A review of selected bee products as potential anti-bacterial, anti-fungal, and anti-viral agents
Main Article Content
Abstract
Antimicrobial resistance (AMR) is one of the greatest medical challenges the world faces. It was estimated recently that by 2050, AMR will account for 10 million extra deaths annually with additional economic costs in the region of $100 trillion. In order to combat this, novel antimicrobial agents with a broad spectrum of activity are required. Bee products, including; honey, propolis, defensins, royal jelly, bee pollen and venom have been used to treat infectious diseases for several centuries, although they were largely disregarded by Western medicine during the antibiotic era. There has since been a resurgence in interest in their antimicrobial properties, especially due to their reported activity against multi-drug resistant pathogens displaying high levels of AMR. In this paper we review the current scientific literature of honey, propolis, honey bee, defensins, royal jelly, bee pollen and bee venom. We highlight the antimicrobial activity each of these products has displayed and potential future research directions.
Article Details
How to Cite
BROWN, Helen , Louise et al.
A review of selected bee products as potential anti-bacterial, anti-fungal, and anti-viral agents.
Medical Research Archives, [S.l.], v. 4, n. 8, dec. 2016.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/887>. Date accessed: 20 apr. 2024.
Keywords
Honey, propolis, bee venom, defensins, antimicrobial, antimicrobial resistance, bee products, royal jelly
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1 Atiba, A. et al. Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-beta and fibroblast growth factor production. The American Journal of Surgery 201, 809-818, doi:10.1016/j.amjsurg.2010.06.017 (2011).
2 Abu-Al-Basal, M. A. Healing potential of Rosmarinus officinalis L. on full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice. Journal of Ethnopharmacology 131, 443-450 (2010).
3 Zhao, L., La, V. D. & Grenier, D. Antibacterial, antiadherence, antiprotease, and anti-inflammatory activities of various tea extracts: potential benefits for periodontal diseases. Journal of medicinal food 16, 428-436 (2013).
4 Harris, J. C., Cottrell, S. L., Plummer, S. & Lloyd, D. Antimicrobial properties of Allium sativum (garlic). Applied Microbiology and Biotechnology 57, 282-286 (2001).
5 Saurav, K. et al. In search of alternative antibiotic drugs: Quorum-quenching activity in sponges and their bacterial isolates. Frontiers in Microbiology 7, 416, doi:10.3389/fmicb.2016.00416 (2016).
6 Cazander, G. et al. Maggot excretions affect the human complement system. Wound Repair and Regeneration 20, 879-886, doi:10.1111/j.1524-475X.2012.00850.x (2012).
7 Mansourian, A., Boojarpour, N., Ashnagar, S., Momen Beitollahi, J. & Shamshiri, A. R. The comparative study of antifungal activity of Syzygium aromaticum, Punica granatum and nystatin on Candida albicans; an in vitro study. Journal of Medical Mycology 24, e163-168, doi:10.1016/j.mycmed.2014.07.001 (2014).
8 Hashemipour, M. A., Tavakolineghad, Z., Arabzadeh, S. A., Iranmanesh, Z. & Nassab, S. A. Antiviral activities of honey, royal jelly, and Acyclovir against HSV-1. Wounds : a compendium of clinical research and practice 26, 47-54 (2014).
9 McGrath, L. J., Becker-Dreps, S., Pate, V. & Brookhart, M. A. Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000-2011. PLoS One 8, e81210, doi:10.1371/journal.pone.0081210
PONE-D-13-29268 [pii] (2013).
10 Martin, D. R., Heffernan, H. M. & Davies, H. G. Methicillin-resistant Staphylococcus aureus: an increasing threat in New Zealand hospitals. New Zealand Medical Journal 102, 367-369 (1989).
11 Kam, K. M. et al. Emergence of multiple-antibiotic-resistant Streptococcus pneumoniae in Hong Kong. Antimicrobial Agents and Chemotherapy 39, 2667-2670 (1995).
12 Filius, P. M. & Gyssens, I. C. Impact of increasing antimicrobial resistance on wound management. American Journal of Clinical Dermatology 3, 1-7, doi:030101 [pii] (2002).
13 Hwang, A. Y. & Gums, J. G. The emergence and evolution of antimicrobial resistance: Impact on a global scale. Bioorganic & Medicinal Chemistry doi:S0968-0896(16)30261-9 [pii]
10.1016/j.bmc.2016.04.027 (2016).
14 Fischbach, M. A. & Walsh, C. T. Antibiotics for Emerging Pathogens. Science 325, 1089-1093, doi:10.1126/science.1176667 (2009).
15 Bragginton, E. C. & Piddock, L. J. UK and European Union public and charitable funding from 2008 to 2013 for bacteriology and antibiotic research in the UK: an observational study. Lancet Infect Dis 14, 857-868, doi:S1473-3099(14)70825-4 [pii]
10.1016/S1473-3099(14)70825-4 (2014).
16 O'Neill, A. J. Tackling a global health crisis:initial steps. 1-21 (London, 2015).
17 Huttner, A. et al. Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum. Antimicrobial Resistance and Infection Control 2, 31, doi:10.1186/2047-2994-2-31
2047-2994-2-31 [pii] (2013).
18 Marc, C. et al. Inappropriate prescription of antibiotics in pediatric practice: Analysis of the prescriptions in primary care. Journal of Child Health Care, doi:1367493516643421 [pii]
10.1177/1367493516643421 (2016).
19 Lima, S. I. et al. Rationality of antimicrobial prescriptions in community pharmacy users. PLoS One 10, e0141615, doi:10.1371/journal.pone.0141615
PONE-D-15-30906 [pii] (2015).
20 Falagas, M. E. et al. Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria. BMC Infectious Diseases 5, 24, doi:1471-2334-5-24 [pii]
10.1186/1471-2334-5-24 (2005).
21 Bathoorn, E. et al. Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call. Journal of Antimicrobial Chemotherapy 71, 1207-1212, doi:dkv467 [pii]
10.1093/jac/dkv467 (2016).
22 Vilacoba, E. et al. Widespread dispersion of the resistance element tet(B)::ISCR2 in XDR Acinetobacter baumannii isolates. Epidemiology & Infection 144, 1574-1578, doi:S0950268815002897 [pii]
10.1017/S0950268815002897 (2016).
23 Weterings, V. et al. An outbreak of colistin-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the Netherlands (July to December 2013), with inter-institutional spread. European Journal of Clinical Microbiology & Infectious Diseases 34, 1647-1655, doi:10.1007/s10096-015-2401-2
10.1007/s10096-015-2401-2 [pii] (2015).
24 Iyamba, J. M., Wambale, J. M., Lukukula, C. M. & za Balega Takaisi-Kikuni, N. High prevalence of methicillin resistant staphylococci strains isolated from surgical site infections in Kinshasa. Pan African Medical Journal 18, 322, doi:10.11604/pamj.2014.18.322.4440
PAMJ-18-322 [pii] (2014).
25 Kulkova, N., Babalova, M., Sokolova, J. & Krcmery, V. First report of New Delhi metallo-beta-lactamase-1-producing strains in Slovakia. Microbial Drug Resistance 21, 117-120, doi:10.1089/mdr.2013.0162 (2015).
26 O'Neill, A. J. Reveiw on antimicrobial resistance, tackling drug resistant infections globally. Infection prevention, control and surveillence: limiting the development and spread of drug resistance 1-32 (London, 2016).
27 Smith, R. & Coast, J. The true cost of antimicrobial resistance. BMJ 346, f1493 (2013).
28 Pfeffer, I. et al. Prevalence and risk factors for carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae among patients prior to bowel surgery. Diagnostic Microbiology and Infectious Disease doi:S0732-8893(16)30078-5 [pii]
10.1016/j.diagmicrobio.2016.04.002 (2016).
29 Getzlaf, M. A. et al. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. Journal of Orthopaedic Research 34, 177-186, doi:10.1002/jor.23068 (2016).
30 Zhang, H. et al. Melittin restores PTEN expression by down-regulating HDAC2 in human hepatocelluar carcinoma HepG2 cells. PLoS One 9, e95520, doi:10.1371/journal.pone.0095520
PONE-D-14-04193 [pii] (2014).
31 Maddocks, S. E., Jenkins, R. E., Rowlands, R. S., Purdy, K. J. & Cooper, R. A. Manuka honey inhibits adhesion and invasion of medically important wound bacteria in vitro. Future Microbiology 8, 1523-1536, doi:10.2217/fmb.13.126 (2013).
32 Tonks, A. J. et al. Honey stimulates inflammatory cytokine production from monocytes. Cytokine 21, 242-247, doi:S1043466603000929 [pii] (2003).
