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DOI: 10.1055/s-0033-1363229
Natural Honey: A New and Potent Anti-Angiogenic Agent in the Air-Pouch Model of Inflammation
Publikationsverlauf
received 16. Juli 2013
accepted 26. November 2013
Publikationsdatum:
19. Dezember 2013 (online)

Abstract
Despite reports indicating anti-inflammatory effects of honey, the anti-angiogenic effect of honey and its impact on inflammatory mediators in the air pouch model of inflammation have not yet been studied. The aims of present study were to investigate the effects of honey on angiogenesis, inflammatory cytokine vascular endothelial growth factor (VEGF) level as an important marker of angiogenesis and prostaglandin E2 (PGE2) in the rat air pouch model of inflammation. Male Wistar rats were anesthetized, and then 20ml and 10ml of sterile air were injected subcutaneously in the back on days 0 and 3, respectively. On day 6, inflammation was induced by injection of 1ml of carrageenan 1% into pouches. After 72h, the rats were sacrificed; pouch fluid was collected in order to determine PGE2 concentration and VEGF level. The Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using a hemoglobin kit. Honey was able to reduce granulation tissue weight and angiogenesis as well as showing potent inhibitory activities against PGE2 and VEGF in air pouch model of inflammation. The decrease in angiogenesis correlates with the inhibition of PGE2 and VEGF. Honey is potentially useful in the treatment of granulomatous inflammatory conditions. It seems that the anti-angiogenic activities of honey are mediated through modulation of PGE2 and VEGF production.
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References
- 1 Carmeliet P. Angiogenesis in health and disease. Nat Med 2003; 9: 653-660
- 2 Colville-Nash PR, Scott DL. Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications. Ann Rheum Dis 1992; 51: 919-925
- 3 Paleolog E. Angiogenesis in rheumatoid arthritis. Arthritis Res 2002; 4: S81-S90
- 4 Clavel G, Bessis N, Boissier MC. Recent data on the role for angiogenesis in rheumatoid arthritis. Joint Bone Spine: revue du rhumatisme 2003; 70: 321-326
- 5 Clavel G, Valvason C, Yamaoka K et al. Relationship between angiogenesis and inflammation in experimental arthritis. Eur Cytokine Netw 2006; 17: 202-210
- 6 Makhni E. Angiogenesis: An Examination of both Tumorigenic and Rehabilitative Properties. MURJ 2003; 8: 23-26
- 7 Kubota Y. Tumor angiogenesis and anti-angiogenic therapy. Keio J Med 2012; 61: 47-56
- 8 Esser RE, Miserendino-Molteni R, Sharr M et al. Pharmacodynamic behaviour of the selective cyclooxygenase-2 inhibitor lumiracoxib in the lipopolysaccharide-stimulated rat air pouch model. Eur J Pharm Sci 2005; 25: 25-30
- 9 Mohd Zohdi R, Abu Bakar Zakaria Z, Yusof N et al. Gelam (Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing. eCAM 2012; 843025
- 10 Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther 2002; 96: 67-202
- 11 Zumla A, Lulat A. Honey – a remedy rediscovered. J R Soc Med 1989; 82: 384-385
- 12 Chowdhury MM. Honey: is it worth rubbing it in?. J R Soc Med 1999; 92: 663
- 13 Eteraf-Oskouei T, Najafi M. Traditional and modern uses of natural honey in human diseases: A review. Iran J Basic Med Sci 2013; 16: 731-742
- 14 Medhi B, Puri A, Upadhyay S et al. Topical Application of Honey in The Treatment of Wound Healing: A Metaanalysis. Alter Med 2008; 10: 166-169
- 15 Bansal V, Medhi B, Pandhi P. Honey – a remedy rediscovered and its therapeutic utility. KUMJ 2005; 3: 305-309
- 16 Olaitan PB, Adeleke OE, Ola IO. Honey: A reservoir for microorganisms and an inhibitory agent for microbes. Afr Health Sci 2007; 7: 159-165
- 17 Evans J, Flavin S. Honey: a guide for healthcare professionals. Br J Nurs 2008; 17: S24 S26, S28-30
- 18 Ediriweera ER, Premarathna NY. Medicinal and cosmetic uses of Bee’s Honey – A review. Ayu 2012; 33: 178-182
- 19 Tonks AJ, Cooper RA, Jones KP et al. Honey stimulates inflammatory cytokine production from monocytes. Cytokine 2003; 21: 242-247
- 20 Tonks AJ, Dudley E, Porter NG et al. A 5.8-kDa component of manuka honey stimulates immune cells via TLR4. J Leukoc Biol 2007; 82: 1147-1155
- 21 Bashkaran K, Zunaina E, Bakiah S et al. Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study. BMC Complement Altern Med 2011; 11: 90
- 22 Bilsel Y, Bugra D, Yamaner S et al. Could honey have a place in colitis therapy? Effects of honey, prednisolone, and disulfiram on inflammation, nitric oxide, and free radical formation. Dig Surg 2002; 19: 306-311 discussion 311-302
