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Identification and quantification of methylglyoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand
Abstract
The 1,2-dicarbonyl compounds 3-deoxyglucosulose (3-DG), glyoxal (GO), and methylglyoxal (MGO) were measured as the corresponding quinoxalines after derivatization with orthophenylendiamine using RP-HPLC and UV-detection in commercially available honey samples. Whereas for most of the samples values for 3-DG, MGO, and GO were comparable to previously published data, for six samples of New Zealand Manuka (Leptospermum scoparium) honey very high amounts of MGO were found, ranging from 38 to 761 mg/kg, which is up to 100-fold higher compared to conventional honeys. MGO was unambigously identified as the corresponding quinoxaline via photodiodearry detection as well as by means of mass spectroscopy. Antibacterial activity of honey and solutions of 1,2-dicarbonyl towards Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were analyzed using an agar well diffusion assay. Minimum concentrations needed for inhibition of bacterial growth (minimum inhibitory concentration, MIC) of MGO were 1.1 mM for both types of bacteria. MIC for GO was 6.9 mM (E. coli) or 4.3 mM (S. aureus), respectively. 3-DG showed no inhibition in concentrations up to 60 mM. Whereas most of the honey samples investigated showed no inhibition in dilutions of 80% (v/v with water) or below, the samples of Manuka honey exhibited antibacterial activity when diluted to 15-30%, which corresponded to MGO concentrations of 1.1-1.8 mM. This clearly demonstrates that the pronounced antibacterial activity of New Zealand Manuka honey directly originates from MGO.
... al [20] reported that MGO is responsible for the heightened and unique non-peroxide antibacterial activity associated with MH, and the minimum inhibitory concentrations (MIC) of MGO in the form of both MH and isolated synthetic compound required to have an antibacterial effect have been established. For MGO, a MIC of 1.1 mM is required to induce an antibacterial effect, whilst a range of MIC values has been observed in the case of MH, in light of inherent variations in MGO content. ...
... For example, five MHs with MGO concentrations ranging between 347 to 761 ± 25 mg kg -1 were shown to exhibit an antibacterial effect when the MH was diluted to 15 to 30% (w/v). These resulting MGO concentrations correspond to MIC values between 1.1 mM and 1.8 mM, and therefore compare with the 1.1 mM MIC value associated with synthetic MGO [20]. The antibacterial activity of MGO in the form of solution [20,21], hydrogel [21], polymer-based formulation [22], and poly (vinyl alcohol) fibres [23] has also been studied. ...
... These resulting MGO concentrations correspond to MIC values between 1.1 mM and 1.8 mM, and therefore compare with the 1.1 mM MIC value associated with synthetic MGO [20]. The antibacterial activity of MGO in the form of solution [20,21], hydrogel [21], polymer-based formulation [22], and poly (vinyl alcohol) fibres [23] has also been studied. With respect to MH, MGO has attracted attention because of its ability to act as a lone compound at defined concentration for the inhibition of bacterial growth, as well as its carcinostatic properties [24][25][26][27][28] and anti-proliferative effects on leukaemia cells [29,30]. ...
Manuka honey (MH) is used as an antibacterial agent in bioactive wound dressings via direct impregnation onto a suitable substrate. MH provides unique antibacterial activity when compared with conventional honeys, owing partly to one of its constituents, methylglyoxal (MGO). Aiming to investigate an antibiotic-free antimicrobial strategy, we studied the antibacterial activity of both MH and MGO (at equivalent MGO concentrations) when applied as a physical coating to a nonwoven fabric wound dressing. When physically coated on to a cellulosic hydroentangled nonwoven fabric, it was found that concentrations of 0.0054 mg cm-2 of MGO in the form of MH and MGO was sufficient to achieve 100 CFU% bacteria reduction against gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae, based on BS EN ISO 20743:2007. A 3- to 20- fold increase in MGO concentration (0.0170 - 0.1 mg cm-2) was required to facilitate a good antibacterial effect (based on BS EN ISO 20645:2004) in terms of zone of inhibition and lack of growth under the sample. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was also assessed for MGO in liquid form against three prevalent wound and healthcare-associated pathogens, i.e. Staphylococcus aureus, gram-negative Pseudomonas aeruginosa and gram-positive Enterococcus faecalis. Other than the case of MGO-containing fabrics, solutions with much higher MGO concentrations (128 mg L-1 - 1024 mg L-1) were required to provide either a bacteriostatic or bactericidal effect. The results presented in this study therefore demonstrate the relevance of MGO-based coating as an environment-friendly strategy for the design of functional dressings with antibiotic-free antimicrobial chemistries.
... Although the advent and efficacy of antibiotics overshadowed many traditional antimicrobial therapies, honey included, the ABR crisis has resurrected research interest in the antibacterial efficacy of this natural product and its potential clinical use. In 1999, medical-grade honey was registered as a topical agent in Australia, and elsewhere since, and has been primarily used globally as a topical antibacterial in wound dressings (burn sites, bed sores, and ulcers), with reportedly rapid infection resolve particularly in cases where such infections had been recalcitrant to conventional therapy (Molan and Allen, 1996;Mavric et al., 2008;Blair et al., 2009). Currently, medical-grade honeys include brands such as Revamil1, Surgihoney, and Medihoney ™ (Mavric et al., 2008;Kwakman and Zaat, 2012;Nolan et al., 2020). ...
... In 1999, medical-grade honey was registered as a topical agent in Australia, and elsewhere since, and has been primarily used globally as a topical antibacterial in wound dressings (burn sites, bed sores, and ulcers), with reportedly rapid infection resolve particularly in cases where such infections had been recalcitrant to conventional therapy (Molan and Allen, 1996;Mavric et al., 2008;Blair et al., 2009). Currently, medical-grade honeys include brands such as Revamil1, Surgihoney, and Medihoney ™ (Mavric et al., 2008;Kwakman and Zaat, 2012;Nolan et al., 2020). Revamil, originates in the Netherlands and is carefully processed to ensure its quality and specific characteristics (Henry et al., 2019). ...
... Mass spectroscopy studies comparing conventional honeys to MH samples found the latter contained up to 1000-fold higher concentrations of this nonperoxide compound. Isolation and characterisation identified the compound as MGO, which is produced mainly as a by-product of glycolysis (Adams et al., 2008;Mavric et al., 2008). Tests against Escherichia coli and S. aureus (origin unknown) showed pronounced antibacterial activity from MH comparable to their reference MGO product. ...
The antibiotic resistance (ABR) crisis is an urgent global health priority. Staphylococci are among the problematic bacteria contributing to this emergency owing to their recalcitrance to many clinically important antibiotics. Staphylococcal pathogenesis is further complicated by the presence of small colony variants (SCVs), a bacterial subpopulation displaying atypical characteristics including retarded growth, prolific biofilm formation, heightened antibiotic tolerance, and enhanced intracellular persistence. These capabilities severely impede current chemotherapeutics, resulting in chronic infections, poor patient outcomes, and significant economic burden. Tackling ABR requires alternative measures beyond the conventional options that have dominated treatment regimens over the past 8 decades. Non-antibiotic therapies are gaining interest in this arena, including the use of honey, which despite having ancient therapeutic roots has now been reimagined as an alternative treatment beyond just traditional topical use, to include the treatment of an array of difficult-to-treat staphylococcal infections. This literature review focused on Manuka honey (MH) and its efficacy as an anti-staphylococcal treatment. We summarized the studies that have used this product and the technologies employed to study the antibacterial mechanisms that render MH a suitable agent for the management of problematic staphylococcal infections, including those involving staphylococcal SCVs. We also discussed the status of staphylococcal resistance development to MH and other factors that may impact its efficacy as an alternative therapy to help combat ABR.
... For many honeys, their antibacterial activity stems from hydrogen peroxide content. However, Manuka honey exhibits a significant amount of non-peroxide antibacterial activity which is largely due to the presence of MGO (5,6). MGO itself is a molecule that is found in a range of other foodstuffs and beverages, such as wine, bread, and dairy products (7)(8)(9). ...
... MGO itself is a molecule that is found in a range of other foodstuffs and beverages, such as wine, bread, and dairy products (7)(8)(9). However, Manuka honey is unique in that upon testing samples of Manuka honey, researchers have reported the presence of large amounts of methylglyoxal in each sample which correlated with its non-peroxide activity (6). It is also well known among NZ beekeepers that MGO content and hence non-peroxide antibacterial activity increase over time with storage (10) Manuka honey can also be used to treat wounds. ...
... A study by Weigel et al. (27) showed evidence of 1,2-dicarbonyl compounds in honey, specifically 3-deoxyglucosulose (3-DG), methylglyoxal (MGO), and glyoxal (GO). Mavric et al. (6) tested the inhibiting effects of these three 1,2-dicarbonyl compounds found in Manuka Honey on two different strains of bacteria, E. coli and S. aureus, finding that MGO had the most pronounced antibacterial effect out of all three compounds at a minimum inhibitory concentration (MIC) of 1.1mM for both strains of bacteria ( Table 1). The researchers were also able to verify that MGO was the main contributor to antibacterial activity using an Agar well diffusion assay with S. aureus as the bacteria. ...
The unique ecosystems of New Zealand have produced a diverse range of honey over the years, with Manuka honey being one of the most renowned. Produced by Western honeybees extracting nectar from Manuka flowers, this monofloral honey has become known for its distinct antibacterial and anti-inflammatory properties. Whilst antibacterial activity in other honey tend to stem from factors such as hydrogen peroxide content, high viscosity, osmotic effect, and acidic pH, the antibacterial activity of Manuka honey is mainly attributed to methylglyoxal (MGO), a dicarbonyl compound which is found in high concentrations in Manuka honey. This review paper will focus on the antibacterial properties of Manuka honey and the role that MGO plays. Understanding the specific chemical mechanisms that of attack on different strains of bacteria by Manuka honey and the role of MGO is crucial to potentially understanding how new drugs or medicines can combat antibacterial resistance to antibiotics.
... Unlike other honey, the antimicrobial properties of Manuka honey are derived not from hydrogen peroxide, but rather from a compound called methylglyoxal (MGO), produced from the conversion of dihydroxyacetone (DHA), which is abundant in fresh Manuka honey [21,22]. The antimicrobial properties of Manuka honey are determined by testing, and the results are used to calculate the unique Manuka factor (UMF), which ranges in potency from 1-25 [2]. ...
... To be classified as Manuka honey, it must be produced in New Zealand. It must pass independent laboratory tests to ensure that it meets the minimum standard for concentrations of methylglyoxal (MGO), dihydroxyacetone (DHA), and leptosperin [19,21,22]. ...
Plant propagation is a labor-intensive process in the nursery and greenhouse industry, with labor accounting for 41.4% of expenditures in 2019—11.6 billion total. Labor availability remains a critical issue, and current methods of applying root-promoting compounds to cuttings often yield inconsistent rooting responses. This research investigated honey as a rooting adjuvant and its effects on rooting in Red Cascade™ miniature rose (Rosa ‘MOORcap’), common camellia (Camellia japonica), and southern magnolia (Magnolia grandiflora ‘Little Gem’). For Red Cascade™ rose, adding honey to water-soluble indole-3-butyric acid (IBA) solutions did not improve root counts compared to IBA alone. However, 1000 µL∙L⁻1 IBA produced more roots than 250 µL∙L⁻1 IBA. Camellia and magnolia cuttings were treated with multiflora, Manuka, or commercial honey, alongside IBA rates of 0 to 4500 µL∙L⁻1. In camellia, honey type or auxin rate did not significantly affect rooting, but local and multiflora honey combined with higher IBA rates increased root counts. For magnolia, multiflora honey improved both root number and quality, outperforming other treatments. While honey showed limited benefits for camellia and rose, multiflora honey demonstrated potential economic advantages for magnolia propagation, enhancing root quality and quantity for producers.
... The antimicrobial activity exerted by honey against Citrobacter species and E.coli were comparable with that of ceftraxone, a reference antibiotic (p>0.05). The observed activity of honey could be due to its acidity, osmolarity and hydrogen peroxide contents which have been reported to display antimicrobial activity [20,21]. Despite the slight numerical variation between our observation and others, the overall broad spectrum antibacterial effect of honey is in a good agreement with previously published reports [20][21][22]. ...
... The observed activity of honey could be due to its acidity, osmolarity and hydrogen peroxide contents which have been reported to display antimicrobial activity [20,21]. Despite the slight numerical variation between our observation and others, the overall broad spectrum antibacterial effect of honey is in a good agreement with previously published reports [20][21][22]. In fact, the antimicrobial effect of honey can be influenced by the type of flowers from which it is made, which in turn influenced by geographic variations and flowering seasons [22]. ...
... Honey's pharmacological prowess, inhibiting bacterial and fungal grow plemented by the osmotic effect and acidic pH, contributing to its preservati [88,[104][105][106]. This antimicrobial and antioxidant-rich nature positions honey a managing chronic inflammation and provides analgesic effects, fostering tissue tion [107][108][109]. ...
... Honey's pharmacological prowess, inhibiting bacterial and fungal growth, is complemented by the osmotic effect and acidic pH, contributing to its preservation quality [88,[104][105][106]. This antimicrobial and antioxidant-rich nature positions honey as an ally in managing chronic inflammation and provides analgesic effects, fostering tissue regeneration [107][108][109]. ...
