The Impact of Paeoniflorin on α-Synuclein Degradation Pathway.

Zenglin Cai,Xinzhi Zhang,Jing Xu,Xiaomin Li,Xiuming Li,Yongjin Zhang

doi:10.1155/2015/182495

Abstract

Paeoniflorin (PF) is the major active ingredient in the traditional Chinese medicine Radix. It plays a neuroprotective role by regulating autophagy and the ubiquitin-proteasome degradation pathway. In this study, we found PF significantly reduced cell damage caused by MPP+, returning cells to normal state. Cell viability significantly improved after 24 h exposure to RAPA and PF in the MPP+ group (all P < 0.01). CAT and SOD activities were significantly decreased after PF and RAPA treatment, compared with MPP+ (P < 0.001). In addition, MPP+ activated both LC3-II and E1; RAPA increased LC3-II but inhibited E1. PF significantly upregulated both LC3-II (autophagy) and E1 (ubiquitin-proteasome pathway) expression (P < 0.001), promoted degradation of α-synuclein, and reduced cell damage. We show MPP+ enhanced immunofluorescence signal of intracellular α-synuclein and LC3. Fluorescence intensity of α-synuclein decreased after PF treatment. In conclusion, these data show PF reversed the decline of proteasome activity caused by MPP+ and significantly upregulated both autophagy and ubiquitin-proteasome pathways, promoted the degradation of α-synuclein, and reduced cell damage. These findings suggest PF is a potential therapeutic medicine for neurodegenerative diseases.

Highlights

Genetic, pathological, and biochemical studies show αsynuclein plays a role in Parkinson’s disease (PD) and Lewy body associated disease
Paeoniflorin significantly reduced the damage caused by MPP+, and cells returned to normal state (Figures 1(c) and 1(f))
To investigate the protective effect of PF and RAPA on cell damage caused by MPP+, we examined superoxide dismutase (SOD) and CAT activity in PC12 cells

Summary

Introduction

Pathological, and biochemical studies show αsynuclein plays a role in Parkinson’s disease (PD) and Lewy body associated disease. It is unclear how αsynuclein causes neurodegenerative disease [1]. Α-synuclein readily forms oligomeric species, which are cytotoxic [2]. Recent studies show PF has neuroprotective effects via modulation of ROS production and apoptosis in the mitochondrial pathway in injured neurons in vitro [3]. Our team previously showed that, in addition to inhibiting inflammation, PF plays a neuroprotective role in a neuronal injury model by regulating autophagy [6].

Materials and Methods

Results

Conclusion