The anti-inflammatory and wound healing properties of honey

European Food Research and Technology

Volumn 239, Issue 6, 2014, Pages 1003-1014

  Hadagali, Manjunatha Devagondanahalli ^a   Chua, Lee Suan ^a  

^a UNIVERSITI TEKNOLOGI MALAYSIA   (Malaysia)

Author keywords

Anti inflammatory activity; Honey; Mechanism of action; Side effects; Wound healing

Indexed keywords

BIOACTIVITY; DIETARY SUPPLEMENTS; MEDICAL APPLICATIONS; TISSUE REGENERATION;

ANTI-INFLAMMATORY ACTIVITY; HONEY; MECHANISM OF ACTION; SIDE EFFECT; WOUND HEALING;

FOOD PRODUCTS;

EID: 84911988353     PISSN: 14382377     EISSN: 14382385     Source Type: Journal    
DOI: 10.1007/s00217-014-2297-6     Document Type: Article

References (128)

1. Cooper R, Gray D (2012) Is manuka honey a credible alternative to silver in wound care? Wounds UK 8:54–64
2. Fatemeh SR, Akram B, Amir AZ, Younes S (2014) The effect of honey-impregnated human placenta membrane on burn wound healing in rat. Comp Clin Pathol. doi:10.1007/s00580-014-1887-9
3. Thomas KE (2014) Honey in the treatment of periodontitis. Int J Pharm Bio Sci 5:B315–B318
4. Gheldof N, Engeseth NJ (2002) Antioxidant capacity of honeys from various floral sources based on the determination of oxygen radical absorbance capacity and inhibition of in vitro lipoprotein oxidation in human serum samples. J Agric Food Chem 50:3050–3055
5. Lansing P, John PH, Donald AK (1999) Microbiology, 4th Edition, International edn. WCB/McGraw-Hill, Boston
6. Shapiro RL, Hatheway C, Swerdflow DL (1998) Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med 129:221–228
7. Effendy NM, Mohamed N, Muhammad N, Mohamad IN, Shuid AN (2012) The effects of tualang honey on bone metabolism of postmenopausal women. Evid-Based Compl Alt Med Article ID 938574, 7 pages, doi:10.1155/2012/938574
8. Ahmed S, Othman NH (2013) Review of the medicinal effects of tualang honey and a comparison with manuka honey. Malays J Med Sci 20:6–13
9. Markovic V, Nikolic I, Binjovic V (2012) Biološka aktivnost i medicinska upotreba meda (Biological activity and medical use of honey). Medicinski Casopis 46:221–226
10. Patel DK, Patel K, Gadewar M, Tahilyani V (2012) Pharmacological and bioanalytical aspects of galangin-a concise report. Asian Pac J Tropical Biomed 2:S449–S455
11. Eteraf-Oskouei T, Najafi M (2013) Traditional and modern uses of natural honey in Human diseases: a review. Iran J Basic Med Sci 16:731–742
12. Stewart JA, McGrane OL, Wedmore IS (2014) Wound care in the wilderness: is there evidence for honey? Wilder Environ Med 25:103–110
13. Jull AB, Walker N, Deshpande S (2013) Honey as a topical treatment for wounds Cochrane Database Syst Rev 2. doi:10.1002/14651858CD005083pub3
14. Vandamme L, Heyneman A, Hoeksema H, Verbelen J, Monstrey S (2013) Honey in modern wound care: a systematic review. Burns 39:1514–1525
15. Ferrero ML, Nielsen OH, Andersen PS, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Cli Exp Immunol 147:227–235
16. Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF (2007) Impaired wound healing. Clin Dermatol 25:19–25
17. Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ, Schreiber R, Mark TW, Bloom BR (1995) Tumor necrosis factor-α is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2:561–572
18. Kingsley A (2002) Wound healing and potential therapeutic options. Prof Nurse 17:539–544
19. Martos I, Ferreres F, Yao L, D’Arcy B, Caffin N, Tomas-Barberan FA (2000) Flavonoids in monospecific Eucalyptus honeys from Australia. J Agric Food Chem 48:4744–4748
