A Miracle Food Supplement Obtained from Beehives: Propolis

Abstract

In recent years, propolis has garnered substantial global attention as a dietary supplement, owing to its multifaceted nature and diverse biological properties. Derived from beehives, this natural product, characterized by its sticky, waxy consistency, and aromatic scent, is a complex amalgamation of plant and animal origins. Produced by honeybees through the enzymatic processing of resinous substances from herbal extracts, propolis serves an array of structural and functional roles, from insulating beehives to fortifying their defense against diseases. Raw propolis, collected from hives, is harnessed for various formulations as a food supplement following extraction using different solvents. Ethanol (70%) stands as the preferred solvent for propolis extraction, with oil-based and water-based extracts also viable options. Non-toxic propolis extracts are commonly consumed, often encapsulated within natural polymers like chitosan, pectin, alginate, and dextran. Renowned for its diverse array of biological activities, propolis showcases a broad spectrum of functionalities. These encompass antioxidant, antimicrobial, antiviral, anti-inflammatory, anti-tumoral, anti-diabetic, immuno-modulating, hepatoprotective, and neuroprotective properties. This book chapter aims to delve into propolis’ composition and its widespread popularity as a dietary supplement. Furthermore, it will explore the multifaceted impact of propolis on human health.

1. Introduction

Over the past four to five decades, there has been a significant surge in people’s inclination toward herbal and bee-derived products for both preventive and therapeutic purposes. Bee-derived substances like honey, pollen, propolis, bee pollen, bee bread, and royal jelly, classified as hybrid plant-animal products, boast diverse applications as complementary health products [1, 2]. Propolis, with its pleasant aroma, finds extensive application in various industries, including food, beverages, and consumer goods [3]. The utilization of herbal extracts, medicines, and natural products, alongside conventional treatments, has notably expanded, gaining recognition as traditional and complementary medicine as well as dietary supplements. The natural substance resembling a paste, is sourced by scraping it from beehives. It is a dark and adhesive material formed through honeybees processing different resinous elements from nature along with their own secretions. This amalgam is created by blending diverse natural secondary metabolites, beeswax, and various enzymes. Serving as a vital insulating material for the hive, propolis exhibits robust antibacterial, antiviral, and anti-inflammatory properties that contribute to the colony’s health [4].

The diversity of propolis sources corresponds to geographical, climatic, regional, and botanical variations in production areas [5, 6, 7, 8, 9]. Regions within temperate climate zones, such as Europe, North America, New Zealand, and Western Asia, are conducive to propolis production, generating what is referred to as poplar temperate propolis. This resinous material, procured and processed by western honeybees, exhibits variable colors including green, yellow, red, and brown. It is sourced from leaves, flowers, buds, stems, fruits, and bark crevices of various tree species, such as poplar, pine, chestnut, alder, birch, willow, eucalyptus, fir, and acacia [9, 10, 11]. Propolis obtained from beehives is not used as ham propolis but as a food supplement after extraction. Its biological benefits have been discovered, and interest in propolis is increasing day by day.

1.1 History

Throughout history, propolis has held a significant place in treating wounds, diseases, and diverse ailments due to its potent antimicrobial, anti-inflammatory, and wound-healing properties. Cultures across various ancient civilizations incorporated propolis into their medical practices, rooted in observed benefits and traditional knowledge. The therapeutic use of propolis in apitherapy can be traced back thousands of years, with evidence of its distribution in ancient Egyptian practices, even being employed in the mummification process and transactional activities. It was also valued for wound care and its potential health benefits [11, 12].

During ancient Greek times, renowned philosophers like Hippocrates recognized propolis’ healing capabilities, utilizing it as an antiseptic agent for treating wounds. In ancient Rome, propolis was highly regarded for its therapeutic potential, particularly in topical applications for wound healing and managing various health issues. Traditional Chinese medicine also emphasizes propolis, employing it for treating a spectrum of ailments. Recorded formulas integrated propolis with herbal mixtures for topical use, addressing skin problems and sports-related issues [1].

