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Introduction:

Ancient Use of Honey as a Medicine:

Honey has been used for 1000s of old ages as nutrient, medical specialty and in cosmetics. Mentions to honey as a medical specialty are found in ancient coils, tablets and books – Sumarian clay tablets estimated to be from 6200 BC and Veda ( Hindu Bible ) of about 5000 old ages old. Early Egyptian were foremost to utilize honey as a constituent in the topical intervention of lesions as seen from their Hagiographas in the Smith papyrus ( 1650BC ) . They combined honey and animate being fat to forestall patchs from drying out and adhering to the lesion. They used honey for Circumcision, to cut down redness and loosen stiff articulations ( Jones, 2001 ) . Since 1430 AD, honey was mentioned in the Quran as a drink of changing colorss manufactured in bee ‘s tummy that can bring around people ( Surah Al-Nahal ; The bee 16:68-69 ) . Honey besides was mentioned in the Talmud, the Bible, sacred books of India, China, Persia and Egypt ( Beck and Smedley, 1997 ) . All the hints point to the medicative usage of honey throughout human history.

Honey was used for a assortment of intents including phalacrosis, contraceptive method and largely in lesion intervention. Honey was frequently assorted with herbs, grain and other botanicals depending on the geographic country. In add-on, honey has been used for coughs and sore pharynxs for centuries.

Honey as a Modern Medicine:

In the last 20 old ages the involvement in the usage of honey as a medical specialty has increased. Most research that has been undertaken has concentrated on the usage of honey in the intervention of lesions, particularly those lesions which were non mending utilizing conventional methods. Besides, the recent developments in medical specialty have discovered many antibiotics, and the usage of honey has been overlooked in favor of the new drugs. Over the past 3 or 4 decennaries, new jobs have arisen in footings of antibiotic opposition, and the development of multi-drug immune beings such as MRSA ( methicillin resistant Staphylococcus aureus ) , VRE ( vancomicin-resistant enterococci ) , and MDR TB. In this scenario, honey has been ”rediscovered ” in recent times as it has shown outstanding value in footings of over 4000 old ages of use as a lesion dressing ( Zumla and Lulat, 1989 )

Composition of Honey

Honey is a mixture of sugars, H2O, and other compounds, the specific composing depending mostly on the mix of flowers consumed by the bees. It has been reported that about 181 substances are present in honey ( Terrab et al. , 2003 ) . A typical honey analysis is shown in Figure 1 harmonizing to the U.S. National Honey Board, where it has an mean composing of fructose 38.2 % , glucose 31 % , sucrose 1.5 % , maltose 7.2 % and 17-20 % H2O. In add-on, acids, minerals, enzymes, vitamins and proteins are besides found. About 18 free amino acids are known to happen in honey. However, they are present in little sums, although proline is the most common ( White, 1979 ; Atrouse et al. , 2004 ) .

The composing of honey varies from one honey to another depending on several factors. A major factor is the flowered beginning, as the nectar from different workss will incorporate different composings of the chief sugars and hint elements. These composings are influenced by dirt type, climatic conditions ( seasons ) and the environment environing the works ( Crane, 1979 ) .

Many workss such as flowers and trees are first-class beginnings of nectar for honey. The coloring material, smell and spirit of honey can change depending on the nectar beginning. Colours scope from about H2O white to dark brown, with darker honey holding more antioxidant potency and a stronger spirit. The spirits vary from delectably mild to distinctively bold, depending on where the Apis melliferas worked ( hypertext transfer protocol: //www.fao.org ) .

Figure 1: Diagram represents the chemical composing of U.S honey

( Adopted from the website hypertext transfer protocol: //www.nhb.org )

Composition

It is observed that some chemical alterations occur when the nectar is grown to organize honey. These alterations are chiefly because of the enzymes present in the honey. Raw honey contains several enzymes that help in its digestion. These enzymes are invertase ( hydrolysed sucrose into glucose and fructose ) , amylase ( diastase ) and glucose oxidase ( that produces gluconic acid and H peroxide from glucose in diluted honey ) . Other enzymes which are besides present in the honey are catalase and acerb phosphatase. In add-on, honey contains several B vitamins such as vitamin B2, niacin, folic acid, and B6. Antioxidants and hints of pollen are besides present in the honey ( Atrouse et al. , 2004 ) . Furthermore, honey contains a figure of minerals such as Ca, Fe, Zn, K, P, Mg, Se, Cr and manganese ( White, 1975 ; Atrouse et al. , 2004 ) .