33 Jenkins, R., Burton, N. & Cooper, R. Manuka honey inhibits cell division in methicillin-resistant Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 66, 2536-2542, doi:dkr340 [pii]
10.1093/jac/dkr340 (2011).
34 Jenkins, R. & Cooper, R. Improving antibiotic activity against wound pathogens with manuka honey in vitro. PLoS One 7, e45600, doi:10.1371/journal.pone.0045600 (2012).
35 Roberts, A. E., Maddocks, S. E. & Cooper, R. A. Manuka honey is bactericidal against Pseudomonas aeruginosa and results in differential expression of oprF and algD. Microbiology 158, 3005-3013, doi:mic.0.062794-0 [pii]
10.1099/mic.0.062794-0 (2012).
36 Toreti, V. C., Sato, H. H., Pastore, G. M. & Park, Y. K. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evidence-Based Complementary and Alternative Medicine 2013, 697390, doi:10.1155/2013/697390 (2013).
37 Müller, P. et al. Synergism between Medihoney and Rifampicin against Methicillin-Resistant Staphylococcus aureus (MRSA). PLoS One 8, e57679, doi:10.1371/journal.pone.0057679 (2013).
38 Zumla, A. & Lulat, A. Honey--a remedy rediscovered. Journal of the Royal Society of Medicine 82, 384-385 (1989).
39 Dustman. J, H. Antibacterial effects of honey. Apiacta 1 (1979).
40 Brogan, D. M. & Mossialos, E. A critical analysis of the review on antimicrobial resistance report and the infectious disease financing facility. Global Health 12, 8, doi:10.1186/s12992-016-0147-y
10.1186/s12992-016-0147-y [pii] (2016).
41 Alvarez-Suarez, J., Gasparrini, M., Forbes-Hernández, T., Mazzoni, L. & Giampieri, F. The composition and biological activity of honey: A focus on manuka honey. Foods 3, 420 (2014).
42 Olaitan, P. B., Adeleke, O. E. & Ola, I. O. Honey: a reservoir for microorganisms and an inhibitory agent for microbes. African Health Sciences 7, 159-165 (2007).
43 Cooper, R. A., Molan, P. C. & Harding, K. G. The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds. Journal of Applied Microbiology 93, 857-863, doi:1761 [pii] (2002).
44 Danforth, B. N., Sipes, S., Fang, J. & Brady, S. G. The history of early bee diversification based on five genes plus morphology. Proceedings of the National Academy of Sciences 103, 15118-15123, doi:10.1073/pnas.0604033103 (2006).
45 Michez, D., Patiny, S., Rasmont, P., Timmermann, K. & Vereecken, N. J. Phylogeny and host-plant evolution in Melittidae s.l. (Hymenoptera: Apoidea). Apidologie 39, 146-162, doi:10.1051/apido:2007048 (2008).
46 Blair, S. E. in Honey in modren wound management eds R. Cooper, P. C. Molan, & R. White) Ch. 3, 21-47 (Wounds UK publishing, 2009).
47 Al-Waili, N. S. Topical honey application vs. acyclovir for the treatment of recurrent herpes simplex lesions. Medical Science Monitor 10, MT94-98 (2004).
48 Feas, X. & Estevinho, M. L. A survey of the in vitro antifungal activity of heather (Erica sp.) organic honey. Journal of medicinal food 14, 1284-1288, doi:10.1089/jmf.2010.0211 (2011).
49 Irish, J., Carter, D. A., Shokohi, T. & Blair, S. E. Honey has an antifungal effect against Candida species. Medical Mycology 44, 289-291, doi:10.1080/13693780500417037 (2006).
50 Shahzad, A. & Cohrs, R. J. In vitro antiviral activity of honey against varicella zoster virus (VZV): A translational medicine study for potential remedy for shingles. Translational Research in Biomedicine 3, doi:10.3823/434 (2012).
51 Watanabe, K., Rahmasari, R., Matsunaga, A., Haruyama, T. & Kobayashi, N. Anti-influenza viral effects of honey in vitro: Potent high activity of manuka honey. Archives of Medical Research 45, 359-365, doi:http://dx.doi.org/10.1016/j.arcmed.2014.05.006 (2014).
52 Eteraf-Oskouei, T. & Najafi, M. Traditional and modern uses of natural honey in human diseases: a review. Iranian Journal of Basic Medical Sciences 16, 731-742 (2013).
53 Kato, Y. et al. Identification of a novel glycoside, leptosin, as a chemical marker of manuka honey. Journal of Agricultural and Food Chemistry 60, 3418-3423, doi:10.1021/jf300068w (2012).
54 Kwakman, P. H. et al. How honey kills bacteria. FASEB Journal 24, 2576-2582, doi:fj.09-150789 [pii]
10.1096/fj.09-150789 (2010).
55 Carter, D. A. et al. Therapeutic Manuka Honey: No Longer So Alternative. Frontiers in Microbiology 7, 569, doi:10.3389/fmicb.2016.00569 (2016).
56 Maddocks, S. E. & Jenkins, R. E. Honey: a sweet solution to the growing problem of antimicrobial resistance? Future Microbiology 8, 1419-1429, doi:10.2217/fmb.13.105 (2013).
57 Blair, S. E., Cokcetin, N. N., Harry, E. J. & Carter, D. A. The unusual antibacterial activity of medical-grade Leptospermum honey: antibacterial spectrum, resistance and transcriptome analysis. European Journal of Clinical Microbiology & Infectious Diseases 28, 1199-1208, doi:10.1007/s10096-009-0763-z (2009).
58 Roberts, A., Brown, H. L. & Jenkins, R. On the antibacterial effects of manuka honey: mechanistic insights. Research and Reports in Biology 6, 215-224 (2015).
59 Jenkins, R., Wootton, M., Howe, R. & Cooper, R. A demonstration of the susceptibility of clinical isolates obtained from cystic fibrosis patients to manuka honey. Archives of Microbiology 197, 597-601, doi:10.1007/s00203-015-1091-6 (2015).
60 Khalil, A. T. et al. Synergistic antibacterial effect of honey and Herba Ocimi Basilici against some bacterial pathogens. Journal of Traditional Chinese Medicine 33, 810-814 (2013).
61 Daglia, M., Ferrari, D., Collina, S. & Curti, V. Influence of in vitro simulated gastroduodenal digestion on methylglyoxal concentration of Manuka (Lectospermum scoparium) honey. Journal of Agricultural and Food Chemistry 61, 2140-2145, doi:10.1021/jf304299d (2013).
62 Pietta, P. G., Gardana, C. & Pietta, A. M. Analytical methods for quality control of propolis. Fitoterapia 73 Suppl 1, S7-20, doi:S0367326X02001867 [pii] (2002).
63 Burdock, G. A. Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology 36, 347-363, doi:S0278-6915(97)00145-2 [pii] (1998).
64 Sforcin, J. M. & Bankova, V. Propolis: is there a potential for the development of new drugs? Journal of Ethnopharmacology 133, 253-260, doi:S0378-8741(10)00735-X [pii]
10.1016/j.jep.2010.10.032 (2011).
65 Barrientos, L. et al. Chemical and botanical characterization of Chilean propolis and biological activity on cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. Brazilian Journal of Microbiology 44, 577-585, doi:10.1590/S1517-83822013000200038
bjm-44-577 [pii] (2013).
66 Gonsales, G., Orsi, R., Fernandes Júnior, A., Rodrigues, P. & Funari, S. Antibacterial activity of propolis collected in different regions of Brazil. Journal of Venomous Animals and Toxins Including Tropical Diseases 12, 276-284 (2006).
67 Veloz, J. J. et al. Antibiofilm activity of Chilean propolis on Streptococcus mutans is influenced by the year of collection. BioMed Research International 2015, 291351, doi:10.1155/2015/291351 (2015).
68 Sforcin, J. M., Fernandes, A., Jr., Lopes, C. A., Bankova, V. & Funari, S. R. Seasonal effect on Brazilian propolis antibacterial activity. Journal of Ethnopharmacology 73, 243-249, doi:S0378-8741(00)00320-2 [pii] (2000).
69 Orsi, R. d. O., Sforcin, J. M., Funari, S. R. C., Fernandes Junior, A. & Bankova, V. Synergistic effect of propolis and antibiotics on the Salmonella Typhi. Brazilian Journal of Microbiology 37, 108-112 (2006).
70 Park, Y. K., Alencar, S. M. & Aguiar, C. L. Botanical origin and chemical composition of Brazilian propolis. Journal of Agricultural and Food Chemistry 50, 2502-2506 (2002).
