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Potential Mechanisms and Application of Honeybee Products in Wound Management: Wound Healing by Apitherapy

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Burns, Infections and Wound Management

Abstract

Honey is an ancient remedy for its medicinal application, as a treatment for burns, ulcers, and wound healing. Honey is mainly composed of carbohydrates, enzymes, amino acids, lipids, vitamins, minerals, and aromatic substances. Flavonoids and phenolic acids are the most important compounds in honey that display a wide range of biological activities. Depending on its origin, climate, and honeybee species, honey has different colors, compositions, aromas, and flavors. Therefore, various types of honey have different therapeutic effects. Honey affects the wound healing processes by several mechanisms. It rapidly removes bacteria from the colonized and infected wounds due to its hydrogen peroxide, high osmolality, acidity, non-peroxide factors, nitric oxide, and phenols. As a dressing on wounds, honey promotes autolytic debridement, stimulates anti-inflammatory activities, and enhances fibroplasia and angiogenesis in the wound bed. This chapter aims to review the medicinal properties of honey and describe its mechanism of action on wound healing.

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References

  1. Dorai AA (2012) Wound care with traditional, complementary and alternative medicine. Indian J Plast Surg 45(2):418–424

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kigen GK, Ronoh HK, Kipkore WK, Rotich JK (2013) Current trends of traditional herbal medicine practice in Kenya: a review. Afr J Pharmacol Therapeut 2(1):32–37

    Google Scholar 

  3. Rickard AH, Gilbert P, High NJ, Kolenbrander PE, Handley PS (2003) Bacterial coaggregation: an integral process in the development of multi-species biofilms. Trends Microbiol 11(2):94–100

    Article  CAS  PubMed  Google Scholar 

  4. Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR (2016) Topical application of aloe vera accelerated wound healing, modeling, and remodeling: an experimental study. Ann Plast Surg 77(1):37–46

    Article  CAS  PubMed  Google Scholar 

  5. Oryan A, Zaker S (1998) Effects of topical application of honey on cutaneous wound healing in rabbits. Zentralbl Veterinärmed A 45(3):181–188

    Article  CAS  PubMed  Google Scholar 

  6. Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR (2015) Avocado/soybean unsaponifiables: a novel regulator of cutaneous wound healing, modelling and remodelling. Int Wound J 12(6):674–685

    Article  PubMed  Google Scholar 

  7. Padhi S, Panda SK (2017) Evaluation of wound healing potential of crude leave extracts of Bixa Orellana Linn. in wistar rat. World J Pharm Phamaceut Sci 5(8):1388–1395

    Google Scholar 

  8. Tabandeh MR, Oryan A, Mohhammad-Alipour A, Tabatabaei-Naieni A (2013) Silibinin regulates matrix metalloproteinase 3 (stromelysine1) gene expression, hexoseamines and collagen production during rat skin wound healing. Phytother Res 27(8):1149–1153

    Article  CAS  PubMed  Google Scholar 

  9. Oryan A, Naeini AT, Nikahval B, Gorjian E (2010) Effect of aqueous extract of Aloe vera on experimental cutaneous wound healing in rat. Veterinarski Arhiv 80(4):509–522

    Google Scholar 

  10. Tabandeh MR, Oryan A, Mohammadalipour A (2014) Polysaccharides of Aloe vera induce MMP-3 and TIMP-2 gene expression during the skin wound repair of rat. Int J Biol Macromol 65:424–430

    Article  CAS  PubMed  Google Scholar 

  11. Lim M, Sadarangani P, Chan H, Heng J (2005) Complementary and alternative medicine use in multiracial Singapore. Complement Ther Med 13(1):16–24

    Article  CAS  PubMed  Google Scholar 

  12. Fratellone PM, Tsimis F, Fratellone G (2016) Apitherapy products for medicinal use. J Altern Complement Med 22(12):1020–1022

    Article  PubMed  Google Scholar 

  13. Majtán J (2009) Apitherapy--the role of honey in the chronic wound healing process. Epidemiol Mikrobiol Imunol 58(3):137–140

    PubMed  Google Scholar 

  14. Lusby P, Coombes A, Wilkinson J (2002) Honey: a potent agent for wound healing? J Wound Ostomy Continence Nurs 29(6):295–300

    CAS  PubMed  Google Scholar 

  15. McLoone P, Warnock M, Fyfe L (2016) Honey: a realistic antimicrobial for disorders of the skin. J Microbiol Immunol Infect 49(2):161–167

    Article  CAS  PubMed  Google Scholar 

  16. Murray J (2005) Honey--a modern wound management product. Nurs Standard 19(51):36–37

    Article  Google Scholar 

  17. Alqarni AS, Owayss AA, Mahmoud AA (2016) Physicochemical characteristics, total phenols and pigments of national and international honeys in Saudi Arabia. Arab J Chem 9(1):114–120

    Article  CAS  Google Scholar 

  18. da Silva PM, Gauche C, Gonzaga LV, Costa ACO, Fett R (2016) Honey: chemical composition, stability and authenticity. Food Chem 196:309–323