Evidence of Antimicrobial Activity of Honey:

In 1892 the antibacterial activity of honey was foremost recognised by Van Ketel ( Dustmann, 1979 ) . Since so there have been many pieces of research which have proved the antibacterial activity of honey against many bacterial pathogens and Fungis ( Efem, 1992 ; Molan, 1992a ; Molan 1992b ; Cooper et al. , 1999 ) .

A study was carried with respect to 345 samples of New Zealand honey to measure the antibacterial activity of honey. Four types of honey were shown to hold high antibacterial activity equivalent to phenol criterion. In this check, most of the honeys showed no noticeable antibacterial activity when catalase was added to take H peroxide. However, manuka and vipers bugloss honeys showed mensurable sum of H peroxide which is believed to help antibacterial activity ( Allen et al. , 1991 ) .

Efem ( 1992 ) found that undiluted honey prevented the growing of Candida albicans. Wahdan ( 1998 ) showed that undiluted honey could be used in the intervention of superficial fungous infections such as tinea and superficial candidiases.

Cooper et al. , ( 1999 ) showed that honey has a important antibacterial activity against the major lesion infecting species including methicillin-resistant Staphylococcus aureus ( MRSA ) . In the same twelvemonth, Cooper et al. , compared grazing land and manuka honey and found out that the antibacterial activity of honey against Staph.aureus was non entirely due to its high osmolarity. It has been shown that there is non much difference in sensitiveness to honey between methicillin-sensitive and methicillin-reisitant staphylococcus. In 2000, Cooper et Al. besides reported the sensitiveness of multi-resistant strains of Burkholderia cepacia isolated from cystic fibrosis patients to manuka honey at concentrations below 6 % ( v/v ) . Six commercial honey samples were tested against control beings, Staph.aureus, Escherichia coli, Pseudomonas aeruginosa and assorted clinical isolates. It was found that some samples had high broad-spectrum disinfectant activity which resisted infrigidation temperature for six months and being boiled for 15 proceedingss ( Nezeako & A ; Hamdi 2000 ) .

Cooper et Al. ( 2002b ) showed the antimicrobic activity of manuka and grazing land honey against 18 strains of MRSA isolated from lesions, and 8 strains of vancomycin-sensitive enterococci ( VSE ) . The survey showed MIC for both honeys was below 10 % ( v/v ) for all strains. This means that the antibacterial activity of honey is non restricted to osmolarity, whereas unreal honey required a concentration 3 times higher to suppress the growing. In 2002c Cooper et al. , compared the antimicrobic activity of two honeys, a grazing land and manuka honey against 17 strains of Pseudomonas aeruginosa isolated from Burnss. Both honeys maintained disinfectant activity when diluted more than 10-fold. In add-on, the survey showed that honey has a possible activity to command and forestall infection with coagulase-negative staphylococcus ( Gallic et al. , 2005 )

Al-Jabri et Al. ( 2002 ) compared the antibacterial activity of 16 honeys from different parts of Oman, and 8 from different states in Africa, against three control organisms Staph.aureus, Escherichia coli, Pseudomonas aeruginosa. It was found that Dhofar honey ( Oman ) and Eucalyptus honey ( Uganda ) had highest degree of activity against all the three control beings.

