Antimicrobial Properties of Natural Honey

Abstract

In present time, drug resistance in microbes is a very serious problem. The consequences of antibiotic resistance are significant. It can lead to the persistence of infections, increased healthcare costs, prolonged hospital stays and higher mortality rates. The research to obtain new antimicrobial compounds is vitally important. Hence, natural products are considered as safe alternatives to synthetic drugs. Honey is highly regarded for its nutritional value and therapeutic properties it has been used in traditional medicine in many countries for thousands of years. Its effectiveness as an antimicrobial agent is primarily due to its unique chemical composition natural hydrogen peroxide content, low water activity and acidic pH. The antimicrobial activity of honey can vary depending on factors such as floral source, geographical origin and processing methods. Honey has a strong antimicrobial effect and it may be an alternative natural source of medicine to prevent and treat many diseases caused by pathogenic microorganisms.

1. Introduction

Microbial resistance to modern antimicrobial drugs is a serious problem worldwide. It has a significant consequences and leads to the persistence of infections and increased healthcare costs. It’s important to solve this problem by developing new drugs to which microbes have little or no resistance [1]. Honey has been known for its antimicrobial properties for thousands of years [2]. It is a complex mixture, its chemical composition and biological properties vary according to its geographical and botanical origins [3]. The effectiveness of honey as an antimicrobial agent is associated with many factors such as low pH, high osmolarity, hydrogen peroxide content, presence of methylglyoxal (MGO) and defensin-1. Furthermore, flavonoids and phenolic compounds contribute to the antibacterial effect of honey [4]. Honey’s antimicrobial activity can vary depending on factors such as flower source, geographic origin and processing methods [5]. In addition, honey showed no side effects and was inexpensive, which is an additional advantage when used for medicinal purposes [6]. Honey has an important antimicrobial activity and it can be used as an alternative natural agent in a number of medicines.

2. Chemical composition of honey

Honey consists mainly of sugar (approx. 80%) and water (approx. 17%), in addition to many secondary components (approx. 3% in total), such as proteins, amino acids and organic acids, vitamins, minerals, polyphenols and volatile compounds [7, 8]. The principal sugars in honey are fructose and glucose, although very small amounts of other mono, dior-oligosaccharides (maltose, sucrose, nigerose, isomaltose, furanose and maltose) have also been identified (see Table 1) [9]. The chemical composition of honey varies fundamentally depending on the flower source, but seasons, environmental factors and processing conditions are also important.

Substance	Content (%)
Water		17.2
Sugars	Levulose (d-fructose)	38.19
	Dextrose (d-glucose)	31.28
	Sucrose (saccharose)	1.31
	Maltose and other reducing disaccharides	7.31
	Higher sugars	1.50
	Total sugars	79.59
Acids	(Gluconic, citric, malic, succinic, formic, etc.); total acids calculated as gluconic acid	0.57
Proteins	(Amino acids: glutamic acid, alanine, arginine, glycine, leucine, isoleucine, aspartic acid, valine, histidine and lycine)	0.26
Ashes	(Minerals: potassium, sodium, magnesium, calcium, phosphorus, iron, manganese, copper, etc.)	0.17
Minor component	Mainly comprising pigments, aromatic substances, sugar alcohols, tannins, enzymes and diastases including amylase, peroxidase, succindehydrogenase, phosphatase and invertases, vitamins including thiamine, riboflavin, acid nicotinic acid, vitamin K, folic acid, biotin, pyridoxine and pantothenic acid	2.21

Table 1.

The main components of honey.

2.1 Carbohydrates (sugars)

Honey contains three principal types of sugar. These are fructose, which is one of the highest at 41%, glucose, which has around 34% and sucrose, which is between 1 and 2% [10]. The ratio of one type of sugar to another depends on the flower source and the level of the enzyme invertase, which breaks down sucrose into glucose and fructose. This enzyme is found in the flower from which the bees collect nectar, but it is also found in the bee’s body [11].