Within the domain of conventional oncochemotherapeutics, anticancer chemotherapy (AC) has emerged as a potent strategy for the treatment of cancers. AC is the mainstay strategy for solid and non-solid cancer treatment. Its mechanistic action targets the blockage of DNA transcription and the dysregulation of cell cycle machinery in cancer cells, leading to the activation of death pathways. However, the attendant side effect of toxicity inflicted by AC on healthy tissues presents a formidable challenge. The crucial culprit in the AC side effect of toxicity is unknown, although oxidative stress, mitochondrial impairment, inflammatory cascades, autophagy dysregulation, apoptosis, and certain aberrant signaling have been implicated. Honey is a natural bee product with significant health benefits and pharmacological properties. Interestingly, the literature reports that honey may proffer a protection mechanism for delicate tissue/organs against the side effect of toxicity from AC. Thus, this review delves into the prospective role of honey as an alleviator of the AC side effect of toxicity; it provides an elucidation of the mechanisms of AC toxicity and honey's molecular mechanisms of mitigation. The review endeavors to unravel the specific molecular cascades by which honey orchestrates its mitigating effects, with the overarching objective of refining its application as an adjuvant natural product. Honey supplementation prevents AC toxicity via the inhibition of oxidative stress, NF-κB-mediated inflammation, and caspase-dependent apoptosis cascades. Although there is a need for increased mechanistic studies, honey is a natural product that could mitigate the various toxicities induced by AC.
... The proposed mechanisms of action are summarized in Figure 3. Manuka honey has gained popularity in recent years, and its proposal that methylglyoxal (MGO) is a vital component has led to its marketing based on MGO content. Manuka honey has unusually high levels of non-peroxide activity, and this is attributed to MGO content [82]. Manuka honey comes from New Zealand and Australia, as it is made by bees from the native manuka plant. ...
... There are other systems to rank manuka honey, such as the 'Unique Manuka honey has gained popularity in recent years, and its proposal that methylglyoxal (MGO) is a vital component has led to its marketing based on MGO content. Manuka honey has unusually high levels of non-peroxide activity, and this is attributed to MGO content [82]. Manuka honey comes from New Zealand and Australia, as it is made by bees from the native manuka plant. ...
Chronic wounds are becoming an increasing burden on healthcare services, as they have extended healing times and are susceptible to infection, with many failing to heal, which can lead ultimately to amputation. Due to the additional rise in antimicrobial resistance and emergence of difficult-to-treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. Many natural substances have been identified as having the potential to aid in both preventing infection and increasing the speed of wound closure processes. Manuka honey is already in some cases used as a topical treatment in the form of ointments, which in conjunction with dressings and fish skin grafts are an existing US Food and Drug Administration-approved treatment option. These existing treatment options indicate that fatty acids from fish oil and manuka honey are well tolerated by the body, and if the active components of the treatments were better understood, they could make valuable additions to topical treatment options. This review considers two prominent natural substances with established manufacturing and global distribution—marine based fatty acids (including their metabolites) and manuka honey—their function as antimicrobials and how they can aid in wound repair, two important aspects leading to resolution of chronic wounds.
... 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]. ...
... 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]. ...
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.
... 5 Natural phytochemicals are mostly produced by plants and widely distributed in secretions (e.g., nectar) and various organs such as roots, stems, and leaves. 6 During the last decades, researchers have already identified a variety of phytochemicals such as phenolic acids, 7 aldehydes, 8 flavonoids, 9 and terpenes 10 in plant-derived honey. Gelam and Tualang honeys, for instance, were rich in phenolic acids such as caffeic acid, gallic acid, and ferulic acids, and these chemicals were simultaneously demonstrated to possess anti-inflammatory and antibacterial activities. ...
... For example, methylglyoxal is the most important compound responsible for the antibacterial activity of manuka honey, and some phytochemicals may act as synergists. 8,12,13 Noteworthily, eucalyptus honey contained a diversity of terpenes 14 involving isoborneol, camphor, and 2hydroxycineol. 15 Interestingly, evidence has revealed that some specific phytochemicals can serve as intrinsic markers for identifying the authenticity of honey. ...
We aimed to identify the characteristic phytochemicals of safflower, Chinese sumac, and bauhinia honeys to assess
their authenticity. We discovered syringaldehyde, riboflavin, lumiflavin, lumichrome, rhusin [(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-O-cinnamoyl oxime], bitterin {4-hydroxy-4-[3-(1-hydroxyethyl) oxiran-2-yl]-3,5,5-trimethylcyclohex-2-en-1-one}, and unedone as characteristic phytochemicals of these three types of honeys. The average contents of syringaldehyde, riboflavin, lumiflavin, or lumichrome in safflower honey were 41.20, 5.24, 24.72, and 36.72 mg/kg; lumiflavin, lumichrome, and rhusin in Chinese sumac honey were 39.66, 40.55, and 2.65 mg/kg; bitterin, unedone, and lumichrome in bauhinia honey were 8.42, 26.33, and 8.68 mg/kg, respectively. To our knowledge, the simultaneous presence of riboflavin, lumichrome, and lumiflavin in honey is a novel finding responsible for the bright-yellow color of honey. Also, it is the first time that lumiflavin, rhusin, and bitterin have been reported in honey. We effectively distinguish pure honeys from adulterations, based on characteristic components and high-performance liquid chromatography fingerprints; thus, we seem to provide intrinsic markers and reliable assessment criteria to assess honey authenticity.
... This oxidative agent irreversibly damages the DNA and cell membranes of microorganisms [34][35][36]. However, honey such as Manuka exhibits non-peroxide antimicrobial activity, which is attributed to MGO, a compound derived from dihydroxyacetone found in the nectar of Leptospermum species [37,38]. MGO interferes with bacterial protein structures, causing membrane damage and reducing cellular motility [18]. ...
Hive products, encompassing honey, propolis, bee venom, royal jelly, and pollen, are recognized for their antimicrobial and therapeutic properties. This review examines their chemical composition, explores their mechanisms of action, and discusses their potential applications in both human and veterinary medicine, particularly in addressing the challenge of antimicrobial resistance. This study utilized a comprehensive literature search strategy, gathering data from Google Scholar, MEDLINE PubMed, SciELO, and SCOPUS databases. Relevant search terms were employed to ensure a thorough retrieval of the pertinent literature. Honey, rich in bioactive compounds such as hydrogen peroxide and methylglyoxal, effectively disrupts biofilms and combats multi-drug-resistant pathogens, showing promise in treating a range of infections. Propolis, with its flavonoids and phenolic acids, demonstrates synergistic effects when used in conjunction with antibiotics. Bee venom, particularly its component melittin, exhibits antibacterial and immunomodulatory properties, although further research is needed to address toxicity concerns. Pollen and royal jelly demonstrate broad-spectrum antimicrobial activity, which is particularly relevant to animal health. Existing pre-clinical and clinical data support the therapeutic potential of these hive products. Hive products represent a vast and largely untapped natural resource for combating antimicrobial resistance and developing sustainable therapies, particularly in the field of veterinary medicine. However, challenges remain due to the inherent variability in their composition and the lack of standardized protocols for their preparation and application. Further research is essential to fully elucidate their mechanisms of action, optimize formulations for enhanced efficacy, and establish standardized protocols to ensure their safe and effective clinical use.
... Honey derived from the nectar of the mānuka tree contains unique non-peroxide antibacterial properties and has become a highly valuable commodity [42,43]. The unique antibacterial properties originate in the nectar of the mānuka flower due to the accumulation of a three-carbon sugar called dihydroxyacetone (DHA), which undergoes a chemical conversion to the main antibacterial constituent, called methylglyoxal (MGO), in mature honey [44,45]. However, the quantity of DHA that accumulates in the nectar of the mānuka flower is notoriously variable, consequently causing large regional and annual fluctuations in the antimicrobial efficacy of mānuka honeys [46,47]. ...
Background
A growing body of evidence demonstrates that host-associated microbial communities of plant leaf surfaces (i.e. the phyllosphere) can influence host functional traits. However, it remains unclear whether host selection is a universal driver of phyllosphere community assembly. We targeted mānuka (Leptospermum scoparium) and three neighbouring non-mānuka plant species along an 1800-m transect in a New Zealand native bush to conduct a hypothesis-driven investigation of the relative influence of host species identity and stochastic dispersal on the composition of natural phyllosphere bacterial communities.
Results
We detected significant correlations between host species identity and mānuka phyllosphere communities that are consistent with a dominant role of host selection in the assembly of the mānuka phyllosphere microbiome. In contrast, the phyllosphere community compositions of neighbouring, ecologically similar native plants were highly variable, suggesting that stochastic processes, such as dispersal, had a stronger influence on the phyllosphere microbiomes of those non-mānuka plants compared to the phyllosphere microbiome of mānuka. Furthermore, the distribution of phyllosphere taxa among plant species was congruent with a scenario in which microorganisms had dispersed from mānuka to non-mānuka phyllosphere microbiomes.
Conclusions
We conclude that host selection of phyllosphere communities is not and should not be presumed to be a universal trait across plant species. The specificity of the mānuka phyllosphere microbiome suggests the presence of functionally significant bacteria that are under direct, possibly chemically mediated, selection by the host. Furthermore, we propose that phyllosphere microbiomes under strong host selection, such as that of mānuka, may act as a source of microorganisms for the phyllosphere microbiomes of neighbouring plants.
2ZqHFcd3Z-Di37dyajupxdVideo Abstract
... Antibacterial actions of honeydew and Manuka honey involve two different mechanisms: hydrogen peroxide dependent (in honeydew honey) and non-peroxide antimicrobial activity (in Manuka honey) 70,71 . It is closely associated with the floral sources, mainly from Leptospermum species and MGO content 72,73 and was fully supported by our results that the determined hydrogen peroxide content in analyzed Manuka samples was much lower than that in honeydew honey (Fig. 2). The concentration of H 2 O 2 (determined in 50% honey solutions) in two honeydew honey samples from Slovakia was at the level of 306.9 and 495.8 µM, while for Manuka honey was 78.9 µM, which is 4 to 6 times lower than in honeydew honey. ...
The aim of the present study was to compare the antioxidant, antibacterial and antiviral activities of Podkarpackie coniferous honeydew honey and Manuka honey. The quality of tested honey samples (honeydew-12 and Manuka-4) regarding honey standard was evaluated as well as additional indicators (methylglyoxal, total phenolics and HPTLC phenolic profile, antioxidant potential, glucose oxidase activity, and hydrogen peroxide) were compared. Antibacterial potential was analyzed against Gram-positive (S. aureus and B. cereus) and Gram-negative (E. coli and S. enterica) bacteria. Antiviral activity against different RNA (phi6, MS2) and DNA (T7, phiX174) bacteriophages considered as “viral surrogates” was determined. Based on the determined physicochemical parameters the good quality of tested honeys was confirmed, excluding two samples. The content of polyphenolic compounds in honeydew honey ranged from 583.87 to 1102.42 mg of gallic acid/kg and was strongly correlated with the antioxidant properties. Moreover, for samples with the strongest activity these parameters were comparable to Manuka honey. However, the obtained HPTLC polyphenolic profiles were completely different for honeydew than for Manuka honey which exhibited additional bands (Rf = 0.74 and 0.52). Honeydew honeys were characterized by a strong antiviral and antibacterial properties most of all against Gram-positive bacteria. The MICs (minimal inhibitory concentrations) for S. aureus and B. cereus ranged 15–35% and 8–15% for honeydew and Manuka honeys, respectively. The strongest antiviral properties of honeydew honey were demonstrated mainly against RNA bacteriophages (phi6, MS2) which was even higher than for Manuka honey, especially against MS2 virus. The obtained results suggest that Podkarpackie honeydew honey with the controlled glucose oxidase activity may be a natural substance used to combat viral and bacterial diseases.
... H 2 O 2 can cause oxidative damage to biological molecules such as proteins and DNA in bacterial cells, cell membranes, and cytoplasm, thus inhibiting bacterial growth and reproduction [33]. Another type of non-peroxidase antibacterial substance is MGO, which has been found to inhibit both Gram-positive and Gram-negative bacteria [34]. Additionally, antimicrobial peptides like defensin-I and major royal jelly protein-I, found in most types of honey, could directly affect bacteria [28]. ...
Chronic wounds impose a substantial economic burden on healthcare systems and result in decreased productivity. Honey possesses diverse properties, rendering it a promising, cost-effective, and efficacious intervention strategy for the management of chronic wounds. However, the findings are controversial. We have presented an updated and comprehensive systematic review and meta-analysis to evaluate the efficacy and safety of honey dressings in the management of chronic wounds. Nine electronic databases were systematically searched to identify relevant studies published prior to 22 March 2024. A total of eight studies, including 906 individuals that met the inclusion criteria, were incorporated. The findings demonstrated a significant acceleration in wound healing time with honey dressings (MD = −17.13, 95% CI −26.37 to −7.89, p = 0.0003) and an increase in the percentage of wound healing (MD = 18.31, 95% CI 8.86 to 27.76, p = 0.0001). No statistically significant differences were observed in the healing rate (RR = 2.00, 95% CI 0.78 to 5.10, p = 0.15), clearance time of bacteria (MD = −11.36, 95% CI: −25.91 to 3.18, p = 0.13) and hospital stay duration. Honey may decrease the VAS score but may increase the incidence of painful discomfort during treatment. The topical application of honey is an effective therapeutic approach for managing chronic wounds, but the quality of the evidence was very low due to the quality of risk of bias, inconsistency, and publication bias, highlighting the necessity for larger-scale studies with adequately powered RCTs to ensure the safety and efficacy of honey dressings in chronic wound healing.
... Shankar, K.G., Kumar, S.U., Sowndarya, S., Sridevi, J., Angel, S.S., Rose, C. Rumen tissue derived decellularized submucosa collagen or its LITERATURA neobsahuje MGO vůbec, protože jej nemá z čeho vytvořit. (20)(21)(22)(23) Další, velmi nespecifickou antimikrobiální aktivitou, je snížené pH; většina medů, které se dnes používají v medicíně má pH kolem 4 (3,2-5) . Nízké pH navíc zvyšuje infiltraci okolí a lůžka rány různými buněčnými subpopulacemi (fibroblasty nebo makrofágy). ...