    Article  PubMed  CAS  Google Scholar 

  19. Alvarez-Suarez JM, Gasparrini M, Forbes-Hernández TY, Mazzoni L, Giampieri F (2014) The composition and biological activity of honey: a focus on Manuka honey. Foods 3(3):420–432

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kamal MA, Klein P (2011) Determination of sugars in honey by liquid chromatography. Saudi J Biol Sci 18(1):17–21

    Article  CAS  PubMed  Google Scholar 

  21. Tornuk F, Karaman S, Ozturk I, Toker OS, Tastemur B, Sagdic O, Dogan M, Kayacier A (2013) Quality characterization of artisanal and retail Turkish blossom honeys: determination of physicochemical, microbiological, bioactive properties and aroma profile. Industrial Crops Prod 46:124–131

    Article  CAS  Google Scholar 

  22. Escuredo O, Dobre I, Fernández-González M, Seijo MC (2014) Contribution of botanical origin and sugar composition of honeys on the crystallization phenomenon. Food Chem 149:84–90

    Article  CAS  PubMed  Google Scholar 

  23. Puscas A, Hosu A, Cimpoiu C (2013) Application of a newly developed and validated high-performance thin-layer chromatographic method to control honey adulteration. J Chromatogr A 1272:132–135

    Article  CAS  PubMed  Google Scholar 

  24. Mato I, Huidobro JF, Simal-Lozano J, Sancho MT (2006) Rapid determination of nonaromatic organic acids in honey by capillary zone electrophoresis with direct ultraviolet detection. J Agric Food Chem 54(5):1541–1550

    Article  CAS  PubMed  Google Scholar 

  25. Karabagias IK, Badeka A, Kontakos S, Karabournioti S, Kontominas MG (2014) Characterisation and classification of Greek pine honeys according to their geographical origin based on volatiles, physicochemical parameters and chemometrics. Food Chem 146:548–557

    Article  CAS  PubMed  Google Scholar 

  26. Won S-R, Li C-Y, Kim J-W, Rhee H-I (2009) Immunological characterization of honey major protein and its application. Food Chem 113(4):1334–1338

    Article  CAS  Google Scholar 

  27. Di Girolamo F, D'Amato A, Righetti PG (2012) Assessment of the floral origin of honey via proteomic tools. J Proteome 75(12):3688–3693

    Article  CAS  Google Scholar 

  28. Manzanares AB, García ZH, Galdón BR, Rodríguez ER, Romero CD (2014) Physicochemical characteristics of minor monofloral honeys from Tenerife, Spain. LWT Food Sci Technol 55(2):572–578

    Article  CAS  Google Scholar 

  29. Alqarni AS, Owayss AA, Mahmoud AA, Hannan MA (2014) Mineral content and physical properties of local and imported honeys in Saudi Arabia. J Saudi Chem Soc 18(5):618–625

    Article  CAS  Google Scholar 

  30. Pontis JA, Costa LAMA, Silva SJR, Flach A (2014) Color, phenolic and flavonoid content, and antioxidant activity of honey from Roraima, Brazil. Food Sci Technol (Campinas) 34(1):69–73

    Article  Google Scholar 

  31. Olaitan PB, Adeleke OE, Iyabo O (2007) Honey: a reservoir for microorganisms and an inhibitory agent for microbes. Afr Health Sci 7(3)

    Google Scholar 

  32. Escuredo O, Míguez M, Fernández-González M, Seijo MC (2013) Nutritional value and antioxidant activity of honeys produced in a European Atlantic area. Food Chem 138(2):851–856

    Article  CAS  PubMed  Google Scholar 

  33. Aznan MI, Khan OH, Unar AO, Sharif SET, Khan AH, Aziz SHSA, Zakaria AD (2016) Effect of Tualang honey on the anastomotic wound healing in large bowel anastomosis in rats-A randomized controlled trial. BMC Complement Altern Med 16(1):28

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Mukai K, Komatsu E, Yamanishi M, Hutakuchi M, Kanzaka K, Uno Y, Yamazaki S, Kato S, Yamamoto T, Hattori M (2016) Effectiveness of changing the application of Japanese honey to a hydrocolloid dressing in between the inflammatory and proliferative phases on cutaneous wound healing in male mice. Wounds 29(1):1–9

    PubMed  Google Scholar 

  35. Khoo YT, Halim AS, Singh KK, Mohamad NA (2010) Wound contraction effects and antibacterial properties of Tualang honey on full-thickness burn wounds in rats in comparison to hydrofibre. BMC Complement Altern Med 10(1):48

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zohdi R, Mukhtar S, Said S, Azmi N, Ali A (2014) A comparative study of the wound healing properties of Gelam honey and silver sulfadiazine in diabetic rats. In: Biomedical Engineering and Sciences (IECBES), 2014 IEEE Conference on IEEE. IEEE, Kuala Lumpur, Malaysia, pp 247–250