Anti-Staphylococcal activity of 30 types of Omani honey was tested entirely and in combination with Garamycin. It was observed that 13 of the Omani honeys showed first-class anti-Staphylococcus aureus activity. The best honey had a killing rate of 38 % of Staphylococcus aureus at 50 % concentration in 30 proceedingss. Gentamicin ( 4Aµg/ml ) killed 70 % , while the killing rate for the combination of honey and Garamycin was superior with 92 % violent death in the same continuance ( Al-Jabri et al. , 2005 )

The first survey of the ability of honey to forestall bacterial attachment in vitro was done by Al-Naqdy et al. , ( 2005 ) . Four different types of Omani honey were used in this survey of growing suppression. Bacterial attachment was assayed utilizing Salmonella interitidis cells that had been incubated first with honey and so with enteric epithelial cells. Consequences showed lessenings in the figure of bacteriums attached to the treated epithelial cells from 25.6A±6.5 to 6.7A±3.3 bacteriums per epithelial cell ( P & lt ; 0.001 ) .

Wound infections:

The primary host defense mechanism is the physical barrier afforded by the tegument and mucose membrane ; one time this barrier is breached it provides a path for entry of bacteriums into the organic structure. Infection can be from patients ‘ ain vegetations, infective stuff from bearers or other septic persons that may make the lesion. Microorganisms associated with lesion infection could be bacteriums, Fungis or viruses. The most often isolated lesion pathogens are Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Enterobacteroceas ( Bowler et al. , 2001 ) . A survey done on the prevalence of lesion infection showed that surgical lesions and skin infections were two of four largest classs of hospital-acquired infections ( Emmerson et al. , 1996 ) . The direction of septic lesions costs a considerable sum of money, Plowman et Al. ( 2000 ) reported that the cost per instance of hospital-acquired infection ranges between ?1,618 and ?2,398 per individual.

Honey and wound mending procedure:

Honey is an effectual intervention of lesions because it is non-irritating, non-toxic, self-sterile, easy and simple of application, bactericidal, anti-inflammatory, alimentary, and more comfy than other dressings.

Clinical Evidence of Effectiveness:

In order to find whether honey does excite wound healing, an probe was undertaken and grounds has been derived from several beginnings: animate being surveies, cell line in vitro surveies, clinical observations with instance surveies, cohorts of patients, and clinical trails.

Honey has been used to handle infections in a scope of different lesion types. These are Burnss, leg ulcers, diabetic pes ulcers and force per unit area sores. Cavanagh et al. , ( 1970 ) observed 12 instances of lesion harm after extremist vulvectomy being dressed with honey. The lesions became unfertile after 3-6 yearss. In ( 1981 ) Salem performed a clinical test of 45 patients diagnosed with indigestion who improved after intervention with lone 30mls of honey before each repast. Emarah ( 1982 ) observed the betterment of patients enduring from oculus infection after using honey as an oculus unction. Furthermore, honey was reported to cut down the continuance of diarrhea in clinical tests of babies with stomach flu in which honey was used alternatively of glucose in rehydration fluid ( Haffejee & A ; Moosa 1985 ) .

In 1988, Efem reported the first big clinical cohort survey affecting 59 patients who had a assortment of lesions runing from Fournier ‘s sphacelus, Burnss and a scope of ulcers. Unprocessed honey was applied on cleaned lesions daily. The usage of honey on these patients resulted in successful lesion healing and the clearance of infection. Suprahmanyam ( 1993, 1994, 1996 & A ; 1998 ) reported a clinical tests on Burnss patients with honey compared to different interventions e.g. polyurethane movie ( Opsite ) , potato desquamations, and amnionic membrane. Honey was superior to all the other interventions and the healing clip was less. Tonks et Al. ( 2001 ) showed that grazing land and manuka honey were found to down-regulate the ROIs ( reactive O intermediate ) synthesis from MM6 cells. ROIs are known as toxic byproducts of assorted cellular O2 devouring oxidation-reduction procedures, which are responsible for doing symptoms of oxidative harm if ROI production exceeds the capacity of ROI scavenging reactions. Honey AIDSs in commanding the ROIs which are required for lesion healing.

How does honey advance wound mending?

