Honey By Mayo Clinic Staff
Honey is a sweet fluid made by honeybees using the nectar of flowering plants. There are about 320 different varieties of honey, which vary in color, odor and flavor.
Honey contains mostly sugar, as well as a mix of amino acids, vitamins, minerals, iron, zinc and antioxidants. In addition to its use as a natural sweetener, honey is used as an anti-inflammatory, antioxidant and antibacterial agent. People commonly use honey orally to treat coughs and topically to treat burns and promote wound healing.
Research on honey for specific conditions includes:
Cardiovascular disease. Antioxidants in honey might be associated with reduced risk of heart disease.
Antioxidants in honey might be associated with reduced risk of heart disease. Cough. Studies suggest that eucalyptus honey, citrus honey and labiatae honey can act as a reliable cough suppressant for some people with upper respiratory infections and acute nighttime cough.
Studies suggest that eucalyptus honey, citrus honey and labiatae honey can act as a reliable cough suppressant for some people with upper respiratory infections and acute nighttime cough. Gastrointestinal disease. Evidence suggests honey might help relieve gastrointestinal tract conditions such as diarrhea associated with gastroenteritis. Honey might also be effective as part of oral rehydration therapy.
Evidence suggests honey might help relieve gastrointestinal tract conditions such as diarrhea associated with gastroenteritis. Honey might also be effective as part of oral rehydration therapy. Neurological disease. Studies suggest that honey might offer antidepressant, anticonvulsant and anti-anxiety benefits. In some studies, honey has been shown to help prevent memory disorders.
Studies suggest that honey might offer antidepressant, anticonvulsant and anti-anxiety benefits. In some studies, honey has been shown to help prevent memory disorders. Wound care. Topical use of medical-grade honey has been shown to promote wound healing, particularly in burns.
Results might vary because there are no standardized methods for producing honey or verifying its quality.
Honey is generally safe in adults and children older than age 1. It might be helpful in treating burns, coughs and possibly other conditions.
Safety and side effects
Honey is likely safe for use as a natural sweetener, cough suppressant, and topical product for minor sores and wounds.
Avoid giving honey — even a tiny taste — to babies under the age of 1 year. Honey can cause a rare but serious gastrointestinal condition (infant botulism) caused by exposure to Clostridium botulinum spores. Bacteria from the spores can grow and multiply in a baby's intestines, producing a dangerous toxin.
Some people are sensitive or allergic to specific components in honey, particularly bee pollen. Although rare, bee pollen allergies can cause serious, and sometimes fatal, adverse reactions. Signs and symptoms of a reaction include:
Wheezing and other asthmatic symptoms
Irregular heart rhythms (arrhythmias)
Stinging after topical application
Honey might affect blood sugar levels.
There's currently no evidence to show how honey might interact with other drugs.
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The Chemical and Biological Properties of Propolis
The Antioxidant Properties of Propolis
Metabolic processes within the human body consist of multiple complex reactions which generate natural free radicals. The body also has natural enzymatic antioxidants, which include superoxide dismutase, catalase, and glutathione peroxidase, and non-enzymatic antioxidants including lipid soluble, e.g. vitamin E, and water soluble, e.g. vitamin C and glutathione, compounds for defence against the harmful effects of the reactive oxygen species (ROS) (Valko et al. 2007). A free radical in the body is simply an atom or molecule containing one or more unpaired electrons in its outer orbital, such as the oxygen atom shown in Fig. 7.1. The unpaired electron allows the ROS to participate in many reactions with other free radicals. In low to moderate concentrations, ROS play vital roles in the biological processes of the human body, including stimulating pathways in response to changes in the extracellular environment (cellular signalling), mitogenic response, and immune response for defence against infections in the intracellular environment (Valko et al. 2007; Halliwell and Gutteridge 2015).
Fig. 7.1 Schematic showing the orbitals of the oxygen atom Full size image
As can be seen in Fig. 7.2, oxygen molecules can accept energy in the form of electrons as an outcome of an inflammation process, leading to the production of oxygen-centred free radicals also known as ROS. The generation of ROS is regulated by the action of the enzyme RO synthase and over production results from both the mitochondrial electron transport chain and excessive production of NADH (Valko et al. 2007). Once formed, these ROS are highly reactive and produce a chain of deleterious reactions resulting in damage to cell structures (lipids, membranes, proteins and DNA) and modulation of many biological processes including inflammation and immune response. Oxidative stress occurs when there is an imbalance between the production of free radicals and physiologically active antioxidant metabolites in the body (Valko et al. 2007). The excessive production of ROS may be responsible for causing a large number of diseases, such as cancer (Kinnula and Crapo 2004), cardiovascular disease and inflammatory disorders such as rheumatoid arthritis. In addition, ROS can induce mutations or cause direct damage in DNA which leads to cell transformation and the possibility of developing a variety of malignant conditions (Valko et al. 2007). Also, active free radicals are the main factor involved in cellular aging and are responsible for the development of many CNS related medical conditions such as Parkinson’s and Alzheimer’s diseases. Antioxidant agents can serve as a defensive factor against free radicals in neuronal cells (Metodiewa and Kośka 1999; Martin and Grotewiel 2006; Valko et al. 2007).
