Uleine disrupts key enzymatic and non-enzymatic biomarkers that leads to Alzheimer's disease

Alzheimer´s disease, a progressive and degenerative disorder of the brain, is the most common cause of dementia among the elderly. To face its multifactorial nature, the use of single compounds that can simultaneously modulate different targets involved in the neurodegenerative cascade has emerged as an interesting therapeutic approach. In that context, we investigated the ability of uleine, the major indole alkaloid purified from the stem barks of the Brazilian medicinal plant Himatanthus lancifolius, to interact with crucial Alzheimer´s disease disruptive targets. To that end, we performed experiments of the activities of human acetylcholinesterase and butyrylcholinesterase enzymes, as well as β-secretase, along with the spontaneous aggregation of amyloid-β peptide. The results presented herein reveal the strong inhibitory activities for both cholinesterases (IC50 279.0±4.5 and 24.0±1.5 µM, respectively) and β-secretase (IC50 180±22 nM). Above all, uleine significantly inhibited the self-aggregation of amyloid-β peptide and was not toxic for PC12 or SH-SY5Y neuronal cells. These data show for the first time that the natural compound uleine has a novel, multieffective ability to decelerate or even inhibit the development of Alzheimer´s disease.