Acetylcholinesterase Inhibitory Activity of Uleine from Himatanthus lancifolius

Abstract

Application of acetylcholinesterase (AChE) inhibitors is the primary treatment for Alzheimer’s disease. Alkaloids, such as physostigmine, galanthamine, and huperzine A, play an important role as AChE inhibitors. The aim of this work was to evaluate Himatanthus lancifolius (Muell. Arg.) Woodson, a Brazilian species of Apocynaceae, and its main indole alkaloid uleine, in order to identify new AChE inhibitors. The plant fluid extract, fractions, and uleine were tested for AChE inhibitory activity using Ellman’s colorimetric method for thin-layer chromatography (TLC), 96-well microplates, and also Marston’s TLC colorimetric method. Both TLC assays showed similar results. At 5 mg/mL, the fluid extract inhibited the AChE enzyme by (50.71 ± 8.2)%. The ethyl acetate fraction exhibited the highest level of AChE inhibition, followed by the dichloromethane fraction. The isolated alkaloid uleine displayed an IC50 value of 0.45 μM.

New Acetylcholinesterase Inhibitors for Alzheimer's Disease

“…Seidl et al [20] conducted a study to determine if there were any AChE inhibiting properties from the Himatanthus lancifolius extract and uliene in vitro . The dichloromethane (DCM), and ethyl acetate (EtOAc), fractions showed significant AChE inhibitory effects.…”

Plant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer's disease

“…Rich fractions of lipophilic alkaloids were able to act as AChE-I and uleine ( Figure 1) was isolated from them. 22,26 This alkaloid was firstly isolated from the root bark of Aspidosperma ulei Mgf and was studied from a chemical and synthetic point of view. [27][28][29][30] Furthermore, this alkaloid and its related derivatives were also studied for their anticancer properties, 30 and, more recently, alkaloids-enriched fractions were also studied for their in vitro anti-inflammatory properties.…”

“…26 For this reason, uleine is considered as a new possible candidate for the future development of new anti-AD drugs, but no reports about safety, efficacy, and human studies specific to cognition have been reported to date. 22,26 …”

Aspidosperma species as sources of anti-malarials: uleine is the major anti-malarial indole alkaloid from Aspidosperma parvifolium (Apocynaceae)

“…Uleine stimulated a maximum nitric oxide production in the concentrations of 0.1 µg/mL (20.9 ± 1.4 µM) and 1 µg/mL (41.1 ± 0.2 µM) [16] and exhibited high level of acetylcholinesterase inhibition [17]. Uleine was evaluated for cytotoxicity against 65 cancer cell lines panel and it was inactive in all of them [18].…”