Abstract
In addition to being used as food, honey has been used as an alternative medicine for thousands of years. Honey has a great potential to be used as a medicine because it is not suitable for micro-organisms, it is very acidic and has a very high sugar content, which causes an osmotic effect that prevents the growth of some micro-organisms, moreover, in some honey, hydrogen peroxide is found, which has a strong antibacterial effect. However, properties and appearances of honey vary greatly according to the floral source in which the bee collects the nectar, so some honey also have a strong antioxidant and anti-inflammatory activity. Recently, there are several studies, mainly in vitro, that prove the effectiveness of honey for various medical purposes due to its components and its antibacterial, anti-inflammatory, antioxidant, antiviral, antifungal, and anticancer properties.
Keywords
- anti-inflammatory
- antioxidant
- bee
- cancer
- medicine
1. Introduction
Honey is a compound widely used as a medicine and food source for thousands of years [1]. Several natural products that have been used as medicine have been replaced by modern pharmaceuticals, but recently they have returned to the world stage due to the growing public interest [2]. In ancient Egypt, beekeeping has been practiced for more than 4000 years, and honey has been used as a medicine in the treatment of wounds, ulcers, burns, abscesses, gastrointestinal diseases, inflammations, rigid joints, and even as a contraceptive method [1, 3]. In Asia, honey is recognized for its medicinal value since 2000 BC [1]. There are also references to different uses of honey in the bible and in the Qur’an [1]. The ancient Greek Hippocrates, known as the father of modern medicine, used honey to clean wounds, gastrointestinal diseases, and ulcers [1, 3]. In Ancient Rome, honey was also prescribed alone or in combinations, often used to treat throat problems, pneumonia, and even snake bites [1].
The main components of honey are sugars, among which are predominantly fructose and glucose [4, 5]. However, there are other compounds in smaller quantities and very variable depending on the type of each honey, from the floral source where the bee collects the nectar, such as water and free amino acids [4, 5]. Among them, the most found is proline [4, 6]. Some specific enzymes are also found, the main enzymes of honey are invertase, amylase, and glucose oxidase, but other enzymes such as catalase and phosphatase [6, 7, 8]. Honey is also composed of organic acids that contribute to its characteristic flavor and are responsible for the excellent stability of honey against micro-organisms, for example, formic, acetic, butyric, oxalic, lactic, succinic, folic, malic, citric, and glycolic [6, 7]. Gluconic acid is considered one of the most important organic acids in honey; it is the product of catalytic oxidation of glucose oxidase, in this oxidation, hydrogen peroxide is also formed, which has a strong antibacterial effect [4, 5, 6, 7].
Honey may still have some mineral substances, such as potassium, magnesium, sodium, calcium, phosphorus, iron, manganese, cobalt, and copper; studies show that honey can contain several types of minerals, but potassium is the most abundant in various types of honey [6, 8, 9, 10]. Carotenoids, flavones, and anthocyanins can still be found, which contribute to the antioxidant action of honey [6]. About 80 aromatic compounds have been detected in honey, including carboxylic acids, aldehydes, ketones, alcohols, hydrocarbons, and phenols [6]. These compounds also contribute to the organoleptic properties of honey. The appearance of honey varies from almost colorless to dark brown; it can be liquid, viscous, or solid. Its flavor, aroma, and composition vary enormously, depending on the floral source in which the honeybee collects the nectar. However, some environmental factors can strongly influence honey composition, such as temperature and humidity [6, 7, 11].
Honey is a food that contains high energy carbohydrates, being that 95–99% of the total solids are composed by sugars, which are easily digestible, since they are similar to many fruits [7, 12]. Proteins and enzymes in honey often have no significant nutritional value, as they are usually not present in sufficient amounts [7]. Several of the essential vitamins are present in honey, such as vitamin K, B1, B2, B6, and C, but generally at insignificant levels [7, 8, 13]. The mineral content of honey is variable, usually darker honeys have significant amounts of minerals, but honey can be considered a nutritive sweetener, mainly due to its high fructose content [7, 13].