Fig. 7.2 Diagram illustrating the formation of Reactive Oxygen Species (ROS). When the oxygen molecule accepts an electron, it becomes a superoxide radical which, upon further electronation, produces peroxide. The latter can undergo further reactions with electrons and protons to produce potent hydroxyl radicals. Antioxidants act by donating protons (H+) to free radicals, leading to the formation of water, as shown in Fig. 7.3 Full size image
Fig. 7.3 Illustration of the antioxidant effect of quercetin, a flavonoid, on hydroxyl radicals. Quercetin reduces the free radical to water while it is oxidised to an ortho-quinone Full size image
Fig. 7.4 Illustration of the process of wound healing Full size image
Many scientific papers have been published on the antioxidant effects of propolis (Bittencourt et al. 2015; Olczyk et al. 2013; Piccinelli et al. 2013). The relationship between antioxidant activity and the chemical composition of propolis from different origins has been investigated by several authors (Isla et al. 2001; Kalogeropoulos et al. 2009; Mello and Hubinger 2012; Piccinelli et al. 2013). These studies confirmed that the significant antioxidant activity of propolis is related to the high content of polyphenolic compounds, such as flavonoids, in the sample. Additionally, it has been reported that the essential oil constituents of Thymus vulgaris (thyme) could act as antioxidant agents (Deans et al. 1992). Since one of the main components of propolis has been proven to be essential oils (Bankova et al. 2014; Marcucci 1995), it might be possible that these components contribute to its antioxidant effects. The study conducted by Kumazawa et al. suggested that propolis could act as an antioxidant agent due to the presence of anti-oxidative compounds such as kaempferol and phenethyl caffeate (Kumazawa et al. 2007). Their conclusion came following the investigation of antioxidant activities of various propolis samples from different geographical origins using the DPPH assay.
Another approach to verifying the antioxidant action for potential in human medicine is to analyse the potential alleviating effect of propolis in neurodegeneration by means of cell viability assays on neuronal cells (Imamura et al. 2006). It is well known that the main factor in CNS disorders is oxidative stress. Thus, antioxidant properties play a vital role in the management of CNS disorders induced by oxidative stress. Shimazawa et al. assayed and reported the neuroprotective effect of green Brazilian propolis both in vitro and in vivo. First, the in vitro assay was conducted by exposure of neuronal cell cultures to hydrogen peroxide (H 2 O 2 ), followed by addition of propolis to the neuronal cells. On the other hand, the in vivo experiments studied the effect of propolis against lipid peroxidation in the forebrain of mice and DPPH-induced free radical production (Shimazawa et al. 2005). Furthermore, a recent study found that Turkish propolis contains phenolic components which have the ability to minimize DNA damage by inhibiting the effects of H 2 O 2 in cultured fibroblasts (Darendelioglu et al. 2016). An effective natural antioxidant agent such as propolis could provide a safe and novel treatment for oxidative stress-related diseases, especially in elderly people whose conditions tend to be complex in nature and include cases of neurodegeneration corresponding to aging. In addition, propolis could play a key role in the management and prevention of various disease conditions in which ROS have a causative effect, such as some inflammatory disorders, cancer, cardiovascular and immune diseases.
The Antimicrobial Activity of Propolis
Until now, the most widely investigated property of propolis is its antimicrobial activity, with hundreds of publications on this topic having appeared in the last 40 years (Bogdanov 2012). These findings explain why propolis plays such an important role in bee hives since it can be considered as a chemical weapon against pathogenic microorganisms (Fokt et al. 2010; Bankova 2005a). Different propolis types contain many chemical constituents responsible for their antimicrobial properties (Bankova 2005a) and it seems that the sum of the propolis antimicrobial components, rather than individual substances, is responsible for the observed antimicrobial effect (Kujumgiev et al. 1999; Bogdanov 2012). Propolis shows antibacterial (Silici and Kutluca 2005; Kujumgiev et al. 1999; Grange and Davey 1990), antifungal (Kartal et al. 2003; Kujumgiev et al. 1999; Ota et al. 2001), antiviral (Amoros et al. 1992a, b), antiprotozoal (Freitas et al. 2006; Dantas et al. 2006a, b), anti-tumour (Callejo et al. 2001; Komericki and Kränke 2009; Banskota et al. 2000; Su et al. 1994), anti-inflammatory (Khayyal et al. 1992; Dobrowolski et al. 1991; Fokt et al. 2010), local-anaesthetic (Marcucci 1995), antioxidant (Russo et al. 2002; Fokt et al. 2010; Kumazawa et al. 2007), immunostimulating (Dimov et al. 1992; Oršolić et al. 2004), cytostatic (Banskota et al. 1998) and hepatoprotective (Banskota et al. 2001a; Won Seo et al. 2003) activities.
There are many components which are responsible for the biological activity of propolis and these vary with propolis sample type and the solvents used in its extraction (Ugur and Arslan 2004). Flavonoids and esters of phenolic acids are generally regarded as bioactive compounds which are responsible for antimicrobial activity (Fokt et al. 2010). However, there are many other components with such activity; these are summarised in Tables 7.1 and 7.2 for different types of propolis and two of the main types, respectively.
