Paeoniflorin ameliorates Parkinson’s disease by promoting autophagy to inhibit A1 phenotype astrocyte activation

Abstract

Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Autophagy dysfunction and astrocyte activation are considered important factors contributing to dopaminergic neuron death and the progression of Parkinson’s disease. Paeoniflorin, a monoterpene glycoside, exhibits multiple pharmacological effects, including anti-inflammatory, antioxidant, and immunomodulatory properties. The aim of this study was to investigate the effects of paeoniflorin on Parkinson’s disease and the underlying molecular mechanisms. Methods Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, the pharmacological effects of paeoniflorin were evaluated by behavioral assessment, immunohistochemical staining, and Western blotting. For the in vitro experiments, A1-phenotype astrocytes were induced with supernatant from LPS-stimulated microglia, and the regulatory effects of paeoniflorin on astrocyte activation were evaluated by immunofluorescence and Western blotting. Results Paeoniflorin ameliorated dopaminergic neuron damage and motor dysfunction in the MPTP-induced PD mouse model. Furthermore, paeoniflorin inhibited the activation of A1-phenotype astrocytes by promoting autophagy. Conclusion Paeoniflorin ameliorates Parkinson’s disease pathology by promoting autophagy and inhibiting the activation of A1-phenotype astrocytes. These findings uncover potential therapeutic targets and intervention strategies for Parkinson’s disease. Keywords: Parkinson’s disease; paeoniflorin; autophagy; A1-phenotype astrocytes; mTOR.