    Chapter  Google Scholar 

  37. Molan PC (2001) Potential of honey in the treatment of wounds and burns. Am J Clin Dermatol 2(1):13–19

    Article  CAS  PubMed  Google Scholar 

  38. Oryan A, Alemzadeh E, Moshiri A (2016) Biological properties and therapeutic activities of honey in wound healing: a narrative review and meta-analysis. J Tissue Viabil 25(2):98–118

    Article  Google Scholar 

  39. Raynaud A, Ghezali L, Gloaguen V, Liagre B, Quero F, Petit J-M (2013) Honey-induced macrophage stimulation: AP-1 and NF-κB activation and cytokine production are unrelated to LPS content of honey. Int Immunopharmacol 17(3):874–879

    Article  CAS  PubMed  Google Scholar 

  40. Hussein SZ, Mohd Yusoff K, Makpol S, Mohd Yusof YA (2012) Gelam honey inhibits the production of proinflammatory, mediators NO, PGE2, TNF-α, and IL-6 in carrageenan-induced acute paw edema in rats. Evid Based Complement Alternat Med 2012:109636

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rossiter K, Cooper A, Voegeli D, Lwaleed B (2010) Honey promotes angiogenic activity in the rat aortic ring assay. J Wound Care 19(10):440–446

    Article  CAS  PubMed  Google Scholar 

  42. Nakajima Y, Nakano Y, Fuwano S, Hayashi N, Hiratoko Y, Kinoshita A, Miyahara M, Mochizuki T, Nishino K, Tsuruhara Y (2013) Effects of three types of Japanese honey on full-thickness wound in mice. Evid Based Complement Alternat Med 2013:504537

    PubMed  PubMed Central  Google Scholar 

  43. Molan PC (2002) Re-introducing honey in the management of wounds and ulcers-theory and practice. Ostomy Wound Manage 48(11):28–40

    PubMed  Google Scholar 

  44. Boekema B, Pool L, Ulrich M (2013) The effect of a honey based gel and silver sulphadiazine on bacterial infections of in vitro burn wounds. Burns 39(4):754–759

    Article  CAS  PubMed  Google Scholar 

  45. Al-Jadi A-M, Enchang FK, Yusoff KM (2014) The effect of Malaysian honey and its major components on the proliferation of cultured fibroblasts. Turkish J Med Sci 44(5):733–740

    Article  CAS  Google Scholar 

  46. Subrahmanyam M, Sahapure A, Nagane N, Bhagwat V, Ganu J (2001) Effects of topical application of honey on burn wound healing. Ann Burns Fire Disasters 14(3):143–145

    Google Scholar 

  47. Church D, Elsayed S, Reid O, Winston B, Lindsay R (2006) Burn wound infections. Clin Microbiol Rev 19(2):403–434

    Article  PubMed  PubMed Central  Google Scholar 

  48. Atiyeh BS, Costagliola M, Hayek SN, Dibo SA (2007) Effect of silver on burn wound infection control and healing: review of the literature. Burns 33(2):139–148

    Article  PubMed  Google Scholar 

  49. Poon VK, Burd A (2004) In vitro cytotoxicity of silver: implication for clinical wound care. Burns 30(2):140–147

    Article  PubMed  Google Scholar 

  50. Pećanac M, Janjić Z, Komarčević A, Pajić M, Dobanovački D, Skeledžija-Mišković S (2013) Burns treatment in ancient times. Med Pregl 66(5–6):263–267

    PubMed  Google Scholar 

  51. Choudhary K, Mohanty SK, Soni P (2016) A prospective randomized trial to compare the effectiveness of honey vs. silver sulfadiazine dressing in burn wound management. Int J Med Res Rev 4(1):67–74

    Article  Google Scholar 

  52. Pannerselvam B, Jothinathan MKD, Rajenderan M, Perumal P, Thangavelu KP, Kim HJ, Singh V, Rangarajulu SK (2017) An in vitro study on the burn wound healing activity of cotton fabrics incorporated with phytosynthesized silver nanoparticles in male Wistar albino rats. Eur J Pharm Sci 100:187–196

    Article  CAS  PubMed  Google Scholar 

  53. Aziz Z, Hassan BAR (2017) The effects of honey compared to silver sulfadiazine for the treatment of burns: a systematic review of randomized controlled trials. Burns 43(1):50–57

    Article  PubMed  Google Scholar 

  54. Jull A, Walker N, Parag V, Molan P, Rodgers A (2008) Randomized clinical trial of honey-impregnated dressings for venous leg ulcers. Br J Surg 95(2):175–182

    Article  PubMed  Google Scholar 

  55. Kahle B, Hermanns H-J, Gallenkemper G (2011) Evidence-based treatment of chronic leg ulcers. Dtsch Arztebl Int 108(14):231–237

    PubMed  PubMed Central  Google Scholar 

  56. Gethin G, Cowman S (2008) Bacteriological changes in sloughy venous leg ulcers treated with manuka honey or hydrogel: an RCT. J Wound Care 17(6):241–244

    Article  CAS  PubMed  Google Scholar 

  57. Oluwatosin O, Olabanji J, Oluwatosin O, Tijani L, Onyechi H (2000) A comparison of topical honey and phenytoin in the treatment of chronic leg ulcers. Afr J Med Med Sci 29(1):31–34