- 23 Al-Waili NS, Boni NS. Natural honey lowers plasma prostaglandin concentrations in normal individuals. J Med Food 2003; 6: 129-133
- 24 Al-Waili NS. Effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individuals. J Med Food 2003; 6: 135-140
- 25 Zhang Y, Daaka Y. PGE2 promotes angiogenesis through EP4 and PKA Cgamma pathway. Blood 2011; 118: 5355-5364
- 26 Namkoong S, Lee SJ, Kim CK et al. Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells. Exp Mol Med 2005; 37: 588-600
- 27 Form DM, Auerbach R. PGE2 and angiogenesis. Proc Soc Exp Biol Med 1983; 172: 214-218
- 28 Appleton I, Brown NJ, Willis D et al. The role of vascular endothelial growth factor in a murine chronic granulomatous tissue air pouch model of angiogenesis. J Pathol 1996; 180: 90-94
- 29 Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001; 106: 148-156
- 30 Institute of Standards and Industrial Research of IRAN . Honey: Specifications and test methods. 1998 Standard Number 92, 6th revision
- 31 Wilczyńska A. phenolic content and antioxidant activity of different types of polish Honey – a short report. Pol J Food Nutr Sci 2010; 60: 309-313
- 32 Sedgwick AD, Sin YM, Edwards JC et al. Increased inflammatory reactivity in newly formed lining tissue. J Pathol 1983; 141: 483-495
- 33 Ghosh AK. Regulation by prostaglandin E2 and histamine of angiogenesis in inflammatory granulation tissue. Yakugaku Zasshi 2003; 123: 295-303
- 34 Edwards JC, Sedgwick AD, Willoughby DA. The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. J Pathol 1981; 134: 147-156
- 35 Ghosh AK, Hirasawa N, Ohtsu H et al. Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. J Exp Med 2002; 195: 973-982
- 36 English HK, Pack AR, Molan PC. The effects of manuka honey on plaque and gingivitis: a pilot study. J Int Acad Periodontol 2004; 6: 63-67
- 37 French VM, Cooper RA, Molan PC. The antibacterial activity of honey against coagulase-negative staphylococci. J Antimicrob Chemother 2005; 56: 228-231
- 38 Lin SM, Molan PC, Cursons RT. The controlled in vitro susceptibility of gastrointestinal pathogens to the antibacterial effect of manuka honey. Eur J Clin Microbiol Infect Dis 2011; 30: 569-574
- 39 Lin SM, Molan PC, Cursons RT. The in vitro susceptibility of Campylobacter spp. to the antibacterial effect of manuka honey. Eur J Clin Microbiol Infect Dis 2009; 28: 339-344
- 40 Mani R. Commentary on “the evidence supporting the use of honey as a wound dressing” by P. C. Molan. Int J Low Extrem Wounds 2006; 5: 55
- 41 Molan PC. The evidence supporting the use of honey as a wound dressing. Int J Low Extrem Wounds 2006; 5: 40-54
- 42 Molan PC. Re-introducing honey in the management of wounds and ulcers – theory and practice. Ostomy Wound Manage 2002; 48: 28-40
- 43 Molan PC, Betts JA. Clinical usage of honey as a wound dressing: an update. J Wound Care 2004; 13: 353-356
- 44 Simon A, Traynor K, Santos K et al. Medical honey for wound care – still the ‘latest resort’?. eCAM 2009; 6: 165-173
- 45 Alvarez-Suarez JM, Giampieri F, Battino M. Honey as a source of dietary antioxidants: structures, bioavailability and evidence of protective effects against human chronic diseases. Curr Med Chem 2013; 20: 621-638
- 46 Alvarez-Suarez JM, Gonzalez-Paramas AM, Santos-Buelga C et al. Antioxidant characterization of native monofloral Cuban honeys. J Agric Food Chem 2010; 58: 9817-9824
- 47 Al-Yahya M, Mothana R, Al-Said M et al. Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats. eCAM 2013; 2013: 569037
- 48 Alzahrani HA, Boukraa L, Bellik Y et al. Evaluation of the antioxidant activity of three varieties of honey from different botanical and geographical origins. Glob J Health Sci 2012; 4: 191-196
- 49 Batumalaie K, Qvist R, Yusof KM et al. The antioxidant effect of the Malaysian Gelam honey on pancreatic hamster cells cultured under hyperglycemic conditions. Clin Exp Med 2013; Online published
- 50 Escuredo O, Miguez M, Fernandez-Gonzalez M et al. Nutritional value and antioxidant activity of honeys produced in a European Atlantic area. Food Chem 2013; 138: 851-856
- 51 Fernandez-Cabezudo MJ, El-Kharrag R, Torab F et al. Intravenous administration of manuka honey inhibits tumor growth and improves host survival when used in combination with chemotherapy in a melanoma mouse model. PLoS One 2013; 8: e55993