2.2 Amino acids and proteins

The content of amino acids and proteins in honey is relatively low, at most 0.7%. Proteins are found in honey from nectar and pollen as an essential part of plants. Proteins in honey can be found in simple or in a very complex forms [12]. Honey contains approximately all physiologically essential amino acids. The main amino acid proline is a measure of honey ripeness. In normal honey the proline content should be more than 200 mg/kg. Values less than 180 mg/kg mean that the honey is probably adulterated by added sugar [13].

2.3 Aroma compounds and phenolics

The most volatile compounds found in honey probably come from the plant, but some of them are added by bees. Phenolic acids and polyphenols are secondary plant metabolites. They have been suggested as possible markers for determining the botanical origin of honey [14]. Dark honey is reported to contain more phenolic acid derivatives but fewer flavonoids than light honey [15]. According to many studies the most important phenolic compounds found in honey are: caffeic acid vanillic acid, þ-coumaric acid, syringic acid, quercetin, ferulic acid, myricetin, kaempferol pinocembrin, inobanksin, ellagic acid, chrysin, 3- hydroxybenzoic acid, galangin, chlorogenic acid, 4-hydroxybenzoic acid, gallic acid, rosmarinic acid, hesperetin, benzoic acid and others [16, 17].

2.4 Minerals and trace elements

Honey contains different amounts of minerals. Potassium is the main mineral element, averaging about a third of the total, but there is a wide variety of trace elements. Several studies have shown that the trace element content of honey mainly depends on the botanical origin of the honey. Minerals have about 3.68%. Although this portion of honey does not account for a large amount, the minerals contained in honey add to honey’s value for human consumption. Honey contains most of the minerals: potassium, chlorine, sulphur, calcium, sodium, phosphorus, magnesium, silicon, iron, manganese and copper [18]. At the observed mean, dark honeys are richer in minerals than light ones. Of course, singles can find darker species poorer than lighter species [18].

3. Antimicrobial activity of honey

Honey is characterised by strong antimicrobial activity against both pathogenic and non-pathogenic microorganisms (bacteria, yeasts and fungi), even those that have developed resistance to many antibiotics [18].

3.1 Antibacterial activity of honey

Honey has a proven antibacterial effect against a broad spectrum of bacterial species including aerobes and anaerobes, Gram positives, and Gram negatives (Table 2) [19].

Bacterial species	Disease caused
Bacillus anthracis	Anthrax
Corynebacterium diphtheriae	Diphtheria
Escherichia coli	Diarrhoea, septicaemia, urinary infections, wound infections
Haemophilus influenzae	Ear infections, meningitus, respiratory infections, sinusitis
Klebsiella pneumoniae	Pneumonia
Mycobacterium tuberculosis	Tuberculosis
Proteus spp.	Septicaemia, urinary infections
Pseudomonas aeruginosa	Urinary infections, wound infections
Salmonella spp.	Diarrhoea
Salmonella choleraesuis	Septicaemia
Salmonella typhi	Typhoid
Salmonella typhimurium	Wound infections
Serrata marcescens	Septicaemia, wound infections
Shigella spp.	Dysentery
Staphylococcus aureus	Abscesses, boils, carbuncles, impetigo, wound infections
Streptococcus faecalis	Urinary infections
Streptococcus mutans	Dental caries
Streptococcus pneumoniae	Ear infections, meningitis, pneumonia, sinusitis
Streptococcus pyogenes	Ear infections, impetigo, puerperal fever, rheumatic fever, scarlet fever, sore throat, wound infections

Table 2.

List of bacterial species sensitive to honey and diseases they cause [19].

3.1.1 Factors responsible for the antibacterial activity of honey

Honey’s antibacterial activity is attributed to many factors such as: low water content, high viscosity, acidity, hydrogen peroxide content and non-peroxide components, especially the presence of MGO (Figure 1) [20].

Figure 1.

Schematic diagram presenting the parameters contribute to the antimicrobial activity of honey.

3.1.1.1 Low water content

Water activity is defined as the unbound water molecules in a sample which have a proportional relationship with bacterial contamination. The normal range of water activity (aw) of honey is between 0.562 and 0.62. This is less than the range shown to completely inhibit bacterial growth (0.94–0.99). Pure honey therefore has a very low water content to promote the growth of microorganisms [20].

3.1.1.2 High sugar content

The high sugar content of honey makes the water inaccessible to microorganisms. It creates a hypertonic environment that draws water out of bacterial cells through osmosis, causing them to shrink and eventually die [21].