    CAS  PubMed  Google Scholar 

  58. Mohamed H, Salma M, Al Lenjawi B, Abdi S, Gouda Z, Barakat N, Elmahdi H, Abraham S, Hamza AH, Al Khozaei D (2015) The efficacy and safety of natural honey on the healing of foot ulcers: a case series. Wounds 27(4):103–114

    PubMed  Google Scholar 

  59. Reiber G, Lipsky B, Gibbons G (1998) The burden of diabetic foot ulcers. Am J Surg 176(2):5S–10S

    Article  CAS  PubMed  Google Scholar 

  60. Kamaratos AV, Tzirogiannis KN, Iraklianou SA, Panoutsopoulos GI, Kanellos IE, Melidonis AI (2014) Manuka honey-impregnated dressings in the treatment of neuropathic diabetic foot ulcers. Int Wound J 11(3):259–263

    Article  PubMed  Google Scholar 

  61. Moghazy A, Shams M, Adly O, Abbas A, El-Badawy M, Elsakka D, Hassan S, Abdelmohsen W, Ali O, Mohamed B (2010) The clinical and cost effectiveness of bee honey dressing in the treatment of diabetic foot ulcers. Diabetes Res Clin Pract 89(3):276–281

    Article  CAS  PubMed  Google Scholar 

  62. Delshad E, Tavakkoli-Kakhki M, Motavasselian M (2016) Successful repair of diabetic foot ulcer with honey-based treatment: a case report. Iranian Red Crescent Med J (3):21–24

    Google Scholar 

  63. Insani IB, Widayanti N, Rifki A (2017) Honey as a treatment for diabetic foot ulcer: a systematic review. J Plast Rekonstr 3(2):45–51

    Article  Google Scholar 

  64. Hillitt K, Jenkins R, Spiller OB, Beeton M (2016) Antimicrobial activity of Manuka honey against antibiotic resistant strains of the cell wall free bacteria Ureaplasma parvum and Ureaplasma urealyticum. Lett Appl Microbiol 64(3):198–202

    Article  CAS  Google Scholar 

  65. Sherlock O, Dolan A, Athman R, Power A, Gethin G, Cowman S, Humphreys H (2010) Comparison of the antimicrobial activity of Ulmo honey from Chile and Manuka honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. BMC Complement Altern Med 10(1):47

    Article  PubMed  PubMed Central  Google Scholar 

  66. Halstead F, Webber M, Rauf M, Burt R, Dryden M, Oppenheim B (2016) In vitro activity of an engineered honey, medical-grade honeys, and antimicrobial wound dressings against biofilm-producing clinical bacterial isolates. J Wound Care 25(2):93–102

    Article  CAS  PubMed  Google Scholar 

  67. Brudzynski K, Abubaker K, Wang T (2012) Powerful bacterial killing by buckwheat honeys is concentration-dependent, involves complete DNA degradation and requires hydrogen peroxide. Front Microbiol 3:242

    PubMed  PubMed Central  Google Scholar 

  68. Kwakman PH, Te Velde AA, De Boer L, Vandenbroucke-Grauls CM, Zaat SA (2011) Two major medicinal honeys have different mechanisms of bactericidal activity. PLoS One 6(3):e17709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mandal MD, Mandal S (2011) Honey: its medicinal property and antibacterial activity. Asian Pac J Trop Biomed 1(2):154–160

    Article  PubMed  PubMed Central  Google Scholar 

  70. Oryan A, Alemzadeh E, Moshiri A (2017) Burn wound healing: present concepts, treatment strategies and future directions. J Wound Care 26(1):5–19

    Article  CAS  PubMed  Google Scholar 

  71. Emineke S, Cooper AJ, Fouch S, Birch BR, Lwaleed BA (2017) Diluted honey inhibits biofilm formation: potential application in urinary catheter management? J Clin Pathol 70(2):140–144

    Article  CAS  PubMed  Google Scholar 

  72. Sojka M, Valachova I, Bucekova M, Majtan J (2016) Antibiofilm efficacy of honey and bee-derived defensin-1 on multispecies wound biofilm. J Med Microbiol 65(4):337–344

    Article  CAS  PubMed  Google Scholar 

  73. Al-Waili NS, Salom K, Butler G, Al Ghamdi AA (2011) Honey and microbial infections: a review supporting the use of honey for microbial control. J Med Food 14(10):1079–1096

    Article  CAS  PubMed  Google Scholar 

  74. Brudzynski K (2006) Effect of hydrogen peroxide on antibacterial activities of Canadian honeys. Can J Microbiol 52(12):1228–1237

    Article  CAS  PubMed  Google Scholar 

  75. Loo AEK, Wong YT, Ho R, Wasser M, Du T, Ng WT, Halliwell B (2012) Effects of hydrogen peroxide on wound healing in mice in relation to oxidative damage. PLoS One 7(11):e49215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dart A, Bischofberger A, Dart C, Jeffcott L (2015) A review of research into second intention equine wound healing using Manuka honey: current recommendations and future applications. Equine Veterinary Edu 27(12):658–664