Local application of Manuka honey in the control of infectious complications development in the burned area. The use of various forms of honey-based materials in wound healing of different etiologies has a very long history. New biotechnological procedures extend the use of these materials to other clinical indications. In the case report, we present the case of a young patient who suffered deep burns caused by the passage of an electric current. Due to the presentation of necrotic tissue in the area of the right arm up to the facia, a surgical (fascial) necrectomy was necessary. Materials based on Manuka honey (Algivon ® , Actilite ®) were chosen for the subsequent preparation of the wound bed and precise antimicrobial control. The combined wound closure proceeded without further complications, similar to the subsequent maturation of the scars. According to our previous experience, the application of Manuka honey-based dressings represents a very interesting alternative to other, already fully established materials used for wound healing, not only of thermal etiology. KEY WORDS: Manuka honey-electric burns-deep burns-natural substances-wound-bed preparation-infection control V rámci samotné biologické funkce medu existují již robustní data, která ukazují na skutečnost, že med pozitivním způsobem ovlivňuje všechny fáze hojení rány.
... Many properties of honey that have been described to aid in the process of antimicrobial and wound healing activity-such as activating the innate immune system, inducing the migration of neutrophils and macrophages, stimulating angiogenesis, and enhancing antibody production [13,17,18,25], may also serve to promote antitumor actions in vivo. While Manuka honey shares constituents (such as glucose oxidases) with other types of honey, it also contains other specific phytochemical factors that potentiate its biological activity, such as methylglyoxal [9][10][11][12]. As proposed by others [48,49], we concur that significant evidence suggests that the health benefits of fruits, vegetables, whole grains, and other plant foods can be attributed to the synergy or interactions of bioactive compounds and other nutrients in whole foods. ...
Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.
... Methylglyoxal has been characterized as the primary chemical component responsible for Manuka honey's antimicrobial properties. However, the other half of what makes Manuka honey so promising, its capabilities to reduce inflammation, remains unclear [52]. This expansive and detailed study was designed to split Manuka honey into its constituent flavonoid and phenolic fractions and investigate their effects on two key neutrophil inflammatory behaviors that impede host-biomaterial integration [2]. ...
Background
Neutrophils use both the production of reactive oxygen species (ROS) and a specialized process called NETosis to defend the body from material deemed foreign. While these neutrophil behaviors are critical in preventing infection, a dysregulated response can lead to tissue damage and fibrosis at host-biomaterial interfaces. It was hypothesized that applying the flavonoids found in Manuka honey: chrysin, pinocembrin, and pinobanksin, and the phenolic compound methyl syringate to neutrophils exhibiting pro-inflammatory behavior will reduce ROS activity and prevent NETosis in primary human neutrophils.
Methods
Using primary human neutrophils isolated from donor (n = 5) peripheral blood, concentrations between 1 nM and 10 µM of each flavonoid, 10 µM and 2 mM of methyl syringate, 0.1% v/v and 10% v/v Manuka honey, and combinations of both 1 nM–10 µM of each flavonoid and 10 µM–2 mM of methyl syringate were assayed for reductions in NETosis using Sytox orange extracellular DNA staining and reduction in intracellular ROS activity via standard dichloro-dihydro-fluorescein diacetate (DCFH-DA) oxidation assay.
Results
Compared to positive control levels, individual flavonoids showed moderate effect sizes. Higher concentrations of flavonoids, especially in combination, stimulated ROS activity by up to 105%. Whole Manuka honey reduced neutrophil extracellular trap (NET) levels by up to 91% but only reduced ROS activity by 36%. However, methyl syringate reduced NET levels by up to 68% and ROS activity by 66%.
Conclusions
Methyl syringate and whole Manuka honey are potent inhibitors of neutrophil intracellular ROS activity and NET formation. Methyl syringate potentially drives the anti-inflammatory capabilities of Manuka honey demonstrated by previous studies.
... Honey also contains methylglyoxal, which contributes to its antibacterial properties. It is known to inhibit Escherichia coli and Streptomyces aureus in inhibition assays (Mavric et al. 2008). ...
Honey is a gift of honey bees that collect nectar from a wide variety of flowers and convert it into honey before finally storing it in wax-form structures called honeycombs. Apart from being a sweetener, honey possesses several health benefits where it acts as an antioxidant and anti-inflammatory agent. Honey’s antioxidant property is mainly governed by its polyphenol content. These polyphenols provide medicinal uses by inhibiting enzymes or chelating free radical-producing elements. Since time immemorial, honey is being used to cure many diseases without any side effects. In addition to keeping the wound moist, its high viscosity suppresses the production of inflammatory cells. When it comes to the nutrition status of honey, it contains several oligosaccharides, out of which fructose and glucose being the major constituents. Despite the high carbohydrate content of honey, its glycemic index varies from 32 to 85, in accordance with its floral source. It also contains small amounts of amino acids, trace elements, minerals, proteins, active enzymes, vitamins, and aroma compounds. Intake of honey prevents weight gain by reducing excessive sugar levels. Honey also gives protection against metabolic syndrome, an umbrella of diseases which include hypertension, dyslipidemia, diabetes mellitus, and obesity.
... Manuka honey has a unique antibacterial effect that distinguishes it from other types of honey. While most honey produces hydrogen peroxide through glucose oxidase, Manuka honey has low glucose oxidase activity and instead contains methylglyoxal, which is responsible for its "non-peroxide activity" (NPA) [23][24][25][26]. The presence of methylglyoxal makes Manuka honey an effective treatment for antibiotic-resistant bacteria such as Helicobacter pylori [27]. ...
Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive and antioxidant substances such as polyphenols that contribute to its protective effects against oxidative stress. In this study, commercially available Manuka honey was tested for its total polyphenol content and DPPH radical scavenging ability. It was then tested in vitro on human fibroblast cells exposed to UV radiation to assess its potential to protect cells against oxidative stress. The results showed that the honey itself significantly interfered with cell metabolism, and its presence only slightly alleviated the effects of UV exposure. This study also suggested that the MGO content has a minor impact on reducing oxidative stress in UV-irradiated cells and efficiency in scavenging the DPPH radical.
... The antimicrobial properties of honey are attributed to the high concentrations of glucose and fructose, which impart its hygroscopic properties (18,19), enzymes such as glucose oxidase that converts glucose to gluconic acid and hydrogen peroxide, causing its low pH and high levels of reactive oxygen species (ROS) (20), and a number of antimicrobial peptides, including defensin-1 and the jellein family peptides (21,22). However, for some honey variants, there are additional, as yet undefined features that contribute to their potency (23)(24)(25). The ...
The majority of antibiotics are natural products, with microorganism-generated molecules and their derivatives being the most prevalent source of drugs to treat infections. Thus, identifying natural products remains the most valuable resource for novel therapeutics. Here, we report the discovery of a series of dormant bacteria in honey that have bactericidal activity toward Legionella, a bacterial pathogen that causes respiratory disease in humans. We show that, in response to bacterial products secreted by Legionella, the honey bacteria release diffusible antimicrobial molecules. Remarkably, the honey bacteria only produce these molecules in response to Legionella spp., when compared to a panel of 24 bacterial pathogens from different genera. However, the molecules induced by Legionella have broad activity against several clinically important pathogens, including many high-priority pathogens. Thus, Legionella spp. are potent drivers of antimicrobial molecule production by uncharacterized bacteria isolated from honey, providing access to new antimicrobial products and an unprecedented strategy for discovering novel antibiotics.
IMPORTANCE
Natural products generated by microorganisms remain the most viable and abundant source of new antibiotics. However, their discovery depends on the ability to isolate and culture the producing organisms and to identify conditions that promote antibiotic production. Here, we identify a series of previously undescribed bacteria isolated from raw honey and specific culture conditions that induce the production of antimicrobial molecules that are active against a wide variety of pathogenic bacteria.
... Mavric et al. demonstrates MGO's predominant role in antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) due to their minimum inhibitory concentration when plated on an agar diffusion assay [18]. Previous studies found Manuka honey to be more effective in antibacterial activity than commonly used antimicrobial agents as indicated by their inhibition zones. ...
Honey is a very cost-efficient food source and a valuable export for the country of Uganda, but is commonly adulterated, resulting in consumers not being aware of the contents of their honey. As a result, it is important to be able to authenticate the honey that consumers are purchasing. This study evaluated the physicochemical properties (pH, free acidity, metal determination, moisture content, and FTIR spectra) of Ugandan and Manuka honey. Honey pH values ranged from 3.3 to 4.8 (±0.6) while free acidity values ranged from 34.87 to 62.22 (±8.69). The moisture content values of all honey samples were below 22%. The metal concentrations and functional groups present in Ugandan and Manuka honey were determined. Metal analysis by atomic absorption spectrometry detected five elements (Na, Ca, K, Cu, and Pb) in all honey samples in varying concentrations. The elemental concentrations were found in descending order as follows: sodium (Na) (9.38 ppm), calcium (Ca) (4.99 ppm), potassium (K) (2.48 ppm), copper (Cu) (1.87 ppm), lead (Pb) (0.28 ppm). FTIR analysis revealed similar patterns of spectral curve (O-H stretching and C-H stretching) across all honey samples analyzed, which is consistent with previously analyzed honey samples from other studies. Ugandan honey sample 7 collected in the Masaka Region was found to be most similar to the Manuka honey standard based on its observed physiochemical properties. All properties analyzed suggested Ugandan honey is of good quality and safe for consumption.
... MH is a complex mixture of carbohydrates, fatty acids, proteins, vitamins and minerals containing various kinds of phytochemicals with high phenolic and flavonoid content [7,[9][10][11]. While MH shares constituents with other types of honey, such as glucose oxidases , it also contains other specific phytochemical factors that may potentiate its biologic activity [12]. Of note, natural phytoestrogens may be one such factor [13,14]. ...
Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.
... Honey has multiple elements that contribute to antimicrobial effects, but what sets manuka honey apart is its methylglyoxal (MGO) content. MGO has been identified as a major contributor to antimicrobial abilities [14]. Manuka honey is available widely and often sold according to its MGO content, which varies from 50 mg/kg to 800+ mg/kg. ...
Both honey and fish oil have been historically used in medicine and identified as having antimicrobial properties. Although analyses of the substances have identified different components within them, it is not fully understood how these components interact and contribute to the observed effect. With the increase in multi-drug resistant strains of bacteria found in infections, new treatment options are needed. This study aimed to assess the antimicrobial abilities of fish oil components, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and derived resolvins (RvE1, RvD2, and RvD3), as well as two varieties of manuka honey, against a panel of medically relevant microorganisms and antimicrobial resistant organisms, such as Methicillin Resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were identified; further minimum biofilm eradication concentrations (MBEC) were investigated for responsive organisms, including S. aureus, E. coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent with the existing literature, manuka honey was found to be a broad-spectrum antimicrobial with varied potency according to methylglyoxal content. DHA and EPA were both effective against Gram-positive and negative bacteria, but some drug-resistant strains or pathogens were not protected by a capsule. Only E. coli was inhibited by the resolvins.
... In agreement with previous findings [34,35], we recorded the highest level of MGO in Manuka honey, although this concentration was relatively lower compared with the levels reported in these studies. The average MGO content in all the samples ranged from 1.38 to 28.82 mg/kg. ...
α-Dicarbonyls are significant degradation products resulting from the Maillard reaction during food processing. Their presence in foods can indicate the extent of heat exposure, processing treatments, and storage conditions. Moreover, they may be useful in providing insights into the potential antibacterial and antioxidant activity of U.S. honey. Despite their importance, the occurrence of α-dicarbonyls in honey produced in the United States has not been extensively studied. This study aims to assess the concentrations of α-dicarbonyls in honey samples from different regions across the United States. The identification and quantification of α-dicarbonyls were conducted using reverse-phase liquid chromatography after derivatization with o-phenylenediamine (OPD) and detected using ultraviolet (UV) and mass spectrometry methods. This study investigated the effects of pH, color, and derivatization reagent on the presence of α-dicarbonyls in honey. The quantification method was validated by estimating the linearity, precision, recovery, method limit of detection, and quantification using known standards for GO, MGO, and 3-DG, respectively. Three major OPD-derivatized α-dicarbonyls including methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), were quantified in all the honey samples. 3-Deoxyglucosone (3-DG) was identified as the predominant α-dicarbonyl in all the U.S. honey samples, with concentrations ranging from 10.80 to 50.24 mg/kg. The total α-dicarbonyl content ranged from 16.81 to 55.74 mg/kg, with the highest concentration measured for Southern California honey. Our results showed no significant correlation between the total α-dicarbonyl content and the measured pH solutions. Similarly, we found that lower amounts of the OPD reagent are optimal for efficient derivatization of MGO, GO, and 3-DG in honey. Our results also indicated that darker types of honey may contain higher α-dicarbonyl content compared with lighter ones. The method validation results yielded excellent recovery rates for 3-DG (82.5%), MGO (75.8%), and GO (67.0%). The method demonstrated high linearity with a limit of detection (LOD) and limit of quantitation (LOQ) ranging from 0.0015 to 0.002 mg/kg and 0.005 to 0.008 mg/kg, respectively. Our results provide insights into the occurrence and concentrations of α-dicarbonyl compounds in U.S. honey varieties, offering valuable information on their quality and susceptibility to thermal processing effects.
