Botanical Drug Puerarin Promotes Neuronal Survival and Neurite Outgrowth against MPTP/MPP+-Induced Toxicity via Progesterone Receptor Signaling.

Yingke Zhao,Jianhui Rong,Dan Luo,Lixing Lao,Simon Ming-Yuen Lee,Yuanyuan Cheng,Xiuying Zhang,Jia Zhao,Shi Yuan Xu

doi:10.1155/2020/7635291

Abstract

Background Progesterone receptor (PR) modulates neuroprotective and regenerative responses in Parkinson's disease and related neurological diseases. Objectives The present study was designed to determine whether botanical drug puerarin could exhibit neuroprotective and neurorestorative activities via PR signaling. Methods The neuroprotective and neurotrophic activities of puerarin were investigated in MPTP-lesioned mice and MPP+-challenged primary rat midbrain neurons. Rotarod performance test and tail suspension test were used to assess motor functions. Tyrosine hydroxylase (TH) and PR were determined by immunostaining, Western blotting, and luciferase reporter assays. Neurite outgrowth was assessed by fluorescence staining and immunostaining. Results Puerarin effectively ameliorated the MPTP-induced motor abnormalities in MPTP-lesioned mice and protected primary rat midbrain neurons against MPP+-induced toxicity via PR signaling although progesterone exhibited the neuroprotection. PR antagonist mifepristone (RU486) diminished the neuroprotection of puerarin in MPTP-lesioned mice and MPP+-induced primary rat midbrain neurons. Moreover, puerarin promoted the differentiation of primary rat midbrain neurons and potentiated NGF to induce neuritogenesis in PC12 cells. RU486 and PR-siRNA could inhibit the effect of puerarin. Puerarin and progesterone could enhance the PR promoter. Conclusion Puerarin attenuated MPTP- and MPP+-induced toxicity and potentiated neurite outgrowth via PR. These results suggested that puerarin may become an alternative hormone for suppressing MPTP- and MPP+-induced toxicity in neurodegenerative diseases.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and characterized by motor dysfunctions as well as some other nonmotor symptoms [1]
Enhanced chemiluminescence (ECL) detection reagent was purchased from GE Healthcare (Uppsala, Sweden). 3,3-N-diaminobenzidine tetrahydrochloride (DAB) substrate kit was obtained from Dako Corporation (Carpintera, CA, USA)
To validate the in vivo neuroprotective activity of puerarin, we firstly employed rotarod performance test and tail suspension test to determine the effects of puerarin on the behavioral deficits in MPTP-treated mice

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and characterized by motor dysfunctions (e.g., tremor, rigidity, and dyskinesia) as well as some other nonmotor symptoms (e.g., cognition deficit and depression) [1]. The neuroprotective and neurotrophic activities of puerarin were investigated in MPTP-lesioned mice and MPP+-challenged primary rat midbrain neurons. Puerarin effectively ameliorated the MPTP-induced motor abnormalities in MPTP-lesioned mice and protected primary rat midbrain neurons against MPP+-induced toxicity via PR signaling progesterone exhibited the neuroprotection. PR antagonist mifepristone (RU486) diminished the neuroprotection of puerarin in MPTP-lesioned mice and MPP+-induced primary rat midbrain neurons. Puerarin promoted the differentiation of primary rat midbrain neurons and potentiated NGF to induce neuritogenesis in PC12 cells. Puerarin attenuated MPTP- and MPP+-induced toxicity and potentiated neurite outgrowth via PR. These results suggested that puerarin may become an alternative hormone for suppressing MPTP- and MPP+-induced toxicity in neurodegenerative diseases

Methods

Results

Discussion

Conclusion