In addition to its food value, honey has great potential in medicine; it has been used for thousands of years, and has now been widely studied as an alternative medicine. Honey is not a suitable medium for bacteria, since it is very acidic and has a very high sugar content. This causes an osmotic effect that prevents the growth of bacteria, this effect works literally drying the bacteria [7, 13]. Another type of antibacterial property of honey was called inhibition in 1940 by Dold [7]. And in 1963, Jonathan White proposed that this inhibitory effect described in 1940 was due to the hydrogen peroxide produced and accumulated in the diluted honey, which we know today, is a by-product of the formation of gluconic acid by the enzyme glucose oxidase [5, 7, 11].
Historically, honey has been used for various medical purposes; and recent research has confirmed the effectiveness in the treatment of several diseases due to its components and its properties antibacterial, anti-inflammatory, antioxidants, antiviral, and others that will be addressed in this chapter.
2. Properties of honey
2.1 Anti-inflammatory
Inflammation is nothing more than a defense response of the body to a tissue that has suffered a certain damage, which consists of the recruitment of leucocytes and plasma proteins of the blood [14, 15]. This damage can be caused by physical, chemical, or even microbial agents; inflammation is characterized by edema, erythema, pain, and increased temperature [15, 16].
It is well known that propolis, another product from honeybee colony, has potential anti-inflammatory properties, including
Gastric ulcers are among the most common diseases affecting humans, a study demonstrated that the use of honey in conjunction with other compounds may promote gastroprotection. Later, a recent study investigated the effect of gastric protection using only honey against gastric ulcers induced by ethanol in rats and also suggested this effect as gastroprotection [21, 22]. Manuka honey significantly decreased the ulcer, completely protected the mucus of the lesions and preserved the gastric mucus glycoprotein, significantly increased the mucus levels of gastric nitric oxide, reduced glutathione, glutathione peroxidase, and superoxide dismutase, and also decreased lipid peroxidation of the mucus and tumor necrosis factor-α, interleukins-1β, and concentrations of interleukins-6 [21]. Honey has been shown to be efficient in other types of ulcers, and this Manuka honey exerted an antiulcer effect, keeping enzymes and antioxidants, non-enzymatic and inflammatory cytokines reduced [21, 23].
In addition to the Manuka honey and the Tualang honey, the anti-inflammatory effect of Malaysia’s Gelam honey was also studied, which is associated with anti-inflammatory effects on tissues [24, 25]. Malaysia Gelam honey was tested in rats induced by inflammation [25]. Paw edema was induced by a subplantar injection and the rats were treated with either the anti-inflammatory drug Indomethacin or Gelam honey. Results showed that Gelam honey can reduce dose-dependent edema in inflamed rat paws, decrease the production of nitric oxide, prostaglandin, tumor necrosis factor-α, and interleukin-6 in plasma, and suppress expression of synthase inducible nitric oxide, cyclooxygenase-2, tumor necrosis factor-α, and interleucine-6 in paw tissue [25]. The oral pre-treatment of Gelam honey at 2 g/kg body weight at two times (1 and 7 days) showed a decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory indomethacin, both in plasma and in the tissue, and Gelam honey has anti-inflammatory effects and is potentially useful for the treatment of inflammatory conditions [25]. Another study demonstrated that different types of honey promoted increased release of TNF-α, IL-1β, and IL-6 from monocytes, which are cells that assist in healing [26].
We can also compare the anti-inflammatory activity of honey with another herbal remedy in a study carried out in 2012 to test the activity of honey and brown sugar, surgically treated guinea pigs that were treated with honey, brown sugar, and a control group treated with saline solution, it is already known that sugar can help healing [27, 28]. The honey group showed a decrease in the area of the wound and the formation of granulation tissue before the brown sugar group and control; the honey group was still the only one that presented no crust in any wound and promoted a faster healing by stimulating the faster formation of granulation tissue and re-epithelization [28]. In addition, honey showed a higher antibacterial effect in relation to brown sugar and control group [28]. Another study had the same result, honey was effective in reducing bacterial contamination and wound healing [29].