... The nectar DHA converts to the antimicrobial compound methylglyoxal (MGO) in the derived honey, through a process that has been well-studied (see Owens et al., 2019 and references therein). The nectar DHA content and subsequent MGO concentration underpins the antibacterial activity of the honey (Adams et al., 2008;Mavric et al., 2008), and determines the premium price the honey attracts. M anuka is highly polymorphic, owing to both genotypic and environmental effects (Cockayne, 1967;Yin et al., 1984;Dawson, 2009). ...
Floral nectar composition beyond common sugars shows great diversity but contributing genetic factors are generally unknown. Mānuka (Leptospermum scoparium) is renowned for the antimicrobial compound methylglyoxal in its derived honey, which originates from the precursor, dihydroxyacetone (DHA), accumulating in the nectar. Although this nectar trait is highly variable, genetic contribution to the trait is unclear. Therefore, we investigated key gene(s) and genomic regions underpinning this trait.
We used RNAseq analysis to identify nectary‐associated genes differentially expressed between high and low nectar DHA genotypes. We also used a mānuka high‐density linkage map and quantitative trait loci (QTL) mapping population, supported by an improved genome assembly, to reveal genetic regions associated with nectar DHA content.
Expression and QTL analyses both pointed to the involvement of a phosphatase gene, LsSgpp2. The expression pattern of LsSgpp2 correlated with nectar DHA accumulation, and it co‐located with a QTL on chromosome 4. The identification of three QTLs, some of the first reported for a plant nectar trait, indicates polygenic control of DHA content.
We have established plant genetics as a key influence on DHA accumulation. The data suggest the hypothesis of LsSGPP2 releasing DHA from DHA‐phosphate and variability in LsSgpp2 gene expression contributing to the trait variability.
... Furthermore, historical records have shown that the body of Alexander the Great's body, who died in Babylon (Iraq), was sent to Macedonia in a coffin filled with honey (Crane, 1999). Honey also exhibits antimicrobial activity against fungi (Brady et al., 1996) and bacteria (Al-Waili et al., 2011;Jenkins et al., 2011) due to its high osmolarity, acidity (low pH), high sugar, osmotic effect of low moisture content, gluconic acid properties, hydrogen peroxide content and the presence of non-peroxide phytochemical components such as methylglyoxal (Almasaudi, 2021;Mavric et al., 2008;Weston, 2000). ...
The objective of this study is to assess the efficacy of a solution including honey, ethyl alcohol, liquid paraffin, distilled water and citric acid (HEFS) as a preservative for rabbit cadavers, serving as a potential substitute for formaldehyde. The cadav-ers underwent preservation using three distinct solutions: 10% formalin, 35% alcohol and HEFS. The cadavers were subjected to a total of four sampling events, occurring at 4-month intervals, in order to collect specimens for microanatomical, histologi-cal, microbiological, mycological, colourimetric, texture and odour analysis. In terms of hardness, suitability for dissection and joint mobility metrics, the cadavers fixed with HEFS had superior qualities to those fixed with formalin. The fixation quality of HEFS for histological analyses was deemed acceptable, except kidney and intestinal tissues. In texture analysis, differences only in the elasticity parameter (p < 0.05) in the same sampling period. A total of 10 (13.9) bacteria isolates were identified among which, Metasolibacillus meyeri 3 (30%) was predominantly followed by Staphylococcus aureus 2 (20%), Bacillus siamensis, Bacillus subtilis, Pseudarthrobacter oxydans, Bacillus licheniformis, Bacillus subtilis subsp. subtilis with a proportion of 1 (10%), respectively, by both microbiological and molecular analysis. However, no anaerobic bacteria and fungi were isolated. A considerable percentage of the students had the perception that HEFS was appropriate for utilization in laboratory settings due to its absence of unpleasant odours and detrimental impact on ocular and respiratory functions. In conclusion, we consider that HEFS may serve as a viable substitute for formalin solution in the preservation of rabbit cadavers. K E Y W O R D S cadaver, formalin, honey, rabbit
... The antimicrobial activity is variable among the different honey depending on its geographical, seasonal and botanical source as well as through harvesting, processing and storage conditions. According to Mavric et al. (2008), the antimicrobial activity of honey is recognized largely by osmolality, pH, Hydrogen peroxide production and the presence of other photochemical components eg. methylglyoxal. ...
The present research work was carried out to study the antimicrobial activity of honey sample collected from chalisgaon region during 2012 to 2015. During study, four crude honey samples were applied to evaluate the antifungal and antibacterial study on the basis of zone of inhibition. It was concluded that Escherechia coli and Bacillus subtillis are more susceptible than other experimental bacteria. In the antifungal activity, the Aspergillus terrens had shown more susceptibility than other experimented fungi.
Keywords: Crude honey, Antibacterial activity, antifungal activity, Zone of inhibition.
... Manuka is the common name of Leptospermum scoparium, a tea tree from New Zealand (Lusby et al. 2002). This non-peroxide antibacterial effect is caused by methylglyoxal, found in high doses in Manuka honey (Adams et al. 2008, Mavric et al. 2008. The level of non-peroxide activity in Manuka honey is referred to by a standard NPA (Non Peroxide Activity) value, also trademarked in New Zealand as UMF ("Unique Manuka Factor"). ...
Honey is an ancient natural remedy for the treatment of infected wounds. It has regained attention in the medical profession, as it has recently been reported to have a broad-spectrum inhibitory effect against bacteria. Data concerning Manuka honey of New Zealand origin, which is claimed to provide additional non-peroxide antimicrobial activity (so-called standard NPA) against oral pathogens, is still scarce. Therefore, this study aimed to screen for the antibacterial efficacy of different Manuka honey products against S. mutans (OMZ 918), P. gingivalis (OMZ 925) and A. actinomycetemcomitans (OMZ 299). Chlorhexidine and saline served as positive and negative controls, respectively, whereas a Swiss multifloral honey served as control honey without intrinsic non-peroxide activity. Chlorhexidine showed the highest inhibiting potential against all specimens tested. Manuka honey below an NPA value of 15 showed the least bacterial growth-inhibiting potential, even less although not significantly so than multifloral Swiss honey. Manuka honey above an NPA value of 15 showed a significantly higher antibacterial effect compared to the other honeys tested. All Manuka honey preparations were more effective in inhibiting the growth of P. gingivalis and A. actinomycetemcomitans, rather than S. mutans. In conclusion, the study showed an NPA dose-dependent antibacterial efficacy of Manuka honey. Further investigations of this natural product are now open for scrutiny.
... It was reported that Acacia honey has a wound-healing property [199], presented an antiproliferative effect on melanoma human and murine cells [200], and demonstrated anti-tumor activity in lung cancer cells [201]. Manuka honey contains metylglyoxal, a compound that was proven to be responsible for the antibacterial activity of honey [202]. This type of honey also shows synergistic in vitro effects when administered alongside antiviral drugs [203]. ...
Nowadays, in people’s perceptions, the return to roots in all aspects of life is an increasing temptation. This tendency has also been observed in the medical field, despite the availability of high-level medical services with many years of research, expertise, and trials. Equilibrium is found in the combination of the two tendencies through the inclusion of the scientific experience with the advantages and benefits provided by nature. It is well accepted that the nutritional and medicinal properties of honey are closely related to the botanical origin of the plants at the base of honey production. Despite this, people perceive honey as a natural and subsequently a simple product from a chemical point of view. In reality, honey is a very complex matrix containing more than 200 compounds having a high degree of compositional variability as function of its origin. Therefore, when discussing the nutritional and medicinal properties of honey, the importance of the geographical origin and its link to the honey’s composition, due to potential emerging contaminants such as Rare Earth Elements (REEs), should also be considered. This work offers a critical view on the use of honey as a natural superfood, in a direct relationship with its botanical and geographical origin.
... In more recent years the high value of honey derived from the flowers of mānuka, in part reflecting the medicinal characteristics imparted (i.e. "active mānuka honey"; Mavric et al. 2008), has resulted in mānuka to make the greatest contribution to the economy of NZ than any other indigenous plant. Plant & Food's participation in this more recent refocus of research effort with mānuka, includes the collection of germplasm originally established for breeding ornamental plant species. ...
Māori are the indigenous people of Aotearoa-New Zealand (NZ). In 1840 the Treaty of Waitangi was established between Māori and the Crown, thereby guaranteeing Māori undisturbed possession of taonga (treasured) species. There were many breaches of the Treaty of Waitangi, which resulted in the establishment of the Waitangi Tribunal to rectify those past breaches, and the resulting Settlements with Iwi (the tribal sovereign nations of Māori). One such report, WAI 262, known as the flora and fauna claim, asserts Māori sovereignty over taonga species: those endemic to NZ and of significance to Māori in both traditional and contemporary contexts. The WAI 262 report, alongside international agreements such as the Nagoya Protocol, create a moral and ethical context for authentic partnerships and benefit sharing between indigenous people and industry/science, including breeding and use of taonga plant species. This paper will be co-presented from both an indigenous and a science perspective, providing examples of how indigenous-science partnerships can create innovative opportunities for the international ornamentals industry, within the moral and ethical frameworks of international policies and commitments, when based on best practice principles. The examples include projects spanning several genera (e.g. Leptospermum, Gentianella, Syzygium, and Corynocarpus), illustrating increasing success for authentic partnerships between Māori and industry/science, including governance of data, benefit-sharing agreements, informed consent, and facilitated access.
... New Zealand Manuka honey is known for its high antibacterial activity due to its high level of non-peroxide compounds, with Methylglyoxal (MGO) being the primary compound responsible for these effects (Beitlich et al., 2014;Mavric et al., 2008). Manuka honey is effective against vancomycinresistant enterococci (Cooper et al., 2002) and various types of Pseudomonas aeruginosa (Roberts et al., 2019). ...
Honey has been employed for the treatment of wounds and diseases for ancient time, thanks to its antimicrobial and curative properties. This study aims to present the biochemical characteristics, including the amount of sugar, total phenols, phenolic chemicals, antioxidant properties, and antibacterial activities of a specific type of French honey (Sologne summer forest) in comparison with a manuka honey. According to our findings, the Manuka honey tested has 23% fewer polyphenols total than Sologne summer forest honey. The results showed that the Sologne summer honey had a different polyphenols profile than Manuka honey with specific polyphenol like p- Hydroxybenzoic acid. Additionally, the antioxidant activity of the two honeys is comparable (9 μmole Trolox.g-1 honey). Furthermore, the antibacterial activity of the two honeys is comparable against Pseudomonas aeruginosa and Staphylococcus aureus. Our research indicates for the first time that there are significant nutritional and biological potentials for a French honey from the Sologne summer forest.
... Manuka honey is produced by bees, from the nectar of Leptospermum scoparium [21]. This honey is considered as the gold standard in the assessment of the beneficial effects of honey. ...
The Fynbos biome, Western Cape Province, South Africa, produces a unique honey from Apis mellifera capensis. The bioactivity of Fynbos (FB1-FB6) honeys and Manuka, unique manuka factor 15+ (MAN UMF15+) honey subjected to simulated in vitro digestion, was compared. The effect of each phase of digestion on the antioxidant properties and nitric oxide- (NO-) associated immunomodulatory effects was determined. The total phenolic content of MAN (UMF15+) was higher than that of FB honeys, and following digestion, the percentage bioaccessibility (BA) was 68.6% and 87.1 ± 27.0 % , respectively. With the Trolox equivalent antioxidant capacity assay, the activity of FB1 and FB6 was similar to MAN (UMF15+) but reduced for FB2, FB3, FB4, and FB5 with a %BA of 77.9% for MAN (UMF15+) and 78.2 ± 13.4 % for FB. The oxygen radical absorbance capacity of MAN (UMF15+) and FB honeys was similar and unaltered with digestion. In a cellular environment, using colon adenocarcinoma (Caco-2) cells, both undigested and the gastric digested honey reduced 2,2 ′ -azobis-(2-amidinopropane) dihydrochloride- (AAPH-) mediated peroxyl radical formation. In contrast, following gastroduodenal digestion, the formation of reactive oxygen species (ROS) was increased. In murine macrophage (RAW 264.7) cells, all honeys induced different levels of NO which was significantly increased with digestion for MAN (UMF15+) and FB1. In LPS/IFN-γ stimulated RAW 264.7 macrophages, only undigested MAN (UMF15+) effectively reduced NO levels, and with digestion, NO scavenging activity of MAN (UMF15+) was reduced but increased for FB5 and FB6. In a noncellular environment, MAN (UMF15+), FB1, FB2, and FB6 scavenged NO, and with digestion, this activity was maintained. This study has identified that undigested and gastric-digested FB honey has antioxidant properties with strong potential anticancer effects following gastroduodenal digestion, related to ROS formation. MAN (UMF15+) had anti-inflammatory effects which were lost postdigestion, and in contrast, FB5 and FB6 had anti-inflammatory effects postdigestion.
... Also amylase hydrolyzes starch in honey and, by producing dextrose and maltose, increases the effect of honey's osmotic effect and, as a result, increases its antibacterial activity. The presence of chemical compounds such as methyl glyoxal also influences antimicrobial activity of honey (Paulus et al., 2012;Moussa et al., 2011;Oddo et al., 1999;Boukraa and Amara, 2008;Mavric et al., 2008). ...
