Chemical Survey of Three Species of the Genus Rauhia Traub (Amaryllidaceae)

Abstract

Plant biodiversity is an important source of compounds with medicinal properties. The alkaloid galanthamine, first isolated from Galanthus woronowii (Amaryllidaceae), is approved by the FDA for the palliative treatment of mild to moderate Alzheimer’s disease due to its acetylcholinesterase (AChE) inhibitory activity. Obtaining this active pharmaceutical ingredient, still sourced on an industrial scale from the Amaryllidaceae species, is a challenge for pharmaceutical companies due to its low natural yield and the high cost of its synthesis. The aim of this work was to determine the alkaloid profile of three different Rauhia (Amaryllidaceae) species collected in Peru, and to assess the potential application of their extracts for the treatment of Alzheimer’s disease. The alkaloids were identified by gas chromatography coupled to mass spectrometry (GC-MS), and the AChE inhibitory activity of the extracts was analyzed. Thirty compounds were quantified from the Rauhia species, the R. multiflora extract being the most interesting due to its high diversity of galanthamine-type structures. The R. multiflora extract was also the most active against AChE, with the half maximal inhibitory concentration (IC50) values of 0.17 ± 0.02 μg·mL−1 in comparison with the IC50 values of 0.53 ± 0.12 μg·mL−1 for galanthamine, used as a reference. Computational experiments were carried out on the activity of the galanthamine-type alkaloids identified in R. multiflora toward five different human AChE structures. The simulation of the molecules 3-O-acetylgalanthamine, 3-O-acetylsanguinine, narwedine, and lycoraminone on the 4EY6 crystal structure theoretically showed a higher inhibition of hAChE and different interactions with the active site compared to galanthamine. In conclusion, the results of this first alkaloid profiling of the Rauhia species indicate that R. multiflora is an important natural source of galanthamine-type structures and could be used as a model for the development of biotechnological tools necessary to advance the sustainable production of galanthamine.

The Anti-Cholinesterase Potential of Fifteen Different Species of Narcissus L. (Amaryllidaceae) Collected in Spain

“…Furthermore, the majority of the reported alkaloids of N. jonquilla have been studied in terms of molecular modelling in front of AChE and BuChE, and data reported in the literature support the fact that they could be responsible for the especially high activity of this species inhibiting BuChE and AChE. Galanthamine has been reported to have good docking scores for BuCHE and ACHE [46][47][48][49][50]. Lycoramine has been reported to have molecular docking values of −8.84, −9.08, −8.87, −8.64, and −8.41 kcal•mol −1 for the human acetylcholinesterase X-ray crystals 4EY5, 4EY6, 4Ey7, 4M0E, and 4M0F, respectively, while values for galanthamine were −8.59, −8.75, −9.83, −7.90, and −8.74 kcal•mol −1 , according to Tallini et al, 2022 [50].…”

“…Lycoramine has been reported to have molecular docking values of −8.84, −9.08, −8.87, −8.64, and −8.41 kcal•mol −1 for the human acetylcholinesterase X-ray crystals 4EY5, 4EY6, 4Ey7, 4M0E, and 4M0F, respectively, while values for galanthamine were −8.59, −8.75, −9.83, −7.90, and −8.74 kcal•mol −1 , according to Tallini et al, 2022 [50]. Narwedine has been reported to have better scores (−9.15, −9.70, −10.41, −8.69, and −9.72 kcal•mol −1 ) than lycoramine and galanthamine [50].…”

Alkaloid Profile in Wild Autumn-Flowering Daffodils and Their Acetylcholinesterase Inhibitory Activity

“…Different Amaryllidaceae genera have also shown some anti-cholinesterase potential. For instance, Rauhia multiflora presented high activity against AChE, with IC 50 values of 0.17 ± 0.02 μg/mL [ 19 ]. Additionally, new Amaryllidaceae alkaloids from Crinum jagus have recently been reported [ 20 ].…”