Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction
Andreea Roxana Ungureanu,
Violeta Popovici,
Camelia Oprean,
Corina Danciu,
Verginica Schröder,
Octavian Tudorel Olaru,
Dragoș Paul Mihai,
Liliana Popescu,
Emanuela-Alice Luță,
Carmen Lidia Chițescu,
Cerasela Elena Gîrd
Affiliations
Andreea Roxana Ungureanu
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Violeta Popovici
Department of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, Romania
Camelia Oprean
Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania
Corina Danciu
Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania
Verginica Schröder
Department of Cellular and Molecular Biology, Faculty of Pharmacy, Ovidius University of Constanta, 6 Capitan Al. Serbanescu Street, 900001 Constanta, Romania
Octavian Tudorel Olaru
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Dragoș Paul Mihai
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Liliana Popescu
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Emanuela-Alice Luță
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Carmen Lidia Chițescu
Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, A.I. Cuza 35, 800010 Galați, Romania
Cerasela Elena Gîrd
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Endothelial dysfunction is the basis of the physiopathological mechanisms of vascular diseases. In addition to the therapeutic activity of plant extracts, cytotoxicity is significant. This research evaluates the cytotoxicity of three vegetal extracts (Calendulae flos extract-CE, Ginkgo bilobae folium extract-GE, and Sophorae flos extract-SE). In vitro evaluation was performed using an endothelial cell line model (Human Pulmonary Artery Endothelial Cells—HPAEC) when a dose-dependent cytotoxic activity was observed after 72 h. The IC50 values were calculated for all extracts: Calendulae flos extract (IC50 = 91.36 μg/mL), Sophorae flos extract (IC50 = 68.61 μg/mL), and Ginkgo bilobae folium extract (IC50 = 13.08 μg/mL). Therefore, at the level of HPAEC cells, the cytotoxicity of the extracts follows the order GE > SE > CE. The apoptotic mechanism implied in cell death was predicted for several phytocompounds using the PASS algorithm and molecular docking simulations, highlighting potential interactions with caspases-3 and -8. In vivo analysis was performed through brine shrimp lethality assay (BSLA) when lethal, behavioral, and cytological effects were evaluated on Artemia salina larvae. The viability examined after 24 h (assessment of lethal effects) follows the same sequence: CE > SE > GE. In addition, the predicted cell permeability was observed mainly for GE constituents through in silico studies. However, the extracts can be considered nontoxic according to Clarckson’s criteria because no BSL% was registered at 1200 µg/mL. The obtained data reveal that all three extracts are safe for human use and suitable for incorporation in further pharmaceutical formulations.