71 Oda, H. et al. Effect of Brazilian green propolis on oral pathogens and human periodontal fibroblasts. Journal of Oral Biosciences 58, 50-54, doi:http://dx.doi.org/10.1016/j.job.2015.11.001 (2016).
72 Daugsch, A., Moraes, C. S., Fort, P. & Park, Y. K. Brazilian red propolis--chemical composition and botanical origin. Evidence-Based Complementary and Alternative Medicine 5, 435-441, doi:nem057 [pii]
10.1093/ecam/nem057 (2008).
73 SFORCIN, J. M., Fernandes Júnior, A., Lopes, C., Funari, S. & Bankova, V. Seasonal effect of Brazilian propolis on Candida albicans and Candida tropicalis. Journal of Venomous Animals and Toxins 7, 139-144 (2001).
74 Veloz, J. J. et al. Polyphenol-rich extract from propolis reduces the expression and activity of Streptococcus mutans glucosyltransferases at subinhibitory concentrations. BioMed Research International 2016, 4302706, doi:10.1155/2016/4302706 (2016).
75 Silici, S. & Kutluca, S. Chemical composition and antibacterial activity of propolis collected by three different races of honeybees in the same region. Journal of Ethnopharmacology 99, 69-73, doi:S0378-8741(05)00123-6 [pii]
10.1016/j.jep.2005.01.046 (2005).
76 Silici, S., Koc, N. A., Ayangil, D. & Cankaya, S. Antifungal activities of propolis collected by different races of honeybees against yeasts isolated from patients with superficial mycoses. Journal of Pharmacological Sciences 99, 39-44, doi:JST.JSTAGE/jphs/FPE05002X [pii] (2005).
77 Oksuz, H., Duran, N., Tamer, C., Cetin, M. & Silici, S. Effect of propolis in the treatment of experimental Staphylococcus aureus keratitis in rabbits. Ophthalmic Research 37, 328-334, doi:87943 [pii]
10.1159/000087943 (2005).
78 Casteels, P., Ampe, C., Jacobs, F. & Tempst, P. Functional and chemical characterization of Hymenoptaecin, an antibacterial polypeptide that is infection-inducible in the honeybee (Apis mellifera). Journal of Biological Chemistry 268, 7044-7054 (1993).
79 Jefferson, J. M., Dolstad, H. A., Sivalingam, M. D. & Snow, J. W. Barrier immune effectors are maintained during transition from nurse to forager in the honey bee. PLoS One 8, e54097, doi:10.1371/journal.pone.0054097
PONE-D-12-03945 [pii] (2013).
80 Evans, J. D. et al. Immune pathways and defence mechanisms in honey bees Apis mellifera. Insect Molecular Biology 15, 645-656, doi:IMB682 [pii]
10.1111/j.1365-2583.2006.00682.x (2006).
81 Bachanová, K., Klaudiny, J., Kopernicky, J. & Simúth, J. Identification of honeybee peptide active against Paenibacillus larvae larvae through bacterial growth-inhibition assay on polyacrylamide gel. Apidologie 33, 259-269 (2002).
82 Schwarz, R. S. & Evans, J. D. Single and mixed-species trypanosome and microsporidia infections elicit distinct, ephemeral cellular and humoral immune responses in honey bees. Developmental & Comparative Immunology 40, 300-310, doi:S0145-305X(13)00077-3 [pii]
10.1016/j.dci.2013.03.010 (2013).
83 Evans, J. D. & Pettis, J. S. Colony-level impacts of immune responsiveness in honey bees, Apis mellifera. Evolution 59, 2270-2274 (2005).
84 Xu, P., Shi, M. & Chen, X. X. Antimicrobial peptide evolution in the Asiatic honey bee Apis cerana. PLoS One 4, e4239, doi:10.1371/journal.pone.0004239 (2009).
85 Shen, Y., Stojicic, S. & Haapasalo, M. Bacterial viability in starved and revitalized biofilms: comparison of viability staining and direct culture. Journal of Endodontics 36, 1820-1823, doi:S0099-2399(10)00687-4 [pii] 10.1016/j.joen.2010.08.029 (2010).
86 Shen, L. et al. Mechanism of action of recombinant acc-royalisin from royal jelly of Asian honeybee against gram-positive bacteria. PLoS One 7, e47194, doi:10.1371/journal.pone.0047194
PONE-D-12-09648 [pii] (2012).
87 Hancock, R. E. W. & Patrzykat, A. Clinical Development of Cationic Antimicrobial Peptides: From Natural to Novel Antibiotics. Current Drug Targets - Infectious Disorders 2, 79-83, doi:10.2174/1568005024605855 (2002).
88 Miyasaki, K. T. & Lehrer, R. I. β-sheet antibiotic peptides as potential dental therapeutics. International Journal of Antimicrobial Agents 9, 269-280 (1998).
89 Casteels-Josson, K., Zhang, W., Capaci, T., Casteels, P. & Tempst, P. Acute transcriptional response of the honeybee peptide-antibiotics gene repertoire and required post-translational conversion of the precursor structures. Journal of Biological Chemistry 269, 28569-28575 (1994).
90 Fujiwara, S. et al. A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin. Journal of Biological Chemistry 265, 11333-11337 (1990).
91 Klaudiny, J., Albert, S., Bachanova, K., Kopernicky, J. & Simuth, J. Two structurally different defensin genes, one of them encoding a novel defensin isoform, are expressed in honeybee Apis mellifera. Insect Biochemistry and Molecular Biology 35, 11-22, doi:S0965-1748(04)00160-2 [pii]
10.1016/j.ibmb.2004.09.007 (2005).
92 Casteels, P. et al. Isolation and characterization of abaecin, a major antibacterial response peptide in the honeybee (Apis mellifera). European Journal of Biochemistry 187, 381-386 (1990).
93 Casteels, P., Ampe, C., Jacobs, F., Vaeck, M. & Tempst, P. Apidaecins: antibacterial peptides from honeybees. The EMBO Journal 8, 2387-2391 (1989).
94 Kwakman, P. H. S. et al. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens. European Journal of Clinical Microbiology & Infectious Diseases 30, 251-257, doi:10.1007/s10096-010-1077-x (2011).
95 Majtan, J. et al. Methylglyoxal-induced modifications of significant honeybee proteinous components in manuka honey: Possible therapeutic implications. Fitoterapia 83, 671-677, doi:S0367-326X(12)00051-2 [pii]
10.1016/j.fitote.2012.02.002 (2012).
96 Poulsen, M. W. et al. Advanced glycation endproducts in food and their effects on health. Food and Chemical Toxicology 60, 10-37, doi:10.1016/j.fct.2013.06.052 (2013).
97 Adams, C. J., Manley-Harris, M. & Molan, P. C. The origin of methylglyoxal in New Zealand manuka (Leptospermum scoparium) honey. Carbohydrate Research 344, 1050-1053, doi:http://dx.doi.org/10.1016/j.carres.2009.03.020 (2009).
98 Cao, L. F., Zheng, H. Q., Pirk, C. W., Hu, F. L. & Xu, Z. W. High Royal Jelly-Producing Honeybees (Apis mellifera ligustica) (Hymenoptera: Apidae) in China. Journal of economic entomology, doi:10.1093/jee/tow013 (2016).
99 Zheng, H.-Q., Hu, F.-L. & Dietemann, V. Changes in composition of royal jelly harvested at different times: consequences for quality standards. Apidologie 42, 39-47, doi:10.1051/apido/2010033 (2011).
100 Wongchai, V. & Ratanavalachai, T. Seasonal variation of chemical composition of royal jelly produced in Thailand. Thammasat International Journal of Science and Technology 7, 1 - 8 (2002).
101 Kodai, T., Umebayashi, K., Nakatani, T., Ishiyama, K. & Noda, N. Compositions of royal jelly II. Organic acid glycosides and sterols of the royal jelly of honeybees (Apis mellifera). Chemical and Pharmaceutical Bulletin 55, 1528-1531, doi:JST.JSTAGE/cpb/55.1528 [pii] (2007).
102 Kanelis, D. et al. A suggestion for royal jelly specifications. Archives of Industrial Hygiene and Toxicology 66, 275-284, doi:10.1515/aiht-2015-66-2651 (2015).
103 Bíliková, K., Wu, G. & Šimúth, J. Isolation of a peptide fraction from honeybee royal jelly as a potential antifoulbrood factor. Apidologie 32, 275-283 (2001).