Recent studies proved the anti-inflammatory activity of honey; different types of honey, different regions and different floral sources, were studied and both showed anti-inflammatory responses [17, 21, 25, 28]. Treatment with Tualang honey and Gelam honey showed similar responses to conventional anti-inflammatories used for specific treatments [17, 25]. Honey still has a better anti-inflammatory activity than brown sugar, promoting faster healing [28]. Also, honey is a relatively cheap and easily accessible anti-inflammatory compound that needs to be further studied and later applied in modern medicine [17, 21, 25, 28].
2.2 Antibacterial
One of the advances of modern medicine has been the development of antibiotics; these antibiotics can be bactericidal, which kill the micro-organisms directly, or bacteriostatic, which prevent the growth of micro-organisms [30]. However, micro-organisms are increasingly developing resistance to these antibiotics, which is a major concern. In addition to antibiotics, the prevention of bacterial diseases can be carried out with the use of vaccines and with basic sanitary methods [30, 31].
Many different micro-organisms can cause disease and be transmitted even by contaminated water, and among the major aquatic pathogens are
The bacteria
Salmonellosis is a gastrointestinal disease caused by eating food contaminated with
Another form of food poisoning is caused by enterotoxins produced by Gram-positive bacteria, such as
Honey has an excellent antibacterial effect against different types of bacteria, as previously mentioned; honey is very acidic and has a very high sugar content, which does not serve as a suitable medium for bacteria [4, 5, 6, 7]. Moreover, in some honeys, the peroxide of hydrogen is found, which has a strong antibacterial effect [4, 5, 6, 7]. Remavil® honeys, Manuka honey, Tualang honey, and Gelam honey were tested with different types of bacteria and had positive results [34, 36, 41, 42]. The bacteria tested and susceptible to some of these honeys were
2.3 Antivirals
Of all human infectious diseases, the most prevalent and difficult to treat are those that are caused by viruses, because viruses usually remain infectious in dry mucus for a long time [14]. Also, viruses need a host cells to occur its replication; so killing the virus means killing your host cell as well. Hence, vaccination is the most efficient way to prevent these diseases [14, 46].
Chickenpox is caused by the varicella-zoster virus and it is a very common childhood disease that usually does not cause many problems; but when it affects the elderly, it can be easily fatal [14, 47]. Varicella-zoster is highly contagious and is transmitted by infectious droplets, which results in a systemic rash on the skin [14]. As honey can be conveniently applied to the skin, it is easily found and relatively inexpensive, it can be considered an excellent remedy against Zoster rash, especially in developing countries, or in countries where antiviral drugs are relatively expensive and difficult to access. Therefore, a study determined
Respiratory syncytial virus is the most common cause of viral respiratory infections in infants and young children, also seriously affects adults, the elderly and immunocompromised, causing deaths mainly in the elderly [50, 51]. The antiviral activity of honey was tested for its action against the respiratory syncytial virus. A variety of tests using cell culture was developed to assess the susceptibility of respiratory syncytial virus to honey. The results confirmed that treatment with honey promoted inhibition of viral replication [50]. Attempts to isolate the antiviral component in honey demonstrated that sugar was not responsible for the inhibition of respiratory syncytial virus, but could be methylglyoxal; this component of honey may play a role in the increased potency of Manuka honey against respiratory syncytial virus [50]. Thus, honey may be an alternative and effective antiviral treatment for the therapy of respiratory viral infections, such as respiratory syncytial virus; however, other measures, such as an effective vaccine, are still necessary for the control of this disease [50, 52].