3.1.1.3 Acidity

Acidity is one of the most important parameters that contribute to the antibacterial activity of honey. It is attributed to the presence of certain acids, in particular gluconic acid (approx. 0.5% w/v). The acidity of honey (pH 3.24.5) is significantly lower than the favourable pH (6.5–7.5) for the growth of most bacteria [22].

3.1.1.4 Hydrogen peroxide

Hydrogen peroxide (H₂O₂) is one of the most essential factors responsible for the antibacterial activity of honey. In honey, hydrogen peroxide is produced by an enzymatic reaction during the transformation of nectar into honey by gluco-oxidase under aerobic conditions [23].

$$\text{Glucose}+{\text{H}}_2\text{O}+{\text{O}}_2\frac{\text{Glucose oxidase}}{}\text{Glucose Acid}+{\text{H}}_2{\text{O}}_2$$E1

3.1.1.5 Methylglyoxal (MGO)

Methylglyoxal is one of the dicarbonyl components resulting from the Maillard reaction which takes place in all products very rich in sugars, such as nectar. This molecule has a powerful bactericidal power and its content varies according to the geographical and floral origin of the honey and it has a strong correlation with its antibacterial effect [24].

3.1.1.6 Defensin-1

Bee defensin-1 is a small peptide with molecular weights ranging from 3.5 to 6 kDa made by the hypopharyngeal and mandibular glands of bees, and possesses a strong antibacterial activity but only against Gram-positive bacteria including B. cereus, S. aureus and Paenibacillus larvae [2].

3.1.1.7 Phenolic compounds and flavonoid

Honey contains various phenolic and flavonoid compounds that play a role in its antibacterial effects and inhibit bacterial growth [22].

3.1.2 Mechanisms of the antibacterial effect of honey

Several mechanisms have been proposed for the antibacterial action of honey. Some examples are as follows:

• The antibacterial activity of several honeys is due to their ability to degrade bacterial DNA.

• Honey’s high sugar content creates an osmotic effect, drawing water out of bacterial cells and dehydrating them, which inhibits their growth. Also, the high sugar content of honey leads to the denaturation of bacterial proteins, disrupting their function and inhibiting bacterial growth.

• Honey’s thick consistency can create a physical barrier that prevents bacteria from accessing nutrients and adhering to surfaces.

• The bactericidal effect of honey was based on the disruption of cell division. These effect was also associated with extensive cell destruction (loss of structural integrity), lysis and changes in cell form and surface area of pathogenic bacteria.

• Honey has been found to block bacterial attachment to tissues (an important step to initiate infection) and inhibit biofilm formation (which protects bacteria from antibiotics) [25].

3.2 Antifungal activity of natural honey

The incidence of fungal infections is increasing and has emerged as a leading cause of illness and death. Most clinically used antifungal drugs have various drawbacks in terms of toxicity, efficacy and cost. The resistance of pathogenic fungal strains to commonly used antifungal drugs has necessitated the search for new types of antifungal drugs. Honey is a natural product that has been used for its antifungal activity and can be used as an alternative for the treatment of severe fungal infections [26]. Several in vitro studies have demonstrated the antifungal properties of honey.

In a study done by Abdellah et al. [27] they reported that Daucus carota honey has an antifungal effect against Candida albicans.

Anyanwu [28] has demonstrated that honey samples used in his study showed different levels of antimycotic activity against the tested fungal isolates, namely, Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Microsporum gypseum, Candida albicans and Saccharomyces sp.

Estevinho et al. [29] reported that lavender honey inhibited the growth of the pathogenic yeasts Candida albicans, Candida krusei and Cryptococcus neoformans.

Alzahrani et al. [26] indicated that four varieties of honey from different botanical and geographical origins (Manuka, Acacia, Lavender and Wild carrot) were effective against Candida albicans.

In a study done in Australia by Irish et al. [30] they reported that four varieties of honey inhibit the growth of Candida species (C. albicans, C. glabrata and C. dubliniensis).

The result of a study done by Koc et al. [31] demonstrated the capacity of honey samples from different floral sources to inhibit the growth of four yeast strains (Candida albicans, C. krusei, C. glabrata and Trichosoporon spp.).

