FULL ARTICLE In vivo wound healing potential and HPLC-PDA-ESI-MS profiling of Zizyphus lotus L. (Desf.) leaves methanol extract Halima Saiah 1 | Meriem Mokhtar 2 | Wassila Saiah 3 | Ahmed Aichouni 1 | Fatima Zohra EL Kebir 4 | Rachida Allem 1 1 Laboratory of Natural Bioresources, Faculty of Natural and Life Sciences, Hassiba Ben Bouali University, Chlef, Algeria 2 Laboratory of Beneficial Microorganisms, Functional Food and Health, Faculty of Life and Natural Sciences, University of Abdelhamid Ibn Badis, Mostaganem, Algeria 3 Laboratory of Bioenergetics and Intermediary Metabolism, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene, Algiers, Algeria 4 Department of Biology, Faculty of Life and Natural Sciences, University Oran 1 Ahmed Benbella, Oran, Algeria Correspondence Halima Saiah, Laboratory of Natural Bioresources, Faculty of Natural and Life Sciences, Hassiba Ben Bouali University, Chlef, Algeria. Email: h.saiah@univ-chlef.dz Abstract This study was performed to evaluate the wound healing potential and antioxidant effect of meth- anol extract of Zizyphus lotus leaves (MZL), and to identify its phenolic profile by HPLC-PDA-ESI- MS. Wound healing activity was assessed in vivo using excision model. Biochemical and histopath- ological analyses were conducted. In vitro antioxidant potential of MZL was tested using 2,2- diphenyl-1-picrylhydrazyl and b-carotene bleaching methods. HPLC-PDA-ESI-MS was used for the phenolic profiling. Animals treated with MZL ointment showed a significant reduction in epitheliali- zation time and high contraction rate compared to controls. Proteins, hydroxyproline, and hexosamines contents of ointment-treated animals were higher than controls. Marked cross- linking of collagen fibers and lack of inflammatory cells were observed in the granulation tissue of the ointment-treated animals. Chemical profiling of MZL revealed that quercetin-3-O-rutinoside and catechin are the major constituents. Phenolic compounds of the methanol extract of Zizyphus lotus leaves may be engaged in the acceleration of the healing process activity. Practical application In Mediterranean region, like Algeria, Zizyphus lotus is used in nutrition, health, and cosmetics. Sev- eral parts of this plant are employed to treat urinary troubles, diabetes, skin infections, fever, diarrhea, insomnia, bronchitis, and hypoglycemia. There is no scientific paper investigating the phe- nolic composition of Z. lotus leaves using a mass spectrometry coupled high-performance liquid chromatography, as well as examining their wound healing potential. Results from this study revealed the presence of many flavonoids exhibiting important antioxidant and wound healing potentials through specific mechanisms. Z. lotus leaves are a source of pharmacologically active compounds with benefits for human nutrition, health-promoting, and disease preventing. KEYWORDS antioxidant, HPLC-PDA-ESI-MS, phenolic compounds, wound healing, Zizyphus lotus 1 | INTRODUCTION Wound healing is an active process leading to tissue reconstruction of damaged skin and its fascia (Goel, Kumar, Singh, & Bhatia, 2010). It includes constant cell-cell and cell-matrix interactions that enable the procedure to continue in three stages involving irritation (0–3 days), cell proliferation (3–12 days), and remodeling (3–6 months) (Karodi, Jadhav, Rub, & Bafna, 2009). Angiogenesis, collagen deposition, and granulation tissue formation portray the proliferative phase, which is also characterized by epithelial cells proliferation, myofibroblasts contraction and growth factors release by platelets (Shenoy, Patil, & Kumar, 2009). Different tissues and cell lineages cooperate during the healing process giving rise to platelet aggregation and blood clotting, the formation of a fibrin clot, the inflammatory reaction to the lesion, alteration in the ground substances, neovascularization and reepithelial- ization. Once the damaged surface is intertwined with collagen, the healing process is complete (Karodi et al., 2009). The wound healing process relies on several parameters including nonviable tissue debridement, tissue perfusion and oxygenation, adequate nutrition and moist environment (Barua et al., 2009). The J Food Biochem. 2018;e12570. https://doi.org/10.1111/jfbc.12570 wileyonlinelibrary.com/journal/jfbc V C 2018 Wiley Periodicals, Inc. | 1 of 11 Received: 17 November 2017 | Revised: 2 March 2018 | Accepted: 2 March 2018 DOI: 10.1111/jfbc.12570