20. Benhanifia MB, Boukraâ L, Hammoudi SM, Sulaiman SA, Manivannan L (2011) Recent patents on topical application of honey in wound and burn management. Recent Pat Inflam Aller Drug Disc 5:81–86
21. Song JJ, Salcido R (2011) Use of honey in wound care: an update. Adv Skin Wound Care 24:40–44
22. Efem S (1993) Recent advances in the management of Fournier’s gangrene: preliminary observations. Surgery 113:200–204
23. Subrahmanyam M (1996) Honey dressing versus boiled potato peel in the treatment of burns: a prospective randomized study. Burns 22:491–493
24. Subrahmanyam M (1998) A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine. Burns 24:157–161
25. ®) in the treatment of burns-a prospective randomised study. Br J Plast Surg 46:322–323
26. Al-Waili Haq A (2004) Effect of honey on antibody production against thymus-dependent and thymus-independent antigens in primary and secondary immune responses. J Med Food 7:491–494
27. Alcaraz A, Kelly J (2002) Treatment of an infected venous leg ulcer with honey dressings. Br J Nurs 11:859–860
28. Ahmed AK, Hoekstra MJ, Hage JJ, Karim BB (2003) Honey-medicated dressing: transformation of an ancient remedy into modern therapy. Ann Plast Surg 50:143–148
29. Al-Waili NS, Saloom KY (1999) Effects of topical honey on post-operative wound infections due to gram positive and gram negative bacteria following caesarean sections and hysterectomies. Eur J Med Res 4:126–130
30. Dunford C, Cooper R, Molan PC (2000) Using honey as a dressing for infected skin lesions. Nurs Times 96(14):7–9
31. Dunford C, Cooper R, Molan PC, White R (2000) The use of honey in wound management. Nurs Stand 15:63–68
32. Oryan A, Zaker SR (1998) Effects of topical application of honey on cutaneous wound healing in rabbits. J Vet Med Series A 45:181–188
33. Esmon CT (2004) Crosstalk between inflammation and thrombosis. Maturitas 47:305–314
34. Al-Waili NS, Boni NS (2003) Natural honey lowers plasma prostaglandin concentrations in normal individuals. J Med Food 6:129–133
35. Molan PC (1999) The role of honey in the management of wounds. J Wound Care 8:415–418
36. Alzubier AA, Okechukwu PN (2011) Investigation of anti-inflammatory, antipyretic and analgesic effect of yemeni sidr honey. World Aca Sci Eng Tech 80:47–52
37. Kassim M, Mansor M, Al-Abd N, Yusoff KM (2012) Gelam honey has a protective effect against lipopolysaccharide (LPS)-induced organ failure. Intl J Mol Sci 13:6370–6381
38. Kassim M, Mansor M, Suhaimi A, Ong G, Yusoff KM (2012) Gelam honey scavenges peroxynitrite during the immune response. Intl J Mol Sci 13:12113–12129
39. Keenan JI, Salm N, Wallace AJ, Hampton MB (2012) Using food to reduce H pylori-associated inflammation. Phytother Res 26:1620–1625
40. Prakash A, Medhi B, Avti PK, Saikia UN (2008) Effect of different doses of manuka honey in experimentally induced inflammatory bowel disease in rats. Phytother Res 22:1511–1519
41. Karuppannan B, Embong Z, Shaharuddin B, Siti AS, Sirajudeen KNS, Venkatesh N (2011) Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study. BMC Compl Alt Med 11:90–101
42. Nasuti C, Gabbianelli R, Falcioni G, Cantalamessa F (2006) Antioxidative and gastroprotective activities of anti: inflammatory formulations derived from chestnut honey in rats. Nutr Res 26:130–137
43. van den Berg A, van den Worm E, van Ufford HC, Halkes SB, Hoekstra MJ, Beukelman CJ (2008) An in vitro examination of the antioxidant and anti-inflammatory properties of buckwheat honey. J Wound Care 17:172–178