Table 7.1 Biological effects of propolis components adapted from Bogdanov (2012) Full size table
Table 7.2 Biologically active ingredients in Poplar and Baccharis propolis adapted from Bogdanov (2012) Full size table
Antibacterial Activity of Propolis
Antimicrobial activity is recognised as the most important property of propolis, particularly activity against bacteria. Several studies have been performed to evaluate this property against a large group of Gram-positive and Gram-negative bacteria; both aerobic and anaerobic types. The bacteria studied are summarized in Table 7.3. These bacteria were either from laboratory collections or isolated from clinical samples. The studies used propolis of different geographical origins and chemical composition, and employed different experimental approaches such as disc diffusion and disc dilution to investigate the antibacterial activity. In the disc diffusion method, antibacterial activity is determined by measuring the diameter of the bacterial growth inhibition zone in the agar layer surrounding a disc containing propolis extracts (Kujumgiev et al. 1999). The dilution method is used to determine the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) which are, respectively, the lowest concentrations that inhibit visible bacterial growth and the lowest concentration that kills bacteria (Grange and Davey 1990; Stepanović et al. 2003). The vast majority of antibacterial activity studies were carried out using in vitro bioassays, as mentioned above. Although the composition of propolis differs considerably depending on its botanical origin, all examined types of propolis have revealed strong antibacterial activity (Kujumgiev et al. 1999; Bankova 2005b; Bankova et al. 2007). Also, the activity of propolis may depend on the type of bee collecting it since it was found that poplar propolis collected by Apis mellifera caucasica had a higher antibacterial activity than that collected by Apis mellifera anatolica and Apis mellifera carnica (Silici and Kutluca 2005).
Table 7.3 Bacteria used in the determination of the antibacterial activity of propolis adapted from Fokt et al. (2010) Full size table
Tests for the antibacterial activity of propolis were carried out against a range of different pathogenic bacteria in several studies, as summarised in Table 7.3 (Banskota et al. 2001b; Burdock 1998; Ghisalberti 1979; Grange and Davey 1990). It has been reported that propolis is more active against Gram-positive pathogens, but many Gram-negative bacteria are also inhibited (see Table 7.3) (Fokt et al. 2010; Wagh 2013).
The data collected from a range of studies on the antibacterial properties of propolis support the fact that propolis is active mainly against Gram-positive bacteria and either displays much lower activity against Gram-negative ones or is not active at all (Marcucci 1995; Silici and Kutluca 2005; Kujumgiev et al. 1999; Drago et al. 2007; Grange and Davey 1990; Kartal et al. 2003; Dobrowolski et al. 1991; Fadaly and El-Badrawy 2001).
Such results can be seen in the study by Kujumgiev et al., who evaluated propolis samples from different geographic regions (tropical and temperate zones) against Staphylococcus aureus and Escherichia coli. All of the extracts exhibited significant antibacterial activity against S. aureus but none were active against E. coli (Kujumgiev et al. 1999).
However, it was reported that ethanolic extracts from propolis (EEP) completely inhibited the growth of S. aureus, Enterococcus spp. and Bacillus cereus, and moderately inhibited the Gram-negative organisms Pseudomonas aeruginosa and E. coli. (Grange and Davey 1990). The antibacterial activity of EEP from Brazilian propolis, collected during four seasons, was found to inhibit the growth of Gram-positive bacteria and higher concentrations of EEP were needed to inhibit Gram-negative bacterial growth, but the extracts had no effect on Klebsiella pneumoniae.
More recent research has revealed antibacterial activity of propolis against Micrococcus luteus, Salmonella typhimurium (Uzel et al. 2005) and K. pneumonae (Victorino et al. 2007); and although in earlier studies (Grange and Davey 1990) it was stated that Listeria monocytogenes is not sensitive to propolis, more recent studies revealed significant activity against this organism (Ozcan et al. 2004; Yang et al. 2006). It was also found that propolis showed strong antibacterial activity against 13 different bacterial plant pathogens (Basim et al. 2006).
The antibacterial effect of propolis is bactericidal (Grange and Davey 1990) and it is proposed to work by inhibiting bacterial mobility. In addition, it has been shown that the antibacterial activity of poplar propolis is based on inhibition of quorum sensing (QSI), with the flavonoid pinocembrin being an important QSI agent (Savka et al. 2015).
The flavonoids galangin, pinocembrin and pinostrobin have been most associated with the antibacterial properties of propolis, as shown in Table 7.1 (Dimov et al. 1992), but it has also been reported that propolis samples containing only traces of flavonoids demonstrate antibacterial action (Tomás-Barberán et al. 1993). In addition, ferulic and caffeic acids, prenylated coumaric acid, benzophenone derivatives and diterpenic acids have also been reported as antibacterial compounds (Ghisalberti 1979; Burdock 1998; Castaldo and Capasso 2002; Kujumgiev et al. 1999; Popova et al. 2007; Mirzoeva et al. 1997).
In recent years, there has been considerable interest in using propolis in hospitals as an antibacterial agent due to the increase in antibiotic resistance (Bogdanov 2012). It has been shown that the components in propolis act synergistically against bacteria (Onlen et al. 2007; Orsi et al. 2006; Scazzocchio et al. 2006; Speciale et al. 2006; Stepanović et al. 2003). Several authors point out that the antimicrobial activity of propolis is related to its highly complex and variable constituents and their synergistic action (Bonvehí and Coll 1994; Burdock 1998; Freitas et al. 2006; Scazzocchio et al. 2006; Mirzoeva et al. 1997; Takaisi-Kikuni and Schilcher 1994).
