Antioxidants 2023, 12, 34. https://doi.org/10.3390/antiox12010034 www.mdpi.com/journal/antioxidants Review Synergic Effect of Honey with Other Natural Agents in Developing Efficient Wound Dressings Angela Spoială 1,2, *, Cornelia-Ioana Ilie 1,2 , Denisa Ficai 2,3 , Anton Ficai 1,2,4 and Ecaterina Andronescu 1,2,4 1 Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Chemical Engineering and Biotechnologies, University Politehnica of Bucharest, 1-7 Gh. Polizu Street, 011061 Bucharest, Romania 2 National Centre for Micro and Nanomaterials & National Centre for Food Safety, Faculty of Chemical Engineering and Biotechnologies, University Politehnica of Bucharest, 313 Splaiul Independentei, 060042 Bucharest, Romania 3 Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, Faculty of Chemical Engineering and Biotechnologies, University Politehnica of Bucharest, 1-7 Gh. Polizu Street, 011061 Bucharest, Romania 4 Academy of Romanian Scientists, 3 Ilfov Street, 050045 Bucharest, Romania * Correspondence: angela.spoiala@upb.ro Abstract: Honey has been used for therapeutic and nutritional purposes since ancient times. It was considered one of the essential medical assets in wound healing. According to research, honeybees have significant antibacterial, antioxidant, anti-inflammatory, antitumor, and wound-healing prop- erties. Lately, scientific researchers have focused on apitherapy, using bee products to protect and strengthen the immune system. Since honey is the most important natural product rich in minerals, proteins, and vitamins, it has been intensively used in such therapies. Honey has gained significant consideration because of the beneficial role of its antioxidant compounds, such as enzymes, pro- teins, amino and organic acids, polyphenols, and carotenoids, but mainly due to flavonoids and phenolic acids. It has been proven that phenolic compounds are responsible for honey’s biological activity and that its physicochemical properties, antioxidants, and antimicrobial potential are sig- nificant for human health. The review also presents some mechanisms of action and the medical applications of honey, such as wound healing dressings, skin grafts, honey-based nanofibers, and cochlear implants, as the most promising wound healing tools. This extensive review has been writ- ten to highlight honey’s applications in medicine; its composition with the most important bioactive compounds also illustrates its synergistic effect with other natural products having remarkable ther- apeutic properties in wound healing. Keywords: honey; bioactive compounds; biological activity; mechanisms of action; synergic effect; wound healing 1. Background The word “honey” comes from the Latin word “melem” and Greek “μελιττα”, which means “bee,” and is a product obtained through processing and manufacturing the nectar produced by bees and stored in honeycomb cells to feed the beehive population. Since ancient times, honey procurement has been the primary purpose of apiculture, and its origin appears untraceable. A Mesolithic rock was found in a cave in Valencia, Spain, da- ting back at least 8000 years, with illustrations of two honey hunters collecting honey and a honeycomb from a wild bee’s nest. The pictures describe the hunters carrying baskets and using a ladder or series of ropes to reach the nest [1]. In Georgia, archaeologists discovered honey remains inside an ancient tomb dating back between 4700 and 5500 years [2,3]. In Georgia, there is a custom that the buried per- son has a jar of honey nearby to take with them on their journey to the afterlife [4]. Citation: Spoială, A.; Ilie, C.-I.; Ficai, D.; Ficai, A.; Andronescu, E. Synergic Effect of Honey with Other Natural Agents in Developing Efficient Wound Dressings. Antioxidants 2023, 12, 34. https://doi.org/10.3390/ antiox12010034 Academic Editor: Stanley Omaye Received: 9 November 2022 Revised: 18 December 2022 Accepted: 21 December 2022 Published: 24 December 2022 Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/license s/by/4.0/).