parkinsonian effects. Notably, water extract of OJ from Sichuan (COJ_W) was the only group that significantly improved cognitive performance compared with the MPTP group. Concurrently, differential gut microbiota modulation patterns were observed across treatment groups. All OJ extracts significantly altered the abundance of Conclusion: Geographical origin and extraction method influence the gut microbiota modulation patterns of OJ, which are associated with its anti-Parkinsonian effects across different functional domains. These findings highlight the importance of raw material selection and processing strategy in the functional evaluation of edible medicinal plants and provide insights into the complex relationship between gut microbiota modulation and health outcomes.