Compounds which were active against Mycobacterium marinum, the closest genetic relative to Mycobacterium tuberculosis, were isolated from Saudi Arabian propolis. The strongest activity was found for the flavonoid psiadiarabin which showed an activity only 5 times less than that of the gentamycin control (Almutairi et al. 2014a). Twelve ethanolic extracts of propolis from different areas within Libya were tested against M. marinum in order to determine whether or not the observed activity was associated with specific components in the samples. The extracts showed moderate to strong activity against M. marinum (Siheri et al. 2016).
Commonly, the biological activity of a natural medicinal product decreases with increasing storage time, but Meresta (1997) stated that ethanolic solutions of propolis stored for 10–15 years had increased antibacterial activity (Meresta 1997).
Antiviral Activity of Propolis
Many recent reviews have reported on the various antiviral activities of propolis samples from different geographical origins against different strains of viruses, such as Adenovirus, HSV, Influenza A and B viruses, Newcastle disease virus, Polio virus, Vaccinia, Rotavirus, vesicular stomatitis virus (VSV), and Corona virus (Starzyk et al. 1977; Fokt et al. 2010; Bogdanov and Bankova 2012), as summarised in Table 7.4. Studies have reported that propolis has significant antiviral activity and interferes with the replication of some different viruses that cause human diseases, including Herpes simplex, genitalis and zoster, influenza and smallpox (De Castro 2001; Bogdanov 2012; Silva-Carvalho et al. 2015).
Table 7.4 Antiviral activity of the different propolis constituents from different geographical origins (1992–2016) adapted from Silva-Carvalho et al. (2015) Full size table
Studies over the past two decades have provided further important information on the antiviral properties of propolis. The effect of propolis on several DNA and RNA viruses, including herpes simplex type 1 (HSV-1), an acyclovir resistant mutant, herpes simplex type 2 (HSV-2), adenovirus type 2, VSV, and poliovirus type 2, was studied. The inhibition of poliovirus propagation was observed through a plaque reduction test and a multistep virus replication assay. At a concentration of 30 μg/ml, propolis reduced the titer of HSV by 1000, whereas VSV and adenovirus were less susceptible. The antiviral effect of propolis along with the major flavonoids found therein, such as galangin, kaempferol, chrysin, apigenin, luteolin and quercetin, against HSV was also studied. Flavonols were found to be more active than flavones, with the order of importance from least to most active being galangin, kaempferol and quercetin, demonstrating that activity increases with the number of hydroxyl groups in the molecule. The efficacy of binary flavone-flavonol combinations against HSV-1 was also investigated. It was concluded that synergism might occur between two or more compounds, leading to enhanced antiviral activity of propolis (Amoros et al. 1992a).
A number of other studies have suggested an association between the antiviral activity of propolis and certain compounds which are found therein. Some flavonoids have an inhibitory effect on human immunodeficiency virus (HIV) infection and replication. It was found that luteolin was more active than quercetin, but less active than caffeic acid and some esters of substituted cinnamic acids found in propolis. Isopentyl ferulate significantly inhibited the infectious activity of influenza virus A. It has previously been observed that the antiviral activity is due to both the major constituents in propolis and the minor components such as 3-methylbut-2-enyl caffeate and 3-methylbutyl ferulate (Amoros et al. 1992a; Maksimova-Todorova et al. 1985; Vanden Berghe et al. 1986; Marcucci 1995). 3-Methylbut-2-enyl caffeate showed strong inhibition of HSV-1 growth (Amoros et al. 1992a, b).
In addition, it has been reported that some propolis constituents and their analogues (esters of substituted cinnamic acids) significantly inhibited infection by influenza virus A/Hong Kong (H3N2) (Serkedjieva et al. 1992). A study of the antiviral effect of caffeic acid, a constitutent of propolis, found that Vaccinia and adenovirus were more sensitive to caffeic acid than polio and parainfluenza viruses, but it exhibited only minor activity against influenza virus (Fokt et al. 2010).
The antiviral activity of aqueous and ethanol extracts of propolis and constituents, such as flavonoids caffeic acid, p-coumaric acid, benzoic acid, galangin, pinocembrin and chrysin, was tested against herpes simplex virus type 1 (HSV-1). Both propolis extracts demonstrated high levels of antiviral activity against HSV-1 in viral suspension tests; plaque formation was significantly reduced by >98%. Galangin and chrysin were proposed to greatly contribute to the observed activity (Schnitzler et al. 2010).
Besides its inhibitory effect on viral growth, propolis also shows virucidal action on enveloped viruses HSV and VSV (Marcucci 1995). The activity of Brazilian propolis against HSV-1 infection was studied after its oral administration to infected mice three times daily and on days 0–6 after treatment. The results revealed a significant effect on the development of herpetic skin lesions (Shimizu et al. 2011).
The antiviral activities of four propolis samples from Austria, Egypt, France and Germany were investigated against avian reovirus (ARV) and infectious bursal disease virus (IBDV). The results indicated that all propolis samples reduced the viral infectivity to a different degree and that the Egyptian propolis showed the highest antiviral activity against ARV and IBDV (Hegazi et al. 2000; El Hady and Hegazi 2002). The activity of 13 ethanol extracts of Brazilian green propolis against viruses was investigated. The extracts displayed antiviral activity against influenza virus in vitro and in vivo. The effect was attributed to the flavonoid and phenolic acid constituents (Shimizu et al. 2008).