    Article  Google Scholar 

  77. Grainger MN, Manley-Harris M, Lane JR, Field RJ (2016) Kinetics of conversion of dihydroxyacetone to methylglyoxal in New Zealand mānuka honey: Part I–Honey systems. Food Chem 202:484–491

    Article  CAS  PubMed  Google Scholar 

  78. Majtan J (2011) Methylglyoxal—a potential risk factor of manuka honey in healing of diabetic ulcers. Evid Based Complement Altern Med 2011:295494

    Article  Google Scholar 

  79. Majtan J, Bohova J, Prochazka E, Klaudiny J (2014) Methylglyoxal may affect hydrogen peroxide accumulation in manuka honey through the inhibition of glucose oxidase. J Med Food 17(2):290–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rabie E, Serem JC, Oberholzer HM, Gaspar ARM, Bester MJ (2016) How methylglyoxal kills bacteria: an ultrastructural study. Ultrastruct Pathol 40(2):107–111

    Article  PubMed  Google Scholar 

  81. Ilyasov R, Gaifullina L, Saltykova E, Poskryakov A, Nikolaenko A (2013) Defensins in the honeybee antiinfectious protection. J Evolutionary Biochem Physiol 49(1):1–9

    Article  CAS  Google Scholar 

  82. Stewart JA, McGrane OL, Wedmore IS (2014) Wound care in the wilderness: is there evidence for honey? Wilderness Environ Med 25(1):103–110

    Article  PubMed  Google Scholar 

  83. Yaghoobi R, Kazerouni A (2013) Evidence for clinical use of honey in wound healing as an anti-bacterial, anti-inflammatory anti-oxidant and anti-viral agent: a review. Jundishapur J Natural Pharmaceut Prod 8(3):100–104

    Article  Google Scholar 

  84. Bittmann S, Luchter E, Thiel M, Kameda G, Hanano R, Längler A (2010) Does honey have a role in paediatric wound management? Br J Nurs 19(15):19

    Article  Google Scholar 

  85. Molan P (2001) Why honey is effective as a medicine: 2. The scientific explanation of its effects. Bee World 82(1):22–40

    Article  Google Scholar 

  86. Malik KI, Malik M, Aslam A (2010) Honey compared with silver sulphadiazine in the treatment of superficial partial-thickness burns. Int Wound J 7(5):413–417

    Article  PubMed  PubMed Central  Google Scholar 

  87. Alzahrani HA, Boukraâ L, Yuva Bellik FA, Bakhotmah BA, Kolayli S, Sahin H (2012) Evaluation of the antioxidant activity of three varieties of honey from different botanical and geographical origins. Glob J Health Sci 4(6):191

    Article  PubMed  PubMed Central  Google Scholar 

  88. Kishore RK, Halim AS, Syazana MN, Sirajudeen K (2011) Tualang honey has higher phenolic content and greater radical scavenging activity compared with other honey sources. Nutr Res 31(4):322–325

    Article  CAS  PubMed  Google Scholar 

  89. Chung T-W, Moon S-K, Chang Y-C, Ko J-H, Lee Y-C, Cho G, Kim S-H, Kim J-G, Kim C-H (2004) Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. The FASEB J 18(14):1670–1681

    Article  CAS  PubMed  Google Scholar 

  90. Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflamm 2007:45673

    Article  CAS  Google Scholar 

  91. Majtan J (2014) Honey: an immunomodulator in wound healing. Wound Repair Regen 22(2):187–192

    Article  PubMed  Google Scholar 

  92. Kassim M, Achoui M, Mansor M, Yusoff KM (2010) The inhibitory effects of Gelam honey and its extracts on nitric oxide and prostaglandin E 2 in inflammatory tissues. Fitoterapia 81(8):1196–1201

    Article  CAS  PubMed  Google Scholar 

  93. Nagai T, Sakai M, Inoue R, Inoue H, Suzuki N (2001) Antioxidative activities of some commercially honeys, royal jelly, and propolis. Food Chem 75(2):237–240

    Article  CAS  Google Scholar 

  94. Nayik GA, Nanda V (2016) Effect of thermal treatment and pH on antioxidant activity of saffron honey using response surface methodology. J Food Measure Characterization 10(1):64–70

    Article  Google Scholar 

  95. Beretta G, Granata P, Ferrero M, Orioli M, Facino RM (2005) Standardization of antioxidant properties of honey by a combination of spectrophotometric/fluorimetric assays and chemometrics. Analytica Chim Acta 533(2):185–191

    Article  CAS  Google Scholar 

  96. Habtemariam S (1997) Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-α in L-929 tumor cells. J Nat Prod 60(8):775–778

    Article  CAS  PubMed  Google Scholar 

  97. Kassim M, Achoui M, Mustafa MR, Mohd MA, Yusoff KM (2010) Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity. Nutr Res 30(9):650–659

