Tianma Gouteng Decoction improve neuronal synaptic plasticity and oligodendrocyte apoptosis in Parkinson's disease...

Parkinson's disease (PD) is a complex and multifactorial disorder of the nervous system. Tianma Gouteng Decoction (TGD) is a clinical prescription of traditional Chinese medicine for PD, but its neuroprotective effects and mechanisms for PD are poorly understood.

The aim of this study was to explore the mechanism of TGD in the treatment of PD.

Serum pharmacochemistry, single cell sequencing, network pharmacology, and validation experiment were combined to study the effect of TGD in PD model.

TGD water extract and its distribution in serum of PD mice were analyzed by secondary metabolomics. The crossing blood-brain barrier components and targets were preliminarily identified. Target cells and pathways of TGD were analyzed by network pharmacology and single cell sequencing.

TGD treatment improved the movement disorders in MPTP-induced PD mice, restoring dopaminergic neurons in the substantia nigra region and suppressing the expression of α-synuclein. We identified 1272 components in TGD, among which 73 were distributed in the serum of PD mice after oral administration. Network pharmacological analysis demonstrated that these components were involved in the regulation of apoptosis, and 15 of them could across the blood-brain barrier and bind to PD pathological proteins. Single nucleus RNA sequencing analysis identified 18 cell subpopulations, and TGD treatment restored the neuron-oligodendrocyte crosstalk. Neurons were identified as the most widely responding target cells, while oligodendrocytes were the core response target cells to TGD therapy. After treatment, the apoptosis of oligodendrocytes was inhibited, and the secretion of trophic factor was enhanced, facilitating the improvement of neuronal synaptic plasticity and neuroinflammation.

This study systematically elucidates the molecular mechanism of TGD improving movement disorders, which is helpful to provide new ideas for drug development of PD.