In contemporary times, modern apitherapy acknowledges propolis as a vital natural elixir, continuing its widespread usage. Today, propolis is recognized as a crucial fortifying agent incorporated into diverse formulations due to its antioxidant, antimicrobial, and anti-inflammatory properties.

1.2 Composition of propolis

Propolis, a complex substance harvested by bees from plant resins, encompasses diverse compounds including tree components, resins, beeswax, and essential oils. Bees gather resins from various botanical sources like buds and bark, forming the foundational element of propolis essential for its health benefits. This resinous part, termed the balsamic component, comprises a secondary metabolite shell rich in polyphenols, with variations in polyphenol types and quantities depending on the plant sources. Ethanol at concentrations of 70–80% stands as the most effective solvent for extracting propolis polyphenols, yielding a mixture of hydrophilic and hydrophobic compounds [1, 13, 14].

Phenolic acids such as caffeic acid, ferulic acid, coumaric acid, gallic acid, syringic acid, benzoic acid, and protocatechuic acid are extracted using high-polarity solvents, while flavonoids like rutin, quercetin, pinocembrin, and hesperetin are obtained using low-polarity solvents. However, the prevalent solvent for both polarities’ compounds remains at 65–70% ethanol.

The first step when preparing propolis extracts is to pulverize the raw propolis extracted from beehives and then extract it by maceration using a 70% ethanol solution. After being filtered, it is used either directly as drops or after being converted into encapsulated products with different encapsulation agents (Figure 1). Yet, a contemporary challenge revolves around the use of ethanolic propolis extracts due to concerns regarding ethanol’s side effects and religious sensitivities. As alternatives, propolis extracts and capsules can be developed using environmentally friendly solvents like water, glycerol, various polyalcohols (PPG and PEG), and natural agents like honey and olive oil. Although extracts in these green solvents may not match ethanolic extracts in quantity, they still serve as significant sources of polyphenols. Additionally, encapsulated derivatives of ethanolic propolis extracts, prepared using various agents such as alginate, chitosan, dextran, cellulose, pectin, inulin, gelatin, whey proteins, and arabinogalactans, are utilized as food supplements [14, 15].

Figure 1.

(A) raw propolis, (B) powder propolis, (C) ethanolic extract.

The potent and distinct scent of propolis is attributed to its volatile compounds. This fragrance can vary, sometimes appearing sweeter, more bitter, herbal, or slightly pungent, potentially due to propolis originating from different sources or a blend of various plant extracts. The types and quantities of volatiles in propolis, typically emanating a woody resin aroma, differ based on the flora it’s collected from. However, the primary volatiles in propolis include essential oils like terpenes, fatty acids, esters, aldehydes, and ketones [8, 15].

Volatile compounds, although a small portion of propolis’s overall mass, play a crucial role in maintaining the hygiene, antibacterial, and antiviral properties within the beehive. They contribute to fostering a healthy hive environment. While there’s limited research on this aspect, some studies suggest that these compounds exhibit potent antibacterial and antiviral activities. However, the complete spectrum of functions carried out by these volatile compounds in propolis is yet to be fully understood due to the limited available studies in this area [8, 16].

The volatile components found in propolis, comprising a diverse array of compounds like terpenes, terpenoids, sesquiterpenes, short-chain fatty acids, alkanes, and alkenes, exhibit qualitative and quantitative variations based on the local flora where it’s collected. Within most temperate regions, sesquiterpenes are the dominant volatile oils, followed by aromatic compounds like benzyl acetate, benzyl alcohol, and benzyl benzoate. For instance, European propolis typically contains β-eudesmol as a major constituent, which is identified as a significant sesquiterpene in essential oils derived from leaf buds of Pinus spp. Conversely, in propolis from Southeastern Anatolia, major essential oils like α-terpinene and α-terpineol were detected. These compounds, shaping the aromatic characteristics of propolis, showcase a wide spectrum of biological activities. They possess antimicrobial, antiviral, and antioxidant properties, alongside serving as insect repellents [8, 14, 16].

