OBJECTIVE To analyze the effect of Huanglian Jiedu Decoction (HLJDD) on the intestinal flora and metabolites of Parkinson's disease (PD) model mice, and explore the mechanism of HLJDD in intervening in PD based on 16S rRNA technology and non-targeted metabolomics technology.

METHODS The PD model of mice was induced by subcutaneous injection of MPTP 20 mg ·kg^-1·d^-1 and peritoneal injection of probenecid 200 mg ·kg^-1·d^-1, and the weight and behavior indexes of mice were measured after drug intervention. HPLC-QTRAP-MS/MS technique was used to detect the levels of neurotransmitters in the striatum of mice. The levels of striatal inflammatory factors were detected by ELISA. The changes of intestinal flora in mice were analyzed by 16S rRNA technology. UHPLC-Q-TOF-MS was used to detect endogenous metabolites in mouse striatum, Orthogonal partial least squares discriminant analysis (OPLS-DA) was adopted to screen potential differential metabolites, and MetaboAnalyst 5.0 was introduced to predict metabolic pathways associated with PD.

RESULTS HLJDD significantly improved the motor symptoms and neuroinflammation of PD mice (P < 0.01), regulated the level of neurotransmitters, and corrected the intestinal microbiota disorder of PD mice, manifested by the increase of intestinal microbial diversity and the restoration of microbiota profile. After treatment with HLJDD, the abundance of Prevotella and Akkermansia in PD mice was significantly increased, and the abundance of Clostridium was decreased (P < 0.01). The abnormal metabolite levels were restored mainly by regulating the tryptophan metabolic pathway in the feces and striatum of PD model mice.

CONCLUSION HLJDD can significantly improve the pathological damage of PD model mice, and the regulation of disordered intestinal flora and tryptophan metabolism pathway may be the potential mechanism of HLJDD to intervene in PD.