104 Stratev, D., Vashin, I., Balkanska, R. & Dinkov, D. Antibacterial activity of royal jelly and rape honey against Aeromonas hydrophila (ATCC 7965). Journal of Food and Health Science 1, 67-74, doi:10.3153/JFHS15006 (2015).
105 Dinkov, D., Stratev, D., Balkanska, R. & Sergelidis, D. Antibacterial activity of royal jelly and rape honey agaist methicillin resistant Staphylococcus aureus strains. Journal of Food and Health Science 2, 67-73, doi:10.3153/JFHS16007 (2016).
106 Boukraa, L. Additive activity of royal jelly and honey against Pseudomonas aeruginosa. Alternative Medicine Review 13, 330-333 (2008).
107 Nascimento, A. P. et al. The lyophilization process maintains the chemical and biological characteristics of royal jelly. Evidence-Based Complementary and Alternative Medicine 2015, 825068, doi:10.1155/2015/825068 (2015).
108 Sabatini, A. G., Marcazzan, G. L., Caboni, M. F., Bogdanov, S. & Almeida-Muradian, L. Quality and standardisation of royal jelly. Journal of ApiProduct and ApiMedical Science 1, 1-6 (2009).
109 Schmitzova, J. et al. A family of major royal jelly proteins of the honeybee Apis mellifera L. Cellular and molecular life sciences : CMLS 54, 1020-1030 (1998).
110 Kimura, Y. et al. Structural features of N-glycans linked to royal jelly glycoproteins: structures of high-mannose type, hybrid type, and biantennary type glycans. Bioscience, Biotechnology and Biochemistry 64, 2109-2120 (2000).
111 Fontana, R. et al. Jelleines: a family of antimicrobial peptides from the Royal Jelly of honeybees (Apis mellifera). Peptides 25, 919-928, doi:10.1016/j.peptides.2004.03.016 (2004).
112 Romanelli, A. et al. Peptides from royal jelly: studies on the antimicrobial activity of jelleins, jelleins analogs and synergy with temporins. Journal of Peptide Science 17, 348-352, doi:10.1002/psc.1316 (2011).
113 Schonleben, S., Sickmann, A., Mueller, M. J. & Reinders, J. Proteome analysis of Apis mellifera royal jelly. Analytical and Bioanalytical Chemistry 389, 1087-1093, doi:10.1007/s00216-007-1498-2 (2007).
114 Bilikova, K., Huang, S. C., Lin, I. P., Simuth, J. & Peng, C. C. Structure and antimicrobial activity relationship of royalisin, an antimicrobial peptide from royal jelly of Apis mellifera. Peptides 68, 190-196, doi:S0196-9781(15)00059-5 [pii]
10.1016/j.peptides.2015.03.001 (2015).
115 Shen, L. et al. Expression of Acc-royalisin gene from royal jelly of Chinese honeybee in Escherichia coli and its antibacterial activity. Journal of Agricultural and Food Chemistry 58, 2266-2273 (2010).
116 Townsend, G. F. et al. Studies on the in vitro antitumor activity of fatty acids I. 10-hydroxy-2-decenoic acid from royal jelly. Cancer research 20, 503-510 (1960).
117 Hattori, N., Nomoto, H., Fukumitsu, H., Mishima, S. & Furukawa, S. Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro. Biomedical Research 28, 261-266 (2007).
118 Wang, J. et al. 10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K–AKT pathway. International Immunopharmacology 28, 97-104 (2015).
119 Takikawa, M. et al. 10‐Hydroxy‐2‐decenoic acid, a unique medium‐chain fatty acid, activates 5'‐AMP‐activated protein kinase in L6 myotubes and mice. Molecular Nutrition & Food Research 57, 1794-1802 (2013).
120 Yousefi, B. et al. Hydroxy decenoic acid down regulates gtfB and gtfC expression and prevents Streptococcus mutans adherence to the cell surfaces. Annals of clinical microbiology and antimicrobials 11, 21, doi:1476-0711-11-21 [pii]
10.1186/1476-0711-11-21 (2012).
121 Morais, M., Moreira, L., Feas, X. & Estevinho, L. M. Honeybee-collected pollen from five Portuguese Natural Parks: palynological origin, phenolic content, antioxidant properties and antimicrobial activity. Food and Chemical Toxicology 49, 1096-1101, doi:S0278-6915(11)00029-9 [pii]
10.1016/j.fct.2011.01.020 (2011).
122 Almeida-Muradian, L., Pamplona, L. C., Coimbra, S. l. & Barth, O. M. Chemical composition and botanical evaluation of dried bee pollen pellets. Journal of food composition and analysis 18, 105-111 (2005).
123 Hansen, M. The healing power of pollen and other products form the beehive, propolis, royal jelly and honey. (Thorsons, 1979).
124 Mărghitaş, L. A. et al. In vitro antioxidant capacity of honeybee-collected pollen of selected floral origin harvested from Romania. Food Chemistry 115, 878-883 (2009).
125 Gebara, E. C., Lima, L. A. & Mayer, M. Propolis antimicrobial activity against periodontopathic bacteria. Brazilian Journal of Microbiology 33, 365-369 (2002).
126 Cook, N. & Samman, S. Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry 7, 66-76 (1996).
127 Garcia, M., Pérez-Arquillue, C., Juan, T., Juan, M. & Herrera, A. Note. Pollen analysis and antibacterial activity of Spanish honeys. Food Science and Technology International 7, 155-158 (2001).
128 Proestos, C., Chorianopoulos, N., Nychas, G. J. & Komaitis, M. RP-HPLC analysis of the phenolic compounds of plant extracts. investigation of their antioxidant capacity and antimicrobial activity. Journal of Agricultural and Food Chemistry 53, 1190-1195, doi:10.1021/jf040083t (2005).
129 Almaraz-Abarca, N. et al. Variability of antioxidant activity among honeybee-collected pollen of different botanical origin. Interciencia 29, 574-578 (2004).
130 Balch, P. A. Prescription for Nutritional Healing: The A-to-Z Guide to Supplements. (Avery, 2002).
131 Carpes, S. T., Begnini, R., Alencar, S. M. d. & Masson, M. L. Study of preparations of bee pollen extracts, antioxidant and antibacterial activity. Ciência e Agrotecnologia 31, 1818-1825 (2007).
132 Broadhurts, C. L. Bee product: medicine from the hive. Nutrition science news 4, 366-368 (1999).
133 Freire, K. R. et al. Palynological origin, phenolic content, and antioxidant properties of honeybee-collected pollen from Bahia, Brazil. Molecules (Basel, Switzerland) 17, 1652-1664, doi:10.3390/molecules17021652 (2012).
134 Campos, M. G. et al. Pollen composition and standardisation of analytical methods. Journal of Apicultural Research 47, 154-161 (2008).
135 Campos, M., Frigerio, C., Lopes, J. & Bogdanov, S. What is the future of Bee-Pollen. Journal of ApiProduct and ApiMedical Science 2, 131-144 (2010).
136 Rzepecka-Stojko, A. et al. Polyphenols from bee pollen: Structure, absorption, metabolism and biological activity. Molecules (Basel, Switzerland) 20, 21732-21749, doi:molecules201219800 [pii]
10.3390/molecules201219800 (2015).
137 Baltrušaitytė, V., Venskutonis, P. R. & Čeksterytė, V. Antibacterial activtiy of honey and beebread of different origin agaist Staphylococcus aureus and S. epidemidis. Food Technology and Biotechnology 45, 201-208 (2007).
138 Erkmen, O. & Ozcan, M. M. Antimicrobial effects of Turkish propolis, pollen, and laurel on spoilage and pathogenic food-related microorganisms. Journal of medicinal food 11, 587-592, doi:10.1089/jmf.2007.0038 (2008).
139 Graikou, K. et al. Chemical analysis of Greek pollen - Antioxidant, antimicrobial and proteasome activation properties. Chemistry Central Journal 5, 33-33, doi:10.1186/1752-153x-5-33 (2011).
140 Nakamura, K. et al. Bactericidal activity and mechanism of photoirradiated polyphenols against Gram-Positive and -Negative Bacteria. Journal of Agricultural and Food Chemistry 63, 7707-7713, doi:10.1021/jf5058588 (2015).
141 Cushnie, T. T. & Lamb, A. J. Antimicrobial activity of flavonoids. International Journal of Antimicrobial Agents 26, 343-356 (2005).
142 Tichy, J. & Novak, J. Detection of antimicrobials in bee products with activity against viridans streptococci. The Journal of Alternative and Complementary Medicine 6, 383-389 (2000).