The wax fraction, which constitutes the third part of propolis and can be extracted with diethyl ether or chloroform, comprises long-chain nonpolar compounds, predominantly beeswax. This portion primarily consists of wax produced by bees, contributing significantly to hive insulation and the mummification of deceased bees and other insects. Propolis typically contains between 4% and 20% of this wax fraction [17, 18].

The wax component of propolis holds substantial value and finds diverse applications across industries. It serves as an encapsulation agent in cosmetics and pharmaceuticals, as well as in the production of candles, fragrances, and nutritional supplements. Moreover, due to its latent heat storage capacity, wax is utilized in solar energy systems [19].

1.3 Food supplement properties

Interest in propolis extracts has surged significantly in recent years, leading to the development of diverse products formulated with various solvents and packaging methods, serving as potent reinforcing agents. The quality and standards of these propolis products, whether in extract form or encapsulated with natural polymers, are regulated by multiple authorities, including International Honey Commission (IHC), International Organization for Standardization (ISO-24381:2023), among other countries [12, 20, 21]. The primary attributes that distinguish propolis are its robust antioxidant and antimicrobial properties. Numerous scientific studies endorse propolis as the natural product boasting the highest antioxidant activity [21, 22].

While propolis boasts diverse bioactive compounds like polyphenols, flavonoids, and phenolic acids, it is not considered a significant nutritional source. Despite trace amounts of minerals, vitamins, or proteins present in its structure, their contribution to nutritional value is negligible. Although propolis might contain some amino acids attributed to the inclusion of pollen, used by bees in the propolis-making process alongside plant resins, its protein content is notably lower compared to other sources. The focus on propolis does not typically emphasize its protein content due to its relatively meager quantities [23, 24].

1.4 Natural antioxidant source

Oxidation is an inevitable reaction chain for all living and inanimate objects exposed to oxygen. It is caused by the continued presence of reactive oxidant species formed as a result of oxidative stress, and with the progression of inflammation, treatable disease, diabetes, cancer, or neurodegenerative disease develops [25].

The most important triggering agent of aging, cardiovascular diseases, neurodegenerative diseases, and cancer is oxidative stress. However, living conditions, smoking and alcohol use, exposure to radioactive light, and poor nutritional habits are known to increase oxidative stress. However, living conditions, smoking and alcohol use, exposure to radioactive light, and poor nutritional habits are known to increase oxidative stress. Any effect that reduces, slows down, or prevents oxidative stress is called antioxidant. Many free oxygen radicals and their derivatives (SOR) formed by oxidative stress cause the oxidation of macromolecules such as lipids, proteins, and DNA in the environment. This causes many damages ranging from cardiovascular diseases to cancer. Endogenous and exogenous antioxidants are biomolecules that reduce oxidative stress, scavenge free oxygen radicals, or prevent the formation of radicals. Epidemiological investigations have consistently demonstrated that populations adhering to dietary patterns rich in antioxidants exhibit a reduced risk of developing neurodegenerative diseases, including cardiovascular diseases and Alzheimer’s [26, 27, 28]. Plant foods rich in ascorbic acid, α-tocopherol, β-carotene, and various polyphenols are also rich sources of antioxidants. Propolis is an important antioxidant source rich in polyphenols. Studies have shown that propolis has a higher antioxidant value than herbal sources. It shows that it has a higher polyphenol content than fruits such as blueberries, aronia, pomegranates, oranges, apples, rose hips, and strawberries [28, 29, 30, 31, 32]. The antioxidant capacity of propolis is closely related to the amount of polyphenol contents. Table 1 presents a comparative analysis of the total phenolic content (TPC) and total flavonoid content (TFC) levels among select antioxidant-rich natural products.