44. Kassim M, Yusoff KM, Ong G, Sekaran S, Yusof MYBM, Mansor M (2012) Gelam honey inhibits lipopolysaccharide-induced endotoxemia in rats through the induction of heme oxygenase-1 and the inhibition of cytokines, nitric oxide, and high-mobility group protein B1. Fitoterapia 83:1054–1059
45. Liu JR, Ye YL, Lin TY, Wang YW, Peng CC (2013) Effect of floral sources on the antioxidant, antimicrobial, and anti-inflammatory activities of honeys in Taiwan. Food Chem 139:938–943
46. Chepulis LM, Francis E (2012) An initial investigation into the anti inflammatory activity and antioxidant capacity of alpha-cyclodextrin-complexed manuka honey. J Compl Integrat Med (Article 25) 9:1–14
47. 2induced oxidative and inflammatory responses in human middle ear epithelial cells. Intl J Pediatric Otorhinolaryngol 76:675–679
48. Al-Malki1 AL, Sayed AAR (2013) Bees’ honey attenuation of metanil-yellow-induced hepatotoxicity in rats. Evid-Based Compl Alt Med Article ID 614580, 9 pages doi:10.1155/2013/614580
49. Ahmad A, Khan RA, Mesaik MA (2009) Anti-inflammatory effect of natural honey on bovine thrombin-induced oxidative burst in phagocytes. Phytother Res 23:801–808
50. Zare A, Ahmadi M, Hedayat A (2007) Study on anti-inflammatory effect of subcutaneous honey bee venom injection and dermal application of cream containing honey bee venom in adjuvant-induced arthritic rats. Arch Razi Inst 62:223–227
51. Gao HM, Hong JS (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29:357–365
52. Lull ME, Block ML (2010) Microglial activation and chronic neurodegeneration. Neurotherapeutics 7:354–365
53. Candiracci M, Piatti E, Barragán MD, Antrás DGB, Morgado D, Ruano JF, Gutiérrez J, Parrado J, Castaño A (2012) Anti-inflammatory activity of a honey flavonoid extract on lipopolysaccharide-activated N13 microglial cells. J Agric Food Chem 60:12304–12311
54. Bean A (2012) Thesis: investigating the anti-inflammatory activity of honey
55. 2in inflammatory tissues. Fitoterapia 81:1196–1201
56. Reth M (2002) Hydrogen peroxide as second messenger in lymphocyte activation. Nat Immunol 3:1129–1134
57. Reichner JS, Meszaros AJ, Louis CA, Henry WL Jr, Mastrofrancesco B, Martin BA, Albina JE (1999) Molecular and metabolic evidence for the restricted expression of inducible nitric oxide synthase in healing wounds. Am J Pathol 154:1097–1104
58. Tonks A, Cooper R, Price AJ, Molan PC, Jones KP (2001) Stimulation of TNF-alpha release in monocytes by honey. Cytokine 14:240–242
59. Kassim M, Achoui M, Mustafa MR, Mohd MA (2010) Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti–inflammatory activity. Nutr Res 30:650–659
60. Henriques A, Jackson S, Cooper R, Burton N (2006) Free radical production and quenching in honeys with wound healing potential. J Antimicrob Chemother 58:773–777
61. Mesaik MA, Azim MK, Mohiuddin S (2008) Honey modulates oxidative burst of professional phagocytes. Phytother Res 22:1404–1408
62. Molan PC (2011) The evidence and the rationale for the use of honey as a wound dressing. Wound Pract Res 19:204–220
63. Leong AG, Herst PM, Harper JL (2012) Indigenous New Zealand honeys exhibit multiple anti-inflammatory activities. Innate Immun 18:459–466
64. Hussein SZ, Mohd Yusoff K, Makpol S, Mohd Yusof YA (2012) Gelam honey inhibits the production of proinflammatory, mediators NO, PGE(2), TNF-α, and IL-6 in carrageenan-induced acute paw edema in rats. Evid Based Compl Alt Med (Article ID 109636), 1–12
