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Mohammad Asif., PharmaBitika.,2014.1(1),115-132 PharmaBiotika/2014/1/1/115-132-©2014www.pharmaBiotikaworld.com All rights reserved. 115 Research Article ISSN 2408-9702 Physical and Chemical Characterizations, Storing conditions, Health Benefits and Medicinal Uses of Honey Mohammad Asif* 1 Department of Pharmacy, GRD (P.G) I MT, Dehradun, (U.K), 248009, India Abstract: Honey is sweet, thick transparent syrupy liquid made by honeybees. It contain so little water, microbes cannot grow in it. Due to this reason, honey can be stored for a long time. Honey contains simple sugars that are readily absorbed by the body. Pollen grains and other substances such as minerals and vitamins are also present in small quantities. Differences in honey color, smell and taste are determined by the flower source, not by the honeybees. On storing in a cool place, sugar crystals are formed. The bees use the honey as a source of nutrient or carbohydrate. More than 95% of the solids in honey are carbohydrate. Analytical and separation techniques have revealed that honey is to be a highly complex mixture of sugars, most of which are in the immediately digestible form in the small intestine. Honey is used in the treatment of various human disorders that are supported by various researches. The antimicrobial effect of honey on the growth of several strains of pathogenic bacteria, the influence of honey on gastroenteritis, gastric ulcers, wounds, inflammation and other disorders also. Key words: Honey; natural products, biological activities, gastroenteritis, ulcers, wounds. Introduction: Honey is sweet, thick syrupy liquid made by honeybees from nectar. Nectar contains approximately 70% water and 17% honey. After the bee has collected the nectar, female bees will store it in a special organ called the honey sac. Enzymes in the honey sac change large complex sugars in nectar, called polysaccharides, into simple sugars monosaccharide. Upon return to the hive, the foraging bee will transfer the partially converted nectar to house bees, which will then remove most of the water through evaporation. When the water content of the honey has been reduced to less than 20%, the bees will store the honey in the cells of the wax comb. The excess moisture is removed by evaporation as a result of the rapid fanning of the bees wings over the nectar cells in the hive. Since honey contains so little water, microbes such as bacteria and molds cannot grow in it. For this reason, honey can be stored for a long time. Honey contains simple sugars that are readily absorbed by the body. Pollen grains and a wide variety of other substances such as minerals and vitamins are also present in small quantities (1-10). Differences in honey color, aroma and taste are determined by the flower source, not by the honeybees. Honey formed crystal of sugar on standing in a cool place for long lime. This is a natural process and can be "undone" by warming the honey. The bees use the honey as a energy source. Honey is used in the treatment of various human disorders which are supported by clinical tests and published in medical journals and magazines. People have collected honey for thousands of years, as the primary sweetener in food. For every pound of honey produced, bees fly over 50 000 km, which is more than once around the Earth. Honey contained more than 95% of the solids are carbohydrate, it is a highly complex mixture of sugars, most of which are in the immediately digestible form in the small intestine. Honey are effected against various strains of pathogenic bacteria. It is also effective on gastroenteritis, gastric ulcers and wounds healing (11-15). Honey is the natural sweet substance from nectar or from the secretion of living parts of plants or excretions of plants, which honey bees collect, transform, and combine with specific substances of their own to ripen and mature (16).

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Mohammad Asif., PharmaBitika.,2014.1(1),115-132

PharmaBiotika/2014/1/1/115-132-©2014www.pharmaBiotikaworld.com All rights reserved. 115

Research Article ISSN 2408-9702

Physical and Chemical Characterizations, Storing conditions, Health Benefits and Medicinal Uses of

Honey Mohammad Asif*

1Department of Pharmacy, GRD (P.G) I MT, Dehradun, (U.K), 248009, India

Abstract: Honey is sweet, thick transparent syrupy liquid made by honeybees. It contain so little water, microbes cannot grow in it. Due to this reason, honey can be stored for a long time. Honey contains simple sugars that are readily absorbed by the body. Pollen grains and other substances such as minerals and vitamins are also present in small quantities. Differences in honey color, smell and taste are determined by the flower source, not by the honeybees. On storing in a cool place, sugar crystals are formed. The bees use the honey as a source of nutrient or carbohydrate. More than 95% of the solids in honey are carbohydrate. Analytical and separation techniques have revealed that honey is to be a highly complex mixture of sugars, most of which are in the immediately digestible form in the small intestine. Honey is used in the treatment of various human disorders that are supported by various researches. The antimicrobial effect of honey on the growth of several strains of pathogenic bacteria, the influence of honey on gastroenteritis, gastric ulcers, wounds, inflammation and other disorders also. Key words: Honey; natural products, biological activities, gastroenteritis, ulcers, wounds. Introduction: Honey is sweet, thick syrupy liquid made by honeybees from nectar. Nectar contains approximately 70% water and 17% honey. After the bee has collected the nectar, female bees will store it in a special organ called the honey sac. Enzymes in the honey sac change large complex sugars in nectar, called polysaccharides, into simple sugars monosaccharide. Upon return to the hive, the foraging bee will transfer the partially converted nectar to house bees, which will then remove most of the water through evaporation. When the water content of the honey has been reduced to less than 20%, the bees will store the honey in the cells of the wax comb. The excess moisture is removed by evaporation as a result of the rapid fanning of the bees wings over the nectar cells in the hive. Since honey contains so little water, microbes such as bacteria and molds cannot grow in it. For this reason, honey can be stored for a long time. Honey contains simple sugars that are readily absorbed by the body. Pollen grains and a wide variety of other substances such as minerals and vitamins are also present in small quantities (1-10). Differences in honey color, aroma and taste are determined by the flower source, not by the honeybees. Honey formed crystal of sugar on standing in a cool place for long lime. This is a natural process and can be "undone" by warming the honey. The bees use the honey as a energy source. Honey is used in the treatment of various human disorders which are supported by clinical tests and published in medical journals and magazines. People have collected honey for thousands of years, as the primary sweetener in food. For every pound of honey produced, bees fly over 50 000 km, which is more than once around the Earth. Honey contained more than 95% of the solids are carbohydrate, it is a highly complex mixture of sugars, most of which are in the immediately digestible form in the small intestine. Honey are effected against various strains of pathogenic bacteria. It is also effective on gastroenteritis, gastric ulcers and wounds healing (11-15). Honey is the natural sweet substance from nectar or from the secretion of living parts of plants or excretions of plants, which honey bees collect, transform, and combine with specific substances of their own to ripen and mature (16).

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Honey is widely used in traditional medicine throughout the world. However, it has a limited use in modern medicine due to lack of scientific support (17). Ayurveda, Unani, and Siddha Systems of health care treat as food for health while recommending it as an ancient medicine. It is mainly used orally, in some conditions it is also used externally. It is known to cure anemia and improves calcium fixation in infants. Honey also reduces and cures eye cataracts and conjunctivitis and applied honey directly to the eye cures various diseases of the cornea (18). Honey is being very effective as dressing of wounds, burns, skin ulcers and inflammations. The antibacterial properties of honey speed up the growth of new tissue to heal the wound (19). The anti bacterial effect of honey is to be dependent on concentration of honey used and the nature of the bacteria (20, 21). The bactericidal action of honey due to accumulation of hydrogen peroxide, which is produced by natural glucose oxidize system in honey (23, 24). Its inhibitory effect on both Gram-positive and Gram-negative strains and various clinical isolates (2). Honey consists of various constituents such as water, carbohydrates, proteins, vitamins, amino acid and minerals. Besides the major ones, there must also be several minor constituents in honey, which may be playing a key role in determining the antimicrobial behavior of honey. In the past, antimicrobial activity of honey had been reported only by using aqueous solution of honey (25-30). Composition of honey: The precise composition of honey varies according to the plant species on which the bee forages, but the main constituents are the same in all honeys. The composition and properties of honey varies with the plant source, climate, geography and some other factors (31-35). Table 1 Average composition of honey

S No. Components Average (%) 1 Moisture 17.2 2 Fructose 38.19 3 Glucose 31.28 4 Sucrose 1.31 5 Disaccharides, calculated as maltose 7.31 6 Higher sugars 1.5 7 Lactone as gluconolactone 0.43 8 Free acid as gluconic 0.57 9 Ash 0.169 10 Nitrogen 0.041 11 Reducing sugars 76.75 12 Fructose/Glucose Ratio 1.23 13 True protein mg/100g 168.6 14 Total acidity, meq/kg 29.12

Data was collected from 490 samples of US honey (9,10). Chemical Composition of Honey: Honey is composed mainly of carbohydrates, proteins, amino acids, vitamins, minerals and antioxidants with some other organic compounds (2,18,31). Carbohydrates: Carbohydrates are the major components of the honey. They present in the form of monosaccharides namely fructose (levulose) and glucose (dextrose); and disacharides including sucrose, maltose, isomaltose, maltulose, nigerose, turanose, kojibiose, laminaribiose, trehalose and gentiobiose. Besides these, there are also some oligosaccharides (erlose, theanderose and panose). Oligosaccharides form as result of incomplete breakdown of the higher saccharides present in nectar and honeydew. Fructose or levulose is the major constituent in honey and it provides honey with sweetness.