143 Abouda, Z., Zerdani, I., Kalalou, I., Faid, M. & Ahami, M. The antibacterial activity of Moroccan bee bread and bee-pollen (fresh and dried) against pathogenic bacteria. Research Journal of Microbiology 6, 376 (2011).
144 Kačániová, M. et al. Antimicrobial activity of bee collected pollen against Clostridia. Lucrari Stiintifice : Zootehnie si Biotehnologii 47, 362-365 (2014).
145 Kacániová, M. et al. The antimicrobial activity of honey, bee pollen loads and beeswax from Slovakia. Archives of Biological Sciences 64, 927-934 (2012).
146 Mohdaly, A. A. A., Mahmoud, A. A., Roby, M. H. H., Smetanska, I. & Ramadan, M. F. Phenolic extract from propolis and bee pollen: Composition, antioxidant and antibacterial activities. Journal of Food Biochemistry 39, 538-547, doi:10.1111/jfbc.12160 (2015).
147 MĂRGĂOAN, R. A. et al. Antimicrobial activity of bee pollen ethanolic and methanolic extracts on Staphylococcus aureus bacterial strain. Bulletin of the University of Agricultural Sciences and Veterinary Medicine 72, 78-80 (2015).
148 Khider, M., Elbanna, K., Mahmoud, A. & Owayss, A. A. Egyptian honeybee pollen as antimicrobial, antioxidant agents, and dietary food supplements. Food Science and Biotechnology 22, 1-9 (2013).
149 Pascoal, A., Rodrigues, S., Teixeira, A., Feás, X. & Estevinho, L. M. Biological activities of commercial bee pollens: Antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food and Chemical Toxicology 63, 233-239 (2014).
150 Koc, A. N. et al. Antifungal activity of the honeybee products against Candida spp. and Trichosporon spp. Journal of medicinal food 14, 128-134, doi:10.1089/jmf.2009.0296 (2011).
151 Özcan, M., Ünver, A., Ceylan, D. A. & Yetisir, R. Inhibitory effect of pollen and propolis extracts. Food/Nahrung 48, 188-194 (2004).
152 Nogueira, C., Iglesias, A., Feás, X. & Estevinho, L. M. Commercial bee pollen with different geographical origins: A comprehensive approach. International Journal of Molecular Sciences 13, 11173-11187, doi:10.3390/ijms130911173 (2012).
153 Bogdanov, S. Bee venom: composition, health, medicine: a review. Peptides 1 (2012).
154 Lee, G. & Bae, H. Bee venom phospholipase A2: Yesterday’s enemy becomes today’s friend. Toxins 8, 48 (2016).
155 Ali, M. Studies on bee venom and its medical uses. International Journal of Advancements in Research & Technology, 1, 1-15 (2012).
156 Schumacher, M. J., Schmidt, J. O., Egen, N. B. & Dillon, K. A. Biochemical variability of venoms from individual European and Africanized honeybees (Apis mellifera). Journal of Allergy and Clinical Immunology 90, 59-65 (1992).
157 Ferreira Junior, R. S. et al. Africanized honey bee (Apis mellifera) venom profiling: Seasonal variation of melittin and phospholipase A(2) levels. Toxicon : official journal of the International Society on Toxinology 56, 355-362, doi:10.1016/j.toxicon.2010.03.023 (2010).
158 Banks, B. E. C. & Shipolini, R. A. in Venoms of the Hymenoptera: Biochemical, Pharmacological and Behavioural Aspects (ed T. Piek) (Academic Press, 1986).
159 Danneels, E., Van Vaerenbergh, M., Debyser, G., Devreese, B. & de Graaf, D. Honeybee venom proteome profile of Queens and winter bees as determined by a mass spectrometric approach. Toxins 7, 4468 (2015).
160 Fennell, J. F., Shipman, W. H. & Cole, L. J. Antibacterial action of melittin, a polypeptide from bee venom.
Experimental Biology and Medicine 127, 707-710 (1968).
161 Han, S. M. et al. Antibacterial activity and antibiotic-enhancing effects of honeybee venom against methicillin-resistant Staphylococcus aureus. Molecules (Basel, Switzerland) 21, 79, doi:10.3390/molecules21010079 (2016).
162 Gauldie, J., Hanson, J. M., Rumjanek, F. D., Shipolini, R. A. & Vernon, C. A. The peptide components of bee venom. European Journal of Biochemistry 61, 369-376 (1976).
163 Benton, A. W. & Morse, R. A. Venom toxicity and proteins of the genus Apis. Journal of Apicultural Research 7, 113-118 (1968).
164 Boutrin, M. C., Foster, H. A. & Pentreath, V. W. The effects of bee (Apis mellifera) venom phospholipase A2 on Trypanosoma brucei brucei and Enterobacteria. Experimental parasitology 119, 246-251, doi:10.1016/j.exppara.2008.02.002 (2008).
165 Leandro, L. F. et al. Antimicrobial activity of apitoxin, melittin and phospholipase A(2) of honey bee (Apis mellifera) venom against oral pathogens. Anais da Academia Brasileira de Ciencias 87, 147-155, doi:10.1590/0001-3765201520130511 (2015).
166 Mollay, C. & Kreil, G. Enhancement of bee venom phospholipase A2 activity by melittin, direct lytic factor from cobra venom and polymyxin B. FEBS Letters 46, 141-144, doi:http://dx.doi.org/10.1016/0014-5793(74)80354-6 (1974).
167 Mollay, C., Kreil, G. & Berger, H. Action of phospholipases on the cytoplasmic membrane of Escherichia coli. Stimulation by melittin. Biochimica et Biophysica Acta - Biomembranes 426, 317-324, doi:http://dx.doi.org/10.1016/0005-2736(76)90340-0 (1976).
168 Choi, J. H. et al. Melittin, a honeybee venom derived antimicrobial peptide, may target methicillin resistant Staphylococcus aureus. Molecular Medicine Reports 12, 6483-6490 (2015).
169 Dosler, S., Karaaslan, E. & Alev Gerceker, A. Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria. Journal of Chemotherapy, 1973947815Y0000000004, doi:10.1179/1973947815y.0000000004 (2015).
170 Al-Ani, I., Zimmermann, S., Reichling, J. & Wink, M. Pharmacological synergism of bee venom and melittin with antibiotics and plant secondary metabolites against multi-drug resistant microbial pathogens. Phytomedicine 22, 245-255, doi:10.1016/j.phymed.2014.11.019 (2015).
2 Abu-Al-Basal, M. A. Healing potential of Rosmarinus officinalis L. on full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice. Journal of Ethnopharmacology 131, 443-450 (2010).
3 Zhao, L., La, V. D. & Grenier, D. Antibacterial, antiadherence, antiprotease, and anti-inflammatory activities of various tea extracts: potential benefits for periodontal diseases. Journal of medicinal food 16, 428-436 (2013).
4 Harris, J. C., Cottrell, S. L., Plummer, S. & Lloyd, D. Antimicrobial properties of Allium sativum (garlic). Applied Microbiology and Biotechnology 57, 282-286 (2001).
5 Saurav, K. et al. In search of alternative antibiotic drugs: Quorum-quenching activity in sponges and their bacterial isolates. Frontiers in Microbiology 7, 416, doi:10.3389/fmicb.2016.00416 (2016).
6 Cazander, G. et al. Maggot excretions affect the human complement system. Wound Repair and Regeneration 20, 879-886, doi:10.1111/j.1524-475X.2012.00850.x (2012).
7 Mansourian, A., Boojarpour, N., Ashnagar, S., Momen Beitollahi, J. & Shamshiri, A. R. The comparative study of antifungal activity of Syzygium aromaticum, Punica granatum and nystatin on Candida albicans; an in vitro study. Journal of Medical Mycology 24, e163-168, doi:10.1016/j.mycmed.2014.07.001 (2014).
8 Hashemipour, M. A., Tavakolineghad, Z., Arabzadeh, S. A., Iranmanesh, Z. & Nassab, S. A. Antiviral activities of honey, royal jelly, and Acyclovir against HSV-1. Wounds : a compendium of clinical research and practice 26, 47-54 (2014).
9 McGrath, L. J., Becker-Dreps, S., Pate, V. & Brookhart, M. A. Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000-2011. PLoS One 8, e81210, doi:10.1371/journal.pone.0081210
PONE-D-13-29268 [pii] (2013).
10 Martin, D. R., Heffernan, H. M. & Davies, H. G. Methicillin-resistant Staphylococcus aureus: an increasing threat in New Zealand hospitals. New Zealand Medical Journal 102, 367-369 (1989).
