Yerba mate (Ilex paraguariensis) favors survival and growth of dopaminergic neurons in culture

BALLESTERO, PEDRO; GÓMEZ, GIMENA; TARAVINI, IRENE; FERRARIO, JUAN E.; BERNARDI, ALEJANDRA; FERRARIO, MARIANA; AVALE, ELENA; GUERRERO, SANDRA; SCHENK, MARCELA; RIVERO, ROY; GERSHANIK, OSCAR

MOVEMENT DISORDERS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2019 vol. 34 p. 920 - 922

0885-3185

The infusion from Ilex paraguariensis (popularly known asYerba mate [YM]) produces the very popular South Americanbeverage called mate (pronounced as ?mateI? or maté), andits intake has been inversely associated with the developmentof Parkinson?s disease (PD) in a large population study inArgentina.1 Given that the influence of diet on health (and disease)of the brain is currently a major issue, and the improvementin the tools to detect the signs and symptoms of PD in itsprodromal period,2 it becomes highly relevant to identify andvalidate potential neuroprotective dietary products that maypositively impact on the progression of the disease.We tested whether YM could be protective to dopaminergicneurons in a well-established model of neurodegeneration in culture.To this end, we developed a standardized ultrasoundassistedextraction method from dried leaves (?canchada?)3 anddetermined by high-performance liquid chromatography (HPLC)that it had a similar profile to that reported elsewhere,4 indicatingthat all the main compounds were preserved in the extract(Fig. 1A). We then tested the neuroprotective effect of YM onmesencephalic primary cultures on which dopaminergic neuronsdie spontaneously throughout a 2-week period.5 We found thatYM extracts significantly prevented dopaminergic death, showinga dramatic dose-dependent neuroprotective effect at eachtested concentration (Fig. 1B). We further determined that thetwo major compounds, theobromine and chlorogenic acid(CGA), tested individually were also neuroprotective. However,in both cases, the protective effect was slightly lower than thatof YM extract as a whole, but stronger than that of the alreadyknown neuroprotective compounds, caffeine, nicotine + TEA(tetraethyl ammonium), and the antioxidant, Trolox5 (Fig. 1C).In addition, we observed that axonal length and branchingof dopaminergic neurons treated with YM showed a pronouncedincrease compared to control. Notably, a similareffect was induced by CGA whereas theobromine preservedthe total number of dopaminergic cell bodies having no effectover arborization (Fig 1D,F). Analysis of neurite complexityshowed that neurons treated either with YM or CGA have apredominance of secondary and tertiary neurites, demonstratinga high level of growth and development (Fig 1E).The neuroprotective role of antioxidants in models of PD iswidely known, and because of the well-recognized antioxidantproperties of YM,4 a similar effect was expected. However, ourresults show that both YM and CGA provide a stronger neuroprotectivesupport for dopaminergic neurons than Trolox. CGAregulates cell metabolism and has beneficial effects on humanhealth,6 which may be relevant in the case of prevention of PDprogression. Thus, mate becomes an attractive dietary supplementgiven that Ilex paraguariensis is one of the highest naturalsources of CGA,7 and no side effects have been associated withits consumption.There are still many unanswered questions about the cellularmechanisms involved in death or survival of dopaminergic neuronsand how natural compounds may influence the progressionof PD or other neurodegenerative disorders. In this context, ourwork provides the first evidence supporting yerbamate as a promisingnovel neuroprotective agent for dopaminergic neurons.