The biological activities of bee products vary according to plant origin, geographical region and climatic characteristics. This study aimed to investigate the antibacterial activity of honey and propolis samples from different geographical regions with different climate. Samples included three honey samples and three propolis samples were collected from three areas of the Plain, Mountain and Forest of Golestan province in north of Iran. Antibacterial activity was evaluated by agar well diffusion method and MIC and MBC were determined by broth macrodilution tube method. The results of the present study revealed that antibacterial activity of the honey collected from forest areas is higher than other honey samples so that the MIC of this honey sample was in the range of 12.5 to 25%. The propolis collected from plain areas showed the highest antibacterial activity with MBC in the range of 12.5 to 50 mg/ml. The gram-positive bacteria in comparison of gram-negative bacteria and standard strains in comparison of native isolates were showed more sensitive to these bee products. The standard strain of S. aureus and the native isolate of P. aeroginosa were the most sensitive and the most resistant of the bacteria respectively. Difference and variation of antibacterial activity of bee products can be due to the difference in the various plants that bees have fed. Due to the complications associated with antimicrobial chemical compounds, identifying of effective compounds of these products can hope for us to introduce a natural drug combination or a natural food additive.
... The antibacterial properties of honey are mainly attributed to its 'bee origin' factors such as acidic pH, high osmolarity and release of hydrogen peroxide by glucose oxidase and 'plant origin' non-peroxide factors like methylglyoxal (MGO) 5 . The speculated concentration of MGO in manuka honey (Leptospermum scoparium), for example, is up to 100-fold higher than in other flora of honeys 6 . MGO, a dicarbonyl compound, acts by formation of advanced glycation end products (AGEs) and glutathione adducts in the cytoplasm of cells, including bacteria. ...
... The family Myrtaceae is divided into two subfamilies, the capsular Leptospermoideae and the fleshy-fruited Myrtoideae. One of the most pronounced species of this family is Leptospermum scoparium, which is the botanical source of the well-known manuka honey, with different mechanisms of antibacterial action depending on the MGO level [46,47]. Based on the enzymatic activity of GOX and the production of H 2 O 2 , supported by the results of the catalase honey treatment, we can conclude that the antibacterial effect of none of the analysed honey samples was mediated through the action of MGO. ...
Honey is an attractive natural product with various health benefits. A few honey-based commercial products have successfully been adopted in clinics to improve wound healing. However, screening of other potential sources of medical-grade honey, in particular, honeys from territories with high floral species diversity and high endemicity, is highly needed. The goal of this study was to characterise the physicochemical and antibacterial properties of New Caledonian honey samples (n = 33) and to elucidate the major mechanism of their antibacterial action. Inhibitory antibacterial activity of honeys against Staphylococcus aureus and Pseudomonas aeruginosa was determined with a minimum inhibitory concentration (MIC) assay. Enzymatic activity of glucose oxidase and the content of hydrogen peroxide (H2O2) in honey samples were analysed. Furthermore, total protein content of honeys together with their electrophoretic protein profiles were also determined in the study. The antibacterial efficacy of 24% of the tested honey samples was slightly superior to that of manuka honey with unique manuka factor 15+. The antibacterial activity of catalase-treated honey sample solutions was significantly reduced, suggesting that H2O2 is a key antibacterial compound of diluted honeys. However, the kinetic profiles of H2O2 production in most potent honeys at a MIC value of 6% was not uniform. Under the experimental conditions, we found that a H2O2 concentration of 150 μM in diluted honeys is a critical concentration for inhibiting the growth of S. aureus. In contrast, 150 μM H2O2 in artificial honey solution was not able to inhibit bacterial growth, suggesting a role of phytochemicals in the antibacterial activity of natural honey. In addition, the continuous generation of H2O2 in diluted honey demonstrated an ability to counteract additional bacteria in re-inoculation experiments. In conclusion, the tested New Caledonian honey samples showed strong antibacterial activity, primarily based on H2O2 action, and therefore represent a suitable source for medical-grade honey.
... 5 MGO within MH is primarily formed by the conversion of dihydroxyacetone to MGO by nonenzymatic Maillard reactions. 8 MH collected from the hive often contains relatively low levels of MGO and a high concentration of dihydroxyacetone. During storage, this relationship inverts, and MGO levels within the honey increase, due to the conversion of dihydroxyacetone. ...
Aim of the study was to find out the effectiveness of Manuka honey (MH) in various applications to treat drug resistant ENT infections as an adjuvant therapy. The antibacterial properties and antioxidant properties of MH is attributed to the presence of high concentration of methylglyoxal (MGO) and flavonoid, phenolic compounds respectively. Unique manuka factor (UMF) rating is a scale used to determine the antibacterial potency of MH which directly correlates to the MGO and phenolic components in MH. Various cases of nasal crusting in post operative period with multidrug resistant bacterial cultures were included in the study. Each case was started on thorough nasal douching as well as manuka honey topical application. Regular and meticulous follow up was done for each case via endoscopic examination and medical record was kept of any potential side effects. Perichondritis of pinna was included in the study with potentially unique application the above-mentioned condition. MH is a natural antibiotic with low toxicity profile, allowing for prolonged use when necessary. Moreover, the development of bacterial resistance to honey has yet to be reported, making it an attractive alternative or adjunctive therapy, particularly in cases where antimicrobial resistance is a concern. While Manuka honey's antimicrobial properties have been observed in various studies, translating this knowledge into clinical practice requires rigorous investigation to ensure its effectiveness, safety, and proper integration with conventional antibiotic therapies.
... Some resources categorize honey's antibacterial activity as hydrogen peroxide (H 2 O 2 )-mediated versus non-peroxide mediated (Girma et al., 2019;Nader et al., 2021). Manuka Honey (MH) in particular, is well-characterized as a non-peroxide honey, with its broadspectrum antibacterial properties, primarily attributed to its substantial methylglyoxal (MGO) component (Mavric et al., 2008;Carter et al., 2016;Cokcetin et al., 2016). MH's MGO activity has been trademarked as the unique manuka factor (UMF ® ), graded to represent antibacterial potency the higher the UMF value is (Cokcetin et al., 2016). ...
Introduction
Staphylococci are among the list of problematic bacteria contributing to the global antibiotic resistance (ABR) crisis. Their ability to adopt the small colony variant (SCV) phenotype, induced by prolonged antibiotic chemotherapy, complicates staphylococcal infection control options. Novel and alternative approaches are needed to tackle staphylococcal infections and curb ABR. Manuka honey (MH), a non-antibiotic alternative is recognized for its unique antibacterial activity based on its methylglyoxal (MGO) component.
Methods
In this study, MH (MGO 830+) was tested in combination with gentamicin (GEN), rifampicin (RIF), or vancomycin (VA) against staphylococcal wildtype (WT) and SCVs. To our knowledge, there are no current studies in the literature documenting the effects of MH on staphylococcal SCVs. While Staphylococcus aureus is well-studied for its international ABR burden, limited data exists demonstrating the effects of MH on S. epidermidis and S. lugdunensis whose pathogenic relevance and contribution to ABR is also rising.
Results & discussion
The three staphylococci were most susceptible to RIF (0.06-0.24 μg/ml), then GEN (0.12-0.49 μg/ml), and lastly VA (0.49-0.96 μg/ml). The MICs of MH were 7%, 7-8%, and 6-7% (w/v), respectively. Fractional inhibitory concentration (FIC) evaluations showed that the combined MH + antibiotic effect was either additive (FICI 1-2), or partially synergistic (FICI >0.5-1). While all three antibiotics induced SCVs in vitro, stable SCVs were observed in GEN treatments only. The addition of MH to these GEN-SCV-induction analyses resulted in complete suppression of SCVs (p<0.001) in all three staphylococci, suggesting that MH’s antibacterial properties interfered with GEN’s SCV induction mechanisms. Moreover, the addition of MH to growth cultures of recovered stable SCVs resulted in the inhibition of SCV growth by at least 99%, indicating MH’s ability to prevent subsequent SCV growth. These in vitro analyses demonstrated MH’s broad-spectrum capabilities not only in improving WT staphylococci susceptibility to the three antibiotics, but also mitigated the development and subsequent growth of their SCV phenotypes. MH in combination with antibiotics has the potential to not only resensitize staphylococci to antibiotics and consequently require less antibiotic usage, but in instances where prolonged chemotherapy is employed, the development and growth of SCVs would be hampered, providing a better clinical outcome, all of which mitigate ABR.
"Natural Medicine for Natural Defence" mengeksplorasi peran vital pengobatan alami dalam memperkuat sistem pertahanan kesehatan manusia. Buku ini menggabungkan kearifan tradisional dengan bukti ilmiah modern, menawarkan perspektif komprehensif tentang bagaimana pengobatan alami dapat diintegrasikan kedalam sistem kesehatan kontemporer.
Melalui sepuluh bab yang disusun secara sistematis, buku ini membahas sejarah pengobatan alami, dasar-dasar sistem pertahanan tubuh, potensi tanaman obat, peran nutrisi, dan praktik gaya hidup dalam meningkatkan kekebalan. Pembahasan dilanjutkan dengan analisis tantangan dalam penelitian dan pengembangan obat alami, serta visi masa depan integrasi pengobatan alami dalam sistem kesehatan global. Dilengkapi dengan studi kasus, data penelitian terkini, dan panduan praktis, buku ini menjadi sumber referensi berharga bagi praktisi kesehatan, peneliti, pembuat kebijakan, dan masyarakat umum yang tertarik pada pendekatan holistik dalam menjaga kesehatan.
The aim of this study was to observe the effect of topical application of manuka honey in healing of nasal mucosa in Post Endoscopic Sinus Surgery. A total of 50 patients were selected and were operated for sinonasal diseases. Post operative after nasal pack removal manuka honey was applied. Post– operative healing was assessed and scoring was done. The present study was to evaluate and observe faster healing after application of Manuka honey. The median time to achieve clean cavity, mucosal transition and complete epithelialization was 14.0 (14.0–14.0) days. The present study concluded that application of manuka honey promotes faster healing of nasal cavity and lessens chances of postoperative infections.
The beneficial properties of honey arise from the intricate interactions between microorganisms in flower nectar, the digestive systems of bees, and the interplay between honey bees and plants. This synergy leads to the production of protective compounds, including antimicrobial peptides, antibiotics, antioxidants, anti-inflammatory and immunomodulatory substances, and biofilm inhibitors. The composition of honey is influenced by geographical location, botanical origins, and bee breeds (lines). Key constituents of honey encompass carbohydrates (primarily glucose and fructose), enzymes, minerals, vitamins, organic and inorganic acids, phytohormones, and phytoncides. The presence of organic and inorganic acids, minerals, B vitamins, and antioxidants in honey contributes to its health benefits, such as enhancing the immune system, calming the nervous system, mitigating stress, providing analgesic effects, and improving gastrointestinal function. The fermentation process during honey production significantly impacts its composition, potentially enhancing its antibacterial properties. Additionally, honey contains probiotic bacteria, both viable and non-viable, derived from bee stomachs and flower nectar. As a natural postbiotic substance, honey encompasses microbial metabolites, metabolic products from flowers, and bee digestion byproducts, which collectively endow honey with its therapeutic and adaptive properties for both honey bees and human.
Introduction
Honey possesses several positive properties, making it effective in wound healing mechanisms. However, very little information is available on the different honey types for wound healing activity.
Method
In the first “Academy of Sciences”, a public engagement project with high school students, we assessed the properties of thirteen kinds of honey from the Piedmont area (Nord West Italy). In particular, we characterized the color intensity (by Pfund scale), total phenolic content (TPC), total flavonoid content (TFC), H2O2 production, and wound closure rate.
Results
Then, we tried to verify the presence of a correlation between these parameters, finding a positive correlation between H2O2 and wound closure rate.
Conclusion
These data pave the way to characterize different types of Italian honey to completely understand its potential.
The term "glycation compounds" comprises a wide range of structurally diverse compounds that are formed endogenously and in food via the Maillard reaction, a chemical reaction between reducing sugars and amino acids. Glycation compounds produced endogenously are considered to contribute to a range of diseases. This has led to the hypothesis that glycation compounds present in food may also cause adverse effects and thus pose a nutritional risk to human health. In this work, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) summarized data on formation, occurrence, exposure and toxicity of glycation compounds (Part A) and systematically assessed potential associations between dietary intake of defined glycation compounds and disease, including allergy, diabetes, cardiovascular and renal disease, gut/gastrotoxicity, brain/cognitive impairment and cancer (Part B). A systematic search in Pubmed (Medline), Scopus and Web of Science using a combination of keywords defining individual glycation compounds and relevant disease patterns linked to the subject area of food, nutrition and diet retrieved 253 original publications relevant to the research question. Of these, only 192 were found to comply with previously defined quality criteria and were thus considered suitable to assess potential health risks of dietary glycation compounds. For each adverse health effect considered in this assessment, however, only limited numbers of human, animal and in vitro studies were identified. While studies in humans were often limited due to small cohort size, short study duration, and confounders, experimental studies in animals that allow for controlled exposure to individual glycation compounds provided some evidence for impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to dicarbonyl compounds, albeit at dose levels by far exceeding estimated human exposures. The overall database was generally inconsistent or inconclusive. Based on this systematic review, the SKLM concludes that there is at present no convincing evidence for a causal association between dietary intake of glycation compounds and adverse health effects.
The aim of present study was to observe the effect of topical application of manuka honey in healing in the healing of postoperative mastoid cavity. A total of 100 patients diagnosed with chronic suppurative otitis media with cholesteatoma underwent canal wall down mastoidectomy, Manuka honey-soaked roller gauze pack was placed on Day 10 and was removed on day 17 and manuka honey was applied on day 17. Cavity was assessed on day 47 and day 90 on follow-up. Otoendoscopy was done on every visit to assess mastoid cavity. The primary outcome measure was the creation of a dry cavity as measured by a semi-quantitative scale as described by Merchant et al. Then Mastoid Cavity Healing Score was calculated on every visit and scoring was done at the end. On intragroup comparison it appeared that both the treatment methods exhibited improvised merchant grade score with the course of time (p-value = < 0.001). At 47th day and 90th day, the healing score in Group A was significantly higher than in Group B [p-value = < 0.001 and 0.001] respectively. We recommend Manuka honey as an adjunct to achieve a safe, dry ear in view of faster epithelization after mastoidectomy.