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Enzymes: Honey contains some enzymes; one of them is amylase, which is responsible for breaking down starch into smaller units. Invertase converts sucrose to glucose and fructose. Glucose oxidase transforms glucose to gluconolactone. Gluconolactone itself is another enzyme that yields gluconic acid and hydrogen peroxide. The peroxide formed by glucose oxidase is then broken down by catalase forming water and hydrogen. Acid phosphorylase removes inorganic phosphate from organic phosphates. Out of the eighteen free amino acids present in honey, proline is the most abundant one. Vitamins, Minerals and Antioxidants: There are considerable amounts of the B vitamins found in honey, namely riboflavin, niacin, folic acid, pantothenic acid and vitamin B6. It also contains ascorbic acid (vitamin C) and some minerals such as calcium, iron, zinc, potassium, phosphorus, magnesium, selenium, chromium, manganese, chloride, sulphur, sodium, silica and copper. These minerals only compromise a very small content, in the unit of ppm, in honey. Flavonoids form the major group of antioxidants in honey. To name one, pinocembrin, is unique to honey and bee propolis. Besides this, ascorbic acid, catalase and selenium also serve as antioxidants. Other Compounds: Huge number of organic acids can be found in honey. Acetic, butanic, formic, citric, succinic, lactic, malic, pyroglutamic and gluconic acids and a number of aromatic acids are those that are present. Gluconic acid is the primary acid present that is produced as a result of the breakdown of glucose by glucose oxidase. When simple sugars are break down below pH 5, another product is formed, hydroxymethyfurfural. Medicinal activity of honey: In ancient times honey has been used for its medicinal properties in many cultures. The use of honey for the treatment of many human diseases can be found in general magazines, journals and natural products leaflets. In contrast, medical reports supported by tests are few and far between. In this review, we describe the constituents of honey and examine the information available that is supported by clinical studies in which honey has shown positive results for the control of pathogens or the improvement of human health (18). Antibacterial activity of honey: The anti-bacterial activity of raw and processed honey was carried out on the extracts of honey using solvents such as methanol, ethanol and ethyl acetate and compared it with the popular antibiotics. The inhibitory action of the extracts of honey were evaluated against bacterial strains, Gram-positive bacteria viz., Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi. The extracts of raw and processed honey showed the zone of inhibition ranged from 6.94 mm to 37.94 mm. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) value were the most susceptible to S. typhi, E. coli and P. aeruginosa. MIC and MBC values of extracts were found in the range of 0.625-5.000 mg/ml. The solvent extract of honey showed better antibacterial behaviors against Gram-negative bacteria than the standard antibiotics such as tetracycline and Ciprofloxacin (36). The in vitro antimicrobial activity of honey (13) observed that honey stopped the growth of Salmonella and E. coli. All the extracts of honey samples exhibited varying level of antibacterial activity against all the selected strains. In case of raw honey, the maximum inhibition as produced by extracts was observed against P. aeruginosa, S. typhi, E. coli, B. cereus, S. aureus and B. subtilis. The effective bactericidal activity of aqueous solution of honey on Salmonella spp, Shigella spp, and entero pathogens such as E. coli, Vibrio cholerae and other Gram-negative and Gram-positive bacteria (26,27). Similarly, the antibacterial properties of honey against two laboratory isolates e.g. P. aeruginosa and E.coli (37). The ethanol extract showed inhibitory activity only against Gram-negative bacteria B. subtilis and B. cereus and both bacteria showed resistance to methanol extract. Residue obtained after extraction was also found inactive against all the tested strains. Gram-negative bacteria were found more susceptible then Gram-positive bacteria. Honey showed strong inhibitory properties against P. aeruginosa and E. coli (20, 36).

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The use of honey as a traditional remedy for microbial infections dates back to ancient times (30). The difference in antimicrobial potency among the different honeys can be more than 100-fold, depending on its geographical, seasonal and botanical source as well as through harvesting, processing and storage conditions. The antimicrobial activity of honey is attributed largely to osmolarity, pH, hydrogen peroxide production and the presence of other phytochemical components e.g. methylglyoxal (MGO). The presence of MGO in honey contributes to its uniqueness and has been termed the unique factor, which have been confirmed its activity against a wide range of medically important bacteria including methicillin-resistant Staphylococcus (8-10). A substance ‘inhibine’ which inhibited bacteria and hydrogen peroxide was responsible for the antibacterial activity of honey (1). Hydrogen peroxidase which is produced by the glucose oxidase of honey could be the inhibitory substance against bacteria (35) because The antibacterial activity of honey and hydrogen peroxide were destroyed by light. However, it is known that honey itself, as well as bacteria produce a catalase that eliminates hydrogen peroxide. But although catalase is active with high concentrations of hydrogen peroxide, it is of low activity with physiological levels. The amount of catalase necessary to destroy the antibacterial activity was found to be unexpectedly high (1,38). Hydrogen peroxide rapidly breakdown into water and oxygen and its production and decomposition are continuous. The hydrogen peroxide concentration remains stable under a given set of conditions of temperature, sugar concentration etc., and is sufficiently high to give good protection against some harmful microorganisms by a biochemical mechanism which disrupts their metabolism. The same system is thought to operate when honey is diluted with water and for this reason; honey has been successfully used as a microbicidal wound dressing. Light sensitive, heat-stable antibacterial factors in honey which inhibited the growth of Bacillus subtilis, B. alvei, Escherichia coli, Pseudomona pyocyanes, Salmonella and Staphylococcus aureus. Conversely, microorganisms that survive well in honey are the sugar-tolerant (osmophilic) yeasts, mostly belonging to the genera Saccharomyces and Zygosaccharomyces (39). Non-dissociated organic acids also play a role in the antimicrobial activity of honey (33) since they are very soluble in cell membranes and induce alterations in the cellular permeability and in oxidative phosphorylation (40). The extracted flavonoids, is also noted for their antibacterial activity of honey. Molan and Russel (16) have reported that the floral source of honey may also be responsible for some of the antibacterial activities of honey. Most commercial honey is produced by the species, Apis mellifera. However other species of bees are also studied. In their work, a comparison was made between the physico-chemical properties and antibacterial activity of honey produced by Africanized honey bees (A. mellifera) and Melliponinae (stingless bees) in Brasil. For both types of honey at a concentration of 5-25%, B. stearothermophilus was found to be the most susceptible and E. coli the least susceptible of the seven bacterial isolates tested (the other five being, B. subtilis, B. subtilis Caron, Staphylococcus, Klebsiella pneumoniae and P. aeruginosa). Honey produced by africanized honey bees Mimosa and Eucalyptus had the greatest antibacterial activity. Melipona subnitida honey produced from Mimosa bimucronata and Plebia species honey produced from Borreria/Mimosa exhibited the greatest antibacterial activities (41-43). Generous soaking of wounds and abscess cavities with honey, sometimes using castor oil to facilitate dressing, was found to include the following advantages: first, cross-infection of wounds often encountered with conventional therapy, was prevented because honey forms a mechanical and/or chemical barrier to infectious agents; second, the acceptance of grafts was prompt, in contrast to the inconsistent acceptance of grafts following antibiotic application; and third, a shorter duration of treatment and therefore hospitalization. Honey was also found to be more effective as an antibacterial agent against several Pseudomonas and Staphylococcus strains than the antibiotic, gentamicin (2,3). In a clinical study involving 59 patients with wounds and ulcers, most of which had failed to respond to conventional treatments, 15-30 ml fresh honey was applied daliy. The bacteria isolated from 58 of these wounds (E. coli, S. aureus, P. mirabilis, mixed coliforms, Klebsiella species, and S. faecalis) were all susceptible to honey in vitro. In one case in which the patient had a Buruli ulcer infected with Mycobacterium ulcerans, honey treatment