	TPC	TFC	Reference
Raw propolis Anatolian	110–190 mg GAE/g	16–59 mg QUE/g	[11]
Brown Brazilian propolis	55.74 mg GAE/g	30.89 mg QUE/g	[32]
Red Brazilian propolis	91.32 mg GAE/g	31.48 mg QUE/g	[32]
Green Brazilian propolis	90.55 mg GAE/g	59.45 mg QUE/g	[32]
Anatolian bee pollen	7–31 mg GAE/g	1.24–4.60 mg QUE/g	[33]
Bee bread	11.90–32.40	—	[34]
Rhododendron honey	16.10 mg GAE/g	1.00 QUE/g	[35]
Chestnut honey (Castania sativa L)	0.85 mg GAE/g	0.02 mg QUE/g	[36]
Figus (Ficus carica L.)	0.35–0.48 mg GAE/g	0.01–0.03	[37]
Aronina (Aronia melanocarpa)	14.94–50.02 mg GAE/ g dry matter	5.70–15.27 mg QUE/g dry matter	[31]
Blueberry (Vaccinium spp.)	1.71–4.35 mg GAE/ g dry matter		[30]
Grape’s pulp (Vitis labrusca)	3.57 mg GAE/ g dry matter	0 < 35 mg QUE/g dry matter	[38]
Grape’s seed (Vitis labrusca)	0.20 mg GAE/ g	0.030 mg QUE/g dry matter	[38]
Green tea extract	59.8 mg Cat/ g dry matter	—	[28]
Black tea extract	59.8 Cat/ g dry matter	—	[28]
Ginkgo extract	10–40 mg GAE/g	—	[39]
Olive fruits	19.95–26.57 mg GAE/g		[40]
Apricot pollen	—	10.29 ± 1.16	[41]

Table 1.

Comparison of some important natural products in terms of total phenolic substances.

In Table 1, propolis is one of the natural products with the highest total phenolic substance amounts. The closest bee products to propolis are bee bread and bee pollen, but propolis contains approximately 3–4 times higher polyphenols than these two products. The fruit closest to propolis is aronia, and green and black tea extracts also contain high polyphenols. Depending on the total amount of phenolic substances, the total antioxidant capacities of these products were found to be significantly higher in propolis.

As a matter of fact, studies have shown that antioxidant-rich propolis plays an important role in preventing diseases caused by oxidative stress [25]. In various experimental animal studies on oxidative stress modeling, it has been reported that propolis reduces stress induced by agents such as hydrogen peroxide, paraquat, CCl₄, the ischemia-reperfusion model, heavy metals, pesticides, and other xenobiotics [42, 43]. In the partial diabetes-oxidative stress model induced by streptozotocin (STZ), propolis administration notably mitigated protein and lipid oxidation, reflected in the reduced levels of malondialdehyde (MDA) and protein carbonyl (PC). Furthermore, propolis treatment led to an elevation in tissue glutathione (GSH) levels. Concurrently, interleukin and C-reactive protein (CRP) levels exhibited a decrease following propolis intervention [44]. In a clinical study, administered propolis (1000 mg/day) and melatonin (20 mg/day) to primary pneumo-sepsis patients for 10 days, observing reduced inflammation, improved organ function, and enhanced gastrointestinal tolerance. While survival rates increased, they were not statistically significant [45].