Although the H2O activity of honey is really low, it provides a moist environment for optimal curative conditions. The tissue does non acquire dehydrated because of the osmotic consequence of honey in that it draws fluid through the lesion tissue from the underlying circulation ( Chirife et al. , 1983 ) . The topical application of foods to lesions has been shown to increase the growing rate of granulation tissue ( Kaufman, 1984 ) . The viscousness of honey provides a protective barrier to forestall cross-infection of lesions ( Efem, 1988 ) . Honey has been proved to hold a deodorizing belongings on lesions. It is thought to be due to the high glucose content consumption by infecting bacteriums as an option to amino acids, ensuing in production of lactic acid instead than malodourous compounds such as ammonium hydroxide, sulfur compounds and aminoalkanes ( Molan, 1998 ) . Furthermore, the acidification of lesion ( pH 3-4 ) causes more O to be released from hemoglobin, thereby advancing mending ( Efem, 1988 ) .

Some research workers have observed that honey promotes tissue regeneration through the stimulation of angiogenesis and the growing of fibroblasts and epithelial cells ( Efem 1988, 1993 ; Subrahmanyam 1994, 1998 ) , hence speedy healing can understate the demand for skin transplants ( Subrahmanyam 1998 ) .

This is due to hapless blood supply that limits the handiness of O and foods to the cells in a skin necrotic lesion. The osmotic consequence ( high glucose ) and mixture content of vitamins, minerals and aminic acids in honey plays a function in get the better ofing these restrictions ( Molan, 1999 ) .

In add-on, after honey is applied to the lesion, it forms a movie of liquid between the lesion and the dressing that prevents the dressing from lodging to the lesion, cut downing hurting and non damaging the freshly formed cells. As honey has no inauspicious effects on tissue, it can be used safely on lesions and introduced into pits and fistulas to clear infection ( Molan, 2000 ) .

Factors Lending Antibacterial Properties of Honey:

It was thought that the antimicrobic belongingss of honey are chiefly because of H peroxide, but recent surveies have indicated that other physical factors like sourness, osmolarity and electrical conduction and chemical factors, volatile compounds, beeswax, propolis and pollen play a considerable function in antimicrobic activity ( Cooper & A ; Molan, 1999 ) . It good established that honey inhibits many bacterial species. There are many studies of it being bacteriostatic and bacteriocidal ( Molan, 1992b ) .

Osmotic consequence:

Honey is a ace concentrated solution of sugar ( 80 % ) and H2O ( 17 % ) . The osmolarity of honey inhibits microbic growing because of the strong interaction of sugar molecules with H2O molecules therefore, bacteriums gets deficient H2O supply for their normal growing ( Molan, 1999 ) . Hence, the H2O activity ( aw ) of honey is excessively low to back up the growing of any species. Fungi can digest a low aw than bacteriums, so studies of fungicidal activity with diluted honey indicate that there is more involved than merely the sugar content of honey. Besides, Staph aureus has a high tolerance of low aw but it is one of the most sensitive species to the antibacterial activity of honey ( Molan, 1992a ) . The consequence of the extra antibacterial activity in honey can be seen where honey and sugar have been used comparably ( Cooper et al. , 2002b ; 2002c ) .

Sourness

Honey is rather acidic ; usually, it has an mean pH of 3.9 ( with a typical scope of 3.2 to 4.5 ) . It contains a figure of acids that include aminic acids and organic acids which are known as flavonids. The major organic acid is gluconic acid that is produced in honey by enzyme action on glucose ( White, 1975 ; Crane, 1980 ) . It has been noted that the sourness is based on the gluconolactone/ gluconic acid content ( Molan, 2001a ; 2001b ) . The optimal pH for growing of many species is 7.2 – 7.4. Therefore, the low pH of honey is of import to decelerate down or inhibits bacterial growing ( Bogdanove, 1997 ; Molan 2000 ) . It has been noted that the pH of honey besides generates and maintains good environment for fibroblast activity ( Lusby et al. , 2002 ) .

Hydrogen peroxide production

In 1919, Sackett reported that the antibacterial belongingss of honey are increased when diluted. This is because when honey diluted H peroxide is released with aid of an enzyme ( glucose oxidase ) that found in honey ( Molan, 1992b ) . This enzyme is secreted from hypopharyngeal secretory organ of the bees that add to the nectar to help in honey formation ( Borland, 2000 ) .