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was ineffective an in vitro tests showed the mycobacteria to be resistant to honey. This may be due to the higher lipid content of its cell wall, preventing dehydration of the bacteria as well as the penetration by inhibine, the thermolabile and photolabile bactericidal substance in honey. Chemical debridement action of honey has been reported to be of greatest advantange in Fourier’s gangrene, Cancum oris and decubitus ulcers, as the sloughs of these separated more quickly in these than in other types (44). Another clinical study (43) comprising of 50 patients with wounds, compared the use of honey as a treatment with the antiseptic Salvon (15% cetrimide, 1.5% chlorohexidine gluconate). Honey cleared 60% of the treated wounds in 6 days whereas Salvon cleared only 36% of wounds within the same period. Bacteria isolated form the wounds were P. mirabilis, Staphylococcus, coliform bacteria, enterococci, E. coli, Haemophilus, Pseudomonas and Klebsiella. In a more recent report on honey treatment of wounds, ulcers and skin graft preservation, the importance of sterile, residue-free honey for medical use was pointed out (14). They advise to use honey derived from specifiedpathogen-free hives, which have not been treated with drugs, and are gathered in areas where no pesticides are used. In this work, it was found that the antibacterial activity of their honey samples remained constant over more than a year. In an extensive review on the antibacterial activity of honey (22), it was suggested than honeys intended for therapeutic use, should be assayed for their antibacterial activity as a form of quality assurance. It is also recommended that honey is protected from light to prevent possible reduction of its antibacterial activity. Gastroenteritis: Infections of the intestinal tract are common throughout the world, affecting people of all ages. The infectious diarrhoea exacerbates nutritional deficiencies in various ways, but as in any infection, the calorific demand is increased. Pure honey has bactericidal activity against many enteropathogenic organisms, including those of the Salmonella and Shigella species, and enteropathogenic E. coli (26). In vitro studies of Helicobacter pylori isolates which cause gastritis have been shown to be inhibited by a 20% solution of honey. Even isolates that exhibited a resistance to other antimicrobial agents were susceptible (17). In a clinical study, the administration of a bland diet and 30 mL of honey three times a day was found to be an effective remedy in 66% of patients and offered relief to a further 17%, while anaemia was corrected in more than 50% of the patients (45). A clinical study of honey treatment in infantile gastroenteritis was reported (46). They found that by replacing the glucose (111 mmol/l) in the standard electrolyte-containing oral rehydration solution recommended by the World Health Organisation (WHO)/UNICEF, as well as the solution of electrolyte composition 48 mmol/l sodium, 28 mmol/l potassium, 76 mmol/l chloride ions, with 50 ml/l honey, the mean recovery times of patients (aged 8 days to 11 years) were significantly reduced. Honey was found to shorten the duration of diarrhoea in patients with bacterial gastroenteritis caused by organisms such as Salmonella, Shigella and E. coli. They recommended that honey was a safe substitute for glucose as long as it provided 111 mmol/l each of glucose and fructose. The high sugar content of honey means that it could be used to promote sodium and water absorption from the bowel. Gastric ulcers: The management of a patient who received manuka honey as a therapeutic intervention for the treatment of a recalcitrant surgical wound (47). The clinical problem was clearly identified, but no outcomes are specified. The study was retrospective, which increases the risk of bias. The observational data could have been greatly improved by using objective data, such as wound measurement repeated at predetermined intervals. The paper did not report a standardized dressing procedure or provide enough detail to reproduce the dressing technique. Despite the limitations of the paper in terms of case study reporting, the authors reported a positive outcome, describing tissue stimulation, antibacterial activity and anti-inflammatory action. Kingsley (48) described the care of two patients with chronic wounds and topical honey selected as almost a last resort to facilitate wound healing. Clinical and animal studies have shown that honey reduces the secretion of gastric acid. Additionally, gastric ulcers have been successfully treated by the use of honey as a dietary supplement. An 80% recovery rate of 600 gastric ulcer patients treated with oral administration of honey has been reported (49). Radiological examination showed that ulcers disappeared in 59% of patients receiving honey. Animal experiments have shown that the administration

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of a honey solution via a tube in the stomach of rabbits prior to them being administered with 0.5 g ethanol per kg body weight accelerated alcoholic oxidation. A more recent animal study showed that honey administered subcutaneously or orally before oral administration of ethanol affords protection against gastric damage and reverses changes in pH induced by ethanol. A controlled clinical trial demonstrated the use of fructose in the treatment of acute alcoholic intoxication. A small but significant increase occurred in the rate of fall of blood-ethanol levels and it was concluded that fructose may be beneficial in shortening the duration of alcoholic intoxication (50). Honey as a dressing for chronic wounds in adults: Honey has been used in wound care since the time of the ancient Egyptians. As more reports of its effectiveness are published, it is becoming increasingly popular as a modern wound dressing material. Honey contains digested sugars, vitamins, minerals and enzymes, and there are numerous reports of animal model clinical studies and randomized controlled trials demonstrating the benefits of honey as a wound dressing. Clinical observations from these studies are that: Infection is rapidly cleared Inflammation, swelling and pain are quickly reduced Odour is reduced Shedding of necrotic tissue is induced Granulation and epithelialization are hastened Healing occurs rapidly with minimal scarring (51). Laboratory studies have demonstrated the significant antibacterial activity of honey. In addition, the antimicrobial properties of honey prevent microbial growth in a moist healing environment (47). Unlike other antiseptics honey is said to cause no tissue damage. Complete inhibition of the major wound infecting species of bacteria has been achieved (47). Solutions of high osmolarity, such as honey, inhibit microbial growth because the sugar molecules ‘tie up’ the water molecules so that the bacteria have insufficient water to support their growth. Dilution by wound exudate may reduce the osmolarity to a level where it ceases to control infection (51). Nevertheless, the antibacterial activity of honey has been demonstrated in vivo, with reports of improvement in infected wounds. Honey’s antibacterial activity is thought to be primarily due to the presence of hydrogen peroxide, generated by the action of an enzyme that the bees add to nectar. Some types of honey (e.g. manuka honey) may also contain antibacterial substances derived from flowers visited by the bee (11). Honey is reported to have a powerful deodorizing action, probably due to the rich provision of glucose, which is used by bacteria in preference to amino acids, resulting in the formation of lactic acids and not malodourous compounds (51). Histological studies using experimental wounds in animals have shown that honey has an anti-inflammatory action, confirming a number of clinical observations (52). Honey is also thought to stimulate tissue growth (12). Evidence exists to support the use of honey as a wound dressing for burns and infected surgical wounds, but requests are frequently made by both patients and clinicians to use topical honey as a treatment for chronic wounds. Practitioners must then make a clinical decision as to the potential effectiveness of honey as a dressing for chronic wounds. Given the increasing interest, a review of the clinical evidence is timely and pertinent in order to reveal whether the use of honey as a wound dressing improves wound management outcomes in adults with chronic wounds (53). Improvement in wound management outcomes includes factors such as wound healing, exudate management, odour control, pain reduction, management of infection and reduction in devitalized tissue. These were reviewed using a framework broadly based on wound care case study guidelines (24) and cohort study guidelines (4). Based on the case studies reviewed, honey appears to be a useful dressing in adults with chronic wounds, but the available evidence is weak and therefore must be interpreted with caution. Wound healing properties: The use of topical honey as a treatment for chronic wounds still have to be made in clinical practice. Moreover, studies that explored the impact of topical honey on acute wounds (including burns)