Tonsillectomy is one of the most common surgical procedures in childhood. While generally safe, it often is associated with a difficult early recovery phase with poor oral intake, dehydration, difficult or painful swallowing, postoperative bleeding, infection and/or otalgia. Better pain management and the availability of more child friendly medications are within the top consumer priorities in perioperative medicine, highlighting the importance of alternative pain treatments. This review focuses on the potential role of honey in the postoperative setting, its effects, and mechanisms of action. While the application of honey post-tonsillectomy may offer analgesic and healing benefits, it may also reduce postoperative bleeding. A systematic search was carried out using the search terms honey, tonsillectomy. Filters were applied to human studies and English. No other search terms were used or age filters applied to yield a broader range of results. Seven pediatric, four adult, and two studies of mixed pediatric and adult patients with sample sizes ranging from 8 to 52 patients were included in this review. Effect sizes ranged from small to huge across the studies. While the application of honey post-tonsillectomy may offer analgesic and healing benefits, it may also reduce postoperative bleeding. However, while there are potential benefits based on the chemical composition of honey, the current literature is of variable quality and there is need for high quality clinical trials.
This study aimed to compare incisional wound healing in cats and dogs after the topical application of Μanuka honey and a new medical device, Dermapliq. Comparisons were made between each treatment and control, between the two treatments, and between dogs and cats. Twelve cats and twelve dogs were included in this study, and the impact of the two substances was examined through cosmetic, clinical, ultrasonographical, and histological evaluation. The use of Dermapliq in first-intention wound healing achieved a significantly better cosmetic evaluation score and better total clinical score at days 20–41, compared to the control, in both dogs and cats. The ultrasonographically estimated wound area was smaller with Dermapliq compared to the control. Wounds treated with Dermapliq showed histologically less inflammation compared to the control. The use of Manuka honey did not show a significantly better cosmetic score compared to the control. Skin thickening was significantly higher after using Manuka honey compared to the control and so was the total clinical score. However, the median wound area, as was evaluated ultrasonographically, was significantly smaller when wounds were treated with Manuka honey, the difference being more apparent in dogs. Dermapliq was proven to be a better choice in achieving favorable wound healing than Manuka honey in dogs and cats in first-intention healing. In our study, cats had a statistically better cosmetic score and less skin thickening and scar width compared to dogs. Histologically, cats showed significantly less edema, higher inflammation and angiogenesis scores, and lower fibroblast and epidermis thickening scores when compared to dogs.
This study was conducted at a laboratory in the Biology, College of Education, University of Salahaddin, from February to May 2022 to investigate propolis, honey and royal jelly’s chemical composition, antioxidant and antibacterial activities. The honeybee production extract showed that Gram (+) bacteria were more resistant to the antibacterial compounds of honey and propolis than Gram (-) bacteria and fungi. E. coli was a more sensitive isolate than all the other bacteria examined against the honey types tested. At the same time, it revealed more resistance against all types of propolis. Royal jelly with honey displayed more antimicrobial activity than other bee products and exhibited superior activity; the minimum inhibitory concentration of honey and propolis samples ranged from 32 to 512µg/mL. The MIC value of the most effective honey (Honey 1, Honey 2 and Royal jelly) was 32µg/mL. The lowest concentration of Qaladze propolis was (32µg/mL) for E. coli ATCC 25922, followed by 128µg/mL in some other propolis types. Keywords: Apis mellifera; antimicrobial activities; honey; propolis; royal jelly.
Diabetic foot ulcers (DFUs) are considered a major problem for public health, leading to high rates of lower-limb amputations. Moreover, due to the high prevalence rate of predisposing factors, the incidence rate of DFU is still rising. Although DFUs are complex in nature, foot ulceration usually precedes diabetic foot amputations. These impaired chronic wounds usually promote a microbial biofilm, commonly characterized by the presence of multidrug-resistant microorganisms, hampering the efficacy of conventional antibiotic treatments. Honey has been shown to be an effective antibacterial component, including against multidrug-resistant bacteria. Honey’s physical–chemical characteristics, such as the presence of hydrogen peroxide, its low pH levels, and its high sugar and phenolic contents, promote anti-inflammatory and antioxidative activities, improving wound healing. This review aims to explore honey’s effects in wound healing, especially for DFUs, and to show how the different physical–chemical features among different honey types might influence the treatment’s effectiveness. For this, the mechanisms by which honey can promote wound healing and the potential use of honey dressings in diabetic wounds were investigated in animal models and humans. After revising the diabetic wound impairment mechanisms, we found that most of the clinical studies that treated DFUs with honey in animal models or humans reported accelerated wound healing, greater wound contraction, and lower amputation or hospitalization rates; however, few studies characterized the features of honeys used for wound treatment, hindering the possibility of extensively comparing the different types of honey and identifying characteristics that most successfully promote wound healing. According to this review, honey is a cost-effective and safe option for DFU management.
1Introduction: Study in order to introduce new antimicrobial agents with natural origin to prevent the
antibiotic resistance and eliminating its effects, employing chemical agents is an indispensable necessity. Honey,
as an important food with natural origin has high antimicrobial potential. Several factors have contributed to the
antibacterial activity of honey. For example, acidity, osmolarity, hydrogen peroxide, phenolic and flavonoid
compounds, including these factors. Also, small amounts of glucose oxidase, protease, amylase, catalase and
phosphatase enzymes and chemical compounds such as methylglyoxal are also effective. Floral origin of honey
is effective on its biological properties including antimicrobial, anti-tumor, anti-inflammatory, antioxidant and
antiviral activity. So this study was done to evaluate the antibacterial activity and physico-chemical analysis of
four types of honey with different floral origin including: Thyme, Eryngium, Pennyroyal and Dill collected from
the bee hives in Golestan province.
Materials and methods: Four honey samples with different floral origin including, Thyme, Eryngium,
Pennyroyal and Dill were collected from the bee hive in the Golestan province in north of Iran. The bacterial
strains used in this study, including two species of gram-negative of Escherichia coli and Shigella dysenteriae
and the two species of gram-positive of Staphylococcus aureus and Bacillus cereus were provided in
lyophilized. Bacterial strains in BHI broth were activated and from each of them were prepared bacterial
suspensions equivalent to the McFarland 0.5 turbidity standard (1.5×108 CFU/ml). Evaluation of antibacterial
activity using agar well diffusion method was performed. For this purpose serial dilutions of honey samples were
prepared aseptically in sterilized distilled water. Surface of Mueller Hinton agar were uniformly inoculated with
bacterial suspension containing of 1.5×108 CFU/ml. Then wells of 8 mm in diameter were prepared and these
wells were filled with different dilutions of honey samples. After incubation at 37°C for 24 h, antibacterial
activity was analyzed by measuring the zones of inhibition. Minimum inhibitory concentration (MIC) and
minimum bactericidal concentration (MBC) of honey samples were determined by using broth macro-dilution
method. For this purpose, each of the tubes from different dilutions of honey samples were added by 5×105
CFU/ml from each of the tested bacteria and incubated for 24 h at 37°C. The results for microbial turbidity of
visible were recorded. The last dilution (lowest concentration) in which microbial turbidity was not observed, as
the MIC was considered. For the determination of MBC, from the tube that contained honey concentrations
higher than the MIC were cultured onto the agar medium. The MBC was defined as the lowest concentration that
allowed no visible growth on the agar. Also the studied physico-chemical properties were moisture content, pH,
acidity, ash content and reducing sugars that was performed according to the Iranian National Standard No. 92.
Results and Discussion: The results indicated that the antibacterial effects of the tested honeys, and the
difference between floral origins honeys is effective in antibacterial properties. MIC and MBC values obtained
for the tested honeys were in the range of %6.25-50% (vol/vol). Highest antibacterial activity was recorded for
Eryngium honey by agar well diffusion method with zone of inhibition of 15.5, 14,11 and 11 mm against S.
dysenteriae, S. aureus, B. cereus and E. coli at concentration of 50% v/v respectively and its MIC for this
bacteria were, 6.25%, 10%, 10% and 25% respectively. also low antibacterial activity of Pennyroyal honey was confirmed so that MIC of the this honey for E. coli, S. aureus, B. cereus and S.dysenteriae was, 50%, 25%,
12.5% and 10%, respectively. The quality of honey depends on a number of physico-chemical properties such as
moisture, ash content, pH, acidity, the amount of sugars. For this reason, standards for honey have been set by
different countries. The physico-chemical analysis of honeys showed moisture contents in the range of 22.56-
25.36%, acidity in the range of 12.58-13.59 meq/kg, pH in the range of 4.15-4.26, reducing sugars in the range
of 63.7-63.8%. Also the ash content of Eryngium honey with 0.183% was higher than the other honey samples.
This higher level might be due to the higher pollen count in this region. High ash contents may also depend upon
the floral origin of honey and the material collected by bees during foraging. The low acidity of honey samples
studied in the present study was due to the fact that there was no unwanted fermentation in these samples.
Overall, the results implied that honey samples with different floral origin collected from the bee hive in the
Golestan province in north of Iran have variable potential antibacterial activity. The variety of antibacterial
effects of different types of honey can be due to differences in plants that honey is obtained from. In other words,
different species of plants in different regions have different compounds and their obtained honey will not be the
similar and thus its biological effects also will be different.
Keywords: Honey, Antibacterial activity, Physico-chemical properties, Floral origin
Study in order to the introduction of new antimicrobial agents with natural origin is an indispensable necessity. Honey, as a food has antibacterial and antioxidant high potential and the floral origin of honey plays an important role on its biological properties. This research , In order to investigation of antibacterial activity of four types of monofloral honey with different floral origin and a moltifloral honey
collected from the bee hive in the golestan province in north of Iran. Evaluation of antibacterial activity against four bacteria using agar well diffusion method was performed. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of honey samples were determined by using broth
macro dilution tube method. Results showed antibacterial activity of tested honey samples. Highest antibacterial activity was recorded for multi floral honey by agar well diffusion method at a concentration
of 50% with zone of inhibition of 22, 21,16 and 13.66 mm against Shigella dysenteriae , Staphylococcus
aureus , Bacillus cereus and Escherichia coli respectively. MIC and MBC values of obtained for
multifloral, linden, maple and Astragalus honeys were in the range of %6.25-25% (V/V) and citrus honey showed the lowest antibacterial activity. Overall, the results imply that antibacterial activity of honey samples from different botanical origin is variable and difference between the types of plants used in the production of bee products affect its antibacterial properties.
Keywords: Honey, Monofloral and multifloral ,Floral origin, Antibacterial activity
PHYTOCHEMISTRY OF HONEY AND ITS PHARMACOLOGICAL ADVANTAGES
There are two types of antibacterial agents in honey. The peroxide one is destructed when honey is heated or stored in the light. The other one is a non-peroxide one and is stable to heat and storage. The chemical properties of the non-peroxide activity are determined. Most of the non- peroxide antibacterial activity originates from the bee, but some of it comes from the honey source (nectar or honeydew).
High performance liquid chromatograms of the phenolic fraction of 19 samples of New Zealand manuka honey, some with high levels of non-peroxide antibacterial activity and some with no such activity, were identical, which indicated that phenolic components of this honey are not responsible for the presence or absence of this activity in manuka honey. Similarly, the result showed that geography does not influence the phenolic composition of manuka honey. Antibacterial bee peptides and the antibacterial β-triketone leptospermone were not detected in manuka honey. Methyl syringate constituted approximately 70% w/w of the phenolic fraction of manuka honey and can be regarded as a floral marker for this honey. High performance liquid chromatographic profiles of the phenolic components of manuka, heather, clover and beech honeydew honeys were significantly different and could be used to differentiate honeys if they can be shown to be as consistent as those of manuka honey.
The physiologic process of wound healing is impaired and prolonged in pediatric patients receiving chemotherapy. Due to profound immunosuppression, wound infection can easily spread and act as the source of sepsis. Referring to in vitro studies, which confirmed the antibacterial potency of special honey preparations against typical isolates of nosocomially acquired wound infections (including Methicillin-resistant Staphylococcus aureus and Vancomycin-resistant enterococci) and considering the encouraging reports from other groups, Medihoney has now been used in wound care at the Department of Pediatric Oncology, Children's Hospital, University of Bonn for 3 years. Supplemented with clinical data from pediatric oncology patients, this article reviews the scientific background and our promising experience with Medihoney in wound care issues at our institution. To collect and analyze the available experience, we prepare an internet-based data documentation module for pediatric wound care with Medihoney.
The inhibine values of 25 honeys were diminished or destroyed by the action of catalase. All the honeys had a ‘peroxide value’ as determined iodometrically; this was destroyed by the action of catalase.
The results of gas chromatagraphic analyses of the concentrated diethyl ether liquid-liquid extracts of 10 honey samples from a variety of floral sources are presented. The chemical composition was compared with the pollen composition and found to be related to the floral source. The gas chromatographic profile of honey extractives is proposed as a guide to the purity of unifloral honeys.
A range of New Zealand monofloral honeys was assayed for antibacterial activity with and without the hydrogen peroxide present (inactivated by the addition of catalase). It was found that in the honeys with high antibacterial activity a large part of this activity was due to a factor other than hydrogen peroxide. The test micro-organism used, Staphylococcus aureus, was not inhibited by the osmolarity or the acidity of the honey. The association of high antibacterial activity with particular floral sources suggests that the non-peroxide antibacterial activity is of floral origin. The activity of manuka honey was tested and found to be heat-stable.
