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ORIGINAL RESEARCH ARTICLE

Wound-healing potential of citrus lemon honey: Antioxidant, anti-inflammatory, antibacterial, and immunomodulatory effects on keratinocyte proliferation and migration

Soumaya Touzani1,2 ,  Mahmud Masalha3 ,  Abdalsalam Kmail4 ,  Shawqi Amour4 ,  Haneen Qalalweh4 ,  Donia Jarrar4 ,  Doha Weldali4 ,  Badiaa Lyoussi1* ,  Bashar Saad3,5*
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1 Laboratory of Natural Substances, Pharmacology, Environment, Modelling, Health, and Life Quality, Department of Biology, Faculty of Sciences Dhar El Mehraz, University Sidi Mohamed Ben Abdellah, Fez, Fès-Meknès, Morocco
2 Laboratory of Mini-Invasive Surgery, Robotics, Artificial Intelligence and Educational Innovations, Faculty of Medicine Pharmacy and Dentistry, University Sidi Mohamed Ben Abdellah, Fez, Fès-Meknès, Morocco
3 Qasemi Research Center, Faculty of Medicine, Arab American University, Jenin, Palestine
4 Department of Biology and Biotechnology, Faculty of Sciences, Arab American University, Jenin, Palestine
5 Department of Biochemistry, Faculty of Medicine, Arab American University, Jenin, Palestine
MI, 026060016 https://doi.org/10.36922/MI026060016
Received: 2 February 2026 | Revised: 21 April 2026 | Accepted: 6 May 2026 | Published online: 26 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Honey from citrus limon is of interest for wound healing due to its antimicrobial, antioxidant, and immunomodulatory properties . This in vitro study investigates whether citrus lemon honey (CLH) can modulate key cellular and biochemical processes involved in wound healing, in comparison with Manuka honey. Antioxidant, anti-inflammatory, and antibacterial activities were evaluated alongside keratinocyte (HaCaT) proliferation and migration assays. Physicochemical analysis showed high water-soluble protein content (480.9 ± 28.4 mg equivalent [Eq] bovine serum albumin/100 g), acidic pH (3.4 ± 0.02), low moisture (19.5%), and moderate electrical conductivity (41.6 ± 2.61 μS/cm). In addition, CLH exhibited notable phenolic (313.6 ± 0.6 mg Eq gallic acid/100 g) and flavonoid contents (6.9 ± 2.6 mg Eq quercetin/100 g), accompanied by strong antioxidant activity (total antioxidant capacity: 3.5 ± 0.05 g Eq ascorbic acid/100 g). CLH demonstrated antibacterial activity against both Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations of 0.8–3.1 w/w%), including clinically relevant wound-associated pathogens, highlighting its potential to reduce microbial burden and prevent infection in wound environments. Furthermore, CLH modulated nitric oxide production in lipopolysaccharide-activated THP-1 macrophages. Functionally, CLH promoted keratinocyte viability and migration in a concentration-dependent manner, with an approximately 20% increase in cell viability at 1–2 mg/mL and a 35% enhancement in migration, without cytotoxicity. These effects were comparable in trend, though less pronounced, to those observed with Manuka honey. Taken together, the combined antibacterial, anti-inflammatory, and pro-regenerative effects suggest that CLH may support wound healing by enhancing tissue repair and limiting infection. From a host–microbe interaction perspective, the antibacterial and immunomodulatory effects of CLH suggest a coordinated role in wound healing, where reduced microbial burden and controlled regulation of inflammation may act synergistically to support tissue repair and restore skin integrity. However, further in vivo and clinical studies are required to confirm its therapeutic relevance.

Keywords
Citrus lemon honey
Immunomodulatory
Antibacterial
Antioxidant activity
Wound healing
HaCaT cells
Funding
This study was financially supported by the Al-Qasemi Research Foundation and the Arab American University- Palestine (AAUP) Research Foundation.
Conflict of interest
Bashar Saad is the Editorial Board Member of this journal and the Guest Editor of this special issue but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
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