    Article  CAS  PubMed  Google Scholar 

  98. Afroz R, Tanvir E, Paul S, Bhoumik NC, Gan SH, Khalil M (2016) DNA damage inhibition properties of Sundarban honey and its phenolic composition. J Food Biochem 40(4):436

    Article  CAS  Google Scholar 

  99. Downe A (2014) How wound cleansing and debriding aids management and healing. J Comm Nurs 28(4):25–29

    Google Scholar 

  100. Shukla VK (2015) Honey debridement. Skin Necrosis Springer, Wien, pp 273–275

    Google Scholar 

  101. Molan PC (2011) The evidence and the rationale for the use of honey as wound dressing. Wound Pract Res 19(4):204–220

    Google Scholar 

  102. Gannabathula S, Krissansen GW, Bisson-Rowe L, Skinner M, Steinhorn G, Schlothauer R (2017) Correlation of the immunostimulatory activities of honeys with their contents of identified bioactives. Food Chem 221:39–46

    Article  CAS  PubMed  Google Scholar 

  103. Al-Waili N, Salom K, Al-Ghamdi AA (2011) Honey for wound healing, ulcers, and burns; data supporting its use in clinical practice. Sci World J 11:766–787

    Article  Google Scholar 

  104. Gannabathula S, Krissansen GW, Skinner M, Steinhorn G, Schlothauer R (2015) Honeybee apisimin and plant arabinogalactans in honey costimulate monocytes. Food Chem 168:34–40

    Article  CAS  PubMed  Google Scholar 

  105. Chepulis LM (2007) The effects of honey compared with sucrose and a sugar-free diet on neutrophil phagocytosis and lymphocyte numbers after long-term feeding in rats. JCIM 4(1):1–7

    Article  Google Scholar 

  106. Martinotti S, Ranzato E (2015) Propolis: a new frontier for wound healing? Burns Trauma 3(1):9

    PubMed  PubMed Central  Google Scholar 

  107. Wagh VD (2013) Propolis: a wonder bees product and its pharmacological potentials. Adv Pharmacol Sci 2013:308249

    PubMed  PubMed Central  Google Scholar 

  108. Ramos A, Miranda JL (2007) Propolis: a review of its anti-inflammatory and healing actions. J Venom Anim Toxins Trop Dis 13(4):697–710

    Article  CAS  Google Scholar 

  109. De Castro S (2001) Propolis: biological and pharmacological activities. Therapeutic uses of this bee-product. Ann Rev Biomed Sci 3:49–83

    Google Scholar 

  110. Barroso PR, Lopes-Rocha R, Pereira EMF, Marinho SA, de Miranda JL, Lima NL, Verli FD (2012) Effect of propolis on mast cells in wound healing. Inflammopharmacol 20(5):289–294

    Article  Google Scholar 

  111. Hozzein WN, Badr G, Al Ghamdi AA, Sayed A, Al-Waili NS, Garraud O (2015) Topical application of propolis enhances cutaneous wound healing by promoting TGF-beta/Smad-mediated collagen production in a streptozotocin-induced type I diabetic mouse model. Cell Physiol Biochem 37(3):940–954

    Article  CAS  PubMed  Google Scholar 

  112. de Almeida EB, Cordeiro Cardoso J, de Lima AK, de Oliveira NL, de Pontes-Filho NT, Oliveira Lima S, Souza IC, de Albuquerque-Júnior RL (2013) The incorporation of Brazilian propolis into collagen-based dressing films improves dermal burn healing. J Ethnopharmacol 147(2):419–425

    Article  PubMed  CAS  Google Scholar 

  113. Jacob A, Parolia A, Pau A, Amalraj FD (2015) The effects of Malaysian propolis and Brazilian red propolis on connective tissue fibroblasts in the wound healing process. BMC Complement Altern Med 15(1):294

    Article  PubMed  PubMed Central  Google Scholar 

  114. Abreu AM, Oliveira DWD, Marinho SA, Lima NL, de Miranda JL, Verli FD (2012) Effect of topical application of different substances on fibroplasia in cutaneous surgical wounds. ISRN Dermatol 2012:282973

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Abu-Seida AM (2015) Effect of propolis on experimental cutaneous wound healing in dogs. Vet Med Int 2015:672643

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Jastrzębska-Stojko Ż, Stojko R, Rzepecka-Stojko A, Kabała-Dzik A, Stojko J (2013) Biological activity of propolis-honey balm in the treatment of experimentally-evoked burn wounds. Molecules 18(11):14397–14413

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Takzaree N, Hadjiakhondi A, Hassanzadeh G, Rouini MR, Manayi A (2016) Synergistic effect of honey and propolis on cutaneous wound healing in rats. Acta Med Iranica 54(4):233–239

    Google Scholar 

  118. Henshaw FR, Bolton T, Nube V, Hood A, Veldhoen D, Pfrunder L, McKew GL, Macleod C, McLennan SV, Twigg SM (2014) Topical application of the bee hive protectant propolis is well tolerated and improves human diabetic foot ulcer healing in a prospective feasibility study. J Diabetes Complicat 28(6):850–857