The aqueous and ethanolic extracts of propolis were evaluated against HSV-1 and HSV-2. The anti-herpetic effect was analysed in cell culture and both propolis extracts exhibited high levels of antiviral activity against HSV-2. Infectivity was significantly reduced by 49% and direct concentration- and time-dependent antiherpetic activity was demonstrated (Nolkemper et al. 2010).
A hydromethanolic extract of geopropolis (HMG) was evaluated using viral DNA quantification experiments and electron microscopy. The study showed a reduction of viral DNA from herpes virus by about 98% under all conditions and concentrations of HMG tested (Coelho et al. 2015).
The antiviral activity of EEP of Turkish propolis on the replication of both HSV-1 and HSV-2 was investigated. HSV-1 and HSV-2 were suppressed in the presence of 25, 50, and 100 μg/mL of propolis extract when infection of a Hep-G2 cell line was examined. Synergistic effects of propolis with acyclovir were identified against these viruses. The results showed a significant decrease in the number of viral copies (Yildrim et al. 2016).
It was found that propolis suppresses the replication of human immunodeficiency virus type 1 (HIV-1), in addition to modulating immune responses. The antiviral activity of propolis samples against HIV-1 from several geographic regions was investigated in CD4+ lymphocyte and microglial cell cultures. The results showed inhibited viral expression in a concentration-dependent manner (maximal suppression of 85 and 98% was observed at 66.6 μg/ml propolis in CD4+ lymphocyte and microglial cell cultures, respectively) (Gekker et al. 2005).
Propolis flavonoids act by preventing the virus from entering the host cell and by reducing intracellular replication activities. This process contributes to suppression of the growth and development of the virus. Other possible mechanisms of antiviral activity include inhibition of reverse transcriptase and stimulation of the immune system to fight back against the infection (Schnitzler et al. 2010; Boukraâ et al. 2013).
Propolis extracts were screened in a plaque reduction assay and exhibited anti-influenza activity. Mice were infected intranasally with the influenza virus, and the four extracts were orally administered at 10 mg/kg three times daily for seven successive days after infection; the EEP was found to possess anti-influenza activity and to ameliorate influenza symptoms in mice (Shimizu et al. 2008).
Antiprotozoal and Antihelminthic Activity of Propolis
Recently, attention has been focused on the antiparasitic activity of propolis since improvements on existing drugs against several tropical diseases caused by different protozoa are required. Numerous assessments have been performed using different in vivo and in vitro experiments to investigate the activity of raw propolis and active compounds isolated from propolis. Accordingly, significant effects against different parasitic species including Cholomonas paramecium, Eimeria magna, Media perforans, Giardia lambia, Giardia duodenalis, Trichomonas vaginalis, Trypanosoma cruzi and Trypanosoma evansi have been reported in the literature (Freitas et al. 2006; Falcão et al. 2013; Bogdanov 2012; Parreira et al. 2010). Several studies have been performed that show the activity of propolis and its components against a range of protozoan parasites which cause various human diseases, including Trypanosoma brucei which causes sleeping sickness and Trypanosoma cruzi which causes Chagas disease (Higashi and De Castro 1994; De Castro and Higashi 1995; Marcucci et al. 2001; Dantas et al. 2006a, b; Salomão et al. 2010; Falcão et al. 2013; Almutairi et al. 2014b; Siheri et al. 2014, 2016; Omar et al. 2016). Antiprotozoal effects of different propolis samples were reported against Leishmania donovani, which causes visceral leishmaniasis, and for other strains of leishmania (Duran et al. 2008; Pontin et al. 2008; Ozbilge et al. 2010; Monzote et al. 2011; Amarante et al. 2012; Da Silva et al. 2013; Siheri et al. 2016). Recent studies have reported antiprotozoal effects of propolis extracts against Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax and Plasmodium ovale, all of which cause malaria (Olayemi 2014; Siheri et al. 2016). Propolis is also effective against Entamoeba histolytica and Giardia lamblia, which cause intestinal infections (dysentery and diarrhoea), as well as multicellular organisms such as intestinal worms, including helminths such as Schistosoma spp., cestodes such as tapeworms, nematodes such as roundworms, and trematodes such as flukes (Freitas et al. 2006; Issa 2007; Hegazi et al. 2007; Abdel-Fattah and Nada 2007; Noweer and Dawood 2008; Alday-Provencio et al. 2015; Hassan et al. 2016). Some of the studies are described in more detail below.
Extracts of Portuguese propolis and its potential sources such as poplar buds were screened against different protozoa, including Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and Trypanosoma cruzi (Falcão et al. 2013). The toxicity of the extracts against MRC-5 fibroblast cells was also evaluated to assess toxic selectivity. The propolis extracts showed moderate activity against these parasites, with the highest inhibitory effect being observed against Trypanosoma brucei (Falcão et al. 2013).
Recently, extracts from 12 samples of propolis collected from different regions of Libya were tested for their activity against Trypanosoma brucei, Leishmania donovani, Plasmodium falciparum and Crithidia fasciculate, while the cytotoxicity of the extracts was also tested against mammalian cells. All of the extracts were active to some degree against all of the protozoa, exhibiting a range of EC 50 values between 1.65 and 53.6 μg/ml (Siheri et al. 2016), while only exhibiting moderate to negligible cytotoxicity.
The activity of propolis against Chagas disease (caused by Trypanosoma cruzi) was assessed in comparison with crystal violet, a standard drug recommended to prevent the transmission of Chagas disease via blood (De Castro and Higashi 1995). The relationship between trypanocidal activity and the chemical composition of propolis has been widely investigated by several authors and these studies confirmed that Brazilian green propolis is highly active against T. cruzi transmission (Dantas et al. 2006b; De Castro and Higashi 1995; Higashi and De Castro 1994).
