Neuroprotective Potential of Cnidoscolus Aconitifolius Against Dopaminergic Neurotoxicity: A Review of Phytochemical Evidence and in Vitro Parkinson's Disease Models

Parkinson’s disease is the second most common progressive neurodegenerative disorder worldwide and is defined by the gradual loss of dopamine-producing neurons in the substantia nigra pars compacta, which causes both motor and non-motor disability. Available dopamine-replacement drugs relieve symptoms without altering the course of the disease and often cause long-term complications, so disease-modifying agents of natural origin are increasingly sought. Cell-culture systems in which neuronal cells, most often human SH-SY5Y neuroblastoma cells, are injured with 1-methyl-4-phenylpyridinium, 6-hydroxydopamine or rotenone serve as first-line platforms for screening such agents. Cnidoscolus aconitifolius (Euphorbiaceae), a leafy shrub eaten as a vegetable and used in the folk medicine of West Africa, Mexico and Central America, contains flavonoids, phenolic acids, alkaloids, saponins and tannins, and has been reported to show antioxidant, anti-inflammatory, cholinesterase-inhibitory and memory-enhancing effects, mainly in rodent studies and cell-free assays. This review brings together published information on neurotoxin-based in vitro models of Parkinson’s disease, on the tetrazolium-based cell-viability assay and its pitfalls with polyphenol-rich extracts, and on the phytochemistry and neuropharmacology of the plant. On this basis, a mechanistic case is outlined for testing its ethanolic leaf extract against toxin-induced neuronal injury through radical scavenging, protection of mitochondrial function, modulation of apoptosis, reduction of inflammatory mediators and inhibition of monoamine oxidase and acetylcholinesterase. No study testing this plant directly in a Parkinson’s disease cell model was found, which underlines the need for such an investigation.