Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson's Disease.

Sylvester I Omoruyi,Abobaker S Ibrakaw,Ahmed A Hussein,Okobi E Ekpo,Christopher N Cupido,James S Boatwright

doi:10.3390/molecules26133990

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP+ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP+-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting approximately 6.3 million people worldwide, and it is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta part of the mid-brain [1]
MPP+ exerts its neurotoxic activities through the generation of free radicals, which induces the inhibition of the mitochondrial complex I electron transport chain and, in turn, causes a depletion of adenosine triphosphate (ATP) that leads to neuronal cell death
Compounds 2–4 were identified as bufanidrine (2), buphanisine (3), and epibuphanisine (4) [23,24]. These compounds belong to crinine-type alkaloids, and according to the recent review by Berkov et al, so far there are 85 compounds isolated from the Amaryllidaceae family and with a crinine skeleton [25]

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting approximately 6.3 million people worldwide, and it is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta part of the mid-brain [1]. Evolutionary advances in the past two decades have supported findings that understanding PD progression is compromised by genetic factors and by the association of environmental toxins with free radical formation and oxidative stress [6]. These environmental factors include tobacco use and chemical/pesticide exposure [7,8], a notable chemical being MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which is a pro-drug to the neurotoxin MPP+ used in this study. MPP+ is a metabolite of MPTP and causes permanent PD symptoms, especially the death of dopaminergic neurons. MPP+ exerts its neurotoxic activities through the generation of free radicals, which induces the inhibition of the mitochondrial complex I electron transport chain and, in turn, causes a depletion of adenosine triphosphate (ATP) that leads to neuronal cell death

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