11 Kam, K. M. et al. Emergence of multiple-antibiotic-resistant Streptococcus pneumoniae in Hong Kong. Antimicrobial Agents and Chemotherapy 39, 2667-2670 (1995).
12 Filius, P. M. & Gyssens, I. C. Impact of increasing antimicrobial resistance on wound management. American Journal of Clinical Dermatology 3, 1-7, doi:030101 [pii] (2002).
13 Hwang, A. Y. & Gums, J. G. The emergence and evolution of antimicrobial resistance: Impact on a global scale. Bioorganic & Medicinal Chemistry doi:S0968-0896(16)30261-9 [pii]
10.1016/j.bmc.2016.04.027 (2016).
14 Fischbach, M. A. & Walsh, C. T. Antibiotics for Emerging Pathogens. Science 325, 1089-1093, doi:10.1126/science.1176667 (2009).
15 Bragginton, E. C. & Piddock, L. J. UK and European Union public and charitable funding from 2008 to 2013 for bacteriology and antibiotic research in the UK: an observational study. Lancet Infect Dis 14, 857-868, doi:S1473-3099(14)70825-4 [pii]
10.1016/S1473-3099(14)70825-4 (2014).
16 O'Neill, A. J. Tackling a global health crisis:initial steps. 1-21 (London, 2015).
17 Huttner, A. et al. Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum. Antimicrobial Resistance and Infection Control 2, 31, doi:10.1186/2047-2994-2-31
2047-2994-2-31 [pii] (2013).
18 Marc, C. et al. Inappropriate prescription of antibiotics in pediatric practice: Analysis of the prescriptions in primary care. Journal of Child Health Care, doi:1367493516643421 [pii]
10.1177/1367493516643421 (2016).
19 Lima, S. I. et al. Rationality of antimicrobial prescriptions in community pharmacy users. PLoS One 10, e0141615, doi:10.1371/journal.pone.0141615
PONE-D-15-30906 [pii] (2015).
20 Falagas, M. E. et al. Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria. BMC Infectious Diseases 5, 24, doi:1471-2334-5-24 [pii]
10.1186/1471-2334-5-24 (2005).
21 Bathoorn, E. et al. Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call. Journal of Antimicrobial Chemotherapy 71, 1207-1212, doi:dkv467 [pii]
10.1093/jac/dkv467 (2016).
22 Vilacoba, E. et al. Widespread dispersion of the resistance element tet(B)::ISCR2 in XDR Acinetobacter baumannii isolates. Epidemiology & Infection 144, 1574-1578, doi:S0950268815002897 [pii]
10.1017/S0950268815002897 (2016).
23 Weterings, V. et al. An outbreak of colistin-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the Netherlands (July to December 2013), with inter-institutional spread. European Journal of Clinical Microbiology & Infectious Diseases 34, 1647-1655, doi:10.1007/s10096-015-2401-2
10.1007/s10096-015-2401-2 [pii] (2015).
24 Iyamba, J. M., Wambale, J. M., Lukukula, C. M. & za Balega Takaisi-Kikuni, N. High prevalence of methicillin resistant staphylococci strains isolated from surgical site infections in Kinshasa. Pan African Medical Journal 18, 322, doi:10.11604/pamj.2014.18.322.4440
PAMJ-18-322 [pii] (2014).
25 Kulkova, N., Babalova, M., Sokolova, J. & Krcmery, V. First report of New Delhi metallo-beta-lactamase-1-producing strains in Slovakia. Microbial Drug Resistance 21, 117-120, doi:10.1089/mdr.2013.0162 (2015).
26 O'Neill, A. J. Reveiw on antimicrobial resistance, tackling drug resistant infections globally. Infection prevention, control and surveillence: limiting the development and spread of drug resistance 1-32 (London, 2016).
27 Smith, R. & Coast, J. The true cost of antimicrobial resistance. BMJ 346, f1493 (2013).
28 Pfeffer, I. et al. Prevalence and risk factors for carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae among patients prior to bowel surgery. Diagnostic Microbiology and Infectious Disease doi:S0732-8893(16)30078-5 [pii]
10.1016/j.diagmicrobio.2016.04.002 (2016).
29 Getzlaf, M. A. et al. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. Journal of Orthopaedic Research 34, 177-186, doi:10.1002/jor.23068 (2016).
30 Zhang, H. et al. Melittin restores PTEN expression by down-regulating HDAC2 in human hepatocelluar carcinoma HepG2 cells. PLoS One 9, e95520, doi:10.1371/journal.pone.0095520
PONE-D-14-04193 [pii] (2014).
31 Maddocks, S. E., Jenkins, R. E., Rowlands, R. S., Purdy, K. J. & Cooper, R. A. Manuka honey inhibits adhesion and invasion of medically important wound bacteria in vitro. Future Microbiology 8, 1523-1536, doi:10.2217/fmb.13.126 (2013).
32 Tonks, A. J. et al. Honey stimulates inflammatory cytokine production from monocytes. Cytokine 21, 242-247, doi:S1043466603000929 [pii] (2003).
33 Jenkins, R., Burton, N. & Cooper, R. Manuka honey inhibits cell division in methicillin-resistant Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 66, 2536-2542, doi:dkr340 [pii]
10.1093/jac/dkr340 (2011).
34 Jenkins, R. & Cooper, R. Improving antibiotic activity against wound pathogens with manuka honey in vitro. PLoS One 7, e45600, doi:10.1371/journal.pone.0045600 (2012).
35 Roberts, A. E., Maddocks, S. E. & Cooper, R. A. Manuka honey is bactericidal against Pseudomonas aeruginosa and results in differential expression of oprF and algD. Microbiology 158, 3005-3013, doi:mic.0.062794-0 [pii]
10.1099/mic.0.062794-0 (2012).
36 Toreti, V. C., Sato, H. H., Pastore, G. M. & Park, Y. K. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evidence-Based Complementary and Alternative Medicine 2013, 697390, doi:10.1155/2013/697390 (2013).
37 Müller, P. et al. Synergism between Medihoney and Rifampicin against Methicillin-Resistant Staphylococcus aureus (MRSA). PLoS One 8, e57679, doi:10.1371/journal.pone.0057679 (2013).
38 Zumla, A. & Lulat, A. Honey--a remedy rediscovered. Journal of the Royal Society of Medicine 82, 384-385 (1989).
39 Dustman. J, H. Antibacterial effects of honey. Apiacta 1 (1979).
40 Brogan, D. M. & Mossialos, E. A critical analysis of the review on antimicrobial resistance report and the infectious disease financing facility. Global Health 12, 8, doi:10.1186/s12992-016-0147-y
10.1186/s12992-016-0147-y [pii] (2016).
41 Alvarez-Suarez, J., Gasparrini, M., Forbes-Hernández, T., Mazzoni, L. & Giampieri, F. The composition and biological activity of honey: A focus on manuka honey. Foods 3, 420 (2014).
42 Olaitan, P. B., Adeleke, O. E. & Ola, I. O. Honey: a reservoir for microorganisms and an inhibitory agent for microbes. African Health Sciences 7, 159-165 (2007).
43 Cooper, R. A., Molan, P. C. & Harding, K. G. The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds. Journal of Applied Microbiology 93, 857-863, doi:1761 [pii] (2002).
44 Danforth, B. N., Sipes, S., Fang, J. & Brady, S. G. The history of early bee diversification based on five genes plus morphology. Proceedings of the National Academy of Sciences 103, 15118-15123, doi:10.1073/pnas.0604033103 (2006).
45 Michez, D., Patiny, S., Rasmont, P., Timmermann, K. & Vereecken, N. J. Phylogeny and host-plant evolution in Melittidae s.l. (Hymenoptera: Apoidea). Apidologie 39, 146-162, doi:10.1051/apido:2007048 (2008).
46 Blair, S. E. in Honey in modren wound management eds R. Cooper, P. C. Molan, & R. White) Ch. 3, 21-47 (Wounds UK publishing, 2009).
47 Al-Waili, N. S. Topical honey application vs. acyclovir for the treatment of recurrent herpes simplex lesions. Medical Science Monitor 10, MT94-98 (2004).
48 Feas, X. & Estevinho, M. L. A survey of the in vitro antifungal activity of heather (Erica sp.) organic honey. Journal of medicinal food 14, 1284-1288, doi:10.1089/jmf.2010.0211 (2011).
49 Irish, J., Carter, D. A., Shokohi, T. & Blair, S. E. Honey has an antifungal effect against Candida species. Medical Mycology 44, 289-291, doi:10.1080/13693780500417037 (2006).