1.5 Mouth and dental health

Propolis is an important antibacterial and anti-inflammatory agent, especially in oral hygiene and some oral and gum diseases. One of the oral and dental diseases for which propolis is most used is gingivitis. Gingivitis is a common gum disease characterized by inflammation of the gums, often caused by the accumulation of plaque on the teeth. It manifests through redness, swelling, and potential bleeding of the gums during brushing or flossing. If left untreated, gingivitis can progress to more severe periodontal diseases, leading to potential tooth loss. Gingivitis has the potential to progress into periodontitis, where both gingival and bone tissues suffer destruction. Adequate mechanical plaque removal may not be practiced by most of the population. It has been reported in many clinical studies that patients diagnosed with periodontitis received a positive response to treatment with propolis supplementation [46, 47, 48, 49]. Numerous comparative studies with propolis and chlorhexidine have shown that ethanolic propolis extracts are as effective as chlorhexidine. It has been shown to prevent the formation of dental plaque. It has been reported in many studies that propolis toothpastes and propolis mouthwashes are valuable for oral and dental health [50, 51].

1.6 Natural antibacterial and antiviral effects

It has been proven by numerous studies that propolis extracts show antimicrobial activity against a wide range of pathogenic microorganisms. It has been shown to be effective against infections of the gastrointestinal tract such as the upper respiratory tract and stomach-intestinal tract in humans, and against microorganisms resistant to various antibiotics. Although it has not been determined exactly which compound the antimicrobial activity of propolis comes from, it has been shown that this activity is due to the phenolic acids, flavonoids, and volatile compounds it contains. It is stated in the literature that these natural antimicrobial compounds show different inhibition mechanisms against bacterial species. Antimicrobial activity varies depending on the type of propolis. However, bacteriostatic, and bactericidal action mechanisms vary depending on the botanical properties of propolis. The capacity of propolis to prevent antibacterial sensing and antibiofilm formation indicates that it has a strong potential, especially against antibiotic-resistant bacteria. Additionally, propolis can stimulate the body’s immune system, activating natural defense mechanisms to fight infection [52, 53]. There are many in vitro and clinical studies showing that propolis is also effective on Helicobacter pylori, which causes ulcers in the stomach. Helicobacter pylori, one of the few bacteria that can survive in an acidic stomach environment, is treated with double or triple antibiotics. Studies have shown that propolis extracts stop the proliferation of bacteria. It has also been shown that it inhibits the urease enzyme that bacteria secrete into the extracellular environment in order to adapt to the acidic stomach environment [54, 55]. It is also reported that propolis has an antibacterial effect against other bacteria that can live in the gastrointestinal tract, such as Campylobacter spp, Escherichia coli, and Salmonella spp. [55]. Additionally, propolis extracts are also used as antifungal agents against various Candida spp, Aspergillus spp, and Cryptococcus neoformans. It has been reported in many studies that it stops the growth of species [56, 57].

Propolis is a highly preferred natural supplement due to its potential anti-viral effects against various types of viruses. Many studies have shown that propolis may be effective against several viruses, such as influenza viruses, herpes simplex virus (HSV), HIV, and hepatitis B and C viruses [58]. Molecular docking studies against the COVID-19 virus have shown that flavonoids prevent the COVID-19 virus from binding to ACE receptors. It has also been confirmed that propolis has a significant adjuvant effect in COVID-19 patients. However, the effect of propolis on a particular type of virus may vary depending on factors such as its concentration and application methods. Therefore, more research is needed to better understand the antiviral effects of propolis [22, 59]. In fact, with the COVID-19 pandemic, propolis production and sales in the world have peaked.

1.7 Propolis and cancer

There exists a plethora of cell cultures and experimental studies demonstrating the potential of propolis as a natural agent in cancer treatment. Extracts from propolis have exhibited the ability to impede the growth of diverse cancer cells and induce apoptosis in cell culture settings. These studies indicate that propolis may hinder or arrest cancer development by modulating cell cycle pathways, activating caspase enzymes, and inhibiting angiogenesis. Moreover, its antioxidant and anti-inflammatory properties suggest potential in thwarting cancer initiation or curbing the metastatic spread of cancer cells. However, the absence of human clinical studies hinders definitive conclusions on the efficacy of propolis in cancer treatment. Therefore, further extensive research is imperative to establish conclusive evidence regarding the role of propolis in cancer therapy. Nevertheless, numerous clinical studies have demonstrated propolis’ adjunctive role in cancer treatments [60, 61]. The findings obtained so far show that propolis is promising in cancer treatment as a complementary medicine tool.