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were also excluded. One case study was excluded, as the paper was old and focused on the use of comb honey (54). One systematic review (55) was identified but not included as it did not present any evidence on chronic wounds. Wet dressings or any form of irrigation moisten the tissues and therefore delay healing. Dry dressings adhere to the surface, causing pain and injure the granulating surface every time they are changed. Oily dressings prevent the surface secretions from escaping freely and may cause them to spread onto the neighbouring skin surfaces and cause undesirable reactions or toxic effects. Conversely, honey is an effective treatment of wounds because it is non-irritating, non-toxic, selfsterile, bactericidal, nutritive, easily applied and more comfortable than other dressings. The treatment of wounds with honey has rendered them bacteriologically sterile within 7-10 days of the start of the treatment and promoted healthy granulation of tissue (56). Patients suffering from wound breakdown after operation for carcinoma of the vulva were treated by pouring honey into the wounds twice daily. The wounds became bacteriologically sterile within 3-6 days and in vitro studies of bacteria cultured from the wounds showed that undiluted honey not only failed to sustain growth of the bacteria (Proteus mirabilis, Ps. aeruginosa, E.coli, Streptococcus faecalis, Clostridium perfingens and S. aureus), but actually killed them. The in vitro anti-fungal activity of honey has been also tested on Candida albicans, C. pseudotropicalis, C. stellatoidea and C. tropicalis. They were all found to be susceptible. Diabetes: There is a need for sweetners in the diabetic diet to improve overall dietary compliance. Since fructose is absorbed more slowly from the gastrointestinal tract than glucose and is rapidly taken up by the liver, blood sugar levels rise only minimally after fructose ingestion (57, 58). The sucrose or honey at breakfast has no additional acute hyperglycaemic effect over and isoglucocidic amount of bread in type II diabetic patients (59). In addition, a clinical study (60), indicated that honey could be a suitable sweetner for the type II diabetic diet since fat-rich foods added to honey result in higher triglyceride and insulin serum concentrations. Honey - an ancient remedy "rediscovered": The usage of honey as a medicine is referred to in the most ancient written records, it being prescribed by the physicians of many ancient races of people for a wide variety of ailments. It has continued to be used in folk medicine ever since, but in recent times there has been a renaissance of the use of honey in the medical profession: discussing this expressed the opinion "The therapeutic potential of uncontaminated, pure honey is grossly underutilized. It is widely available in most communities and although the mechanism of action of several of its properties remains obscure and needs further investigation, the time has now come for conventional medicine to lift the blinds off this 'traditional remedy' and give it its due recognition." The wounds, of a type notoriously difficult to keep free from infection, were found to become sterile in 3– 6 days, have a clean healthy granulating (healing) appearance, required the minimum of surgical removal of dead tissue, and to not need skin grafting as would normally be required. Honey was found to be non-irritant and much more effective than topical antibiotics, the time in hospital being reduced from the usual 7–8 to 3–4 weeks. Efem (44) reported clinical observations on the healing with honey of 59 cases of wounds and skin ulcers that had not been healing for 1–24 months with conventional treatment. The wounds were found to become sterile and odourless in 1 week, pus and gangrenous tissue separating by themselves painlessly. Swelling and exudation of lymph subsided rapidly and there was rapid development of new tissue to repair the wounds. The honey caused no adverse reactions. Efem (52) reported a trial where 20 cases of Fournier's gangrene (a form of necrotising fasciitis) were treated by daily application of honey with no surgery, compared with 21 similar cases treated by surgical removal of infected tissue and systemic antibiotics. Similar outcomes were achieved with both treatments but with a faster response to treatment with honey, the wounds becoming sterile within 1 week with honey, and with the group treated with honey not requiring plastic surgery. Subrahmanyam (12) reported a randomised controlled trial in which honey was compared with silver sulfadiazine for efficacy as a dressing for burns. With silver sulfadiazine, the most widely used agent to prevent or clear infection in burns, 7% of the patients had infection in the burns controlled within 7 days,

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whereas with honey 91% of the wounds were sterile within 7 days. Honey was observed to remove dead tissue and offensive smell from the burns. Healthy granulation tissue was observed to appear nearly twice as fast with honey, and new skin cover developed faster also. There was better relief of pain, less exudation of lymph, and less irritation with honey. Honey also gave a lower incidence of raised scars and contractures. A detailed review of the published literature on the use of honey in wound healing has been published by Molan. This literature provides a convincing body of evidence from clinical observation, clinical trials and experiments on animals for the effectiveness of honey as a wound dressing. The published literature reporting other therapeutic uses of honey has also been reviewed by Molan (16,22,51). This review also cites historical and traditional therapeutic uses of honey. Some examples of the modern professional reports are given here: Haffejee and Moosa (46) reported a clinical trial in which honey was used in place of glucose in a rehydration fluid (solution of electrolytes) given to infants and children admitted into hospital with gastroenteritis. The treatment with honey gave a statistically significant reduction in the duration of diarrhoea caused by bacterial infection. Preparing liquid honey for competition: Tasty honey is very important, while some of these qualities are beyond the control of the beekeeper, steps can be taken to reduce or eliminate many of the factors that downgrade honey entries. Extracted honey is the most popular type of honey submitted in contests, and it will be the only type discussed here. Honey, discusses the characteristics used in judging honey. This note gives recommendations for submitting high quality honey for competition or for sale (61). Density (Moisture content over 18.6%-Disqualified) Absence of granulation or crystallization Cleanliness: absence of lint, dirt, wax & foam Flavor: absence of overheating & fermentation Color & brightness Container appearance: cleanliness & uniformity Uniformity of entries in class Density: One important factor is density which is related to the moisture content of the honey. The moisture content is not to exceed 18.6%. The main reason moisture content is so important is that excessive moisture will allow yeasts to grow, thereby causing fermentation. Using honey frames that are at least 75% capped will usually assure that the honey has low enough moisture content. Always test your honey for the proper viscosity before submitting an entry. Absence of granulation or crystallization: Another factor involved in the judging of honey is the absence of granulation. While granulation is a natural process, measures can be taken to keep this factor under control. One way to reduce the risk of granulization is to submit a type of honey that has a low glucose content, as this type honey tends to granulate less. Both tulip poplar and sourwood honey are good choices of honey that are low in glucose and high in fructose. (Note: Honey with high fructose levels taste sweeter than high glucose honey.) It is also helpful to heat the honey to remove any crystals or granules that may already be present. This can be done by placing the honey in a water bath having a temperature range of 95-120oF. Finally, any crystals or granules that are still present can be removed by filtering and cleanliness. Cleanliness: The honey is also judged on cleanliness. Submissions will be inspected for any dirt, wax, lint, or foam. Filling the jar with warm honey will cause any wax to float to the top of the jar where it can be skimmed off. In order to prevent foam, pour the honey into the jar slowly. It is also helpful to keep the distance between the honey and the jar in which you are pouring it to a minimum, perhaps even hitting the side of the jar with the honey as you

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pour. Any further dirt, wax, or lint should be filtered out before submission using an appropriate lint-free filter. Pantyhose is a good choice of a filter that does not produce lint, while cheese-cloth is a poor choice, as it does product lint. Flavor: The importance of flavor in judging is usually limited to overheating, fermentation, and obviously, unpleasant flavors. Overheating will cause a burnt sugar flavor, while fermentation can cause the honey to taste sour. Certain floral sources such as tobacco can produce unpleasant, even disagreeable-tasting honey. Always taste the honey you plan to submit. This is an obvious point but one often overlooked. Color and Brightness: Judges also look at both the color and brightness of honey submissions. While these factors are unrelated to the flavor of the honey, they contribute to the aesthetic value of the honey, which is important to the consumer. Cleaning and filtering the honey as well as slightly heating it prior to competition can improve the color and brightness. This can be done by pouring honey that has been heated through a filter to remove impurities. (Note: Never heat the honey to temperatures over 140oF for more than 30 minutes.) Container Appearance: The cleanliness of the container in which your honey is submitted. Always make sure your containers are free of smudges and imperfections. Imperfections in the glass can appear to be debris in the honey itself. Wiping with a moist, lint-free towel before submission will remove any travel stains from your honey jars. Judges also look under the lid, so be sure to wipe out this area as well. It only takes a small effort to see that your containers are appropriately cleans, so doesn’t miss points on this one! Also, remember to fill the jars to the appropriate level. This is between the groves are the mouth of the jar. Filling over this level will make it easier to spill the honey when the jar is opened, and under filling may make a consumer feel cheated. It is also a good idea to use glass containers for competitions, even though they are more expensive and heavier than plastic ones. Glass jars don’t scratch as easily as plastic ones. Save the less expensive plastic containers for selling your honey. Storing Honey: Honey is one of the finest food, stored under proper conditions will last for years, and can be used for cooking, canning, and general health maintenance. The honey normally sold in stores is not pure, raw honey. It is blended, heated, and generally not of origin, let alone local. In most countries in the world where most honey is sold in liquid form. To attain and maintain that liquid state for a long shelf life in retail stores, honey must be heated to 181 0F for 24 hours, which destroys most of the inherent good qualities of honey. Indeed, the heating produces the chemical hydroxylmethy-furfural (HMF), which in Europe is considered an unwanted adulterant, and heated honey is therefore illegal to sell in Europe due to their pure food laws that unfiltered, unheated honey contains active glucose oxidase which supplies oxygen to the digestive tract. Such natural honey is reputed to prevent botulism poisoning, relieve constipation and prevent congestion in the intestinal tract and that heating and pressure filtering will destroy and/or remove the valuable enzymes in the honey. Studies have shown that pure, raw honey is excellent in the prevention and cure of various allergies, as it contains minute trace amounts of pollen and mold spores, and acts as a homeopathic medicine. Most small scale beekeepers (less than 24 hives) remove the honey supers from the hives and extract it the same day at hive temperature (about 94 F), as the viscosity of honey at that temperature allows easy extraction through centrifugal force. Ideally, you would want them to then filter the honey through a fine grade nylon filter (paint filter) immediately, and pour it into food grade buckets. Raw honey can be expected to granulate or crystallize rapidly, the actual rate depending upon the floral source-(for area) maple (April, May) takes 2 months or more, blackberry (June, July) may granulate in 2 weeks, while fall honey (wildflower/herbal mix) takes about a month to granulate. Mid season honeys are generally preferred for quality. Honey granulates quickest at 57 F, and slower at temperatures