50 Shahzad, A. & Cohrs, R. J. In vitro antiviral activity of honey against varicella zoster virus (VZV): A translational medicine study for potential remedy for shingles. Translational Research in Biomedicine 3, doi:10.3823/434 (2012).
51 Watanabe, K., Rahmasari, R., Matsunaga, A., Haruyama, T. & Kobayashi, N. Anti-influenza viral effects of honey in vitro: Potent high activity of manuka honey. Archives of Medical Research 45, 359-365, doi:http://dx.doi.org/10.1016/j.arcmed.2014.05.006 (2014).
52 Eteraf-Oskouei, T. & Najafi, M. Traditional and modern uses of natural honey in human diseases: a review. Iranian Journal of Basic Medical Sciences 16, 731-742 (2013).
53 Kato, Y. et al. Identification of a novel glycoside, leptosin, as a chemical marker of manuka honey. Journal of Agricultural and Food Chemistry 60, 3418-3423, doi:10.1021/jf300068w (2012).
54 Kwakman, P. H. et al. How honey kills bacteria. FASEB Journal 24, 2576-2582, doi:fj.09-150789 [pii]
10.1096/fj.09-150789 (2010).
55 Carter, D. A. et al. Therapeutic Manuka Honey: No Longer So Alternative. Frontiers in Microbiology 7, 569, doi:10.3389/fmicb.2016.00569 (2016).
56 Maddocks, S. E. & Jenkins, R. E. Honey: a sweet solution to the growing problem of antimicrobial resistance? Future Microbiology 8, 1419-1429, doi:10.2217/fmb.13.105 (2013).
57 Blair, S. E., Cokcetin, N. N., Harry, E. J. & Carter, D. A. The unusual antibacterial activity of medical-grade Leptospermum honey: antibacterial spectrum, resistance and transcriptome analysis. European Journal of Clinical Microbiology & Infectious Diseases 28, 1199-1208, doi:10.1007/s10096-009-0763-z (2009).
58 Roberts, A., Brown, H. L. & Jenkins, R. On the antibacterial effects of manuka honey: mechanistic insights. Research and Reports in Biology 6, 215-224 (2015).
59 Jenkins, R., Wootton, M., Howe, R. & Cooper, R. A demonstration of the susceptibility of clinical isolates obtained from cystic fibrosis patients to manuka honey. Archives of Microbiology 197, 597-601, doi:10.1007/s00203-015-1091-6 (2015).
60 Khalil, A. T. et al. Synergistic antibacterial effect of honey and Herba Ocimi Basilici against some bacterial pathogens. Journal of Traditional Chinese Medicine 33, 810-814 (2013).
61 Daglia, M., Ferrari, D., Collina, S. & Curti, V. Influence of in vitro simulated gastroduodenal digestion on methylglyoxal concentration of Manuka (Lectospermum scoparium) honey. Journal of Agricultural and Food Chemistry 61, 2140-2145, doi:10.1021/jf304299d (2013).
62 Pietta, P. G., Gardana, C. & Pietta, A. M. Analytical methods for quality control of propolis. Fitoterapia 73 Suppl 1, S7-20, doi:S0367326X02001867 [pii] (2002).
63 Burdock, G. A. Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology 36, 347-363, doi:S0278-6915(97)00145-2 [pii] (1998).
64 Sforcin, J. M. & Bankova, V. Propolis: is there a potential for the development of new drugs? Journal of Ethnopharmacology 133, 253-260, doi:S0378-8741(10)00735-X [pii]
10.1016/j.jep.2010.10.032 (2011).
65 Barrientos, L. et al. Chemical and botanical characterization of Chilean propolis and biological activity on cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus. Brazilian Journal of Microbiology 44, 577-585, doi:10.1590/S1517-83822013000200038
bjm-44-577 [pii] (2013).
66 Gonsales, G., Orsi, R., Fernandes Júnior, A., Rodrigues, P. & Funari, S. Antibacterial activity of propolis collected in different regions of Brazil. Journal of Venomous Animals and Toxins Including Tropical Diseases 12, 276-284 (2006).
67 Veloz, J. J. et al. Antibiofilm activity of Chilean propolis on Streptococcus mutans is influenced by the year of collection. BioMed Research International 2015, 291351, doi:10.1155/2015/291351 (2015).
68 Sforcin, J. M., Fernandes, A., Jr., Lopes, C. A., Bankova, V. & Funari, S. R. Seasonal effect on Brazilian propolis antibacterial activity. Journal of Ethnopharmacology 73, 243-249, doi:S0378-8741(00)00320-2 [pii] (2000).
69 Orsi, R. d. O., Sforcin, J. M., Funari, S. R. C., Fernandes Junior, A. & Bankova, V. Synergistic effect of propolis and antibiotics on the Salmonella Typhi. Brazilian Journal of Microbiology 37, 108-112 (2006).
70 Park, Y. K., Alencar, S. M. & Aguiar, C. L. Botanical origin and chemical composition of Brazilian propolis. Journal of Agricultural and Food Chemistry 50, 2502-2506 (2002).
71 Oda, H. et al. Effect of Brazilian green propolis on oral pathogens and human periodontal fibroblasts. Journal of Oral Biosciences 58, 50-54, doi:http://dx.doi.org/10.1016/j.job.2015.11.001 (2016).
72 Daugsch, A., Moraes, C. S., Fort, P. & Park, Y. K. Brazilian red propolis--chemical composition and botanical origin. Evidence-Based Complementary and Alternative Medicine 5, 435-441, doi:nem057 [pii]
10.1093/ecam/nem057 (2008).
73 SFORCIN, J. M., Fernandes Júnior, A., Lopes, C., Funari, S. & Bankova, V. Seasonal effect of Brazilian propolis on Candida albicans and Candida tropicalis. Journal of Venomous Animals and Toxins 7, 139-144 (2001).
74 Veloz, J. J. et al. Polyphenol-rich extract from propolis reduces the expression and activity of Streptococcus mutans glucosyltransferases at subinhibitory concentrations. BioMed Research International 2016, 4302706, doi:10.1155/2016/4302706 (2016).
75 Silici, S. & Kutluca, S. Chemical composition and antibacterial activity of propolis collected by three different races of honeybees in the same region. Journal of Ethnopharmacology 99, 69-73, doi:S0378-8741(05)00123-6 [pii]
10.1016/j.jep.2005.01.046 (2005).
76 Silici, S., Koc, N. A., Ayangil, D. & Cankaya, S. Antifungal activities of propolis collected by different races of honeybees against yeasts isolated from patients with superficial mycoses. Journal of Pharmacological Sciences 99, 39-44, doi:JST.JSTAGE/jphs/FPE05002X [pii] (2005).
77 Oksuz, H., Duran, N., Tamer, C., Cetin, M. & Silici, S. Effect of propolis in the treatment of experimental Staphylococcus aureus keratitis in rabbits. Ophthalmic Research 37, 328-334, doi:87943 [pii]
10.1159/000087943 (2005).
78 Casteels, P., Ampe, C., Jacobs, F. & Tempst, P. Functional and chemical characterization of Hymenoptaecin, an antibacterial polypeptide that is infection-inducible in the honeybee (Apis mellifera). Journal of Biological Chemistry 268, 7044-7054 (1993).
79 Jefferson, J. M., Dolstad, H. A., Sivalingam, M. D. & Snow, J. W. Barrier immune effectors are maintained during transition from nurse to forager in the honey bee. PLoS One 8, e54097, doi:10.1371/journal.pone.0054097
PONE-D-12-03945 [pii] (2013).
80 Evans, J. D. et al. Immune pathways and defence mechanisms in honey bees Apis mellifera. Insect Molecular Biology 15, 645-656, doi:IMB682 [pii]
10.1111/j.1365-2583.2006.00682.x (2006).
81 Bachanová, K., Klaudiny, J., Kopernicky, J. & Simúth, J. Identification of honeybee peptide active against Paenibacillus larvae larvae through bacterial growth-inhibition assay on polyacrylamide gel. Apidologie 33, 259-269 (2002).
82 Schwarz, R. S. & Evans, J. D. Single and mixed-species trypanosome and microsporidia infections elicit distinct, ephemeral cellular and humoral immune responses in honey bees. Developmental & Comparative Immunology 40, 300-310, doi:S0145-305X(13)00077-3 [pii]
10.1016/j.dci.2013.03.010 (2013).
83 Evans, J. D. & Pettis, J. S. Colony-level impacts of immune responsiveness in honey bees, Apis mellifera. Evolution 59, 2270-2274 (2005).
84 Xu, P., Shi, M. & Chen, X. X. Antimicrobial peptide evolution in the Asiatic honey bee Apis cerana. PLoS One 4, e4239, doi:10.1371/journal.pone.0004239 (2009).