1.8 Propolis and cardiovascular

Propolis serves as a significant dietary supplement utilized in both preventing and managing cardiovascular diseases, although its precise mechanisms in this context remain somewhat elusive. Its multifaceted properties involve various mechanisms contributing to its positive impact. Acting as a potent antioxidant, propolis plays a crucial role in inhibiting LDL oxidation, thereby reducing oxidative damage. This antioxidative quality is pivotal in mitigating oxidative stress within vascular walls, diminishing the harmful effects of free radicals, and potentially preventing cardiovascular conditions like atherosclerosis. Additionally, propolis displays anti-inflammatory characteristics, effectively reducing vascular inflammation and contributing to vascular health by regulating inflammatory responses in the vascular system. Studies suggest that propolis influences lipoprotein mechanisms, resulting in decreased LDL levels, elevated HDL levels, and fostering cardiovascular protection. Propolis demonstrates its preventive effect against cardiovascular diseases by inhibiting the lipase enzyme while activating the paraxonase enzyme [61, 62]. Additionally, propolis has been associated with blood-thinning effects and has been reported to play a role in lowering blood pressure, further contributing to its potential to support cardiovascular health [63, 64, 65].

1.9 Anti-inflammatory properties

Studies have extensively demonstrated propolis’s significant anti-inflammatory properties, which operate through diverse mechanisms. Propolis exhibits a capacity to inhibit cyclooxygenase (COX) enzymes, consequently reducing prostaglandin production. This inhibition plays a pivotal role in alleviating symptoms associated with inflammation and pain. Moreover, propolis, endowed with potent antioxidant attributes, effectively neutralizes free radicals, thereby mitigating inflammation. Its ability to curtail nitric oxide synthesis (iNOS) contributes to controlling the inflammatory process. By diminishing the concentration of key inflammatory cytokines like IL-1b, IL-6, and TNF-a, propolis acts to attenuate the overall severity of inflammation. Additionally, propolis showcases regulatory effects on the immune system, further bolstering its capability to modulate inflammatory responses [44, 63, 66].

2. Conclusion

Propolis stands as an extraordinary natural adjunct, showcasing a rich tapestry of therapeutic potential and diverse biological attributes. Its historical roots in ancient medicinal practices have transcended time, finding relevance in contemporary dietary supplementation. The multifaceted properties of propolis span a broad spectrum, notably encompassing robust antioxidant, antimicrobial, and anti-inflammatory characteristics. These attributes underscore its potential contributions to various facets of human health, spanning oral health, cardiovascular disease prevention, and ongoing explorations into potential cancer treatments. Propolis, revered for its potent antioxidant prowess against oxidative damage, is anticipated to gain further prominence in averting diseases spawned by oxidative stress. Its anti-aging efficacy positions it as a prime contender in the realm of apitherapy and the cosmetic industry. Looking forward, propolis emerges as a field ripe for continued investigation. Future trends in propolis research aspire to unearth deeper insights into its mechanisms of action and multifarious applications across diverse industries. The prospective utilization of propolis beyond the realms of health, extending into cosmetics, food, and material sciences, hints at its remarkable versatility. However, materializing these potentials mandates rigorous clinical studies to authenticate and harness the full spectrum of propolis’ benefits. Further research initiatives serve as the linchpin in unlocking its potential across varied industries and maximizing its impact on human health and beyond. As an herbal derivative boasting medicinal properties akin to herbal plants and spices, propolis joins the ranks of natural products rich in secondary metabolites derived entirely from nature. This aligns is not only with the evolution of natural medicine comprehension but also as a harbinger of innovative formulations in functional foods, dietary supplements, and medical applications.