Indeed, healthful importance of honey has been documented among the world's oldest medical literatures, and since the standard times, it has been known to possess antimicrobial property moreover as wound-healing activity. The healing property of honey is attributable to the particular indisputable fact that it offers medicament activity, maintains a wet wound condition, and its high body helps to supply a protective barrier to forestall infection. Its immunomodulatory property has relevance to wound repair too. The antimicrobial activity in most honeys is attributable to the catalyst production of chemical compound. However, another moderately honey, stated as non-peroxide honey (viz., manuka honey), displays vital medicament effects even once the chemical compound activity is blocked. Its mechanism may even be related to the low pH level of honey and its high sugar content (high osmolarity) that is enough to hinder the growth of microbes. The medical grade honeys have potent in vitro bactericidal activity against antibiotic-resistant bacteria inflicting several severe infections to humans. But, there is AN outsized variation among the antimicrobial activity of some natural honeys, that's attributable to spatial and temporal variation in sources of nectar. Thus, identification and characterization of the active principle(s) may provide valuable knowledge on the quality and potential therapeutic potential of honeys (against several health disorders of humans), and therefore we've got an inclination to mentioned the healthful property of honeys with stress on their medicament activities.
Keywords: Honey, medicament activity, Wound healing property, aldose accelerator, Non-peroxide result, Medical-grade honey, Antimicrobial agents, healthful property, Antimicrobial property, Immunomodulatory property
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1. Introduction
Antimicrobial agents ar primarily necessary in reducing the globe burden of infectious diseases. However, as resistant pathogens develop and unfold, the effectiveness of the antibiotics is diminished. this type of being resistance to the antimicrobial agents poses a very serious threat to public health, and for every type of antibiotics, along side the foremost last-resort drugs, the frequencies of resistance ar increasing worldwide[1],[2]. Therefore, numerous antimicrobial ways ar urgently needed, and so this instance has semiconductor diode to a re-evaluation of the therapeutic use of ancient remedies, like plants and plant-based product, along side honey[3]–[5].
The use of ancient medication to treat infection has been practiced since the origin of men, and honey created by bee (A. mellifera) is one in all the oldest ancient medicines thought-about to be necessary among the treatment of the many human ailments. Currently, many researchers have reportable the medicament activity of honey and set that natural cold honey has some broad-spectrum medicament activity once tested against infective bacteria, oral bacteria moreover as food spoilage bacteria[6],[7]. In most ancient cultures honey has been used for every process and medical functions. the concept that honey can be a nutrient, a drug Associate in Nursingd AN ointment has been carried into our days, and thus, another medication branch, stated as apitherapy, has been developed in recent years, providing treatments supported honey and different bee product against many diseases along side being infections. at now style of honeys ar sold-out with standardized levels of medicament activity. The Leptospermum scoparium (L. scoparium) honey,the best known of the honeys, has been reportable to possess Associate in Nursing repressive result on around sixty species of bacteria, along side aerobes and anaerobes, gram-positives and gram-negatives[8]. Tan et al[9] reportable that Tualang honey has variable but broad-spectrum activities against many alternative kinds of wound and eubacterium. not like aldose accelerator, the medicament properties from Leptospermum spp. honeys ar light- and heat-stable. Natural honey of other sources can vary the most quantity as 100-fold among the potency of their medicament activities, that's attributable to number one peroxide[6],[10]. in addition, honey is absorbent , which suggests that it'll draw wet out of the setting and dehydrate bacteria, and its high sugar content and low level pH will even stop the microbes from growth.
Based upon the intensive searches in several bioscience journals and web-based reports, we've got an inclination to mentioned the updated facts and phenomena related to the healthful property of honeys with stress on their medicament activities throughout this review.