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above or below 57 F. Proper storage, then, would be at temperatures as close to 57 F as possible, but cooler is preferred over hotter; basement storage is excellent (5-11). Granulated honey is normal: Honey was traditionally sold as a solid block of honey and wax. To liquefy the honey for normal use, the honey must be heated slowly in a double boiler to 145 F until clear, and then cooled quickly to preserve quality by circulating cold water in the double-boiler. If honey is stored in glass containers, the water in the double-boiler must be high enough to cover the top of the honey in the container. Honey really expands as it liquefies. One tablespoon of honey contains: Calories: 60 Total Fat: 0 g; Total Carbohydrates: 17 g Protein: 0 g. Honey contains a wide complement of several essential vitamins and minerals, including niacin, riboflavin, pantothenic acid, calcium, copper, iron, magnesium, manganese, phosphorous, potassium and zinc. While honey’s vitamins and minerals are present in trace amounts only, the breadth of the array is important to many of today’s health conscious consumers. This is a value which honey adds that many other sweeteners do not. Note: Honey should not be fed to babies under one year of age. Honey is a safe and wholesome food for older children and adults. Honey and Ayurvedic medicines In Ayurveda honey is called as "Madhu". It has sweetness (madhura rasa) with added astringent as end taste (Kashaya anu rasa). It is heavy (guru guna), dry (ruksha) and cold (sheeta). It aggravates vata, scrapes kapha and normalizes pitta and rakta. It promotes healing process. In ayurvedic medicine it is considered that the body consists of three physical humors [doshas] viz, wind [vata], bile [pitta] and phlegm [kapha] (62,63). Harmony between the three physical humors [doshas] and three mental attributes [gunas] leads to health, whereas disharmony is associated with disease (64,65). The three mental attributes [gunas] are divine [sattva], kingly [rajas] and evil [tamas]. Also, imbalance within any one of the three physical doshas i.e, vata, pitta or kapha, leads to dysfunction, imbalance and disease, specifi c to the humor involved (66). Many disorders have been described as being associated with pitta imbalance including pyrexia, hyperacidity, abscesses, stomatitis, aphthous ulcers, and even herpes (described as a condition with painful vesicles). Pitta imbalance is also associated with specifi c symptoms and signs viz, burning, itching, heat, redness and discharge, among others. Honey is one of the remedies recommended to alleviate disorders of pitta (67). Since pitta imbalance is associated with herpes, this suggests that in ayurvedic medicine there is a basis for the use of honey in the treatment of herpes. While there are no published trials on the use of ayurveda in the management of herpes simplex and other conditions related to pitta imbalance, honey is used in the treatment of some of these conditions. For example, honey is effectively used as an adjunct to gargles for aphthous ulcers, stomatitis, and a sore throat (68). Hence it is worth investigating the use of honey in conditions described as being due to pitta imbalance. Use of Honey in Traditional anal Alternatives Medicines Honey is used in the therapy of digestive diseases like peptic ulcers and gastritis, antibacterial and anti-inflammatory effects, against children diarrhea, improvement of gut microbial health and of digestion, prebiotic effect, improvement of immune reaction of the body, regular intake improves cardiovascular health, lowering of blood risk factors and specific heart conditions as extracystoles, arrhythmia and tachycardia, long term ingestion of honey can reduce the risk of human cancer, positive glycemic nutritional effect. Used as a sweetener of people with diabetes type II and also probably type I. Some honeys have a low glycemic index: e.g. acacia honey (69-89). Other fructose rich honeys such as thyme, chestnut, heather and tupelo are good alternatives. Use for the treatment of radiation-induced mucositis, positive effect of honey ingestion on hepatitis. Improvement of cough in children Contact soothing effect, sweet substances, as a sweetener honey causes reflex salivation and increases airway secretions which may lubricate the airway and remove the trigger that causes a dry, nonproductive cough (90-99).

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Types of Honey: Eight types of honey are described in ayurveda depending on the type of bee which collects it. They are Pouttika, Bhramara, Kshoudra, Makshika, Chatra, Arghya, Oudalaka, Dala . Pouttika-This honey is collected by very large bees from the nectar of poisonous flowers. It increases vata, causes gout and burning sensation in chest.It is also sedative and reduces fat. Bhramara-This honey is collected by large bees and Sticky in nature. Kshoudra-(Honey collected by medium sized honey bees ) light and cold in nature. Dissolves Kapha. Makshika-(Honey collected by small honey bees) very light and dry natured. Usefull in Vata Kapha diseases and kapha diseases Chatra-Heavy and cold in nature usefull in gout, Leucoderma (Shwitra), Arghya - Good for eyes but causes arthritis. Oudalaka-Useful in skin diseases, and helps in modulation of voice. Dala-Dry and reduces vomiting. Amongst all the above "Makshika" is considered as the best type with immense medicinal properties. Therapeutic uses of Honey:

As it contains sugars which are quickly absorbed by our digestive system and converted into energy, this can be used as instant energizer.

As it is hygroscopic it speeds up healing, growth of healing tissue and dries it up. Honey acts as a sedative and is very usefull in bed wetting disorders. Honey is very good antioxident which restores the damaged skin and gives soft, young looks. Honey has antibacterial properties due to its acidic nature and enzymically produced hydrogen peroxide. Constant use of honey strengthens the white blood corpuscles to fight bacteria and viral diseases (100-106).

In Ashtanga Hridaya the great classic of ayurveda, the therapeutic uses of honey are explained as follows. Honey is very good for eyes and eye sight. It quenches thirst. Dissolves kapha. Reduces effects of poison. Stops hiccups. It is very useful in urinary tract disorders, worm infestations, bronchial asthma, cough, diarrhea and nausea

-vomiting. Cleanse the wounds. It heals wounds. Helps in quick healing of deep wounds. Initiates growth of healthy granulation tissue. Honey which is newly collected from bee hive increases body weight and is a mild laxative. Honey which is stored and is old helps in metabolism of fat and scrapes Kapha. Ayurveda explains another special quality of honey. Honey is called as “Yogavahi” . The substance which

has a quality of penetrating the deepest tissue is called as Yogavahi. When honey is used with other herbal preparations it enhances the medicinal qualities of those preparations and also helps them to reach the deeper tissues. Precautions to be taken before using honey:

Honey should not be mixed with hot foods. Honey should not be heated.

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Honey should not be consumed when you are working in hot environment where you are exposed to more heat.

Honey should never be mixed with rain water, hot and spicy foods, and Fermented beverages like whisky, rum, brandy etc, Ghee and mustard.

Honey includes nectar of various flowers of which some may be poisonous. Poison has hot or Ushna qualities. When honey is mixed with hot and spicy foods the poisonous properties get enhanced and cause imbalance of doshas.

Few Home remedies with Honey

Mix 2 tea spoon of honey with carrot juice and consume regularly. This helps to improve eyesight and is very helpful for those who sit before computer for long hours.

In cold, cough and congested chest mix 2 tea spoons of honey with equal quantity of ginger juice and should be consumed frequently.

A mixture of black pepper powder, honey and ginger juice in equal quantities, when consumed thrice daily help to relieve the symptoms of asthma.

Regular use of one tea spoon of garlic juice mixed with two tea spoons of honey help to control blood pressure.

One glass of warm water taken with two tea spoons of honey and 1 tea spoon of lemon juice in early morning reduces fat and purifies blood.

Consuming one spoon of honey daily help us to lead a healthy long life.