The activity of ethanol extracts from Brazilian (Et-Bra) and Bulgarian (Et-Blg) propolis against T. cruzi were tested and it was found that, although there were differences in the chemical composition between both extracts, they were both active against T. cruzi. The study also confirmed that in European samples biological activity was associated with the presence of flavonoids and aromatic acids and their esters. In Brazilian propolis, amyrins occur as components that might contribute to the anti-trypanosomal activity (Salomão et al. 2004; Higashi and De Castro 1994).
The activity of acetone and ethanol extracts of two Bulgarian propolis samples (Bur and Lov) against T. cruzi was evaluated. Both extracts showed similar chemical compositions with a high content of flavonoids and strong inhibitory activity against T. cruzi proliferative epimastigotes, which were more susceptible than trypomastigotes. While in the presence of blood, the activity of Et-Bur or Et-Lov against trypomastigotes was similar to that of the standard drug, crystal violet (Prytzyk et al. 2003). It was also found that two different samples from Bulgarian propolis showed significant activity against T. cruzi in vitro (Salomão et al. 2004, 2009; Dantas et al. 2006a, b).
Current therapy for T. evansi infections is not effective for the vast majority of animals with relapsing parasitemia and clinical signs. The susceptibility of T. evansi to a propolis extract in vitro and in vivo was evaluated. A dose-dependent trypanocidal activity of the propolis extract was observed in vitro. All trypomastigotes were killed within 1 h after incubation with 10 μg/ml of the extract. However, in vivo assessment of concentrations of 100, 200, 300 and 400 mg/kg administered orally for 10 consecutive days presented no curative effect, and the rats died from the disease. However, rats treated with the two highest concentrations of propolis extract showed higher longevity than the other groups. Based on these data the study concluded that, despite the lack of curative efficacy observed in vivo at the concentrations tested, propolis extract can prolong life in rats infected with the protozoan (Gressler et al. 2012).
A comprehensive chemical profiling study was carried out on 22 African propolis samples collected from the sub-Saharan region. Results revealed that triterpenoids were the major chemical components in more than half of the propolis samples analysed in this study and some others were classified as temperate and Eastern Mediterranean types of propolis. Based on comparative chemical profiling, one propolis sample from southern Nigeria stood out from the others by containing prenylated isoflavonoids, which indicated that it was more like Brazilian red propolis (Zhang et al. 2014). This propolis was further investigated and ten phenolic compounds were isolated, including a new dihydrobenzofuran. All the isolated compounds were tested against T. brucei and displayed moderate to high activity. Some of the compounds tested showed similar activity against wild type T. brucei and two strains displaying pentamidine resistance. The Nigerian propolis from Rivers State showed some similarities to Brazilian red propolis and exhibited antitrypanosomal activity at a potentially useful level (Omar et al. 2016).
The chemical profile and antitypanosomal activity of Ghanian propolis against T. brucei was also investigated. Two compounds were isolated; a prenylated tetrahydroxy stilbene and a geranylated tetrahydroxy stilbene. These compounds exhibited moderate activity against T. brucei. In the same paper, isolation of a new phloroglucinone analogue from Cameroon propolis was reported. The compound was found to possess high potency, comparable to that of suramin (Almutairi et al. 2014b).
The EEP of Libyan propolis was tested for its activity against T. brucei. One of the samples was fractionated and yielded a number of active fractions. Three of the active fractions contained single compounds, found to be 13-epitorulosal, acetyl-13-epi-cupressic acid and 13-epi-cupressic acid, which had been identified previously in Mediterranean propolis. Two of the compounds had a MIC value of 1.56 μg/mL against T. brucei (Siheri et al. 2014).
The chemical composition and biological activity of a propolis sample collected from Saudi Arabia were investigated. A new diterpene, propsiadin, was isolated along with two flavonoids and a known diterpene, psiadin. The compounds had MICs in the range 30.9–78.1 μM against T. brucei. The propolis was thought to originate from Psiadia arabica and Psiadia punctulata, representing a new type of propolis (Almutairi et al. 2014a).
Leishmaniasis has been reported as an endemic disease in 88 countries in tropical and sub-tropical regions across the world, affecting more than 12 million people. There are no vaccines available for any form of the disease and the chemotherapy of this disease is still inadequate and expensive (Kayser et al. 2003; Croft et al. 2005). An intense search for potential natural products isolated from plants or propolis for the treatment of Leishmaniasis has been carried out during the last decades. The previous literature contains several reports on the activity of a variety of crude natural extracts against Leishmania, especially from plants collected in tropical zones (Croft et al. 2006).
Previous studies have reported that propolis samples from various origins possess activity as anti-leishmanial agents due to the presence of flavonoids and amyrins (Machado et al. 2007).
A study of propolis from Turkey investigated the effects of propolis against Leishmania tropica and it was observed with microscopic examination that propolis inhibited parasite growth at ≥32 μg/ml concentration. It was also found that the antileishmanial effects of propolis increased with increasing concentrations and incubation periods (Ozbilge et al. 2010).