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2. healthful property
Honey is Associate in Nursing ancient remedy for the treatment of infected wounds, that has recently been ‘rediscovered’ by the community, notably where customary modern therapeutic agents fail. the first written relevance honey, a Sumerian pill writing, chemical analysis back to 2100-2000 BC, mentions honey's use as a drug Associate in Nursingd AN ointment. thinker (384-322 BC), once discussing completely totally different honeys, mentioned pale honey as being “good as a salve for sore eyes and wounds”. Manuka honey has been reportable to exhibit antimicrobial activity against infective bacteria like cocci aureus (S. aureus) and Helicobacter pylori (H. pylori) making this honey a promising purposeful food for the treatment of wounds or abdomen ulcers[10].
The honey has been used from history as some way of quick wound healing[11], and so the potential of honey to assist with wound healing has been incontestable repeatedly[12],[13]. Honey is gaining acceptance as Associate in Nursing agent for the treatment of ulcers, bed sores and different skin infections succeeding from burns and wounds[14],[15]. The healing properties of honey ar usually ascribed to the particular indisputable fact that it offers medicament activity, maintains a wet wound setting that promotes healing, and options a high body that helps to supply a protective barrier to forestall infection[6]. There ar many reports of honey being very effective as dressing of wounds, burns, skin ulcers and inflammations; the medicament properties of honey speed up the growth of recent tissue to heal the wound[16]. The medihoney and manuka honey ar shown to possess in vivo activity and ar applicable for the treatment of ulcers, infected wounds and burns[6],[17].
The honey, once applied regionally, quickly clears wound infection to facilitate healing of deep surgical wounds with infection[18]. the applying of honey can promote the healing in infected wounds that do not reply to the quality medical aid, i.e., antibiotics and antiseptics[18], along side wounds infected with methicillin-resistant S. aureus[19],[20]. Moreover, it ar usually used on skins and infected tegument donor sites successfully[21].
The manuka, jelly bush and pasture honeys ar capable of stimulating the monocytes, the precursors of macrophages, to secrete TNF-α[22],[23]. On the other hand, glycosylated proteins can induce TNF-α secretion by macrophages, and this supermolecule is known to induce the mechanism of wound repairing.Furthermore, the ability of honey to chop back ‘reactive intermediates release’[23] would limit tissue damage by activated macrophages throughout wound healing. Thus, the immunomodulatory property of honey has relevance to wound repair.
The support for victimization honey as a treatment program for process ulcers and redness comes from ancient mental object moreover as from reports in modern times[24]. Honey may promote the repair of broken organ mucosa, stimulate the growth of recent tissues Associate in Nursingd work as AN medicinal drug agent[24],[25]. Raw honey contains copious amounts of compounds like flavonoids and different polyphenols which might perform as antioxidants[26]. Clinical observations ar reportable of reduced symptoms of inflammation once honey is applied to wounds. The removal of exudate in wounds dressed with honey is of facilitate in managing inflamed wounds[18].
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3. medicament activity
3.1. Potential medicament agent
The use of honey as a typical remedy for being infections dates back to ancient times[8]. analysis has been conducted on manuka (L. scoparium) honey[27], that has been incontestable to be effective against several human pathogens, along side enteric bacteria (E. coli), Enterobacter aerogenes, salmonella, S. aureus[6],[27]. Laboratory studies have disclosed that the honey is effective against methicillin-resistant S. aureus (MRSA), β-haemolytic streptococci and vancomycin-resistant Enterococci (VRE)[28],[29]. However, the new famous honeys might need blessings over or similarities with manuka honey attributable to accumulated antimicrobial activity, native production (thus availability), and greater property against medically necessary organisms[6]. The coagulase-negative staphylococci ar very reasonably like S. aureus[14],[30] in their susceptibility to honey of comparable medicament potency and plenty of vulnerable than genus Pseudomonas aeruginosa (P. aeruginosa) and Enterococcus species[14].
The disc diffusion technique is very a qualitative take a glance at for police investigation the susceptibility of bacteria to antimicrobial substances; however, the minimum repressive concentration (MIC) reflects the amount needed for being inhibition. Following the in vitro methods, several bacteria (mostly multidrug resistant; MDR) inflicting human infections that were found at risk of honeys ar presented in Table one.
Table 1
Table 1
Antibacterial activity of honey against bacteria inflicting severe infection to humans.