Reprinted from AMERICAN BEE JOURNAL The use of honey as a wound-heal-ing and antiseptic agent has been re-corded since ancient times. Stomfay-Stitz (1960) has reviewed this sub-ject in his interesting article, "Honey: An Ancient Yet Modern Medicine." Examples of this use of honey can be found in the m~dern literature (Bul-man, 1955; Seymour and West, 1951). The presence in honey of an anti-bacterial activity was first shown by Dold, Du and Dziao (1937) about 25 years ago. Their work was confirmed in several other laboratories (Prica, 1937; Plachy, 1944) and in the inter-vening time several other papers have appeared on the subject. It has been generally agreed that "inhibine" (the name used by Dold for the antibac-terial activity) is sensitive to heat and light, and the effect of heating of honey on its inhibine content has been studied by several investiga-tors, including Dold, et al, (1937), Prica (1937), Schade, Marsh and Eckert (1958), Duisberg and War-necke (1959), and Stomfay-Stitz and' Kominos (1960). It is apparent: that heating of honey sufficiently to re-duce markedly or destroy its inhib-ine activity would deny it a market as first-quality honey in several European countries. In fact, Duisberg and Warnecke proposed the use of sucrase and inhibine assays together to determine the heating history of commercial honey. Until the present, no information on the actual nature or constitution of inhibine has been published. During our work on an enzyme in honey that produces acidity it was shown that the acid formed is glu-conic acid and that the enzyme re-sponsible is a glucose oxidase. Details of the identification of this enzyme will appear in a forthcoming publica-IEastern Utilizatlon Research and Develop. ment Division, Agricultural Research ser-vice, U. S. Department of Agriculture. Vol. 102 pp. 430-431 November, 1962 tion. Glucose oxidase has been known to occur in molds and some years ago Gauhe (1941) demonstrated that an enzyme oxidizing glucose to gluconic acid and producing hydrogen per-oxide occurred in the pharyngeal gland of the honey bee. It has not been reported in honey. Enzymes of this type produce hy-drogen peroxide during their action-on glucose according to the equation: glucose + 0, glucose oxidase)0 gluconolactone + H,O, The gluconolactone can further change to gluconic acid, which can exist in equilibrium with the lactone. The enzymic production and accumu-lation of hydrogen peroxide in diluted honey accounts for all of the re-ported properties of inhibine and we cone! ude that the antibacterial ac-tivity of honey as demonstrated in the inhibine assay is actually due to hydrogen peroxide. The work upon which this conclusion is based is sum-marized below and reported in detail elsewhere (White, Subers, and Sche-partz, 1962). A crude enzyme preparation from honey made by alcohol precipitation and dialysis was found to produce hy-drogen peroxide when incubated with glucose, by testing with peroxidase and a dye (o-dianisidine) which be-comes colored in the presence of hy-drogen peroxide and peroxidase. The depth of color (peroxide produced) was proportional to the concentration of the honey enzyme. Paper chroma-tography of the enzyme-glucose solution showed that an acid similar to gluconic acid was produced; a comparison of infrared spectra showed it to be gluconic acid.
Despite the growing interest towards methylglyoxal and glyoxalases their real role in metabolic network is still obscure. In the light of developments several reviews have been published in this field mainly dealing with only a narrow segment of this research area. In this article a trial is made to present a comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methylglyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methylglyoxal on energy production, free radical generation and cell killing. Special attention is paid to the discussion of α-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this α-dicarbonyl in diseases. Concerning the interaction of methylglyoxal with biological macromolecules (DNA, RNA, proteins) an earlier review (Kalapos, Toxicology Letters, 73, 1994, 3–24) means a supplementation to this paper, thus hoping the avoidance of unnecessary bombast. The paper arrives at the conclusion that since the early stage of evolution the function of methylglyoxalase pathway has been related to carbohydrate metabolism, but its significance has been changed over the thousands of years. Namely, at the beginning of evolution methylglyoxalase path was essential for the reductive citric acid cycle as an anaplerotic route, while in the extant metabolism it concerns with the detoxification of methylglyoxal and plays some regulatory role in triose-phosphate household. As there is a tight junction between methylglyoxal and carbohydrate metabolism its pathological role in the events of the development of diabetic complications emerges in a natural manner and further progress is hoped in this field. In contrast, significant advancement cannot be expected in relation to cancer research
Sugar osazones and glycosuloses rapidly and quantitatively react with hydroxylamine to produce oximes that give trimethylsilyl derivatives suitable for g.l.c. and mass spectral analysis. The reaction of d-glucose with benzoylhydrazine to give the bishydrazone of 3-deoxy-d-erythro-hexos-2-ulose (1) [H. El Khadem et al., Carbohydr. Res., 22 (1973) 381-89] was re-investigated, together with the conversion of this compound to the hexosulose. Although by-products are produced in the reaction, including the bis(benzoylhydrazone) (osazone) of d-glucose, the major product is the monohydrate of the bis(benzoylhydrazone) of 1 (colorless). The anhydrous (yellow) form can be prepared from the monohydrate by crystallization from absolute ethanol and has quite different physical properties. Improvements of the original preparation are described that allow the preparation of the bishydrazone and its subsequent conversion to 1via transhydrazonation in 44% overall yield, and with no detectable contamination by d-glucose or d-glucosone. Evidence is presented that the previously reported cyclic form of the bis(benzoylhydrazone) of d-glucose is the bis(benzoylhydrazone) (monohydrate) of 1.
Some components responsible for the exceptionally high antibacterial activity of manuka honey were isolated by testing fractions of the honey for activity against Staphylococcus aureus. An ethanol-ether extract of the honey was separated by preparative-layer chromatography and the fractions thus obtained were assessed for antibacterial activity. One fairly homogeneous fraction was identified as methyl 3,5-dimethoxy-4-hydroxybenzoate (methyl syringate, 1b). Combined gas chromatography-mass spectroscopy indicated the presence of this compound in some of the other antibacterial fractions together with methyl 3,4,5-trimethoxybenzoate (1c) and 3,4,5-trimethoxybenzoic acid (1a). Authentic specimens of 3,5-dimethoxy-4-hydroxybenzoic acid (syringic acid, 1d) and 3,4,5-trimethoxybenzoic acid (1a) and their methyl esters were tested against S. aureus. The acids and, to a lesser extent, methyl syringate were found to possess significant antibacterial activity.
Trace quantities of the mutagen methyl glyoxal in foods and beverages were determined by a newly developed method. Methyl glyoxal was reacted with cysteamine to give 2-acetylthiazolidine in a food or a beverage sample at pH 6. 2-Acetylthiazolidine formed from methyl glyoxal was extracted with dichloromethane and subsequently analyzed by a gas chromatograph equipped with a fused silica capillary column and a thermionic detector. A total of 17 commercial food items were analyzed for methyl glyoxal. The quantities of methyl glyoxal in foods ranged from 0.04 (orange juice) to 47 ppm (decaffeinated brewed coffee).
Wine aldehydes were identified as O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine derivatives by GC-MS or with a GC-electron-capture detector. This method has been used to evaluate levels of glyoxal and methylglyoxal in wine. Reproducibility and linearity studies gave satisfying results. Glyoxal and methylglyoxal are formed during fermentation. Among the factors affecting their production, high musts pH increased the levels found in the corresponding wines. Various microorganisms of the wine such as Saccharomyces cerevisiae and Leuconostoc ænos can produce glyoxal and methylglyoxal. The concentrations in Sherry wines were particularly high. Because of the toxicological properties of these substances, their determination and the knowledge of their metabolism by wine microorganisms are very important.
The 1,2-dicarbonyl compounds 3-deoxyglucosulose (3-DG), methylglyoxal (MGO) and glyoxal (GO) were measured for the first time in 21 honey samples as the corresponding quinoxalines after derivatization with orthophenylenediamine using RP-HPLC and UV-detection. Compared to 5-hydroxymethylfural (HMF), which was also quantified, and ranged between 0.6 and 44mg/kg, up to 100-fold higher amounts of 3-DG were found, ranging from 79 to 1,266mg/kg. During storage of honey at 35C and 45C, a linear increase of 3-DG was observed. Values for GO and MGO were in the ranges 0.2–2.7mg/kg and 0.4–5.4mg/kg respectively, and were not affected by storage. Using semi-preparative RP-HPLC, glucosone, a 1,2-dicarbonyl compound previously unknown to occur in foods was isolated from a honey sample and characterized by LC-MS and NMR spectroscopy.
The influence of light on the peroxide value (inhibine) of honey was determined in Central European honeys of 20 different flow sources.
The light sensitivity of bee honey depends strongly on the flow source of the honey. The honey enzyme glucose-oxidase, the activity of which causes formation of the antibacterial acting inhibine (H2O2), is far more oxidized by visible light in certain nectar honeys than in honeydew honeys. These differences are caused not only by the pH value and color of honey, but also by sensitizing substances. A maximal decrease of peroxide values can be observed in honeys of white clover (Trifolium repens) or rape (Brassica Napus), which had been exposed to full sunlight. The light of fluorescent tubes is more detrimental than that of incandescent bulbs.
The common practice of packing honey in colorless glass jars can result in deterioration of the raw quality of honey, since the peroxide values of light-sensitive honeys decrease after light exposure not only in the external area along the glass edge but also in the middle of the jar.
After heating N--hippuryl-L-arginine (Hip-Arg) with varying amounts of lactose for 1–4h at 100C, a previously unknown arginine derivative could be detected by RP-HPLC and UV-detection. Following semi-preparative isolation, the compound was unequivocally identified as 2-(2-benzoylamino-acetylamino)-5-[5-(3-hydroxypropyl)-4-oxo-imidazolon-2-yl]-L-ornithine (Hippuryl-PIO, Hip-PIO) by electrospray-time of flight-mass spectroscopy as well as one- and two-dimensional 1H- and 13C-nuclear magnetic resonance. Hip-PIO was exclusively formed during incubation of Hip-Arg with disaccharides containing a 1,4-glycosidic linkage. As reference for amino acid analysis, free PIO was synthesized starting from N-(tert-butoxycarbonyl)-L-arginine (t-Boc-Arg) via t-Boc-PIO and final hydrolysis with acetic acid. Preliminary evidence for the formation of protein-bound PIO, which proved to be acid-labile, was obtained using amino acid analysis with ninhydrin detection for enzymatic hydrolysates of casein samples which had been heated in the presence of lactose at 100C. The ornithinoimidazolinone PIO represents a new type of post-translational protein modification formed during food processing, which might be responsible for the major part of arginine derivatisation in disaccharide-containing foods like milk.
A method is reported for determining the α-dicarbonyls glyoxal, methylglyoxal, and diacetyl. The carbonyls were reacted at pH 8 with .05% aqueous solution of o-phenylenediamine for 4 h at 25°C to form quinoxalines. The derivatives were extracted with chloroform, transferred to methanol, and separated by HPLC on a Supelcosil LC-18 column with methanol water as the mobile phase. The method was applied to several dairy cultures and cheese varieties. The amounts of glyoxal, methylglyoxal, and diacetyl in the cultures varied from 2 to 227, 0 to 7, and 1 to 11 µg/ml, respectively, depending on the species, strain, and culture medium.
Several natural products are collected or manufactured by bees to construct their hive and produce honey. These include beeswax, flower volatiles, nectar, pollen, propolis and honey itself. Some of the components of these materials possess antibacterial properties and are discussed briefly to ascertain their contribution to the antibacterial activity of honey. New Zealand's manuka honey is known to possess a high level of “non-peroxide” antibacterial activity and research to identify the origin of this activity is briefly reviewed. Finally a hypothesis is advanced to explain the phenomenon of “non-peroxide” antibacterial activity in honey. The author concludes that this activity should be interpreted as residual hydrogen peroxide activity, which is probably due to the absence of plant-derived catalase from honey, an idea first suggested by Dustman in 1971. [Dustman, J. H. (1971). Über die Katalaseaktivität in Bienenhonig aus der Tracht der Heidekrautgewächse (Ericaceae). Zeitschrift für Lebensmittel-Untersuchung und Forschung, 145, 292–295]
The nonperoxide antibacterial activity of honey and honey fractions was tested withStaphylococcus aureusandMicrococcus luteusbacterial species. Antibacterial activity correlated significantly with the honey acidity but did not correlate with honey pH. There were small differences between the antibacterial activities of different honey types: rhododendron, eucalyptus and orange honeys had a relatively low activity, whereas dandelion, honeydew and rape honeys had a relatively higher activity. These results suggest that a part of the antibacterial activity might be of plant origin. However, the antibacterial activity of sugar-adulterated honeys was the same as that of control honeydew honeys produced in the same apiary suggesting that the major part of the antibacterial activity of honeydew honey is of bee origin.Ten different honeys were fractionated into four fractions using column chromatography or vacuum distillation: acidic; basic; nonvolatile, nonpolar; and volatile. The antibacterial activity of the different fractions tested was: acids > bases = nonpolar, nonvolatiles > volatiles. This order was the same using eitherStaph. aureusorMicrococcus luteusas test strains.An exception was manuka honey from New Zealand where almost the entire activity was found in the acidic fraction.
Honey has been used as a medicine since ancient times in many cultures and is still used in ‘folk medicine’. The use of honey as a therapeutic substance has been rediscovered by the medical profession in more recent times, and it is gaining acceptance as an antibacterial agent for the treatment of ulcers and bed sores, and other infections resulting from burns and wounds. In many of the cases in the cited reports, honey was used on infections not responding to standard effective in rapidly clearing up infection and promoting healing. Honey has also been found to be effective in treating bacterial gastoentertis in infants. This is the published version of an article published in the journal: Bee World. Used with permission.