65. Majtan J, Bohova J, Garcia-Villalba R, Tomas-Barberan FA, Madakova Z, Majtan T, Majtan V, Klaudiny J (2013) Fir honeydew honey flavonoids inhibit TNF-a-induced MMP-9 expression in human keratinocytes: a new action of honey in wound healing. Arch Dermatol Res 305:619–627
66. Bashkaran K, Zunaina E, Bakiah S, Sulaiman SA, Sirajudeen K, Naik V (2011) Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study. BMC Compl Alt Med 11:90
67. Ha SK, Moon E, Kim SY (2010) Chrysin suppresses LPS-stimulated proinflammatory responses by blocking NF-kB and JNK activations in microglia cells. Neurosci Lett 485:143–147
68. Woo KJ, Jeong YJ, Inoue H, Park JW, Kwon TK (2005) Chrisin suppresses lipopolysaccharide-induced cycloooxygenase-2 expression through the inhibition of nuclear factor for IL-6 (NF-IL-6) DNA-binding activity. FEBS Lett 579:705–711
69. Palmieri D, Perego P, Palombo D (2012) Apigenin inhibits the TNFa-induced expression of eNOS and MMP-9 via modulating Akt signalling through oestrogen receptor engagement. Mol Cell Biochem 371:129–136
70. Yang H, Liu Q, Ahn JH, Kim SB, Kim YC, Sung SH, Hwang BY, Lee MK (2012) Luteolin down regulates IL-1b-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signaling pathway. J Enzyme Inhib Med Chem 27:261–266
71. Li DL, Zheng QC, Fang XX, Ji HT, Yang JG, Zhang HX (2009) Theoretical study on potency and selectivity of novel nonpeptide inhibitors of matrix metalloproteinases MMP-2 and MMP-9. J Theor Comp Chem 8:491–506
72. Barbosa NS, Kalaaji AN (2014) CAM use in dermatology Is there a potential role for honey, green tea, and vitamin C? Complement Ther Clin Pract 20:11–15
73. Knottenbelt DC (2014) Honey in wound management: myth, mystery, magic or marvel? Vet J 199:5–6
74. Carnwath R, Graham EM, Reynolds K, Pollock PJ (2014) The antimicrobial activity of honey against common equine wound bacterial isolates. Vet J 199:110–114
75. Mohamed H, El Lenjawi B, Salma MA, Abdi S (2014) Honey based therapy for the management of a recalcitrant diabetic foot ulcer. J Tissue Viability 23:29–33
76. Nicoara CD, Singh M, Jester I, Reda B, Parikh DH (2014) Medicated Manuka honey in conservative management of exomphalos major. Pediatr Surg Intl 30:515–520
77. Kingsley A (2001) The use of honey in the treatment of infected wounds: case studies. Br J Nurs 10:s13–s20
78. Nychas GJ, Dillon VM, Board RG (1988) Glucose, the key substrate in the microbiological changes in meat and certain meat products. Biotechnol Appl Biochem 10:203–231
79. Natarajan S, Williamson D, Grey J, Harding KG, Cooper RA (2001) Healing of an MRSA-colonised, hydroxyurea-induced leg ulcer with honey. J Dermatol Treat 12:33–36
80. Evans J, Mahoney K (2013) Efficacy of medical-grade honey as an autolytic debridement agent. Wounds UK 9:30–36
81. Cullen B, Smith R, McCulloch E, Silcock D, Morrison L (2002) Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen 10:16–25
82. Edwards JV, Howley P, Cohen IK (2004) In vitro inhibition of human neutrophil elastase by oleic acid albumin formulations from derivatized cotton wound dressings. Intl J Pharmacol 284:1–12
83. Maghsoudi H, Moradi S (2014) Honey: a skin graft fixator convenient for both patient and surgeon. Indian J Surg. doi:10.1007/s12262-014-1039-0
84. Terrab A, Gonzalez AG, Diez MJ, Heredia FJ (2003) Characterisation of Moroccan unifloral honeys using multivariate analysis. Eur Food Res Tech 218:88–95
85. Weston JS (2002) Treatment of gram-positive infections: past, present, and future. Crit Care Nurs Clin North Am 14:17–29