3.2. Zone diameter of inhibition
The zone diameter of inhibition (ZDI) of assorted honey samples (5%–20%) has been determined against E. coli O157: H7 (12 metric long measure – twenty four mm) and S. typhimurium (0 metric long measure – twenty mm)[31]. The ZDIs of Nilgiris honeys were found to be (20–21) metric long measure, (15-16) metric long measure and (13–14) metric long measure for S. aureus, P. aeruginosa and E. coli, severally[32]. Agbagwa and Frank-Peterside[33] examined completely totally different honey samples: Western Nigerian honey, Southern Nigerian honey, Japanese Nigerian honey and Northern Nigerian honey, and compared their abilities to inhibit the growth of S. aureus, P. aeruginosa, E. coli and Proteus caryophylloid dicot genus (P. mirabilis) with a median of ZDIs (5.3–11.6) mm, (1.4–15.4) mm, (4.4–13.5) metric long measure and (9.1–17) mm, severally, and with honey concentrations of 80%–100%. The extracts of raw and processed honey showed ZDI (6.94–37.94) mm, against gram-positive bacteria viz., S. aureus, Bacilli, moneran genus Cereus, moreover as gram-negative bacteria like E. coli, P. aeruginosa and S. enterica serovar Typhi[34]. Figure one represents the ZDIs for gram-negative and gram-positive being strains attributable to ulmo and manuka honeys.
Figure 1.
Figure 1.
Antibacterial activity of ulmo and manuka honeys supported the ZDI created for clinical (C) MRSA and customary (S) MRSA, E. coli and P. aeruginosa isolates.
3.3. Minimum repressive concentration
The MIC assay showed that a lower MIC was discovered with ulmo (Eucryphia cordifolia) honey (3.1% – 6.3% v/v) than with manuka honey (12.5% v/v) for MRSA isolates; for the E. coli and genus Pseudomonas strains equivalent MICs were discovered (12.5% v/v)[35]. The MICs for Tualang honey ranged eight.75% - 25%, whereas those for manuka honey ranged eight.75% – 2 hundredth against many infective gram-positive and gram-negative bacteria[9]. The MICs of manuka, heather, khadikraft and native honeys against clinical and environmental isolates of P. aeruginosa were recorded as 100 percent – 2 hundredth, 10% – 20%, 11 November and 100 percent – 2 hundredth, severally[36]. The MICs of A. mellifera honey ranged (126.23 – 185.70) mg/mL and of Tetragonisca angustula honey (142.87 - 214.33) mg/mL against S. aureus[37]. The Egyptian herb honey MIC was 100 mg/mL for S. typhimurium and E. coli O157:H7[31]. The Nilgiri honey MICs were twenty fifth, thirty fifth and 400th for S. aureus, P. aeruginosa and E. coli, respectively[32]. MIC values of honey extracts were found among the vary of (0.625–5.000) mg/mL, for S. aureus, B. subtilis, B. cereus, and gram-negative bacteria (E. coli, P. aeruginosa and S. typhi[34].
By visual scrutiny, the MICs of Tualang honey ranged eight.75% – twenty fifth compared with those of manuka honey (8.75% – 20%) against wound and enteric microorganisms: streptococci pyogenes (S. pyogenes), coagulase-negative Staphylococci, MRSA, streptococci agalactiae, S. aureus, Stenotrophomonas maltophilia (S. maltophilia), Acinetobacter baumannii (A. baumannii), S. Typhi, P. aeruginosa, Proteus caryophylloid dicot genus, eubacterium flexneri, E. coli, Enterobacter cloacae (E. cloacae)[9]. Six being strains from burn- wound patients, namely, Aeromonas schubertii (A. schubertii), Haemophilius paraphrohaemlyticus (H. paraphrohaemlyticus), Micrococcus luteus (M. luteus), Cellulosimicrobium cellulans (C. cellulans), Listonella anguillarum (L. anguillarum) and A. baumannii had MICs of Cirtrus, Clover, flower and Eljabaly honeys 35%–40%, 35%–40%, 35%–40%, 25%–30%, respectively, as has been reportable by Hassanein et al. The honeys were repressive at dilutions all the manner right down to 3.6% – 0.7 % (v/v), for the pasture honey, 3.4% – 0.5% (v/v), and for the manuka honey, against coagulase-negative Staphylococci[10]. The MICs varied|of varied|of assorted} styles of honeys for numerous infective being strains ar determined by many authors[39]; throughout this text for oral being strains and being strains inflicting wound infections, honey MICs ar pictured in Figure a combine of and and33.
