Isoliquiritigenin ameliorates Parkinson's disease via gut microbiota remodeling: potential mediating role of Parabacteroides distasonis.
Isoliquiritigenin ameliorates Parkinson's disease via gut microbiota remodeling: potential mediating role of Parabacteroides distasonis.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Shaoxing, CN · Author affiliation
Department of Neurosurgery, Shaoxing People's Hospital, Zhejiang University Shaoxing Hospital, Shaoxing, Zhejiang, 312000, China.Location evidence
Zhongxing, CN · Author affiliation
Department of Medical Research Center, Shaoxing People's Hospital, No. 568, Zhongxing North Road, Shaoxing, Zhejiang, 312000, P. R. China.Location evidence
Hangzhou, CN · Author affiliation
Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.Location evidence
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Original abstract
BACKGROUND: Increasing evidence implicates the gut microbiota in the pathogenesis of Parkinson's disease (PD). Microbiota-targeted interventions may be a promising therapeutic approach. Isoliquiritigenin (ISL), a natural flavonoid and primary pharmacological constituent of licorice (Glycyrrhiza), has neuroprotective effects. Whether this neuroprotection involves modulation of the gut microbiota is unclear. PURPOSE: The study assessed whether ISL mediates neuroprotective in PD by modulating the gut microbiota, and investigated the functional involvement of Parabacteroides distasonis (P. distasonis) in this process. METHODS: Mice with chemically-induced PD were first treated with ISL via oral gavage to assess its therapeutic effects. To investigate the microbiota-mediated mechanisms, fecal microbiota transplantation (FMT) from ISL-treated donors and direct gavage of live or heat-killed P. distasonis were performed in separate cohorts. Behavioral performance, dopaminergic neuron integrity, intestinal barrier function, neuroinflammation, gut microbiota composition, and serum metabolomic profiles were systematically evaluated. RESULTS: ISL and FMT significantly improved motor deficits and protected dopaminergic neurons in the substantia nigra. ISL treatment compositionally reshaped the gut microbiota by suppressing pro-inflammatory genera and enriching beneficial bacteria, such as Parabacteroides. Oral administration of live P. distasonis fully reproduced the neuroprotective effects of ISL, including improved motor function, reduced neuroinflammation, restoration of blood-brain barrier integrity, and attenuation of intestinal mucosal damage. Heat-killed P. distasonis had no significant effects. Metabolomic analysis revealed that ISL and live P. distasonis jointly regulate neuroprotective pathways and metabolites related to the gut-brain axis. CONCLUSION: ISL alleviates PD-related pathology partly through gut microbiota remodeling, with P. distasonis as a potential mediator.