Hydrogen peroxide ( H2O2 ) is considered to be one of the most of import antibacterial agents of honey. It was referred as inhibine ( White. et al. , 1963 ) beside flavonoids and phenolic acid. The degrees of H2O2 in honey are around 1000 times lower than those traditionally applied on the lesions. As a consequence of non to inflame a lesion or damage the tissue ( Molan, 1992a ) . In add-on, it stays in the honey during storage without losing of its antimicrobic strength.

Weston ( 2000 ) stated that the degree of H2O2 is related to the vegetation beginning, and it depends on the balance between the rate of its production and devastation. The devastation of H2O2 is due to catalase which derives from the pollen and nectar of workss, and the sum of catalase in different beginnings is variable. The enzyme is inactive in full strength honey due to the low pH, so the thining action of fluids produced by the lesion initiates the enzyme.

Non-peroxide Components

Several efforts were made to place the non-peroxide antibacterial constituent nowadays in the honey ( Allen et al. , 1991 ) . One survey has isolated an antibacterial phenolic fraction ( APF ) from the honey which consisted benzonic acids, cinnamic acids and flavonoids. It was suggested that APF plays a little function in non-peroxide antibacterial activity in manuka honey and that there are some other factors which are yet to be identified ( Weston et al. , 1999 ) . Honey contains a assortment of polyphenolic compounds that may be capable of chelating metal ions and diminishing oxidization ( Rasmussen et al. , 2004 ) . Therefore, H peroxide is non the lone inhibine in honey. Two of import categories of inhibines are flavonoids and phenolic acid ( Molan 1992 ; Yao et al. , 2003 ) . In a survey done by Wahdan ( 1998 ) , two phenolic acids were extracted for the first clip ; these were caffeic acerb and ferulic acid. Flavonoids had shown a scope of biochemical and pharmacological actions, which affect the inflammatory cells and the coevals of inflammatory procedures ( Harborne, 1994 ) . The usage of flavonoids in medical specialty is increasing due to their ability to scavenge free groups, to excite endocrines and neurotransmitters, and to suppress specific enzymes ( Havesteen 2002 ) .

However, it has been identified several organic constituents in ether infusion of honey with antibacterial activity ; these include 3,5-dimethoxy-4-hydroxy benzoic acid ( syringic acid ) , and methyl 3,5-dimethoxy-4- hydroxy benzoate ( methyl syringate ) ( Russel et al. , 1988 ) . By utilizing high public presentation liquid chromatography ( HPLC ) , some other flavonoids and phenolic acids have besides been identified in different honeys, for illustration, pinocembrin, pinobanksin and chrysin ( Bogdanove et al. , 1989 ) , caffeic acid and ferulic acid ( Wahdan, 1998 ) , and vanillic acid, cinnamic acid, and benzoic acid ( Weston et al. , 1999 ; Weston et al. , 2000 ) .

Honey has high degrees of antioxidants, which are substances that protect wound tissues from O groups that hydrogen peroxide may bring forth and do cellular harm ( Dunford, 2000 ) .

Gheldof et al. , ( 2002 ) analysed the antioxidant in different honey fractions and determined that the most of the antioxidant constituents was found in water-soluble fraction. These include protein ; gluconic acid ; ascorbic acid ; hydroxymethylfuraldehyde ; and the combined activities of the enzymes glucose oxidase, catalase and peroxidise. Same survey besides showed that the phenolic compounds in honey contributed really significantly to its anti-oxidant capacity.

Manuka Honey:

Manuka honey derived from tree ( Leptospermum scoparium ) is presently approved for curative usage. The honey is chiefly taken from trees of L.scoparium assortment referred to as manuka ; L.ericoides normally referred to as kanuka. These are bushs which form shrubs with tallness of 12-15 ft. they belong to the Myraceae household and are native to New Zealand.

Manuka honey has a alone type of antibacterial activity different from the antibacterial activity due to hydrogen peroxide that is common to all honeys ( Molan & A ; Russell 1988 ) .