86. Bang LM, Buntting C, Molan PC (2003) The effect of dilution on the rate of hydrogen peroxide production in honey and its implications for wound healing. J Alt Compl Med 9:267–273
87. Adams CJ, Boult CH, Deadman BJ, Farr JM, Grainger MNC, Manley-Harris M, Snow MJ (2008) Isolation by HPLC and characterisation of the bioactive fraction of New Zealand manuka (Leptospermum scoparium) honey. Carbohydr Res 343:651–659
88. Mavric E, Wittmann S, Barth G, Henle T (2008) Identification and quantification of methylglyoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honey from New Zealand. Mol Nutr Food Res 52:483–489
89. Antinelli JF, Zeggane S, Dav IR, Rognone C, Faucon JP, Lizzani L (2003) Evaluation of (E)-10-hydroxy dec-2-enoic acid as a freshness parameter for royal jelly. Food Chem 80:85–89
90. Boselli E, Caboni MF, Sabatini AG, Marcazzan GL, Lercker G (2003) Determination and changes of free amino acids in royal jelly during storage. Apidologie 34:129–137
91. Simuth J (2001) Some properties of the main protein of honeybee (Apis mellifera) royal jelly. Apidologie 32:69–80
92. Albert S, Klaudiny J (2004) The MRJP/YELLOW protein family of Apis mellifera: identification of new members in the EST library. J Insect Physiol 50:51–59
93. Keizo K, Iwao O, Osamu S, Norie A, Kanso I, Masao I, Masashi K (2004) Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Biosci Biotech Biochem 68:138–145
94. Majtan J, Kovacova E, Bilikova K, Simuth J (2006) The immunostimulatory effect of the recombinant apalbumin 1-major honeybee royal jelly protein-on TNFalpha release. Intl Immunopharmacol 6:269–278
95. Nagai T, Inoue R (2004) Preparation and the functional properties of water extract and alkaline extract of royal jelly. Food Chem 84:181–186
96. Mohamed FR, Ahmed AG (2012) Bioactive compounds and health-promoting properties of royal jelly: a review. J Funct Foods 4:39–52
97. Gheldof N, Wang XH, Engeseth NJ (2003) Buckwheat honey increases serum antioxidant capacity in humans. J Agric Food Chem 51:1500–1505
98. Schramm DD, Karim M, Schrader HR, Holt RR, Cardetti M, Keen CL (2003) Honey with high levels of antioxidants can provide protection to healthy human subjects. J Agric Food Chem 51:1732–1735
99. Buntting C (2001) Thesis the production of hydrogen peroxide by honey and its relevance to wound healing. University of Waikato, New Zealand
100. Grimble GF (1994) Nutritional antioxidants and the modulation of inflammation: theory and practice. New Horiz 2:175–185
101. Murrell GAC, Francis MJO, Bromley L (1990) Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 265:659–665
102. Schreck R, Rieber P, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J 10:2247–2258
103. Tanaka H, Hanumadass M, Matsuda H, Shimazaki S, Walter RJ, Matsuda T (1995) Hemodynamic effects of delayed initiation of antioxidant therapy (beginning two hours after burn) in extensive third-degree burns. J Burn Care Rehabil 16:610–615
104. Kilicoglu B, Gencay C, Kismet K, Serin KS, Erguder I, Erel S, Sunay AE, Erdemli E, Durak I, Akkus MA (2008) The ultrastructural research of liver in experimental obstructive jaundice and effect of honey. Am J Surg 195:249–256
105. Korkmaz A, Kolankaya D (2009) Anzer honey prevents N-ethylmaleimide-induced liver damage in rats. Exp Toxicol Pathol 61:333–337
106. Peake JM, Suzuki K, Coombes JS (2007) The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise. J Nutr Biochem 18:357–371