The activity of Baccharis dracunculifolia, which is the most important plant source of Brazilian green propolis, against promastigote forms of L. donovani was investigated and IC 50 values of 42 μg/ml were obtained. The extract also displayed high activity in a schistosomicidal assay (Parreira et al. 2010).
The activity of eighteen Cuban propolis extracts collected in different geographic areas were screened against Leishmania amazonensis and Trichomonas vaginalis. The study observed that all propolis extracts produced an inhibitory effect on intracellular amastigotes of L. amazonensis. Only five samples decreased the viability of T. vaginalis trophozoites at concentrations lower than 10 μg/ml (Monzote et al. 2011).
Brazilian green propolis was tested against L. braziliensis by experimental infection of mice. The results showed an IC 50 value of 18.1 μg/ml against promastigote forms of L. brasiliensis. IC 50 values were in the range 78–148 μg/ml against the M2904 strain of L. brasiliensis and the extract also had antiproliferative activity on L. brazilensis promastigotes at 100 μg/ml (Da Silva et al. 2013).
The EEP of Libyan propolis collected from North East Libya was found to be active against L. donovani, and four compounds, three diterpenes and a lignan, were isolated. These compounds exhibited moderate to strong activity against L .donovani, with IC 50 values in the range 5.1–21.9 μg/ml (Siheri et al. 2014). These results were replicated in subsequent assays on L. donovani involving twelve extracts of Libyan propolis where IC 50 values ranged from 2.67 to 16.2 μg/ml (Siheri et al. 2016).
The activity of methanolic extracts of ten Bolivian propolis samples was studied against L. amazonensis and L. braziliensis. The most active samples towards Leishmania species had IC 50 values in the range 78–121 μg/ml against L. amazonensis and L brasiliensis (Nina et al. 2016).
It was reported that an ethanolic extract of European propolis showed activity against Toxoplasma gonodi (De Castro 2001).
The activity of Nigerian propolis was tested against Plasmodium berghei using mice experimentally infected with P berghei, with chloroquine as a positive control. The propolis significantly reduced the level of parasitemia in treated mice, and there was no significant difference from mice treated with chloroquine (Olayemi 2014).
Propolis extract inhibited the growth of the intestinal parasites Giardia lamblia, Giardia intestinalis and Giardia duodenalis. The extract decreased the growth of trophozoites and the level of inhibition varied according to the extract concentration and incubation times. Significant decreases in parasite growth were detected in cultures exposed to 125, 250 and 500 μg/ml of propolis, respectively, for all incubation periods (24, 48, 72 and 96 h). Growth reduction of 50% was observed in cultures treated with 125 μg/ml of the extract, and concentrations of 250 and 500 μg/ml were able to inhibit growth by more than 60% (Freitas et al. 2006).
Mice were orally infected with axenically cultivated Giardia lamblia trophozoites. The trophozoite count in the intestines, measurements of interferon-gamma serum levels, and histopathological examination of duodenal and jejunal sections were carried out. The results showed that propolis as a prophylaxis resulted in a significant decrease in the intensity of infection. As a treatment, propolis caused a more significant decrease in trophozoite count than that obtained by metronidazole. However, mice treated with propolis alone showed a reversed CD4+: CD8+ T-lymphocyte ratio resulting in a strong immune enhancing effect, which resulted in an adverse increase in inflammatory response at the intestinal level. Combined therapy of metronidazole and propolis was more effective in reducing the parasite count than by each drug alone (Abdel-Fattah and Nada 2007).
Propolis was used as a foliar application or soil drench on fava bean plants. Propolis treatment increased total chlorophyll and carotenoid content and the magnitude of increase was more noticeable after applying a higher concentration (1000 mg/l). It was found that fava bean plants treated with propolis extract, either as a foliar application or soil drench, were able to overcome the inhibitory influence of nematode infection on chlorophyll formation (Noweer and Dawood 2008).
A study was carried out in BALB/c mice to investigate the synergistic effect of the EEP of Egyptian propolis and immunization with Taenia saginata crude antigen for the prevention of bovine cysticercosis. After 24 weeks of challenge the mice in G2 (given both EEP and immunisation) showed the highest level of protection (100%) with no cyst being detected as for mice in G1 (which received only immunisation). The latter showed just 33.3% protection. Additionally, the ELISA results in this study showed higher antibody titres in G2, with reduction in the alteration of liver and kidney functions, compared to mice in G1 (Kandil et al. 2015).
There are several papers on the antihelmintic effects of propolis extracts. Propolis inhibited the growth of the helminth parasite Fasciola gigantica (Hegazi et al. 2007). In tests against schistosomiasis in mice, a significant reduction in the number of schistosomules of 59.2% was obtained in the group treated with propolis compared to a reduction of 98.9% in the praziquantel treated group (Issa 2007). A study was carried out to evaluate the effect of Egyptian propolis against Toxocara vitulorum. Adult worms were incubated for 24 h in several concentrations of EEP (100, 50, 25, 12 and 6 μg/ml) and assessed by light and scanning electron microscopy following 24 h incubation. It was observed that the extract possessed anthelmintic efficacy and the mortality rate was concentration dependent: LC 25 was 6.9 μg/ml, LC 50 was 12.5 μg/ml, and LC 90 was 53.4 μg/ml. The authors thus confirmed the nematodicidal effect of Egyptian propolis (Hassan et al. 2016).
Antifungal Properties of Propolis
The activity of an ethanolic extract of Italian propolis was tested against a range of zoophilic fungi and Candida species. The extracts were effective at 5% w/v in inhibiting fungal growth (Cafarchia et al. 1999).