Influenza is a highly infectious respiratory disease of viral origin that causes even more deaths than the respiratory syncytial virus at all ages, except in children less than a year old [14, 51]. Influenza viruses are transmitted from person to person through the air, especially from droplets expelled during coughing and sneezing and are a serious threat to human health, and there is an urgent need for the development of new drugs against these viruses. Therefore, the anti-influenza virus activity of honey from several sources was studied [53]. The results showed that honey, in general, and particularly Manuka honey, has potent inhibitory activity against the influenza virus, demonstrating a potential medicinal value [53]. In addition to honey, propolis has also been studied against the influenza virus and appears to decrease the activity of the influenza virus [54].
Honey, especially Manuka honey, has strong antiviral properties. Studies show that honey has action against the varicella-zoster virus, the respiratory syncytial virus, and also has anti-influenza activity [47, 50, 53]. New studies on this property of honey are necessary, mainly with other types of honey.
2.4 Antifungal
Most people associate fungi with organic matter decomposition or superficial fungal infections, but fungi can cause various human diseases, from mild to firmly established systemic diseases; the most serious infections can even be fatal [14]. The incidence of
As previously stated, honey has antifungal properties and may act against
In addition to the antifungal activity of honey against
Besides the antibacterial and antiviral properties, some honeys also have antifungal properties [56, 57, 59, 61]. Recent studies showed some honey have properties against
2.5 Anticancer
In 2016, the cancer mortality rate has dropped 23% since 1991 [65]. Despite this progress, mortality rates are increasing for liver, pancreatic, and uterine cancers; and cancer is now the leading cause of death in 21 states from United States, lung cancer is still the most lethal, followed by breast cancer [65, 66]. The advance for cancer treatment needs more clinical and basic research [65].
Many scientists have focused on the antioxidant property of honey. Studies indicate that ingestion of honeybee products, such as honey, can prevent cancer [67, 68]. Through the use of human renal cancer cells, the antiproliferative activities, apoptosis, and the antitumor activity of honey were investigated [67]. Honey decreased cell viability in malignant cells regardless of concentration and time [67]. Honey induced apoptosis of human renal cancer cells according to honey concentration, and apoptosis plays an important role, most of the drugs used in the treatment of cancer are apoptotic inducers, so the apoptotic nature of honey is considered vital [67].
The anticancer activity of honey samples was extracted from three different Egyptian floral sources and was tested against colon, breast, and liver tumor lineage [69]. Cassia honey showed moderate cytotoxic activity against colon cancer and breast cancer, with the weakest cytotoxic activity against liver cancer; Citrus honey exhibited the highest cytotoxic activity against breast cancer; and Ziziphus honey showed potent efficiency against colon, liver, and breast cancer [69]. Breast cancer, which is the type of cancer that most affects and kills women, was also tested for another type of honey, the Manuka honey, and the results showed that it is cytotoxic to MCF-7 breast cancer cells
The phytochemical content and antioxidant activity of melon honey and Manuka honey and their cytotoxic properties were tested against human and metastatic colon adenocarcinoma. The ability to induce apoptosis in colon cancer cells depends on the concentration of honey and type of cell line, in addition to having a great relation with the phenolic content and residues of tryptophan. Honey was analyzed for phenolic, flavonoid, amino acid, and protein contents, as well as their free radical scavenging activities [71, 72]. Melon honey presented the highest amount of phenolics, flavonoids, amino acids, and proteins, as well as antioxidant capacity in relation to Manuka honey [71]. Both melon honey and Manuka honey induced cytotoxicity and cell death independently of dose and time in human and metastatic colon adenocarcinoma cells [71]. Melon honey showed to be more efficient in concentrations [71]. The results indicate that melon honey and Manuka honey can induce inhibition of cell growth and the generation of reactive oxygen species in colon adenocarcinoma and metastatic cells, which may be due to the presence of phytochemicals with antioxidant properties. These results suggest a potential chemo-preventive agent against colon cancer; in addition, honey can improve the functioning of other substances already used in cancer treatment [71, 73].
