Chemical and biological properties and biomaterial applications of Egyptian propolis: A review

1. Introduction

Propolis is a combination of substances used by bees to protect their hive [1]. This protection involves filling cavities in the hive's walls, reducing the entrance during chilly days, and mummifying the desired intruders to prevent their decay. It is also called bee glue because it acts as a protective sealant in the hive [2]. Because it serves as a protective sealant in the hive, propolis is also known as bee glue [3]. Propolis, in Greek origin, refers to the area at the entrance to a city [4, 5]. Since ancient times, there have been ongoing discussions regarding the origin of the propolis; whether propolis originates from plants or bees remains uncertain. The approximate composition of propolis and the factors that influence it are now known as a result of the advancement of analytical techniques [2]. Propolis is formed through the incorporation of salivary enzymes secreted by bees into plant resins obtained from buds, exudates, and various plant tissues [6, 7]. The variety of plant species, continents, and regions that utilize propolis in their production gives it a distinct composition. Even though it contains different chemicals, propolis has many of the same health benefits as honey, such as being an antioxidant and fighting bacteria, viruses, parasites, inflammation, and promote cell growth [8, 9].

Chemists and biologists are currently focusing on Egyptian propolis as a valuable health-related product due to its numerous biological properties. Some of these properties are antimicrobial, antioxidant, anti-inflammatory, antiulcer, and antitumor [10]. The fact that there are a lot of beekeepers in Egypt is one reason for the increased interest. Propolis's high antioxidant content contributes to its numerous health and medicinal benefits. These antioxidants are effective at eliminating reactive oxygen species (ROS) and repairing the tissue damage they cause [11]. Egyptian propolis displays diverse colors and shapes. According to information collected from beekeepers in Egypt, it is typically characterized by a dark color, ranging from brown to black [12, 13].

Propolis is sourced from several governorates and regions in Egypt, including El Beheira, Menoufia, Ismailia, Kafr El Sheikh, Assiut, Sohag, Dakahlia, Banha, Beni Suef, Fayoum, and Gharbia (Figure 1). Egyptian propolis has enormous potential as a bioactive component that enhances the properties of various medical materials. Incorporating it into wound dressings and other medical tools improves their efficacy in killing microbes and aids the body in healing and regenerating new tissue [14, 15]. This review will comprehensively examine the chemical and biological properties of Egyptian propolis, highlighting its potential applications as a biomaterial. The study seeks to augment comprehension of the various bioactive compounds found in Egyptian propolis and their significance for medical and industrial applications through the synthesis of previous research findings.

2. Chemical properties

Samples Research on propolis chemical analysis indicates that the composition of propolis can change depending on where it is collected and the time of year [16, 17]. The composition of propolis is intricate, and additional compounds are periodically discovered [18]. To ensure the quality, safety, and efficacy of propolis in Egypt, it is necessary to establish chemical standardization [19]. The chemical composition of propolis is extraordinarily complex and has not yet been fully elucidated. It typically contains resins, waxes, and minor mechanical impurities. Flavones, flavonols, and flavanones represent the major constituents of propolis. In addition, propolis includes terpenes, isovanillin, aromatic unsaturated acids, caffeic acid, and ferulic acid, whose distinct biological activities allow differentiation among these compounds [19–22]. Raw propolis is not suitable for direct use in analysis or treatment. The substance must first be extracted to dissolve and release its most active components. We employ ethanol, methanol, water, hexane, acetone, dichloromethane, and chloroform as extractants, with a concentration of around 70% [23, 24].

The color of propolis typically ranges from creamy to deep brown; the composition of propolis is contingent upon the bees’ environment and is initially determined by the plants in the vicinity [18, 25]. Various plants secrete substances that influence the compounds found in propolis. Aside from the resin, some of these substances are lipophilic materials that are present in the leaves, gums, and lattices [18]. Esters of phenolic acid, beeswax, flavonoid aglycones, triterpenes, and lipids and wax are all present in propolis. It also contains minerals and micronutrients, including zinc, manganese, copper, and pollen [26]. The majority of propolis originates from the buds of black poplar trees in certain regions. Propolis contains many phenolic acids, flavonoids (flavones and flavonones), and esters [18]. Typically, researchers use the capillary zone electrophoresis (CZE) technique to measure the compounds present in propolis (Figure 2) [27, 28].

