title: The use of chemometrics to study multifunctional indole alkaloids from Psychotria nemorosa (Palicourea comb. nov.). Part II: Indication of peaks related to the inhibition of butyrylcholinesterase and monoamine oxidase-A.
abstract: Psychotria nemorosa is chemically characterized by indole alkaloids and displays significant inhibitory activity on butyrylcholinesterase (BChE) and monoamine oxidase-A (MAO-A), both enzymes related to neurodegenerative disorders. In the present study, 43 samples of P. nemorosa leaves were extracted and fractionated in accordance to previously optimized methods (see Part I). These fractions were analyzed by means of UPLC-DAD and assayed for their BChE and MAO-A inhibitory potencies. The chromatographic fingerprint data was first aligned using correlation optimized warping and Principal Component Analysis to explore the data structure was performed. Multivariate calibration techniques, namely Partial Least Squares (PLS1), PLS2 and Orthogonal Projections to Latent Structure (O-PLS1), were evaluated for modelling the activities as a function of the fingerprints. Since the best results were obtained with O-PLS1 model (RMSECV=9.3 and 3.3 for BChE and MAO-A, respectively), the regression coefficients of the model were analyzed and plotted relative to the original fingerprints. Four peaks were indicated as multifunctional compounds, with the capacity to impair both BChE and MAO-A activities. In order to confirm these results, a semi-prep HPLC technique was used and a fraction containing the four peaks was purified and evaluated in vitro. It was observed that the fraction exhibited an IC50 of 2.12μgmL(-1) for BChE and 1.07μgmL(-1) for MAO-A. These results reinforce the prediction obtained by O-PLS1 modelling.
authors: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium; Laboratory of Pharmacognosy and Quality Control of Phytomedicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul - UFRGS, Av. Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil.
authors: Luiz C
authors: LC
authors: Klein-Júnior
authors: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors: Johan
authors: J
authors: Viaene
authors: Natural Products & Food Research and Analysis, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors: Emmy
authors: E
authors: Tuenter
authors: Laboratory of Pharmacognosy and Quality Control of Phytomedicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul - UFRGS, Av. Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil.
authors: Juliana
authors: J
authors: Salton
authors: Herbarium Dr. Roberto Miguel Klein, Department of Natural Sciences, Universidade Regional de Blumenau - FURB, R. Antonio da Veiga 140, 89012-900, Blumenau, SC, Brazil.
authors: André L
authors: AL
authors: Gasper
authors: Natural Products & Food Research and Analysis, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors: Sandra
authors: S
authors: Apers
authors: Research Group Analysis Techniques in the Life Sciences, Avans Hogeschool, University of Professional Education, P.O. Box 90116, 4800 RA Breda, The Netherlands.
authors: Jan P M
authors: JP
authors: Andries
authors: Natural Products & Food Research and Analysis, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors: Luc
authors: L
authors: Pieters
authors: Laboratory of Pharmacognosy and Quality Control of Phytomedicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul - UFRGS, Av. Ipiranga 2752, 90610-000, Porto Alegre, RS, Brazil.
authors: Amélia T
authors: AT
authors: Henriques
authors: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel - VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: yvanvdh@vub.ac.be.
authors: Yvan
authors: Y
authors: Vander Heyden
mesh_terms: D002091:Butyrylcholinesterase / Q000378:metabolism*; D002138:Calibration; D005591:Chemical Fractionation / Q000379:methods*; D002800:Cholinesterase Inhibitors / Q000032:analysis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D026121:Indole Alkaloids / Q000302:isolation & purification* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D016018:Least-Squares Analysis; D016014:Linear Models; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000032:analysis* / Q000494:pharmacology; D025341:Principal Component Analysis; D032069:Psychotria / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D026121:Indole Alkaloids; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D002091:Butyrylcholinesterase
keywords: Chromatographic fingerprinting; Indole alkaloid; Multifunctional compounds; Multivariate calibration technique; Neurodegenerative disorders