    Article  Google Scholar 

  119. Caparica-Santos C, Marcucci MC (2007) Quantitative determination of trans-10-Hydroxy-2-Decenoic Acid (10-HDA) in Brazilian royal jelly and commercial products containing royal jelly. J Apicultural Res 46(3):149–153

    Article  CAS  Google Scholar 

  120. Nagai T, Inoue R (2004) Preparation and the functional properties of water extract and alkaline extract of royal jelly. Food Chem 84(2):181–186

    Article  CAS  Google Scholar 

  121. Fujiwara S, Imai J, Fujiwara M, Yaeshima T, Kawashima T, Kobayashi K (1990) A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin. J Biol Chem 265(19):11333–11337

    Article  CAS  PubMed  Google Scholar 

  122. Kerem Z, Chetrit D, Shoseyov O, Regev-Shoshani G (2006) Protection of lipids from oxidation by epicatechin, trans-resveratrol, and gallic and caffeic acids in intestinal model systems. J Agr Food Chem 54(26):10288–10293

    Article  CAS  Google Scholar 

  123. Kramer KJ, Tager HS, Childs CN, Speirs RD (1977) Insulin-like hypoglycemic and immunological activities in honeybee royal jelly. J Insect Physiol 23(2):293–295

    Article  CAS  PubMed  Google Scholar 

  124. Kohno K, Okamoto I, Norie A, Iwaki K, Ikeda M, Kurimoto M (2004) Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Biosci Biotech Biochem 68(1):138–145

    Article  CAS  Google Scholar 

  125. Kim J, Kim Y, Yun H, Park H, Kim SY, Lee K-G, Han S-M, Cho Y (2010) Royal jelly enhances migration of human dermal fibroblasts and alters the levels of cholesterol and sphinganine in an in vitro wound healing model. Nutr Res Pract 4(5):362–368

    Article  PubMed  PubMed Central  Google Scholar 

  126. Gunaldi O, Daglioglu YK, Tugcu B, Kizilyildirim S, Postalci L, Ofluoglu E, Koksal F (2014) Antibacterial effect of royal jelly for preservation of implant-related spinal infection in rat. Turk Neurosurg 24(2):249–252

    PubMed  Google Scholar 

  127. Romanelli A, Moggio L, Montella RC, Campiglia P, Iannaccone M, Capuano F, Pedone C, Capparelli R (2011) Peptides from Royal Jelly: studies on the antimicrobial activity of jelleins, jelleins analogs and synergy with temporins. J Peptide Sci 17(5):348–352

    Article  CAS  Google Scholar 

  128. Shirzad M, Yousofi M, Zamanzad B, Sedaghat A, Hosseini M, Shahinfard N, Shirzad H (2014) Effects of royal jelly on sterile skin cut repair. J Herb Med Pharmacol 3(2):97–100

    Google Scholar 

  129. Fujii A, Kobayashi S, Kuboyama N, Furukawa Y, Kaneko Y, Ishihama S, Yamamoto H, Tamura T (1990) Augmentation of wound healing by royal jelly (RJ) in streptozotocin-diabetic rats. Jap J Pharmacol 53(3):331–337

    Article  CAS  PubMed  Google Scholar 

  130. Abdelatif M, Yakoot M, Etmaan M (2008) Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. J Wound Care 17(3):108–110

    Article  CAS  PubMed  Google Scholar 

  131. Khan S, Lari QH, Khan MA (2016) Therapeutic uses of Mom Zard (beeswax) in Unani system of medicine-a review. Int J Pharm Bio-Sci 1(1):1–4

    Google Scholar 

  132. Mendoza S, Noa M, Valle M, Mendoza N, Mas R (2013) Ameliorating effects of D-002, a mixture of beeswax alcohols, on monosodium iodoacetate-induced osteoarthritis in rats. Int J Pharm Sci Rev Res 19(1):10–15

    CAS  Google Scholar 

  133. Mendoza S, Noa M, Valle M, Mendoza N, Mas R (2013) Effects of D-002 on formaldehyde-induced osteoarthritis in rats. IOSR J Pharm 3:9–12

    Google Scholar 

  134. Moustafa A, Atiba A (2015) The effectiveness of a mixture of honey, beeswax and olive oil in treatment of canine deep second-degree burn. Glob Veterinaria 14:244–250

    CAS  Google Scholar 

  135. Fu H, Wang X-J, Lu H-F, Xu Q-W (2007) Experimental study on beeswax ointment in diabetic rabbit's model of wound healing. J Dalian Med Univ 4:003

    Google Scholar 

  136. Kroyer G, Hegedus N (2001) Evaluation of bioactive properties of pollen extracts as functional dietary food supplement. Innov Food Sci Emerging Technol 2(3):171–174

    Article  CAS  Google Scholar 

  137. Almaraz-Abarca N (2004) Variability of antioxidant activity among honeybee-collected pollen of different botanical origin. Interciencia 29(10):574–578