3. Biodiversity in propolis composition

There are hundreds of different compounds found in propolis, and their bioactivity and chemical makeup depend on two main things: where they come from botanically and where they were collected (Table 1) [29]. Propolis is mostly identified by the name of the plant from which it came. This name acts as proof that the propolis came from a certain place by recognizing the anatomical features of plant tissues [30]. The propolis type and source are typically determined by comparing the chemical properties of propolis to plant materials and tracing bee collection sites. Furthermore, changes in honeybee species, harvesting season, collection techniques, and post-harvest processing have a significant impact on the overall composition and nutritional value of raw propolis [31, 32]. Propolis is typically classified into various groups, including Poplar, Birch, Green, Red, Pacific, Mediterranean, and others, depending on the botanical sources and the presence of primary constituents [20]. Egypt collects propolis, which has a black color, and many of the trees that produce propolis in Egypt are mango, eucalyptus, acacia, cypress, ficus sycomorus, casuarina, ziziphus, and citrus.

Table 1. Biodiversity Propolis components in some Egyptian places and Arab countries.

HPLC: High-performance liquid chromatography; GC/MS: Gas chromatography/Mass Spectrometry.

4. Biological properties

Human health significantly benefits from the use of propolis, which serves a variety of purposes, as antibacterial, antifungal, anti-inflammatory, antiviral, anesthetic, antioxidant, antitumoral, anticancer, and anti-hepatotoxic properties, among other uses, many studies have also shown that Egyptian propolis is characterized by many of these biological properties (Figure 3) [13, 36, 45, 46].

4.1. Antimicrobial activity

It was found that Egyptian propolis was excellent at killing both Gram-positive and Gram-negative bacteria, even strains that are resistant to many drugs (Table 2). Phytochemicals and other chemicals, like pinocembrin, galangin, and pinobanksin, interact with each other to make propolis work [4, 47]. In the same way, the antibacterial activity is a result of the active compounds, which include flavonoids and aromatic compounds (caffeic acid). Propolis affects bacteria by stopping their cells from dividing, damaging their cell wall and cytoplasm (Figure 4) [48], and stopping them from making proteins [27, 49, 50].

Among the 26 or more constituents of propolis, it was reported that p-coumaric acid, pinobanksin-3-acetate, pinocembrin, 3-acetylpinobanksin and caffeic acid exhibit anti-fungal activity (Table 2) [31]. In vitro inhibitory activity against certain fungi and yeasts was observed by certain authors in the range of 4 to 40 mg of total flavones (extracted from propolis). A concentration of 15-30 mg/ml of pure propolis extract was also discovered to inhibit the growth of Aspergillus flavus, Penicillium virdicatum, Aspergillus ochraceus, Candida albicans, and Penicillium natatum. It was also discovered that a concentration of 15-30 mg/ml of pure propolis extract was required to impede the growth of Candida albicans, Aspergillus flavus, A. Ochraceus, Penicillium viridicatum, and P. notatum. 17 fungal pathogens were treated with 10% propolis extracts. They discovered that propolis extract inhibited Candida and all the tested dermatophytes. discovered that the growth of fungus was inhibited by a propolis concentration of 5% or 10%, while the lower concentration did not completely suppress growth. Also discovered that the minimal inhibitory concentration of Egyptian propolis was between 10 and 30 mg/ml [50, 51].

Table 2. The inhibitory effect of propolis extract on some bacteria and fungi.

*ALg NPs: Alginate nanoparticles. Cellulose nanofiber (CNF)/poly(vinyl alcohol) (PVA).

 (++++) indicates the highest growth inhibition, (+) the lowest growth inhibition.

4.2. Anti-inflammatory action

Propolis' anti-inflammatory properties are attributable to the presence of flavonoids [49, 54–56]. It is responsible for the regulation of NADPH-oxidase, ornithine decarboxylase, myeloperoxidase activity, hyaluronidase from guinea pig mast cells, and tyrosine-protein kinase [27]. The mode of action of these compounds is to restrict the production of leukotrienes and prostaglandins by white blood cells [49] and to slow down the activity of myeloperoxidase, ornithine decarboxylase, tyrosine-protein-kinase, and NADPH-oxidase [57]. In rat models, caffeic acid phenethyl ester and galangin, both constituents of poplar propolis, demonstrated anti-inflammatory activity and inhibited carrageenan-induced pleurisy, carrageenan-induced edema, and adjuvant-induced arthritis [4]. Propolis regulates the inflammatory substances that are produced within the cell as a result of pressure, poisonous material, or pathogenicity [58]. An established assay for evaluating the anti-inflammatory properties of implanted biomaterials is the stabilization of erythrocyte membranes. The release of various enzymes from decomposed lysosomal vesicles is the cause of inflammation. Therefore, it was demonstrated that Egyptian propolis stabilizes the erythrocytic membrane, thereby preventing the leakage of these enzymes and the occurrence of inflammation [45].