- 52 Haza AI, Morales P. Spanish honeys protect against food mutagen-induced DNA damage. J Sci Food Agric 2013; 93: 2995-3000
- 53 Liu JR, Ye YL, Lin TY et al. Effect of floral sources on the antioxidant, antimicrobial, and anti-inflammatory activities of honeys in Taiwan. Food Chem 2013; 139: 938-943
- 54 Moniruzzaman M, Khalil MI, Sulaiman SA et al. Physicochemical and antioxidant properties of Malaysian honeys produced by Apis cerana, Apis dorsata and Apis mellifera. BMC Complement Altern Med 2013; 13: 43
- 55 Erejuwa OO, Sulaiman SA, Ab Wahab MS. Honey: A Novel Antioxidant. Molecules 2012; 17: 4400-4423
- 56 Elnaz Taheri HS-T. Phenology of Veronica beccabungal flowering in NW Iran. Int J Forest Soil Erosion 2011; 2: 74-77
- 57 Mahat M, Patil B. Evaluation of antiinflammatory activity of methanol extract of Phyllanthus amarus in experimental animal models. Indian J Pharm Sci 2007; 69: 33-36
- 58 Sato K, Komatsu N, Higashi N et al. Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1. Clin Immunol 2005; 115: 47-50
- 59 Alizadeh AM, Sohanaki H, Khaniki M et al. The effect of teucrium polium honey on the wound healing and tensile strength in rat. Iran J Basic Med Sci 2011; 14: 499-505
- 60 Owoyele BV, Adenekan OT, Soladoye AO. Effects of honey on inflammation and nitric oxide production in Wistar rats. J Chin Integr Med 2011; 9: 447-452
- 61 Ghosh AK, Hirasawa N, Niki H et al. Cyclooxygenase-2-mediated angiogenesis in carrageenin-induced granulation tissue in rats. J Pharmacol Exp Ther 2000; 295: 802-809
- 62 Nakanishi M, Rosenberg DW. Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol 2013; 35: 123-137
- 63 Chung HJ, Lee HS, Shin JS et al. Modulation of acute and chronic inflammatory processes by a traditional medicine preparation GCSB-5 both in vitro and in vivo animal models. J Ethnopharmacol 2010; 130: 450-459
- 64 Dai ZJ, Ma XB, Kang HF et al. Antitumor activity of the selective cyclooxygenase-2 inhibitor, celecoxib, on breast cancer in Vitro and in Vivo. Cancer Cell Int 2012; 12: 53
- 65 Kassim M, Achoui M, Mansor M et al. The inhibitory effects of Gelam honey and its extracts on nitric oxide and prostaglandin E(2) in inflammatory tissues. Fitoterapia 2010; 81: 1196-1201
- 66 Jiang F, Dusting GJ. Natural phenolic compounds as cardiovascular therapeutics: potential role of their antiinflammatory effects. Curr Vasc Pharmacol 2003; 1: 135-156
- 67 Costa G, Francisco V, Lopes MC et al. Intracellular signaling pathways modulated by phenolic compounds: application for new anti-inflammatory drugs discovery. Curr Med Chem 2012; 19: 2876-2900
- 68 Abubakar MB, Abdullah WZ, Sulaiman SA et al. A review of molecular mechanisms of the anti-leukemic effects of phenolic compounds in honey. Int J Mol Sci 2012; 13: 15054-15073
- 69 Feas X, Iglesias A, Rodrigues S et al. Effect of Erica sp. Honey against Microorganisms of Clinical Importance: Study of the Factors Underlying this Biological Activity. Molecules 2013; 18: 4233-4246
- 70 Khalil MI, Alam N, Moniruzzaman M et al. Phenolic acid composition and antioxidant properties of Malaysian honeys. J Food Sci 2011; 76: C921-C928
- 71 Oelschlaegel S, Gruner M, Wang PN et al. Classification and characterization of manuka honeys based on phenolic compounds and methylglyoxal. J Agric Food Chem 2012; 60: 7229-7237
- 72 Naldini A, Carraro F. Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy 2005; 4: 3-8
- 73 Ribatti D, Crivellato E. Immune cells and angiogenesis. J Cell Mol Med 2009; 13: 2822-2833
- 74 Crivellato E, Ribatti D. Involvement of mast cells in angiogenesis and chronic inflammation. Curr Drug Targets Inflamm Allergy 2005; 4: 9-11
- 75 Rossiter K, Reid PD, Lwaleed BA et al. Honey and angiogenesis. 1st International Conference on the Medicinal Uses of Honey. Malays J Med Sci 2007; 14: 125
- 76 Rossiter K, Cooper AJ, Voegeli D et al. Honey promotes angiogeneic activity in the rat aortic ring assay. J Wound Care 2010; 19: 440 442–446
- 77 Norrby K. In vivo models of angiogenesis. J Cell Mol Med 2006; 10: 588-612
- 78 Szekanecz Z, Koch AE. Targeting Angiogenesis in Rheumatoid Arthritis. Curr Rheumatol Rev 2008; 4: 298-303
- 79 Lu J, Kasama T, Kobayashi K et al. Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis. J Immunol 2000; 164: 5922-5927
- 80 Oak MH, El Bedoui J, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. The Journal of nutritional biochemistry 2005; 16: 1-8
- 81 Miyazawa T, Tsuzuki T, Nakagawa K et al. Antiangiogenic potency of vitamin E. Ann N Y Acad Sci 2004; 1031: 401-404