Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction
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 (<i>Calendulae flos</i> extract-CE, &...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/8/2125 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Andreea Roxana Ungureanu |
| collection | DOAJ |
| description | 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 (<i>Calendulae flos</i> extract-CE, <i>Ginkgo bilobae folium</i> extract-GE, and <i>Sophorae flos</i> 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 IC<sub>50</sub> values were calculated for all extracts: <i>Calendulae flos</i> extract (IC<sub>50</sub> = 91.36 μg/mL), <i>Sophorae flos</i> extract (IC<sub>50</sub> = 68.61 μg/mL), and <i>Ginkgo bilobae folium</i> extract (IC<sub>50</sub> = 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 <i>Artemia salina</i> 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. |
| first_indexed | 2024-03-10T23:39:52Z |
| format | Article |
| id | doaj.art-ba1eb2f316df403b9a6afd09e7420177 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:52Z |
| publishDate | 2023-08-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-ba1eb2f316df403b9a6afd09e74201772023-11-19T02:37:12ZengMDPI AGPharmaceutics1999-49232023-08-01158212510.3390/pharmaceutics15082125Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial DysfunctionAndreea Roxana Ungureanu0Violeta Popovici1Camelia Oprean2Corina Danciu3Verginica Schröder4Octavian Tudorel Olaru5Dragoș Paul Mihai6Liliana Popescu7Emanuela-Alice Luță8Carmen Lidia Chițescu9Cerasela Elena Gîrd10Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaDepartment of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, RomaniaFaculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, RomaniaFaculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, RomaniaDepartment of Cellular and Molecular Biology, Faculty of Pharmacy, Ovidius University of Constanta, 6 Capitan Al. Serbanescu Street, 900001 Constanta, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaFaculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, A.I. Cuza 35, 800010 Galați, RomaniaFaculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaEndothelial 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 (<i>Calendulae flos</i> extract-CE, <i>Ginkgo bilobae folium</i> extract-GE, and <i>Sophorae flos</i> 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 IC<sub>50</sub> values were calculated for all extracts: <i>Calendulae flos</i> extract (IC<sub>50</sub> = 91.36 μg/mL), <i>Sophorae flos</i> extract (IC<sub>50</sub> = 68.61 μg/mL), and <i>Ginkgo bilobae folium</i> extract (IC<sub>50</sub> = 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 <i>Artemia salina</i> 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.https://www.mdpi.com/1999-4923/15/8/2125cytotoxicityendothelial cellsbrine shrimp lethality assay<i>Calendulae flos</i> extract<i>Ginkgo bilobae folium</i> extract<i>Sophorae flos</i> extract |
| spellingShingle | 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 Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction Pharmaceutics cytotoxicity endothelial cells brine shrimp lethality assay <i>Calendulae flos</i> extract <i>Ginkgo bilobae folium</i> extract <i>Sophorae flos</i> extract |
| title | Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction |
| title_full | Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction |
| title_fullStr | Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction |
| title_full_unstemmed | Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction |
| title_short | Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction |
| title_sort | cytotoxicity analysis and in silico studies of three plant extracts with potential application in treatment of endothelial dysfunction |
| topic | cytotoxicity endothelial cells brine shrimp lethality assay <i>Calendulae flos</i> extract <i>Ginkgo bilobae folium</i> extract <i>Sophorae flos</i> extract |
| url | https://www.mdpi.com/1999-4923/15/8/2125 |
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