The antifungal properties of honey can vary depending on factors such as the type of honey, its origin and the specific fungal strain.

3.2.1 Mechanism of antifungal effect of honey

Honey has been exhibiting antifungal properties through various mechanisms of action. Here are a few examples:

Osmotic effect: honey has a high sugar content, mainly fructose and glucose. This high sugar concentration creates an osmotic effect that draws water out of fungal cells, effectively dehydrating and killing them.

Hydrogen peroxide production: some varieties of honey contain an enzyme called glucose oxidase, which produces hydrogen peroxide when honey comes into contact with bodily fluids. Hydrogen peroxide has antifungal properties and can help to inhibit the growth of fungi.

Acidity: the low pH of honey (around 3–4.5) creates an acidic environment that is unfavourable for the growth of many fungi.

Phytochemicals and polyphenols: honey contains various phytochemicals and polyphenols that have been shown to possess antifungal properties. These compounds can disrupt the fungal cell membrane, interfere with cell division and inhibit fungal enzymes and fungal growth.

Immune system modulation: honey’s immunomodulatory effects can indirectly contribute to its antifungal activity. It can help to enhance the immune response, which in turn can better combat fungal infections.

Release antimicrobial peptides: honey contains certain peptides that have antimicrobial properties. These peptides are released when honey comes into contact with body fluids, and they can inhibit the growth of fungi.

3.3 Antiviral proprieties of honey

Since antiquity, many diseases have been treated by honey. It is an important therapy against respiratory pathogens, including viruses that cause coughing. Several studies have demonstrated the antiviral activity of honey against a range variety of viruses [32]. Its effectiveness can vary depending on the type of honey and the specific virus involved.

In 2014 Behbahani [33] reported that Iranian monofloral honey had a potent anti-HIV-1 effect.

The antiviral effect of manuka honey against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported by Elbashir et al. [34].

The results of a study done by Ghapanchi et al. [35] demonstrated that honey has an inhibitory effect against herpes simplex virus type 1.

3.3.1 The components responsible for the antiviral effect of honey

The antiviral properties of honey are attributed to its natural compounds including hydrogen peroxide and other bioactive compounds (Table 3).

Table 3.

Bioactive compounds in honey that could have antiviral activities.

3.3.1.1 Hydrogen peroxide

Hydrogen peroxide (H₂O₂) is one of the most important components in honey reportedly responsible for its antiviral effect. The result of the study done by Mentel et al. [36] showed that H₂O₂ strongly inactivated human coronavirus 229E (HCoV-229E) and influenza viruses (A and B). Another study reported that H₂O₂ has an inhibitory effect against the avian viruses: H5N1, IBV and Newcastle Disease Virus (NDV) [43]. A recent study indicates the virucidal effect of H₂O₂ against feline calicivirus (FCV), which infects domestic cats [44].

3.3.1.2 Ascorbic acid

Ascorbic acid (vitamin C) is a widely used antioxidant that has demonstrated antiviral immune responses, particularly against the influenza virus [41].

3.3.1.3 Acidity

The low pH of honey creates an unfavourable environment for viruses to thrive.

3.3.1.4 High sugar content

Honey’s high sugar content can create a dehydrating environment that limits the virus’s ability to thrive.

3.3.1.5 Fatty acid

The antiviral effect of honey could also be due to the fatty acid 10-hydroxy-2-decenoic acid (10-HAD); which induces adhesion of leukocytes to viruses, leading to their eradication [1].

4. Conclusion

The antimicrobial effect of honey has been well-established through several studies. Honey contains natural compounds like hydrogen peroxide, low water activity and high acidity that create an unfavourable environment for bacteria and other microorganisms. Additionally, certain types of honey contain unique components such as methylglyoxal (MGO), which further enhance their antimicrobial properties. While honey can be effective against a range of bacteria, yeasts and fungi, its potency may vary depending on factors such as honey type, source and processing. Overall, honey’s antimicrobial properties make it a promising natural alternative for various applications, including wound healing and preservation.

Conflict of interest

The author confirms that this chapter’s content has no conflict of interest.