    Google Scholar 

  138. Campos MG, Bogdanov S, de Almeida-Muradian LB, Szczesna T, Mancebo Y, Frigerio C, Ferreira F (2008) Pollen composition and standardisation of analytical methods. J Apicultural Res 47(2):154–161

    Article  CAS  Google Scholar 

  139. Campos M, Frigerio C, Lopes J, Bogdanov S (2010) What is the future of Bee-Pollen. J ApiProd ApiMed Sci 2(4):131–144

    Article  Google Scholar 

  140. Choi EM (2007) Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract. Phytother Res 21(5):471–475

    Article  PubMed  Google Scholar 

  141. Baltrušaitytė V, Venskutonis PR, Čeksterytė V (2007) Antibacterial activity of honey and beebread of different origin against S. aureus and S. epidermidis. Food Technol Biotechnol 45(2):201–208

    Google Scholar 

  142. Erkmen O, Özcan MM (2008) Antimicrobial effects of Turkish propolis, pollen, and laurel on spoilage and pathogenic food-related microorganisms. J Med Food 11(3):587–592

    Article  CAS  PubMed  Google Scholar 

  143. Pascoal A, Rodrigues S, Teixeira A, Feás X, Estevinho LM (2014) Biological activities of commercial bee pollens: antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food Chem Toxicol 63:233–239

    Article  CAS  PubMed  Google Scholar 

  144. Bogdanov S (2014) Pollen: production, nutrition and health: a review. Bee Product Science

    Google Scholar 

  145. Kanashiro A, Souza JG, Kabeya LM, Azzolini C, Elisa A, Lucisano-Valim YM (2007) Elastase release by stimulated neutrophils inhibited by flavonoids: importance of the catechol group. Zeit Naturforsch 62(5–6):357–361

    Article  CAS  Google Scholar 

  146. Komosinska-Vassev K, Olczyk P, Kaźmierczak J, Mencner L, Olczyk K (2015) Bee pollen: chemical composition and therapeutic application. Evid Based Complement Alternat Med 2015:297425

    Article  PubMed  PubMed Central  Google Scholar 

  147. Olczyk P, Koprowski R, Kaźmierczak J, Mencner L, Wojtyczka R, Stojko J, Olczyk K, Komosinska-Vassev K (2016) Bee pollen as a promising agent in the burn wounds treatment. Evid Based Complement Alternat Med 2016:8473937

    PubMed  PubMed Central  Google Scholar 

  148. Han SM, Lee KG, Park KK, Pak SC (2013) Skin sensitization study of bee venom (Apis mellifera L.) in guinea pigs and rats. Cutan Ocul Toxicol 32(1):27–30

    Article  PubMed  Google Scholar 

  149. Vasileiadou K, Pantazidis G, Papadopoulou K, Ligoudistianou C, Kourelis A, Petrakis S, Masmanidou E, Testa T, Kourounakis A, Hadjipetrou L (2010) α1-Acid glycoprotein production in rat dorsal air pouch in response to inflammatory stimuli, dexamethasone and honey bee venom. Exp Mol Pathol 89(1):63–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Han SM, Park KK, Nicholls YM, Macfarlane N, Duncan G (2013) Effects of honeybee (Apis mellifera) venom on keratinocyte migration in vitro. Pharmacogy Mag 9(35):220–226

    Article  CAS  Google Scholar 

  151. Amin MA, Abdel-Raheem IT (2014) Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats. Arch Pharm Res 37(8):1016–1031

    Article  CAS  PubMed  Google Scholar 

  152. Han SM, Kim JM, Hong IP, Woo SO, Kim SG, Jang HR, Pak SC (2016) Antibacterial activity and antibiotic-enhancing effects of honeybee venom against methicillin-resistant staphylococcus aureus. Molecules 21(1):79

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Kocyigit A, Guler EM, Kaleli S (2016) Anti-inflammatory, antioxidant and anti-genotoxic effects of different doses of bee venom on adjuvant induce arthritis in rats. J Int Soc Antioxidants Nutr Health 3(1)

    Google Scholar 

  154. Gajski G, Čimbora-Zovko T, Rak S, Rožman M, Osmak M, Garaj-Vrhovac V (2014) Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines. J Appl Toxicol 34(12):1332–1341

    Article  CAS  PubMed  Google Scholar 

  155. Badr G, Hozzein WN, Badr BM, Al Ghamdi A, Saad Eldien HM, Garraud O (2016) Bee venom accelerates wound healing in diabetic mice by suppressing activating transcription factor-3 (ATF-3) and inducible nitric oxide synthase (iNOS)-mediated oxidative stress and recruiting bone marrow-derived endothelial progenitor cells. J Cell Physiol 231(10):2159–2171

    Article  CAS  PubMed  Google Scholar 

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Oryan, A., Alemzadeh, E. (2017). Potential Mechanisms and Application of Honeybee Products in Wound Management: Wound Healing by Apitherapy. In: Shiffman, M., Low, M. (eds) Burns, Infections and Wound Management. Recent Clinical Techniques, Results, and Research in Wounds, vol 2. Springer, Cham. https://doi.org/10.1007/15695_2017_38

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