Discussion: Honey effect on the growth of several strains of pathogenic bacteria, gastroenteritis, gastric ulcers, wounds, wound healing, antibacterial activity. More than 95% of the solids in honey are carbohydrate, and highly complex mixture of sugars. The identified as constituents of honey: isomaltose, nigerose, turanose, maltulose, kojibiose, alpha beta-trehalose, gentiobiose, laminaribiose; maltotriose, 1-kestose, panose, isomaltosyl glucose, erlose, isomaltosyltriose, theanderose, centose, isopanose, isomaltosyltetraose and isomaltosylpentaose. The pH of honey ranges from 3.2 to 4.5. The mineral and vitamin content of honey is very low, 0.02 % of its weight and given the low consumption of honey they have no significant nutritional benefit to man. Honey also contains a number of amino acids, proline, phenyalanine and aspartic acid being those with a concentration of greater than 200 ppm. The main enzymes found in honey which are derived from the hypopharyngeal glands of worker honeybees, are invertase (which inverts sucrose to glucose and fructose); glucose oxidase (which oxidises glucose to gluconic acid and hydrogen peroxide in the presence of water); and amylase (diastase), which breakdown starch. The enzymes in honey which originate from plants are catalase (a regulator of glucose oxidase activity); acid phosphatase; and a small proportion of amylase (107-115). The enzyme glucose oxidase is of considerable interest because its activity causes the production of hydrogen peroxide which not only stablizes the ripening nectar against spoilage but has microbicidal action. Honey both raw as well as processed can be the potential antimicrobial substance for control of different types of bacterial pathogens. 1) It was found that honey exhibited both bacteriostatic and bactericidal properties on both Gram-positive as well as on Gram-negative bacteria. 2) Residue left after extraction with various solvents exhibited almost negligible antibacterial activity. 3) The antibacterial activity of all the solvent extract was found to be significant against Gram-negative pathogens.

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4) The solvent extracts of honey were found to be bactericidal against P. aeruginosa for which even commonly used synthetic antibiotic such as tetracycline was found ineffective. 5) Chemical antibiotics have been become absolete within a short period of time. The need for an alternative antibacterial substance derived from natural materials on a sustaninabe manner has become a subject of interest for the scientist’s world over. The result of this study clearly shows that the extracts of honey in ethanol, methanol and ethylacetate solvents can become a potential candidate as an antibiotic, which would be useful on a sustainable basis. 6) This study shows that the other bulk components can be utilized elsewhere, while the necessary component is extracted from honey for antibacterial purposes. If found successful, it will pave way for developments leading to the exploitation of honey extracts for antibiotic activity as well as for other conventional uses of honey (bulk components). 7) The bactericidal and bacteriostatic effect of honey reported here has the potential for health care in rural areas once the pharmacological standardization and clinical trials are done, honey would become the house hold product not just for cure but even for preventive cure. 8) Further this study would pave the way to the studies more related to raw and processed honey of different types to understand the antimicrobial properties with special reference to resistant microbial strains. The above information shows that in microbiological and clinical tests, honey offers advantages in controlling bacterial growth and in the treatment of certain health problems. The ease of administration for the treatment of wounds, the absence of antibiotic resistance as found with conventional antibiotics, the lack of side effects in alieviating gastric pain and shortening the duration of diarrhea are all desirable features. Even in modern day society, the medical use of honey still has a place. Conclusions: According to WHO estimates, some 80 percent of people living in developing countries rely on harvested wild plants for their primary health care. In the developing world the use of antibiotics constitute a sizable fraction of medicines consumed. However, because of the microbes turning resistant especially to the synthetic antibiotics in use, the effectiveness of the antibiotics has been diminishing. Several case studies indicate that honey has some actions and attributes that have the potential to make it a useful wound dressing, but case studies offer a low level of validity and credibility. Positive results have been reported on the use of honey as a dressing for chronic wounds in adults in a number of case studies. In clinical practice this creates a dilemma for clinicians approached by patients requesting honey as a therapeutic intervention. Nevertheless the clinician can help the patient to make an informed decision based on the available evidence. At present, clinical decisions on the use of honey as a dressing for chronic wounds must be based on limited and weak evidence, as no cause and effect can be determined from case studies. There is clearly a paucity of high-quality literature relating to the use of topical honey in adults suffering from chronic wounds. References:

1. Adock D. The effect of catalase on inhibine and peroxide values of various honeys. J Apic Res, 1962, 1:38-40.

2. Farouk A, Hassan T, Kashif H, Khalid SA, Mutawali I, Wadi M. Studies on Sudanese bee honey: laboratory and clinical evaluation. Int J Crude Drug Res, 1988; 26:161-168.

3. Farouk HF, Kash SA, Khalid M, Mahasin W, et al., Studies on sudanese bee honey. Int. J. Crude Drug Res, 1988, 26: 161-168.

4. Greenhalgh T, Donald A. Evidence-Based Health Care Workbook 1st edn. BMJ Books, 2000, London 5. Greenhalgh T. How to Read a Paper: The Basics of Evidence-Based Medicine 2nd edn. BMJ Books, 2001,

London.

Mohammad Asif., PharmaBitika.,2014.1(1),115-132

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6. Siddiqui IR, Furgala B. Isolation and characterization of oligosaccharides (Disacharides) from honey. J Apic Res 1967, 6:139-145.

7. Siddiqui IR, Furgala B. Isolation and characterization of oligosaccharides (Trisacharides) from honey. J Apic Res 1968, 7:51-59.

8. Watanabe T, Aso L. Studies on honey, Isolation of kojibiose, nigerose, maltose and isomaltose from honey. Tohoku J Agr Res, 1960, 11:105-115.

9. White JW, Hoban N. Composition of honey, identification of disaccharides. Arch Biochem Biophys 1959, 80: 386-392.

10. White JW, Reithof ML, Subers MH, Kushnir I. Composition of American honeys. US Dept Agr Tech Bull, 1962, 1261:1-124.

11. Willix DJ, Molan PC, Harfoot CG. A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey. J Appl Bacteriol, 1993, 73(5): 388–94

12. Subrahmanyam M. A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazide. Burns, 1998, 24(2): 157–61

13. Radwan SA, El-Essawy, Sarhan MM. et al., Experimental evidence for the occurrence in honey of specific substances active against microorganisms. Zentral Mikrobiol, 1984, 39: 249-255.

14. Postmes T, Van den Bogaard AE, Hazen M. Honey for wounds, ulcers and skin graft preservation. Lancet, 1993; 341:756-757.

15. Natarajan S, Williamson D, Grey J, Harding KG, Cooper RA. Healing of an MRSA colonized, hydroxyurea-induced leg ulcer with honey. J Dermatol Treat, 2001, 12 (1): 33–6

16. Molan PC, Russel KM. Non-peroxide antibacterial activity in some New Zealand honeys. J Apic Res 1988, 27:62-67.

17. Ali AT, Chowdhury MN, Al-Humayyd MS. Inhibitory effect of natural honey on Helicobacter pylori. Tropical Gastroenterol, 1991, 12:139-143.

18. Amy E. Jeffrey, Carlos M. Medical uses of honey. Echazarreta. Rev Biomed 1996; 7:43-49. 19. Lusby PE, Coombes A, Wilkinson JM., et al., Honey: A potent agent for wound healing? J. Wound Ostomy

Continence Nurs, 2002, 29: 295-300. 20. Adeleke OE, Olaitan JO, Okepekpe EI, et al., Comparative antibacterial activity of honey and Gentamicin

against Escherichia coli and P. aeruginosa. Annals of burn and fire disasters, 2006, 19: n4. 21. Basualdo C, Sgroy V, Finola MS, Juam M., et al. Comparison of the antibacterial activity of honey from

different provenance against bacteria usually isolated from skin wounds. Veterinary Microbiology, 2007, 124(3-4): 375-381.

22. Molan PC. The antibacterial activity of honey. Bee World 1992; 73:5-28, 59-76. 23. Namias S. Honey in the management of infections. Surg. Infect (Larchmt), 2003, 4: 219-226. 24. Nelson EA. The use of case reports in wound care. J Wound Care, 2000, 9(1): 23–6 25. Ruiz-Argueso T, Rodriguez-Navarro A. Gluconic acidproducing bacteria from honeybees and ripening

honey. J Gen Microbiol, 1973, 76:211-216. 26. Jeddar A, Kharsany A, Ramsaroop UG, Bhamjee A, Haffejee IE, Moosa A. The antibacterial action of

honey: an in vitro study. S Afr Med J, 1985, 67:257-258. 27. Ibrahim A S. Antibacterial action of honey. Bull. Islam Med, 1985, 1: 363-365. 28. White JW. Honey. En: Chichester CO, ed. Advances in Food Research. New York: Academic Press, 1978,

287-374. 29. White JW. Physical characteristics of honey. En: Crane E, ed. Honey, a comprehensive survey. London:

Bee Research Association and Chalfont St Peter, 1975, 207- 239. 30. World Health Organization. Drug information. WHO, Geneva, 1999, 13(4): 230-233.