Figure 2.
Figure 2.
MIC of four completely totally different honeys (as shown among the figure) to oral being strains (Streptococcus spp., E. coli and S. aureus).
Figure 3.
Figure 3.
MIC of assorted honey kinds for being strains inflicting wound infections.
3.4. Time-kill study
The kill mechanics provides plenty of correct description of antimicrobial activity of antimicrobial agents than can the MIC[2]. In our earlier study, we've got an inclination to explored the time-kill activity of autoclaved honey against E. coli, P. aeruginosa and S. Typhi thus on ascertain the potential effectiveness of such native honey (not studied before) collected from a village of the province state, India[5]. Antibiotic vulnerable and resistant isolates of S. aureus, S. epidermidis, Enterococcus faecium, E. coli, P. aeruginosa, E. cloacae, and enterobacteria oxytoca were killed within twenty four h by 10%–40% (v/v) honey[40]. Thus, plenty of studies ar required to establish varied native honeys based upon kill mechanics and their effective in vivo application against MDR infections.
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4. Mechanism and factors moving medicament activity
4.1. Mechanism of medicament activity
The useful role of honey is attributed to its medicament property with regards to its high osmolarity, acidity (low pH) and content of chemical compound (H2O2) and non-peroxide parts, i.e., the presence of phytochemical parts like methylglyoxal (MGO)[41],[42]. The antimicrobial agents in honey ar predominantly chemical compound, of that the concentration is determined by relative levels of aldose accelerator, synthesized by the bee and accelerator originating from flower pollen[41]. Most styles of honey generate H2O2 once diluted, thanks to the activation of the accelerator aldose accelerator that oxidizes aldose to gluconic acid and H2O2, that so attributes the antimicrobial activity[43]. But, in some cases, the peroxide activity in honey ar usually destroyed just by heat or the presence of accelerator.
Besides H2O2, that's created in most traditional honeys by the endogenous accelerator aldose accelerator, many various non-peroxide factors ar found to be answerable for the distinctive medicament activity of honey[13]. Honey may retain its antimicrobial activity even among the presence of accelerator (absence of aldose oxidase), and so this type of honey is believed to be “non-peroxide honey”[8],[13]. several parts ar known to contribute the non-peroxide activity, just like the presence of radical syringate and methylglyoxal, that ar extensively studied in manuka honey that is derived from the manuka tree (L. scoparium)[42],[44]. not like manuka honey, the activity of ulmo honey is essentially attributable to H2O2 production: twenty 5 the troubles (v/v) resolution of ulmo honey had no detectable medicament activity once tested in presence of accelerator, while, at identical concentration the manuka honey preserved its medicament activity among the presence of accelerator (absence of H2O2)[35]. Neither sort of activity is influenced by the sterilizing procedure of gamma-irradiation[13].
Honey is characteristically acidic with pH between 3.2 and 4.5, that's low enough to be repressive to several being pathogens[45]; Figure four depicts the pH values of assorted honeys. The minimum pH values for growth of some common infective bacteria are: E. coli (4.3), eubacterium spp. (4.0), P. aeruginosa (4.4), S. pyogenes (4.5)[46], and so in undiluted honey the acidity can be a vital medicament issue. The medicament property of honey is in addition derived from the diffusion results of its high sugar content and low wet content, along side its acidic properties of gluconic acid and so the antiseptic properties of its H2O2[47]. A recent study examining the antimicrobial properties of honey in vitro found that H2O2, MGO Associate in Nursingd AN antimicrobial organic compound, bee defensin-1, ar distinct mechanisms involved among the bactericidal activity of honey[48].