4.3. Antitumor action

The antitumor properties of propolis' components have been investigated [59–62]. Additionally, components such as caffeic acid phenethyl ester [47] and artepillin C were found to have antitumor effects [63]. These propolis compounds are involved in the cell cycle arrest, matrix metalloproteinase inhibition, anti-angiogenesis effect, and the prevention of disease transmission from one body part to another [64]. Propolis has the capacity to halt DNA synthesis in tumor cells, induce apoptosis in tumor cells, and activate white blood cells to produce agents that regulate the function of B, T, and natural killer cells [4, 65]. To prevent the rapid division of tumor cells, additional compounds, including galangin, cardanol, nemorosone, and chrysin, are involved [64]. The cytotoxic activity of natural killer cells against murine lymphoma was enhanced by the use of propolis for a period of three days [66, 67]. The apoptosis of C6 glioma cells is induced by the presence of tumor suppressor proteins in Caffeic acid phenethyl ester [64, 68, 69]. Caffeic acid and esters, as well as diterpenoids and phenolic compounds, possessed the ability to destroy tumor cells. The combined function of propolis' polyphenolic constituents is responsible for its antitumor effect [67]. Propolis fulfils the synthesis of glutathione in hematopoietic tissues, which is a consequence of the decrease in glutathione production in tumor cells due to radiation [70].

Studies also showed the effect of propolis against liver, breast, and colorectal cancer. The impact was diverse. The inhibitory concentration of Egyptian propolis was 7.87% on liver cancer, 27.73% on breast cancer, and 73.92% on colorectal cancer [13, 71]. Another study on Egyptian propolis from Kafr El-Sheikh Governorate found that it contains a high concentration of natural bioactive and polyphenolic compounds that have been shown to have a strong effect on cancer cells, including breast cancer and non-small lung cancer cell lines. The results were as follows. After 48 and 72 hours of incubation, propolis extract and Bovine Serum-propolis NPs significantly reduced breast cancer growth by (54 ± 0.01% and 45 ± 0.005%, P ≤ 0.001) and (20 ± 0.01% and 10 ± 0.005%, P ≤ 0.0001), respectively. Propolis extract and albumin-propolis NPs significantly inhibit non-small lung cancer growth after 72 hours of incubation (15 ± 0.03% and 5 ± 0.01%, P ≤ 0.00001, respectively) [72].

4.4. Antioxidant activity

Galangin and pinocembrin, two components of propolis, were observed to possess antioxidant properties [49, 54, 73]. The aqueous extract of propolis was more effective than the ethanolic extract due to its higher polyphenol content. Galangin exhibited greater activity in both extracts than pinocembrin, which is attributable to the structural differences between the two [4]. Vitamin C, lipids, and other compounds were also protected from destruction or oxidation by the antioxidants, which were able to reject free radical particles. The primary cause of cell ageing and deterioration in conditions such as Parkinson's disease, Alzheimer's disease, arthritis, cancer, diabetes, cardiovascular diseases, and insufficient liver function is free radicals and other factors [74]. Vanillin and phenolic acids, among other components of propolis, were able to penetrate the epidermis and dermis, shielding them from free radicals that are generated as a result of radiation or prior to the maturation of dermal cells [58].

Phenolic compounds are responsible for the antioxidant activity of propolis through their ability to donate hydrogen ions to free radicals. This mechanism protects cells against oxidative reactions and contributes to the prevention of oxidative deterioration and contamination during food storage. Propolis has been shown to effectively scavenge free radicals, which are major contributors to the oxidation of lipids, nucleic acids, and proteins [70]. It is known that propolis is characterized by the presence of phenolic compounds, and some of these compounds distinguish Egyptian propolis by being a powerful antioxidant (Figure 5) [50].