Mohammad Asif., PharmaBitika.,2014.1(1),115-132

PharmaBiotika/2014/1/1/115-132-©2014www.pharmaBiotikaworld.com All rights reserved. 129

Research Article ISSN 2408-9702

31. Yee YJ. Green Inhibitors for Corrosion Control: A Study on the Inhibitive Effects of Extracts of Honey and Rosmarinus Officinalis L. (Rosemary). A thesis submitted to the University of Manchester Institute of Science and Technology for the degree of Master of Science. 2004, Corrosion and Protection Centre.

32. Bosi G, Battalglini M. Gas chromatographic analysis of free and protein amino acids in some unifloral honeys. J Apic Res, 1978, 17:152-166.

33. Ingram FJ, Ottoway H, Coppock JE. The preservative action of acid substances in food. Chem Ind, 1956, 42:1154-1163.

34. Sackett D, Strauss S, Richardson W, Rosenberg W, Haynes R, Evidence Based Medicine: How to practice and teach EBM. Churchill Livingstone, 2000, New York

35. White JW, Subers MH. Studies on honey inhibine, a chemical assay. J Apic Res, 1963, 15:23-28. 36. Sherlock O, Dolan A, Athman R, Power A, Gethin G, Cowman S, Humphreys H. Comparison of the

antimicrobial activity of Ulmo honey from Chile and Manuka honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Sherlock et al. BMC Complementary and Alternative Medicine 2010, 10:47.

37. Allen KI, Radwan S, Reid GM., et al. Antimicrobial activity of honey on some microbial isolates. J. Medical and Pharmaceutical Sciences, 2000, 2: 75-79.

38. White JW, Subers MH, Schepartz AI. The identification of inhibine, The antibacterial factor in honey as hydrogen peroxidase and its origin in a honey glucose oxidase system. Biochem. Biophys Act, 1963, 73:57-70.

39. White JW. Composition of honey. En: Crane E, ed. Honey, a comprehensive survey. London: Bee research Association and Chalfont St Peter, 1975, 157-206.

40. Freese E, Sheu CW, Galliers E. Function of lipophilic acids as antimicrobial food additive. Nature, 1973, 241:321-325.

41. Bogdanov S. Characterization of antibacterial substance in honey. Lebensm Wiss Technol, 1984, 17(2): 74-76.

42. Chauhan A, Pandey V, Chacko KM, Khandal R. K. Antibacterial Activity of Raw and Processed Honey. Electronic Journal of Biology, 2010, 5(3): 58-66.

43. Hamdy MH, El-Banby MA, Khakifa KI, Gad EM, Saven EM. The antimicrobial effect of honey in the management of septic wounds. En: Procc 4th Int Conf on Apiculture in Tropical Climates. El Cairo, International Bee Ressearch Association, 1988, 56.

44. Efem SE. Clinical observations on the wound healing properties of honey. Br J Surgery, 1988, 75:679-681. 45. Salem SN. Treatment of gastroenteritis by the use of honey. Islamic Medicine, 1981, 1:358-362. 46. Haffejee IE, Moosa A. Honey in the treatment of infantile gastroenteritis. Br Med J, 1985, 290, 1866-1867. 47. Cooper RA, Molan PC, Krishnamoorthy L, Harding KG. Manuka honey used to heal a recalcitrant surgical

wound. Eur J Clin Microbiol Infect Dis, 2001, 20(10): 758–9 48. Kingsley A. The use of honey in the treatment of infected wounds: case studies. Br J Nurs, 2001, 10(22

supple): S13–20 49. Kandil A, El-Banby M, Abdel-Wahed GK, Abdel-Gawwad M, Fayez M. Curative properties of true floral

and false non-floral honeys on induced gastric ulcers. J Drug Res, 1987, 17:103-106. 50. Ali AT. Prevention of ethanol-induced gastric lesions in rats by natural honey and its possible mechanism

of action. Scand J Gastroenterol, 1991, 26, 281-288. 51. Molan PC. The role of honey in the management of wounds. J Wound Care, 1999, 8(8): 415–8 52. Efem SEE. Recent advances in the management of Fournier’s gangrene: preliminary observations. Surg,

1993, 113(2): 200–04 53. Dealey C. The Care of Wounds 1st edn. Blackwell Science, 1994, Oxford

Mohammad Asif., PharmaBitika.,2014.1(1),115-132

PharmaBiotika/2014/1/1/115-132-©2014www.pharmaBiotikaworld.com All rights reserved. 130

Research Article ISSN 2408-9702

54. Hutton, DJ, Treatment of pressure sores. Nurs Times, 1966, 62(46): 1533–4 55. Moore OA, Smith LA, Campbell F, Seers K, McQuay HR, Moore RA. Systematic review of the use of

honey as a wound dressing. BMC Complement Altern Med, 2001, 1(1): 2 56. Armon PJ. Care and healing of wounds by the use of honey. Tropical Doctor 1980; 10:91. 57. Crapo PA, Kolterman OG, Olefsky JM. Effects of oral fructose in normal diabetic and impaired glucose

tolerant subjects. Diabetic Care 1980; 3:575. 58. Mann JI. Simple sugars and diabetics, Diabetic Med 1987; 4:135. 59. Bornet T, Haardt MJ, Costagliola D, Blayo A, Slama G. Sucrose or honey at breakfast have no additional

acute hyperglycaemic effect over an isoglucidic amount of bread in type II diabetic patients. Diabetologia 1985; 28:213.

60. Katsilambros NL, Philippides P, Touliatou A, et al. La miel en dietas de pacientes con diabetes tipo II. Acta Diabetol Latina 1988, 25:197-203.

61. Tabor Kl. Graduate Student Apiculture, J.T. Ambrose, Extension Apiculturist, 1998. 62. Sharma R (2005), Improve your Health! with Honey, Diamond Pocket Books (P) Ltd., ISBN 978-81-288-

0920-0, http://books.google.com/books?id=h1FkltLNQ-AC&pg=PA9. 63. Dutt UC. The materia medica of the Hindus. Mittal Publications: New Delhi, India, 1995. 64. Endo J, Nakamura T. Comparative studies of the tridosha theory in Ayurveda and the theory of the four

deranged elements in Buddhist medicine. Kagakushi Kenkyu, 1995; 34(193): 1–9. 65. Mishra L, Singh BB, Dagenais S: Ayurveda: a historical perspective and principles of the traditional

healthcare system in India. Altern Ther Health Med, 2001; 7(2): 36–42 66. Chauhan P: Eternal health: the essence of Ayurveda. Jiva Institute: Faridabad, India, 2000 67. Sharma PV. Caraka-Samhita (Volume 1), Chaukhamba Orientalia: Varanasi, India, 1996 68. Graham TJ. Ayurveda materia medica for domestic use. Volume I. Logos Press: New Delhi, India, 2006. 69. Ahmed A, Khan R A, Azim M K, Saeed S A, Mesaik M A, Ahmed S, Imran I. Effect of Natural Honey on

Human Platelets and Blood Coagulation Proteins. Pakistan Journal of Pharmaceutical Sciences, 2011; 24 (3): 389-397.

70. Ahmed AK, Hoekstra MJ, Hage JJ, Karim RB. Honey-medicated dressing: transformation of an ancient remedy into modern therapy. Annals of Plastic Surgery, 2003; 50 (2): 143-147.

71. Bahrami, M; Ataie-Jafari, A; Hosseini, S; Foruzanfar, M H; Rahmani, M; Pajouhi, M. Effects of natural honey consumption in diabetic patients: an 8-week randomized clinical trial. International journal of food sciences and nutrition, 2009; 60 (7): 618-626.

72. Baltuskevicius, A; Laiskonis, A; Vysniauskiene, D; Ceksteryte, V; Racys, J. Use of different kinds of honey for hepatitis A treatment and for reduction of increased acidity of gastric juice. Zemdirbyste, Mokslo Darbai, 2001; 76: 173-180.

73. Bardy J, Slevin NJ, Mais KL, Molassiotis A. A systematic review of honey uses and its potential value within oncology care. Journal of Clinical Nursing, 2008, 17 (19): 2604-2623.