107. Bilsel Y, Bugra D, Yamaner S, Bulut T, Cevikbas U, Turkoglu U (2002) Could honey have a place in colitis therapy? Effects of honey, prednisolone and disulfiram on inflammation, nitric oxide and free radical formation. Digest Surg 19:306–311
108. Owoyele BV, Adenekan OT, Soladoye AO (2011) Effects of honey on inflammation and nitric oxide production in Wistar rats. J Chin Integr Med 9:447–452
109. Erejuwa OO, Sulaiman SA, Ab Wahab MS (2012) Honey: a novel antioxidant. Molecules 17:4400–4423
110. Lusby PE, Combes AL, Wilkinson JM (2002) Honey: a potential agent for wound healing? J WOCN 29:296–300
111. Irish J, Blair S, Carter DA (2011) The antibacterial activity of honey derived from Australian flora. PLoS ONE 6:e18229
112. Brudzynski K (2006) Effect of hydrogen peroxide on antibacterial activities of Canadian honeys. Can J Microbiol 52:1228–1237
113. Mundo MA, Padilla-Zakour OI, Worobo RW (2004) Growth inhibition of food borne pathogens and food spoilage organisms by select raw honeys. Intl J Food Microbiol 97:1–8
114. Taormina PI, Niemira BA, Beuchat LR (2001) Inhibitory activity of honey against food borne pathogens as influenced by the presence of hydrogen peroxide and level of antioxidant power. Intl J Food Microbiol 69:217–225
115. Aljadi AM, Yusoff KM (2003) Isolation and identification of phenolic acids in Malaysian honey with antibacterial properties. Turkish J Med Sc 33:229–236
116. Brudzynski K, Miotto D (2011) Honey melanoidins: analysis of a composition of the high molecular weight melanoidin fractions exhibiting radical scavenging capacity. Food Chem 127:1023–1030
117. Kwakman PHS, de Boer L, Ruyter-Spira CP, Creemers-Molenaar T, Helsper LPFG, Vandenbroucke-Grauls CMJE (2011) Medical-grade honey enriched with antimicrobial peptide has enhanced activity against antibiotic resistant pathogens. Eur J Clin Microbiol Infect Dis 30:251–257
118. 2-induced oxidative effect on bacterial cell growth and on DNA degradation. Food Chem 133:329–336
119. Tatnall FM, Leigh IM, Gibson JR (1991) Assay of antiseptic agents in cell culture: conditions affecting cytotoxicity. J Hosp Infect 17:287–296
120. Poon VK, Burd A (2004) In vitro cytotoxity of silver: implication for clinical wound care. Burns 30:140–147
121. Al-Swayeh OA, Ali ATM (1998) Effect of ablation of capsaicin-sensitive neurons on gastric protection by honey and sucralfate. Hepato-Gastroenterol 45:297–302
122. Oluwatosin OM, Olabanji JK, Oluwatosin OA, Tijani LA, Onyechi HU (2000) A comparison of topical honey and phenytoin in the treatment of chronic leg ulcers. Afr J Med Sci 29:31–34
123. Misirlioglu A, Eroglu S, Karacaoglan N, Akan M, Akoz T, Yildirim S (2003) Use of honey as an adjunct in the healing of split-thickness skin graft donor site. Dermatol Surg 29:168–172
124. Molan PC (2006) The evidence supporting the use of honey as a wound dressing. Intl J Low Extrem Wounds 5:40–54
125. Al-Waili N (2005) Mixture of honey, beeswax and olive oil inhibits growth of Staphylococcus aureus and Candida albicans. Arch Med Res 36:10–13
126. Dunford CE, Hanano R (2004) Acceptability to patients of a honey dressing for non-healing venous leg ulcers. J Wound Care 13:193–197
127. Caya JG, Agni R, Miller JE (2004) Clostridium botulinum and the clinical laboratorian: a detailed review of botulism, including biological warfare ramifications of botulinum toxin. Arch Pathol Lab Med 128:653–662
128. Arnon SS, Midura TF, Damus K, Thompson B, Wood RM, Chin J (1979) Honey and other environmental risk factors for infant botulism. J Pediatr 94:331–336