Research on cancer control has shown the importance of adjuvant therapies [74].
Several types of honey have been studied because of their anticancer properties [65, 67, 69, 70, 71, 74]. Currently, cancer is one of the world’s leading diseases, requiring further studies [65]. Some honey have already been tested against colon, breast, and liver tumor, as well as human kidney cancer and Ehrlich ascites carcinoma cell lines, where most have weak to strong cytotoxic activity depending on the type of honey tested and depending on the dose of honey [67, 69, 70, 71]. The effect of
2.6 Antioxidants
Antioxidants, which are present in large amounts of honey, making it a food with great antioxidative potential, are free radical scavengers that reduce the formation or neutralize free radicals [11, 78]. A comparative analysis of total phenolic content and antioxidant potential of commercially available common honey was performed along with Malaysia’s Tualang honey. Biochemical analyzes revealed a significantly high phenolic content in Tualang honey [78]. In addition, the antioxidant capacity of Tualang honey was higher than that of common honey; these data suggested that the high activity of elimination of free radicals and antioxidant activity observed in Tualang honey were due to the increase in the level of phenolic compounds, it was also observed that the antioxidant activity of honey depends on its botanical origin [78, 79]. Therefore, the favorable antioxidant properties of Tualang honey can be important for nutrition and human health [78].
Type 2 diabetes consists of progressive hyperglycemia, insulin resistance, and β-pancreatic cell failure, which may result from glucose toxicity, inflammatory cytokines, and oxidative stress, and is responsible for 90–95% of all cases of diabetes [80, 81]. A study investigated the effect of pre-treatment with Gelam honey, and the individual flavonoid components chrysin, luteolin, and quercetin on the production of reactive oxygen species, cell viability, lipid peroxidation, and insulin in hamster pancreatic cells, cultured under normal conditions and hyperglycemic, the pre-treatment of cells with Gelam honey extract or flavonoid components showed a significant decrease in the production of reactive oxygen species, glucose-induced lipid peroxidation, and a significant increase in insulin content and viability of cultured cells under hyperglycemic conditions. The results indicated the
Honey contains antioxidants, such as phenolic compounds that prevent cellular oxidative damage that leads to aging, disease such as cancer, metabolic disturbances, cardiovascular dysfunction and even death [83, 84]. The antioxidant effect of honey in young and middle-aged rats was compared, the rats were fed with pure water (control), those supplemented with 2.5 and 5.0 g/kg of Gelam honey for 30 days. Results showed that Gelam honey supplementation reduced DNA damage, plasma malondialdehyde level, and glutathione peroxidase. Liver activity superoxide dismutase also decreased in young rats supplemented with 5 g/kg of Gelam honey [84]. Gelam honey reduces the oxidative damage of young and middle-aged rats by modulating the activities of the antioxidant enzymes that were more prominent in higher concentration compared to the lower concentration [84]. Another study indicates that honey has these antioxidant and free radical sequestering properties, mainly due to its phenolic compounds [85].
Honey has antioxidant properties that can be further explored and studied, because antioxidants reduce free radicals and oxidative stress, which can help to promote and maintain health [80, 82, 84]. Besides the previously described, the antioxidant effect of honey can be an important property to help in the anticancer effect [67, 71].
3. Conclusions
Several studies have proven the effectiveness of honey as an alternative medicine; some have even shown that honey is as good a medicine as conventional medicine. Use of different types of honeys showed anti-inflammatory effect very similar to the conventional drug and that can be used as an alternative medicine in the treatment of diseases or inflammations. Honey can also be used as an antimicrobial agent anti-inflammatory, antibacterial, antivirals, antifungal, anticancer, and antioxidants. However, there is still a need to increase research on honey, especially in its potential as a medicine and also a dissemination of this knowledge to the population and the medical community, so an increase in the use of this powerful compound will be possible.
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