The effectiveness of honey as a therapeutic agent has been unequivocally demonstrated in the literature reviewed in Part 1 of this article published in 1999, but the biochemical explanation of these effects is more hypothetical. However, a rational explanation can be seen when one looks at the scientific literature outside that on honey. Some of the components of honey are substances known to have physiological actions that would explain many of its therapeutic effects. In addition, research on honey has shown directly that it has physiological actions that would give therapeutic effects. This is the published version of an article published in the journal: New Zealand BeeKeeper. Used with permission.
The heating of glucose and fructose in phosphate buffers (pH 5·0 and 7·0) at 100, 110 and 120°C for 30, 60 and 120 min led to increasing inhibitory activities against the growth of Escherichia coli. The inhibitory effects of both heated sugars were rather similar, which was in agreement with the similar compositions of solutions after heating. The antimicrobial activity of solutions was separated into seven different fractions by high performance liquid chromatography (HPLC). Furfural or 5-hydroxymethylfurfural was not responsible for this antimicrobial activity.
A simple, convenient, and quantitative method for the preparation of methylglyoxal (pyruvaldehyde) solutions is described. The method involved acid hydrolysis (5% H2SO4) of pyruvaldehyde dimethyl acetal at 100°C for 25 min. The hydrolysis method is quite reproducible and does not require standardization of the methylglyoxal solutions. The preparations of methylglyoxal by the procedure described have been used in the study of glyoxalase I activity.
A procedure for the assay of methylglyoxal in biological systems is described, together with sample storage, sample processing procedures, and statistical evaluation. Specimen data are presented. Methylglyoxal was assayed by derivatization with 1,2-diamino-4,5-dimethoxybenzene and high-performance liquid chromatography (HPLC) of the resulting quinoxaline, 6,7-dimethoxy-2-methylquinoxaline, with spectrophotometric or fluorescence detection. Derivatization, solid-phase extraction, and HPLC were performed under acid conditions to prevent the spontaneous formation of methylglyoxal from glyceraldehyde 3-phosphate and dihydroxyacetone phosphate during the assay. The limits of detection in the biological matrix were 45 pmol (absorbance detection) and 10 pmol (fluorimetric detection), the recovery was 58%, and the intra- and interbatch coefficients of variance were 7.7 and 30.0%, respectively. The concentration of methylglyoxal in whole blood from normal healthy human individuals was (mean +/- SE, nM) 256 +/- 92 (n = 12) and that from diabetic patients was 479 +/- 49 (n = 55), showing a significant increase in diabetes mellitus (P < 0.01; Mann-Whitney U test). Sample processing under acidic conditions was essential to avoid interferences. Previous estimates of the concentration of methylglyoxal in biological samples require re-evaluation.
To assess the variation in antibacterial activity of honey a survey was carried out on 345 samples of unpasteurized honey obtained from commercial apiarists throughout New Zealand. Most of the honeys were considered to be monofloral, from 26 different floral sources. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay, with reference to phenol as a standard. Antibacterial activity was found to range from the equivalent of less than 2% (w/v) phenol to 58% (w/v) phenol, with a median of 13.6 and a standard deviation of 12.5. Neither the age of the honey samples nor whether they had been processed by the apiarist was associated with lower activity. However, the difference between floral sources in the antibacterial activity was very highly significant. Kanuka (Kunzea ericoides (A. Rich.) J. Thompson. Family: Myrtaceae), manuka (Leptospermum scoparium J. R. et G. Forst. Family: Myrtaceae), ling heather (Calluna vulgaris (L.) Hull. Family: Ericaceae) and kamahi (Weinmannia racemosa Linn. f. Family: Cunoniaceae) were shown to be sources likely to give honey with high antibacterial activity. When antibacterial activity was assayed with catalase added to remove hydrogen peroxide, most of the honeys showed no detectable antibacterial activity. Only manuka and vipers bugloss (Echium vulgare L. Family: Boraginaceae) honeys showed this type of activity in a significant proportion of the samples. The high antibacterial activity of manuka honey was in many cases due entirely to this non-peroxide component.
A simplified and improved method is described for the preparation of pyrraline, a lysine derivative from the advanced Maillard reaction and potential indicator for heat treatment of foods. The compound was obtained in a high degree of purity and with a yield of 31% fromN
α-t-butyloxycarbonyl-L-lysine after heating with 3-deoxy-D-erythro-hexos-2-ulose for 2 h at 70°C in the dry state, preparative fractionation of the resultingN
α-t-butyloxycarbonyl pyrraline with reverse-phase liquid chromatography and final deprotection of the intermediate compound with acetic acid.
Methylglyoxal is a toxic electrophile. In Escherichia coli cells, the principal route of methylglyoxal production is from dihydroxyacetone phosphate by the action of methylglyoxal synthase. The toxicity of methylglyoxal is believed to be due to its ability to interact with the nucleophilic centres of macromolecules such as DNA. Bacteria possess an array of detoxification pathways for methylglyoxal. In E. coli, glutathione-based detoxification is central to survival of exposure to methylglyoxal. The glutathione-dependent glyoxalase I-II pathway is the primary route of methylglyoxal detoxification, and the glutathione conjugates formed can activate the KefB and KefC potassium channels. The activation of these channels leads to a lowering of the intracellular pH of the bacterial cell, which protects against the toxic effects of electrophiles. In addition to the KefB and KefC systems, E. coli cells are equipped with a number of independent protective mechanisms whose purpose appears to be directed at ensuring the integrity of the DNA. A model of how these protective mechanisms function will be presented. The production of methylglyoxal by cells is a paradox that can be resolved by assigning an important role in adaptation to conditions of nutrient imbalance. Analysis of a methylglyoxal synthase-deficient mutant provides evidence that methylglyoxal production is required to allow growth under certain environmental conditions. The production of methylglyoxal may represent a high-risk strategy that facilitates adaptation, but which on failure leads to cell death. New strategies for antibacterial therapy may be based on undermining the detoxification and defence mechanisms coupled with deregulation of methylglyoxal synthesis.
Despite the growing interest towards methylglyoxal and glyoxalases their real role in metabolic network is still obscure. In the light of developments several reviews have been published in this field mainly dealing with only a narrow segment of this research area. In this article a trial is made to present a comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methylglyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methylglyoxal on energy production, free radical generation and cell killing. Special attention is paid to the discussion of alpha-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this a-dicarbonyl in diseases. Concerning the interaction of methylglyoxal with biological macromolecules (DNA, RNA, proteins) an earlier review (Kalapos, Toxicology Letters, 73, 1994, 3-24) means a supplementation to this paper, thus hoping the avoidance of unnecessary bombast. The paper arrives at the conclusion that since the early stage of evolution the function of methylglyoxalase pathway has been related to carbohydrate metabolism, but its significance has been changed over the thousands of years. Namely, at the beginning of evolution methylglyoxalase path was essential for the reductive citric acid cycle as an anaplerotic route, while in the extant metabolism it concerns with the detoxification of methylglyoxal and plays some regulatory role in triose-phosphate household. As there is a tight junction between methylglyoxal and carbohydrate metabolism its pathological role in the events of the development of diabetic complications emerges in a natural manner and further progress is hoped in this field. In contrast, significant advancement cannot be expected in relation to cancer research.
The term "advanced glycation end products" (AGEs) stands for a heterogeneous group of amino acid derivatives that are formed via glycation processes between peptide-bound lysine or arginine derivatives and carbonyl compounds, processes originally known from food systems as "Maillard reactions." AGEs accumulate in plasma and tissues with advancing age, diabetes, and particular renal failure. In vivo and in vitro studies indicate that AGEs represent an important class of uremic toxins. This review focuses on the chemistry behind the formation of AGEs, possible mechanisms underlying the accumulation of AGEs in uremia, clinical and therapeutic implications, and possible nutritional consequences.
The antimicrobial activity of manuka honey has been well documented (Molan, 1992a,b,c, 1997) [Molan, P.C., 1992. The antibacterial activity of honey. 1: the nature of the antibacterial activity. Bee World 73 (1) 5-28; Molan, P.C., 1992. The antibacterial activity of honey. 2: variation in the potency of the antibacterial activity. Bee World 73 (2) 59-76; Molan, P.C., 1992. Medicinal uses for honey. Beekeepers Quarterly 26; Molan, P.C., 1997. Finding New Zealand honeys with outstanding antibacterial and antifungal activity. New Zealand Beekeeper 4 (10) 20-26]. The current bioassays for determining this antimicrobial effect employ a well diffusion (Ahn and Stiles, 1990) [Ahn, C., Stiles, M.E., 1990. Antibacterial activity of lactic acid bacteria isolated from vacuum-packed meats. Journal of Applied Bacteriology 69, 302-310], (Weston et al., 1999) [Weston, R.J., Mitchell, K.R., Allen, K.L., 1999. Antibacterial phenolic components of New Zealand manuka honey. J. Food Chem. 64, 295-301] or disc diffusion (Taormina et al., 2001) [Taormina, Peter J., Niemira, Brendan A., Beuchat, Larry R., 2001. Inhibitory activity of honey against food borne pathogens as influenced by the presence of hydrogen peroxide and level of antioxidant power. Int. J. Food Microbiol. 69, 217-225] assay using zones of inhibition as indicators of bacterial susceptibility. The development of a 24-h spectrophotometric assay employing 96-well microtiter plates, that is more sensitive and more amenable to statistical analysis than the assays currently employed, was undertaken. This simple and rapid assay permits extensive kinetic studies even in the presence of low honey concentrations, and is capable of detecting inhibitory levels below those recorded for well or disc diffusion assays. In this paper, we compare the assay to both well and disc diffusion assays. The results we obtained for the spectrophotometric method MIC values show that this method has greater sensitivity than the standard well and disc diffusion assays. In addition, inter- and intra-assay variance for this method was investigated, demonstrating the methods reproducibility and repeatability.
The Maillard reaction or nonenzymatic browning is of outstanding importance for the formation of flavour and colour of heated foods. Corresponding reactions, also referred to as "glycation", are known from biological systems, where the formation of advanced glycation endproducts (AGEs) shall play an important pathophysiological role in diabetes and uremia. In this review, pathways leading to the formation of individual protein-bound lysine and arginine derivatives in foods are described and nutritional consequences resulting from this posttranslational modifications of food proteins are discussed.
Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in combination with creatine and ascorbic acid on cancer-bearing animals had been investigated by measuring the increase in life span and tumor cell growth inhibition. The results indicated that anticancer effect of methylglyoxal was significantly augmented by ascorbic acid and further augmented by ascorbic acid and creatine. Nearly 80% of the animals treated with methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid of any malignant cells within the peritoneal cavity.
Methylglyoxal (MG), a cytotoxic by-product produced mainly from triose phosphates, is used as a substrate by glyoxalase I. In this paper, we report on the estimation of MG level in plants which has not been reported earlier. We show that MG concentration varies in the range of 30-75 microM in various plant species and it increases 2- to 6-fold in response to salinity, drought, and cold stress conditions. Transgenic tobacco underexpressing glyoxalase I showed enhanced accumulation of MG which resulted in the inhibition of seed germination. In the glyoxalase I overexpressing transgenic tobacco, MG levels did not increase in response to stress compared to the untransformed plants, however, with the addition of exogenous GSH there was a decrease in MG levels in both untransformed and transgenic plants. The exogenous application of GSH reduced MG levels in WT to 50% whereas in the transgenic plants a 5-fold decrease was observed. These studies demonstrate an important role of glyoxalase I along with GSH concentration in maintaining MG levels in plants under normal and abiotic stress conditions.
Methylglyoxal (MG) is a highly reactive alpha-oxoaldehyde formed endogenously in numerous enzymatic and nonenzymatic reactions. It modifies arginine and lysine residues in proteins forming advanced glycation end-products such as N(delta)-(5-methyl-4-imidazolon-2-yl)-L-ornithine (MG-H1), 2-amino-5-(2-amino-5-hydro-5-methyl-4-imidazolon-1-yl)pentanoic acid (MG-H2), 2-amino-5-(2-amino-4-hydro-4-methyl-5-imidazolon-1-yl)pentanoic acid (MG-H3), argpyrimidine, N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidine-2-yl)-L-ornithine (THP), N(epsilon)-(1-carboxyethyl)lysine (CEL), MG-derived lysine dimer (MOLD), and 2-ammonio-6-({2-[4-ammonio-5-oxido-5-oxopently)amino]-4-methyl-4,5-dihydro-1H-imidazol-5-ylidene}amino)hexanoate (MODIC), which have been identified in vivo and are associated with complications of diabetes and some neurodegenerative diseases. In foodstuffs and beverages, MG is formed during processing, cooking, and prolonged storage. Fasting and metabolic disorders and/or defects in MG detoxification processes cause accumulation of this reactive dicarbonyl in vivo. In addition, the intake of low doses of MG over a prolonged period of time can cause degenerative changes in different tissues, and can also exert anticancer activity. MG in biological samples can be quantified by HPLC or GC methods with preliminary derivatization into more stable chromophores and/or fluorophores, or derivatives suitable for determination by MS by use of diamino derivatives of benzene and naphthalene, 6-hydroxy-2,4,5-triaminopyrimidine, cysteamine, and o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine. The methods include three basic steps: deproteinization, incubation with derivatization agent, and chromatographic analysis with or without preliminary extraction of the formed products.
Unique manuka factor fortified honey
- M J Snow
- M Manlye-Harris
- J M Farr
Snow, M.J., Manlye-Harris, M., Farr, J.M., Unique manuka factor fortified honey. PCT Internat. Patent Appl. 2005, Patent Number WO2005120250-A1.
Unique manuka factor fortified honey
- Snow