The activity of Brazilian propolis against 80 strains of Candida yeast was studied: 20 strains of Candida albicans, 20 strains of Candida tropicalis, 20 strains of Candida krusei, and 15 strains of Candida guilliermondii. The propolis showed clear antifungal activity with the following order of sensitivity: C. albicans > C. tropicalis > C. krusei > C. guilliermondii. MICs were in the range 8–12 mg/ml. Patients with full dentures who used a hydroalcoholic propolis extract showed a decrease in the number of Candida in their saliva (Ota et al. 2001). In a further study patients treated with a commercial ethanol extract of propolis showed lesion regression similar to that observed in patients treated with nystatin (Santos et al. 2005).
An alcoholic extract of Brazilian propolis was tested against the fungal isolates Candida parapsilosis, C. tropicalis, C. albicans and other yeast species obtained from onychomycosis lesions. The concentration capable of inhibiting all of the yeasts contained 50 μg/ml flavonoids while 20 μg/ml flavonoids promoted yeast cell-death. Trichosporon sp. were the most sensitive species (Oliveira et al. 2006).
The antifungal activity of propolis ethanol extract (PE) and propolis microparticles (PM) obtained from a sample of Brazilian propolis was tested against vulvovaginal candidiasis (VVC). Yeast isolates obtained from vaginal exudates of patients with VVC were exposed to PE and PM, as well as to conventional drugs used in the treatment of VVC (Fluconazole, Voriconazole, Itraconazole, Ketoconazole, Miconazole and Amphotericin B). Some Candida albicans isolates showed resistance or dose-dependent susceptibility for the azole drugs and Amphotericin B. All yeasts were inhibited by PE and PM, with small variations, independent of the species of yeast. While the activity of the azole drugs was much higher than both PE and PM, the extracts inhibited resistant lines in the range 33–1100 to 174–5574 μg/ml, respectively (Dota et al. 2011).
The antifungal activity of propolis extracts from Argentinian propolis was tested against a range of fungi and yeasts. The most susceptible species were Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. All the dermatophytes and yeasts tested were strongly inhibited by different propolis extracts (MICs between 16 and 125 μg/ml). The main bioactive compounds in the extracts were found to be 2′,4′-dihydroxy-3-methoxychalcone and 2′,4′-dihydroxychalcone. Both were highly active against clinical isolates of T. rubrum and T. mentagrophytes (MICs and MFCs between 1.9 and 2.9 μg/ml) (Agüero et al. 2009).
What is Propolis Good For? Why You Need to Take Propolis Extracts and Its Benefits
Bee propolis is a brown resin-like substance made from a mix of beeswax, resin, sap, botanical compounds and bees’ saliva that is obtained from beehives. Found in the hive, propolis is vital to honey bee survival -- it protects and strengthens the beehive against the external elements, prevents disease and parasites from taking over, and is even used to trap intruders that enter the hive.
Like honey, propolis has a history of medicinal use by the Greeks to Assyrians and Egyptians. It has been used for healing wounds and tumours, abscesses and even used for mummification. These days, propolis is still being used for healing benefits, due to its antibacterial, antiviral and anti-inflammatory effects.
Propolis is often found in all types of pharmaceutical and natural products, such as gels, lipsticks, ointments and mouthwash. It can be applied externally for wounds and sores caused by infection and also taken internally through throat sprays and other propolis extracts.
Benefits of Propolis
Propolis provides support for your general well-being and immunity through its powerful antioxidant benefits and defense against viruses and infections. It can be used to ward off colds, flu, cough, tonsillitis and cystitis and also help with recovery times when sick.
Propolis is rich in flavonoids, enzymes, trace elements, amino acids, polysaccharides and vitamins. Flavonoids are antioxidants present in propolis that can help to reduce oxidative stress in your cells.
Promote Healing of Skin
Propolis has long been used to promote healing of the skin when exposed to burns and wounds. Propolis has been used topically for warts, cold sores, allergies, psoriasis, eczema and other skin issues.
Antibacterial, antifungal and antiviral
Similarly, propolis has been used to guard against harmful bacteria, fungi and viruses like yeast and fungal infections and oral bacteria. Propolis is especially known to help with oral bacteria and the development of cavities through the use of propolis-flavoured toothpaste, mouthwash and gels.
Why You Should Take Nature’s Glory Propolis Extracts
Due to its versatility and natural sources, propolis extracts are one of our favourite supplements. Apply topically or take them daily, you can still get all the beneficial properties for everyday health.
Nature’s Glory Propolis Balls are made from propolis extract, ume plum concentrate, honey and vitamin C to promote healing, ease pain, beautify hair, provide relief from gastric, skin disorders, hoarseness, ulcers, baldness, and asthma. Packed with flavonoids, enzymes, trace elements, organic/amino acids, polysaccharides and vitamins, our propolis balls are a natural antibacterial and rejuvenating agent. It is chemical and pesticide free.
Nature’s Glory Propolis Extract is a high potency liquid propolis extract made from certified organic propolis and manuka honey. It contains anti-viral, antibacterial properties that help ease pain, hoarse throat, gastric, skin disorders and promotes healing.
These propolis extracts are handy to keep in your medicine cabinet to guard against everyday ailments and for long-term immunity and health. If it’s good enough for bees and their hives, it can be good for you too!