An In Vitro and In Silico Study of the Enhanced Antiproliferative and Pro-Oxidant Potential of Olea europaea L. cv. Arbosana Leaf Extract via Elastic Nanovesicles (Spanlastics)

Taghreed S Alnusaire; Ahmed M Sayed; Abeer H Elmaidomy; Mohammad M Al-Sanea; Sarah Albogami; Mha Albqmi; Bassam F Alowaiesh; Ehab M Mostafa; Arafa Musa; Khayrya A Youssif; Hesham Refaat; Eman M Othman; Thomas Dandekar; Eman Alaaeldin; Mohammed M Ghoneim; Usama Ramadan Abdelmohsen

doi:10.3390/antiox10121860

An In Vitro and In Silico Study of the Enhanced Antiproliferative and Pro-Oxidant Potential of Olea europaea L. cv. Arbosana Leaf Extract via Elastic Nanovesicles (Spanlastics)

Antioxidants (Basel). 2021 Nov 23;10(12):1860. doi: 10.3390/antiox10121860.

Authors

Taghreed S Alnusaire¹, Ahmed M Sayed², Abeer H Elmaidomy³, Mohammad M Al-Sanea⁴, Sarah Albogami⁵, Mha Albqmi⁶, Bassam F Alowaiesh¹, Ehab M Mostafa^{7

8}, Arafa Musa^{7

8}, Khayrya A Youssif⁹, Hesham Refaat¹⁰, Eman M Othman^{11

12}, Thomas Dandekar¹², Eman Alaaeldin^{10

13}, Mohammed M Ghoneim¹⁴, Usama Ramadan Abdelmohsen^{15

16}

Affiliations

¹ Biology Department, College of Science, Jouf University, Sakaka 72341, Saudi Arabia.
² Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt.
³ Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
⁴ Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
⁵ Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁶ Chemistry Department, College of Science and Arts, Jouf University, P.O. Box 756 Alqurayyat, Saudi Arabia.
⁷ Pharmacognosy Department, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt.
⁹ Department of Pharmacognosy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11865, Egypt.
¹⁰ Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.
¹¹ Department of Biochemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
¹² Department of Bioinformatics, Biocenter, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
¹³ Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
¹⁴ Department of Pharmacy Practice, College of Pharmacy, Al Maarefa University, Ad Diriyah 13713, Saudi Arabia.
¹⁵ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt.
¹⁶ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

Abstract

The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC₅₀ values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC₅₀ 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC₅₀ 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.

Keywords: Olea; antiproliferative; docking; encapsulation; metabolomic profiling; molecular dynamics simulation; nanocarrier; olive; pro-oxidant; spanlastic.