Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596429
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Multifunctional activity of some isoquinoline alkaloids from Corydalis cava tubers on Alzheimer's disease targets

Authors

  • J Chlebek

    1   ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

  • A De Simone

    2   Department for Life Quality Studies, Alma Mater Studiorum – University of Bologna, Corso d'Augusto 237, 479 21 Rimini, Italy

  • DI Pérez

    3   Centro de Investigaciones Biológicas (CIB-CSIC), Avenida Ramiro de Maetzu 9, 280 40, Madrid, Spain

  • C Pérez

    4   Medicinal Chemistry Institute-CSIC, Juan de la Cierva 3, 280 06 Madrid, Spain

  • L Havlíková

    5   Department of Analytical Chemistry, Charles University, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

  • A Hošťálková

    1   ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

  • L Opletal

    1   ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

  • L Cahlíková

    1   ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

  • V Andrisano

    2   Department for Life Quality Studies, Alma Mater Studiorum – University of Bologna, Corso d'Augusto 237, 479 21 Rimini, Italy
Further Information

Publication History

Publication Date:
14 December 2016 (online)

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Fifteen previously isolated Corydalis cava alkaloids have been investigated for their potential multifunctional activity on Alzheimer's disease (AD) targets. Determination of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibition was carried out using a BACE1-Immobilized Enzyme Reactor (IMER) by validating the assay with a multi-well plate format Fluorescence Resonance Energy Transfer (FRET) assay. Seven alkaloids out of fifteen were found to be active, (-)-corycavamine (IC50 FRET= 41.16 ± 7.82µM; IC50 IMER= 1690 ± 545.0µM) and (+)-corynoline (IC50 FRET = 33.59 ± 0.23µM; IC50 IMER = 89.07 ± 15.08µM) demonstrated the highest BACE1 inhibition activity, in the micromolar range, in a concentration dependent manner. BACE1-IMER was found to be a valid device for the fast screening of inhibitors and the determination of their potency. In a permeation assay (PAMPA) for the prediction of blood-brain barrier (BBB) penetration, the most active compounds (-)-corycavamine (Pe = 16.3 ± 0.9 × 10-6 cm s-1) and (+)-corynoline (Pe = 11.7 ± 0.1 × 10-6 cm s-1) were found to be able to cross the BBB. Not all compounds showed activity against glycogen synthase kinase-3β (GSK-3β) and casein kinase-1δ (CK-1δ). Furthermore, on the basis of the reported results, we found that some Corydalis cava alkaloids have multifunctional activity against AD targets (prolyl oligopeptidase, cholinesterases, and BACE1). Moreover, we tried to elucidate the treatment effectivity (rational use) of its extract in memory dysfunction in folk medicine. Based on a HPLC-UV analysis we found that due to quantitative low content of compounds with neuroprotective activity in the plant material, the use of C. cava extracts in the therapy of memory dysfunction in folk medicine is not corroborated by ascertained data [1].

Acknowledgements: this project was supported by grant SVV UK 260 063, Charles University grant No. 17/2012/UNCE. The publication was also co-financed by the European Social Fund and by the state budget of the Czech Republic, project No. CZ.1.07/2.3.00/20.0235, the title of the project: TEAB and UniRimini.

Keywords: BACE1, immobilized enzyme reactor, Corydalis cava alkaloids, PAMPA assay.

References:

[1] Chlebek J, De Simone A, Hošťálková A, Opletal L, Pérez C, Pérez DI, Havlíková L, Cahlíková L, Andrisano V. Application of BACE1 immobilized enzyme reactor for the characterization of multifunctional alkaloids from Corydalis cava (Fumariaceae) as Alzheimer's disease targets. Fitoterapia 2016; 109: 241 – 247


No conflict of interest has been declared by the author(s).