DiHuangYin decoction protects dopaminergic neurons in a Parkinson's disease model by alleviating peripheral inflammation

Parkinson's disease (PD) is a progressive neurodegenerative disease, which brings increasing threaten for human health and is still lacking of satisfied treatment. Recently, numerous studies have also demonstrated the effect of particular subsets of CD4+ T cells on PD pathology. Th17 cells played an important role in the pathogenesis of PD. Traditional Chinese medicine has been widely used to treat PD clinically, and has a tremendous potential in clinical drug development.The aim of this study was to verify the therapeutic effects of DHY on PD mice model, and investigate the underlying molecular mechanisms.Herein, we verified the effects of a traditional Chinese medicine formula, named DiHuangYin (DHY), on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of PD through behavioral and histopathological tests. High-resolution mass spectrometry combined with molecular networking was applied for substance profiling of DHY. Based on the chemical compositions of DHY, network pharmacology was performed. Immunofluorescence and ELISA were used to evaluate the expressions of cytokines in peripheral immune system. qPCR and immunofluorescence were used to detect the inflammation infiltration of central nervous system.DHY improves the motor function and prevents the loss of dopaminergic neurons in the MPTP induced mouse model of PD. 118 components of DHY were identified or tentatively characterized based on the MS/MS data and molecular networking. Network pharmacology suggested IL-17 signaling pathway and neuroactive ligand-receptor interaction as the important targets. Compared to the MPTP-intoxicated mice, the DHY group showed a decreased number of Th17 cells from splenocytes and a decreased level of IL-17A in the serum. On the other hand, less inflammatory infiltration was found in the midbrain of DHY treatment mice which might be associated with the attenuated peripheral inflammation.Though the underlying pharmacological mechanism of DHY is still lacking, we provided evidence that DHY decoction could protect dopaminergic neurons by mitigating peripheral inflammation.