74. Beretta G, Gelmini F, Lodi V, Piazzalunga A, Facino RM. Profile of nitric oxide (NO) metabolites (nitrate, nitrite and N-nitroso groups) in honeys of different botanical origins: Nitrate accumulation as index of origin, quality and of therapeutic opportunities. Journal of Pharmaceutical and Biomedical Analysis, 2010; 53 (3): 343-349.

75. Biswal, B M; Zakaria, A; Ahmad, N M. Topical application of honey in the management of radiation mucositis. A preliminary study. Supportive Care in Cancer 11 (4): 242-248.

76. Bowen, W H; Lawrence, R A (2005) Comparison of the cariogenicity of cola, honey, cow milk, human milk, and sucrose. Pediatrics, 2003; 116 (4): 921-926.

77. Cooper, R A; Halas, E; Molan, P C. The efficacy of honey in inhibiting strains of Pseudomonas aeruginosa from infected burns. Journal of Burn Care and Rehabilitation, 2002; 23 (6): 366-370.

Mohammad Asif., PharmaBitika.,2014.1(1),115-132

PharmaBiotika/2014/1/1/115-132-©2014www.pharmaBiotikaworld.com All rights reserved. 131

Research Article ISSN 2408-9702

78. Cutting K.; White R. Maceration of the skin: 1. The nature and causes of skin maceration. Journal of Wound Care, 2002, 11: 275-278.

79. Cutting, K F. Honey and contemporary wound care: An overview. Ostomy/Wound Management, 2007; 53 (11): 49-54.

80. Darby-Stewart, A; Dachs, R; Graber, M A . Honey as a Treatment for Cough in Children. American Family Physician, 2009; 80 (2): 120-121.

81. Dunford, C; Cooper, R; Molan, P. Using honey as a dressing for infected skin lesions. NT Plus, 2000 96 (14): 7-9.

82. 39. Frolov, V M; Peressadin, N A. Honey against influenza and sore throat. Pcelovodstvo, 2006; 10 (529): 52-53.

83. 41. Gharzouli, K; Amira, S; Gharzouli, A; Khennouf, S. Gastroprotective effects of honey and glucose-fructose-sucrose-maltose mixture against ethanol-, indomethacin-, and acidified aspirininduced lesions in the rat. Experimental and toxicologic pathology , 2002; 54 (3): 217-221.

84. Heppermann, B; Jones, J S. Honey for the Symptomatic Relief of Cough in Children with Upper Respiratory Tract Infections. Emergency Medicine Journal, 2009; 26 (7): 522-523.

85. 47. Irish, J; Carter, D; Blair, S. Honey kills some of our most dangerous microbial enemies Apimondia abstracts Ireland 2005, Dublin; pp 124.

86. 48. Jones, R. Honey and healing through the ages, In Munn, P; Jones, R (eds) Honey and healing, IBRA International Bee Research Association; Cardiff, GB; 2001; pp 1-4.

87. Krishna, R. Therapeutic uses of Honey in Ayurveda.: 2005; http://www.ezilon.com/articles/articles/356-1/Therapeutic-uses-of-Honey-in-Ayurveda.

88. Lahanas, M. Examples of Ancient Greek Medical Knowledge. 2010: accessed 8.2.2010 on http://www.mlahanas.de/Greeks/Med.htm.

89. Manyi-Loh, C E; Clarke, A M; Munzhelele, T; Green, E; Mkwetshana, N F; Ndip, R N. Selected South African Honeys and Their Extracts Possess In Vitro Anti-Helicobacter pylori Activity. Archives of Medical Research, 2010; 41 (5): 324-331.

90. Molan, P. Mode of action, In White, R; Molan, P; Copper, R (eds) Honey: A modern wound management product, Wounds UK; Aberdeen; 2005; pp 1-23.

91. Molan, P C. Honey for oral health. Journal of Dental Research 80 (special issue): 2001; 1-130. 92. Molan, P C Re-introducing honey in the management of wounds and ulcers - theory and practice.

Ostomy/Wound Management, 2002 48 (11): 28-40. 93. Münstedt, K; Kalder, M. Honey as a treatment option for rhinoconjunctivitis. JAAS 2010; 2: 145-148. 94. 68. Münstedt, K; Hoffmann, S; Hauenschild, A; Bulte, M; Von Georgi, R; Hackethal, A (2009) Effect of

Honey on Serum Cholesterol and Lipid Values. Journal of Medicinal Food 12 (3): 624-628. 95. Nasuti, C; Gabbianelli, R; Falcioni, G; Cantalamessa, F. Antioxidative and gastroprotective activities of

anti-inflammatory formulations derived from chestnut honey in rats. Nutrition Research, 2006; 26 (3): 130-137.

96. Onyesom, I, Honey-induced stimulation of blood ethanol elimination and its influence on serum triacylglycerol and blood pressure in man. Annals of Nutrition and Metabolism, 2005; 49 (5): 319-324.

97. Paul, I M; Beiler, J; Mcmonagle, A; Shaffer, M L; Duda, L; Berlin, C M , Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Archives of Pediatrics & Adolescent Medicine, 2007; 161 (12): 1140-1146.

98. Persano Oddo, L; Piana, L; Bogdanov, S; Bentabol, A; Gotsiu, P; Kerkvliet, J; Martin, P; Morlot, M; Valbuena, A O; Ruoff, K; Von Der Ohe, K. Botanical species giving unifloral honey in Europe. Apidologie, 2004; 35 (special issue): 82-93.

Mohammad Asif., PharmaBitika.,2014.1(1),115-132

PharmaBiotika/2014/1/1/115-132-©2014www.pharmaBiotikaworld.com All rights reserved. 132

Research Article ISSN 2408-9702

99. Piazza, M G; Persano Oddo, L. Bibliographical review of the main European unifloral honeys. Apidologie, 2004; 35 (special issue): S94-S111.

100. Pourahmad, M; Sobhanian, S. Effect of Honey on the Common Cold. Arch Med Re, 2009; s 40: 224-225. 101. Rajan, T V; Tennen, H; Lindquist, R L; Cohen, L; Clive, J. Effect of Ingestion of Honey on Symptoms of

Rhinoconjunctivitis. Annals of allergy, asthma & immunology, 2002; 88 (2): 198-203. 102. Siedentopp, W. Honey: Effective Against Inflammation, Cough and Hoarseness. Deutsche Zeitschrift fuer

Akkupunktur, 2009; 52: DOI: 10.1016/ j .dza.2009.10.004. 103. Simon, A; Sofka, K; Wiszniewsky, G; Blaser, G; Bode, U; Fleischhack, G (2006) Wound care with

antibacterial honey (Medihoney) in pediatric hematology-oncology. Supportive Care in Cancer, 2008; 14 (1): 91-97.

104. Subrahmanyam, M; Sahapure, A; Nagane, N. Effects of topical application of honey on burn wound healing. Ann Burns Fire Disasters, 2001; 14: 143-145.

105. 96. Subrahmanyam, M; Sahapure, A; Nagane, N. Free radical control – the main mechanism of the action of honey in burns. Ann Burns Fire Disasters, 2003; 16: 135-138.

106. 100. Warren, M D; Cooper, W O. Honey improves cough in children compared to no treatment. Journal of Pediatrics, 2008 152 (5): 739-740.

107. Cooper RA, Molan PC, Harding KG. Antibacterial activity of honey against strains of Staphylococcus aureus from infected wounds. J R Soc Med, 1999, 92(6): 283–5

108. Cramer JA, Prestegard JH. NMR studies of pH induces transport of carboxylic acis across phospholipid vesicle membranes. Biophys Res Commun, 1977, 75:295-301.

109. Dunford C, Cooper R, Molan P, White R. The use of honey in wound management. Nurs Stand 2000, 15(11): 63–8

110. Dunford C, Cooper R, Molan P. Using honey as a dressing for infected skin lesions. Nurs Times, 2000, 96(14 supple): S7–9

111. Griffiths, P. Honey as a dressing for chronic wounds in adults British Journal of Community Nursing, 2002, 7(10), 530-34.

112. Macris BJ. Mechanisms of benzioc acid uptake by Saccaromyces cerevisiae. Appl Microbiol, 1975, 30:503-506.

113. Molan PC, Cooper RA. Why honey and sugar as dressing for wound and ulcer. Trop. Doc., 2000, 4: 249-258.

114. Hamdi N. Antimicrobial potential of Honey. Medical Sciences, 2000, 2: 75-79. 115. Shears P. Antimicrobial resistance in the tropics. Tropical Doctor, 2000, 30(2): 114-116.