Figure 4.
Figure 4.
The pH values of assorted honeys having medicament activity
4.2. Factors moving medicament nature of honey
Molan and Cooper[49] reportable that the excellence in antimicrobial potency among the varied honeys ar usually over 100-fold, looking on its geographical, seasonal and biology offer moreover as harvest, method and storage conditions. The medicament nature of honey depends on varied factors operational either singularly or synergistically, the foremost salient of that ar H2O2, synthetic resin compounds, wound pH, pH of honey and force per unit space exerted by the honey. chemical compound is that the most important contributor to the antimicrobial activity of honey, and so the completely totally different concentrations of this compound in many honeys finish in their varied antimicrobial effects[8]. it's extra been reportable that property along side geographical distribution and completely totally different floral sources may play necessary role among the antimicrobial activity of honey[50]. several authors reportable that absolutely totally different honeys vary well among the potency of their medicament activity, that varies with the plant source[6],[7],[51]. Thus, it has been shown that the antimicrobial activity of honey may vary from concentrations < 3 bound to fifty conceive to higher[6],[10],[51]. The bactericidal results of honey is reportable to be captivated with concentration of honey used and so the character of the bacteria[4],[52]. The concentration of honey has a bearing on medicament activity; the higher the concentration of honey the larger its quality as Associate in Nursing medicament agent[31]. Taormina et al[50] reportable that the concentration of honey needed for complete inhibition of S. typhimurium growth is <25%.
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5. Conclusion
Microbial resistance to honey has never been reported[53], that creates it a very promising topical antimicrobial agent against the infection of antibiotic-resistant bacteria (e.g., MDR S. maltophilia) and among the treatment of chronic wound infections that do not reply to antibiotic medical aid. therefore honey has been used as a last-resort medication. Manuka honey has been wide researched and its medicament potential is legendary worldwide. The potency of honeys, like Tualang honey, against microorganisms suggests its potential to be used as another therapeutic agent in sure medical conditions, notably wound infection.
Lusby et al[6] reportable that honeys apart from the commercially getable medicament honeys (e.g., manuka honey) can have equivalent medicament activity against being pathogens. the growth of being species that cause viscus infections, such as S. typhi, S. flexneri and E. coli, ar inhibited by Tualang honey at the low concentrations. The Tualang honey has been reportable to be effective against E. coli, S. typhi and S. pyogenes[54], and thus, once taken orally in its pure undiluted sort, this honey may facilitate speed up recovery from such infections. Honey is effective once used as a substitute for aldose in oral rehydration and its medicament activity shortened the amount of being movability of the bowels.
Currently, the rising antimicrobial resistance trends in burn wound being pathogens ar a big challenge[55]. Thus, honey with effective antimicrobial properties against antibiotic-resistant organisms like MRSA and MDR P. aeruginosa, Acinetobacter spp.. and members of the family, that ar associated with infections of burn wounds and in sanatroium infections, is far anticipated[55],[56].
Overall, the unpredictable medicament activity of non-standardized honey may hamper its introduction as Associate in Nursing antimicrobial agent attributable to variation among the in vitro medicament activity of varied honeys. at now style of honeys ar sold-out with standardized levels of medicament activity, of that the foremost effective known is manuka (Leptospermum) honey moreover as Tualang (Koompassia excelsa) honey. The medical-grade honey (Revamil, medihoney), that has the potential to be a topical medicament bar thanks to its broad-spectrum bactericidal activity, or to be a treatment for topical infections caused by antibiotic-resistant moreover as antibiotic-sensitive bacteria, need to be thought-about for therapeutic use. Moreover, mountain, manuka, capillano and eco-honeys have exhibited repressive activity against H. pylori isolates at concentration 100 percent (v/v)[57], demonstrating that regionally created honeys possess wonderful medicament activity admire the commercial honeys. therefore it's a necessity to envision different regionally created but yet untested honeys for his or her antimicrobial activities.