A study of 345 New Zealand honeys found that manuka activity is retained in the presence of catalase which called non-peroxide activity, while most other types of honey were found to be inactive when catalyse is added. In this survey antibacterial checks were performed utilizing phenol as standard and Staphylococcus aureus as a mention strain. This developed a step of activity associating to per centum of phenol which had the same grade of antibacterial activity ( Allen et al. , 1991 ) . This system was so patented as the UMF or ‘Unique Manuka Factor ‘ to give a criterion for buyers. It is now advised that medical practician ‘s bound the usage of honey to those with a UMF of 10 or higher ( tantamount activity of 10 % phenol ) to guarantee equal activity on diffusion into deeper tissues where terrible lesions are involved. Higher UMF evaluation leads to more antibacterial activity ( Molan 2001 ) . The decision from these observations is that certain honeys contain antimicrobic factors in add-on to saccharify content, low pH and H peroxide coevals.

Dunford et al. , ( 2000 ) observed a instance of multiple skin lesions of lower limbs followed by meningococcal blood poisoning. Pseudomonas, Staphylococcus aureus and Enterococcus was grown from the swabs of patient leg lesions. Active manuka honey UMF ’13 ‘ was applied to the lesions. Complete wound healing was observed after 10 hebdomads with extinguishing infections.

The alone activity in manuka honey was so termed as “ Active Manuka Honey ” by the New Zealand Honey Food & A ; Ingredient Advisory Service in 1998, which said:

‘All of the patients in the tests who were taking the particular active manuka honey, as opposed to those patients taking ordinary inactive manuka honey, had a pronounced betterment in their symptoms ‘ .

Allen et al. , ( 2000 ) reported that the activity of manuka honey was twice than the H peroxide activity of other honey against VRE, nevertheless in MRSA the activity of the two honeys was similar. On lesions, some H peroxide may be broken down, so honey with hydrogen peroxide activity may be less effectual ( Paper conference WWH 2000 ) .

Current survey reported in vitro effectivity of manuka honey against biofilms produced by Pseudomonas aeruginosa and Staphylococcus aureus ( MRSA & A ; MSSA ) with killing rate of 91 % , 63 % and 82 % , severally ( Alandejani et al. , 2009 ) .

However, in order for honey to be accepted as an option to antibiotics, it is necessary to characterize the constituents that are responsible for its activity. Although several of the major constituents of the antibacterial activity of honey are known, like the sugar concentration, pH and H peroxide, these do non account for the entire antibacterial activity observed in many honeys. However, no designation of antibacterial constituents has been achieved because of the complexness of honey itself and the possible interaction between different substances nowadays in the honey.

At present there are two non-hydrogen peroxide honeys has been developed for clinical usage. These are manuka honey in New Zealand and jellybush in Australia. Both honeys are derived from Leptospermum spp ( Cooper 2005b ; Cooper et al. , 1999 ; Cooper et al. , 2002c ) .

It was thought that non-hydrogen peroxide activity in manuka honey may be due to works derived constituents such as flavonoids and phenolic compounds. Recently, two researches have reported that the activity of Leptospermum honeys correlates with the presence of methyglyoxal ( MG ) , an alpha-oxoaldehyde that reacts with supermolecules such as DNA, RNA and proteins ( Adams et al. , 2008 & A ; Mavric et al. , 2008 ) . High sum of MG was present in some manuka honey which is tantamount to the non-peroxide activity. MG was besides identified as a bioactive compound which is responsible for the antibacterial activity in manuka honey ( Mavric et al. , 2008 ) .

Recently, Blair et al. , ( 2009 ) study the antimicrobic activity of Leptospermum Medihoney with high degrees of H peroxide-dependent activity or Comvita manuka woundcare 18+ against MRSA, Acinetobacter and 6 strains of multi-drug immune Enterobacteriaceae. MICs runing from ( 4 to 5 % w/v ) , ( 6.0 to 9.3 % w/v ) and ( 6.3 to 14.8 % w/v ) severally. This indicated that active Leptospermum honey is potentially active against antibiotic-resistant clinical pathogens.

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