Brazilin-Rich Extract from <i>Caesalpinia sappan</i> L. Attenuated the Motor Deficits and Neurodegeneration in MPTP/p-Induced Parkinson’s Disease Mice by Regulating Gut Microbiota and Inhibiting Inflammatory Responses

Parkinson's disease (PD) is a complicated neurological disease with an unclear pathogenesis. However, dysregulation of gut microbiota and inflammation response play crucial roles in the progression of PD. <i>Caesalpinia sappan</i> L., a traditional medicinal plant containing brazilin as its primary active compound, is known for its anti-inflammatory and neuroprotective properties. However, the impact of <i>C. sappan</i> L. extract (SE) on PD through the regulation of the microbiota-gut-brain axis remains unclear. This study investigated the effects and mechanisms of a 91.23% brazilin-enriched SE on MPTP/p-induced PD mice. Results showed that SE significantly ameliorated motor deficits and protected dopaminergic neurons in PD mice. Additionally, SE reduced oxidative stress and inflammation in the brain. SE also restored gut microbiota by increasing Firmicutes and decreasing Bacteroidetes, alongside enhancing the production of short-chain fatty acids (SCFAs) like butyric acid. Furthermore, SE mitigated intestinal barrier damage by enhancing the expression of ZO-1 and occludin, thereby decreasing lipopolysaccharide leakage and inflammatory factor release. Molecular simulations suggested that butyric acid may maintain intestinal integrity by stabilizing ZO-I and occludin conformations. In conclusion, SE exhibited a protective effect on motor deficits and neurodegeneration in PD by regulating gut microbiota and SCFAs, repairing the intestinal barrier, and mitigating inflammatory responses.