Isolation of Secondary Metabolites from Achillea grandifolia Friv. (Asteraceae) and Main Compounds' Effects on a Glioblastoma Cellular Model

Olga S Tsiftsoglou; Nikos Krigas; Christos Gounaris; Christina Papitsa; Maria Nanouli; Evrysthenis Vartholomatos; Georgios S Markopoulos; Rafaela Isyhou; George Alexiou; Diamanto Lazari

doi:10.3390/pharmaceutics15051383

Isolation of Secondary Metabolites from Achillea grandifolia Friv. (Asteraceae) and Main Compounds' Effects on a Glioblastoma Cellular Model

Pharmaceutics. 2023 Apr 30;15(5):1383. doi: 10.3390/pharmaceutics15051383.

Authors

Affiliations

¹ Laboratory of Pharmacognosy, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
² Institute of Plant Breeding and Genetic Resources, Hellenic Agricultural Organization-Demeter, 57001 Thermi, Greece.
³ Neurosurgical Institute, University of Ioannina School of Medicine, 45110 Ioannina, Greece.
⁴ Haematology Laboratory-Unit of Molecular Biology and Translational Flow Cytometry, University Hospital of Ioannina, 45500 Ioannina, Greece.
⁵ Department of Neurosurgery, University Hospital of Ioannina, 45500 Ioannina, Greece.

Abstract

This study aims at the isolation and structural determination of the secondary metabolites of the herbaceous perennial plant Achillea grandifolia Friv. (Asteraceae). The examination of the non-volatile content of the leaves and flowers of A. grandifolia afforded the isolation of sixteen secondary metabolites. On the basis of NMR spectra, the identified compounds included ten sesquiterpene lactones; three guaianolides-rupicolin A (1), rupicolin B (2), and (4S,6aS,9R,9aS,9bS)-4,6a,9-trihydroxy-9-methyl-3,6-dimethylene-3a,4,5,6,6a,9,9a,9b-octahydro-3H-azuleno [4,5-b]furan-2-one (3); two eudesmanolides-artecalin (4) and ridentin B (5); two sesquiterpene methyl esters-(1S,2S,4αR,5R,8R,8αS)-decahydro-1,5,8-trihydroxy-4α,8-dimethyl-methylene-2-naphthaleneacetic acid methylester (6) and 1β, 3β, 6α-trihydroxycostic acid methyl ester (7); three secoguaianolides-acrifolide (8), arteludovicinolide A (9), and lingustolide A (10); and an iridoid-loliolide (11). Moreover, five known flavonoids, i.e., apigenin, luteolin, eupatolitin, apigenin 7-O-glucoside, and luteolin 7-O-glucoside (12-16) were also purified from the aerial parts of the plant material. We also investigated the effect of rupicolin A (1) and B (2) (main compounds) on U87MG and T98G glioblastoma cell lines. An MTT assay was performed to define cytotoxic effects and to calculate the IC50, while flow cytometry was employed to analyze the cell cycle. The IC50 values of reduced viability during the 48 h treatment for compound (1) and (2) were 38 μM and 64 μM for the U87MG cells and 15 μM and 26 μM for the T98G cells, respectively. Both rupicolin A and B induced a G2/M cell cycle arrest.

Keywords: cell lines; flavonoids; glioblastoma; rupicolin A; rupicolin B; sesquiterpene lactones.

Grants and funding

We acknowledge support of this work by the project “Upgrading the Plant Capital (PlantUp)” (MIS 5002803), which was implemented under the action “Reinforcement of the Research and Innovation Infrastructure”, which was funded by the operational program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union (European Regional Development Fund).