The Wound-Healing Potential of Olea europaea L. Cv. Arbequina Leaves Extract: An Integrated In Vitro, In Silico, and In Vivo Investigation

Tarfah Al-Warhi; Abeer H Elmaidomy; Sherif A Maher; Dalia H Abu-Baih; Samy Selim; Mha Albqmi; Mohammad M Al-Sanea; Taghreed S Alnusaire; Mohammed M Ghoneim; Ehab M Mostafa; Shaimaa Hussein; Ashraf K El-Damasy; Entesar Ali Saber; Mahmoud A Elrehany; Ahmed M Sayed; Eman M Othman; Mohamed El-Sherbiny; Usama Ramadan Abdelmohsen

doi:10.3390/metabo12090791

The Wound-Healing Potential of Olea europaea L. Cv. Arbequina Leaves Extract: An Integrated In Vitro, In Silico, and In Vivo Investigation

Metabolites. 2022 Aug 25;12(9):791. doi: 10.3390/metabo12090791.

Authors

Tarfah Al-Warhi¹, Abeer H Elmaidomy², Sherif A Maher³, Dalia H Abu-Baih³, Samy Selim⁴, Mha Albqmi⁵, Mohammad M Al-Sanea⁶, Taghreed S Alnusaire⁷, Mohammed M Ghoneim^{8

9}, Ehab M Mostafa^{8

10}, Shaimaa Hussein¹¹, Ashraf K El-Damasy^{12

13}, Entesar Ali Saber^{14

15}, Mahmoud A Elrehany³, Ahmed M Sayed¹⁶, Eman M Othman^{17

18}, Mohamed El-Sherbiny^{19

20}, Usama Ramadan Abdelmohsen^{21

22}

Affiliations

¹ Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
² Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
³ Department of Biochemistry, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72341, Saudi Arabia.
⁵ Chemistry Department, College of Science and Arts, Jouf University, Alqurayyat 77447, Saudi Arabia.
⁶ Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
⁷ Biology Department, College of Science, Jouf University, Sakaka 72341, Saudi Arabia.
⁸ Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
⁹ Department of Pharmacy Practice, College of Pharmacy, Al Maarefa University, Ad Diriyah 13713, Saudi Arabia.
¹⁰ Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
¹¹ Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
¹² Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
¹³ Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
¹⁴ Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61519, Egypt.
¹⁵ Department of Histology and Cell Biology, Deraya University, Universities Zone, New Minia 61111, Egypt.
¹⁶ Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt.
¹⁷ Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
¹⁸ Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Wuerzburg, Germany.
¹⁹ Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11597, Saudi Arabia.
²⁰ Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
²¹ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
²² Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt.

Abstract

Olea europaea L. Cv. Arbequina (OEA) (Oleaceae) is an olive variety species that has received little attention. Besides our previous work for the chemical profiling of OEA leaves using LC−HRESIMS, an additional 23 compounds are identified. An excision wound model is used to measure wound healing action. Wounds are provided with OEA (2% w/v) or MEBO® cream (marketed treatment). The wound closure rate related to vehicle-treated wounds is significantly increased by OEA. Comparing to vehicle wound tissues, significant levels of TGF-β in OEA and MEBO® (p < 0.05) are displayed by gene expression patterns, with the most significant levels in OEA-treated wounds. Proinflammatory TNF-α and IL-1β levels are substantially reduced in OEA-treated wounds. The capability of several lignan-related compounds to interact with MMP-1 is revealed by extensive in silico investigation of the major OEA compounds (i.e., inverse docking, molecular dynamics simulation, and ΔG calculation), and their role in the wound-healing process is also characterized. The potential of OEA as a potent MMP-1 inhibitor is shown in subsequent in vitro testing (IC50 = 88.0 ± 0.1 nM). In conclusion, OEA is introduced as an interesting therapeutic candidate that can effectively manage wound healing because of its anti-inflammatory and antioxidant properties.

Keywords: LC–HRESIMS; MMP-1; Olea; TGF-β; TNF-α; olive; virtual docking; wound.

Grants and funding

Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R25), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.