85 Shen, Y., Stojicic, S. & Haapasalo, M. Bacterial viability in starved and revitalized biofilms: comparison of viability staining and direct culture. Journal of Endodontics 36, 1820-1823, doi:S0099-2399(10)00687-4 [pii] 10.1016/j.joen.2010.08.029 (2010).
86 Shen, L. et al. Mechanism of action of recombinant acc-royalisin from royal jelly of Asian honeybee against gram-positive bacteria. PLoS One 7, e47194, doi:10.1371/journal.pone.0047194
PONE-D-12-09648 [pii] (2012).
87 Hancock, R. E. W. & Patrzykat, A. Clinical Development of Cationic Antimicrobial Peptides: From Natural to Novel Antibiotics. Current Drug Targets - Infectious Disorders 2, 79-83, doi:10.2174/1568005024605855 (2002).
88 Miyasaki, K. T. & Lehrer, R. I. β-sheet antibiotic peptides as potential dental therapeutics. International Journal of Antimicrobial Agents 9, 269-280 (1998).
89 Casteels-Josson, K., Zhang, W., Capaci, T., Casteels, P. & Tempst, P. Acute transcriptional response of the honeybee peptide-antibiotics gene repertoire and required post-translational conversion of the precursor structures. Journal of Biological Chemistry 269, 28569-28575 (1994).
90 Fujiwara, S. et al. A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin. Journal of Biological Chemistry 265, 11333-11337 (1990).
91 Klaudiny, J., Albert, S., Bachanova, K., Kopernicky, J. & Simuth, J. Two structurally different defensin genes, one of them encoding a novel defensin isoform, are expressed in honeybee Apis mellifera. Insect Biochemistry and Molecular Biology 35, 11-22, doi:S0965-1748(04)00160-2 [pii]
10.1016/j.ibmb.2004.09.007 (2005).
92 Casteels, P. et al. Isolation and characterization of abaecin, a major antibacterial response peptide in the honeybee (Apis mellifera). European Journal of Biochemistry 187, 381-386 (1990).
93 Casteels, P., Ampe, C., Jacobs, F., Vaeck, M. & Tempst, P. Apidaecins: antibacterial peptides from honeybees. The EMBO Journal 8, 2387-2391 (1989).
94 Kwakman, P. H. S. et al. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens. European Journal of Clinical Microbiology & Infectious Diseases 30, 251-257, doi:10.1007/s10096-010-1077-x (2011).
95 Majtan, J. et al. Methylglyoxal-induced modifications of significant honeybee proteinous components in manuka honey: Possible therapeutic implications. Fitoterapia 83, 671-677, doi:S0367-326X(12)00051-2 [pii]
10.1016/j.fitote.2012.02.002 (2012).
96 Poulsen, M. W. et al. Advanced glycation endproducts in food and their effects on health. Food and Chemical Toxicology 60, 10-37, doi:10.1016/j.fct.2013.06.052 (2013).
97 Adams, C. J., Manley-Harris, M. & Molan, P. C. The origin of methylglyoxal in New Zealand manuka (Leptospermum scoparium) honey. Carbohydrate Research 344, 1050-1053, doi:http://dx.doi.org/10.1016/j.carres.2009.03.020 (2009).
98 Cao, L. F., Zheng, H. Q., Pirk, C. W., Hu, F. L. & Xu, Z. W. High Royal Jelly-Producing Honeybees (Apis mellifera ligustica) (Hymenoptera: Apidae) in China. Journal of economic entomology, doi:10.1093/jee/tow013 (2016).
99 Zheng, H.-Q., Hu, F.-L. & Dietemann, V. Changes in composition of royal jelly harvested at different times: consequences for quality standards. Apidologie 42, 39-47, doi:10.1051/apido/2010033 (2011).
100 Wongchai, V. & Ratanavalachai, T. Seasonal variation of chemical composition of royal jelly produced in Thailand. Thammasat International Journal of Science and Technology 7, 1 - 8 (2002).
101 Kodai, T., Umebayashi, K., Nakatani, T., Ishiyama, K. & Noda, N. Compositions of royal jelly II. Organic acid glycosides and sterols of the royal jelly of honeybees (Apis mellifera). Chemical and Pharmaceutical Bulletin 55, 1528-1531, doi:JST.JSTAGE/cpb/55.1528 [pii] (2007).
102 Kanelis, D. et al. A suggestion for royal jelly specifications. Archives of Industrial Hygiene and Toxicology 66, 275-284, doi:10.1515/aiht-2015-66-2651 (2015).
103 Bíliková, K., Wu, G. & Šimúth, J. Isolation of a peptide fraction from honeybee royal jelly as a potential antifoulbrood factor. Apidologie 32, 275-283 (2001).
104 Stratev, D., Vashin, I., Balkanska, R. & Dinkov, D. Antibacterial activity of royal jelly and rape honey against Aeromonas hydrophila (ATCC 7965). Journal of Food and Health Science 1, 67-74, doi:10.3153/JFHS15006 (2015).
105 Dinkov, D., Stratev, D., Balkanska, R. & Sergelidis, D. Antibacterial activity of royal jelly and rape honey agaist methicillin resistant Staphylococcus aureus strains. Journal of Food and Health Science 2, 67-73, doi:10.3153/JFHS16007 (2016).
106 Boukraa, L. Additive activity of royal jelly and honey against Pseudomonas aeruginosa. Alternative Medicine Review 13, 330-333 (2008).
107 Nascimento, A. P. et al. The lyophilization process maintains the chemical and biological characteristics of royal jelly. Evidence-Based Complementary and Alternative Medicine 2015, 825068, doi:10.1155/2015/825068 (2015).
108 Sabatini, A. G., Marcazzan, G. L., Caboni, M. F., Bogdanov, S. & Almeida-Muradian, L. Quality and standardisation of royal jelly. Journal of ApiProduct and ApiMedical Science 1, 1-6 (2009).
109 Schmitzova, J. et al. A family of major royal jelly proteins of the honeybee Apis mellifera L. Cellular and molecular life sciences : CMLS 54, 1020-1030 (1998).
110 Kimura, Y. et al. Structural features of N-glycans linked to royal jelly glycoproteins: structures of high-mannose type, hybrid type, and biantennary type glycans. Bioscience, Biotechnology and Biochemistry 64, 2109-2120 (2000).
111 Fontana, R. et al. Jelleines: a family of antimicrobial peptides from the Royal Jelly of honeybees (Apis mellifera). Peptides 25, 919-928, doi:10.1016/j.peptides.2004.03.016 (2004).
112 Romanelli, A. et al. Peptides from royal jelly: studies on the antimicrobial activity of jelleins, jelleins analogs and synergy with temporins. Journal of Peptide Science 17, 348-352, doi:10.1002/psc.1316 (2011).
113 Schonleben, S., Sickmann, A., Mueller, M. J. & Reinders, J. Proteome analysis of Apis mellifera royal jelly. Analytical and Bioanalytical Chemistry 389, 1087-1093, doi:10.1007/s00216-007-1498-2 (2007).
114 Bilikova, K., Huang, S. C., Lin, I. P., Simuth, J. & Peng, C. C. Structure and antimicrobial activity relationship of royalisin, an antimicrobial peptide from royal jelly of Apis mellifera. Peptides 68, 190-196, doi:S0196-9781(15)00059-5 [pii]
10.1016/j.peptides.2015.03.001 (2015).
115 Shen, L. et al. Expression of Acc-royalisin gene from royal jelly of Chinese honeybee in Escherichia coli and its antibacterial activity. Journal of Agricultural and Food Chemistry 58, 2266-2273 (2010).
116 Townsend, G. F. et al. Studies on the in vitro antitumor activity of fatty acids I. 10-hydroxy-2-decenoic acid from royal jelly. Cancer research 20, 503-510 (1960).
117 Hattori, N., Nomoto, H., Fukumitsu, H., Mishima, S. & Furukawa, S. Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro. Biomedical Research 28, 261-266 (2007).
118 Wang, J. et al. 10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K–AKT pathway. International Immunopharmacology 28, 97-104 (2015).
119 Takikawa, M. et al. 10‐Hydroxy‐2‐decenoic acid, a unique medium‐chain fatty acid, activates 5'‐AMP‐activated protein kinase in L6 myotubes and mice. Molecular Nutrition & Food Research 57, 1794-1802 (2013).
120 Yousefi, B. et al. Hydroxy decenoic acid down regulates gtfB and gtfC expression and prevents Streptococcus mutans adherence to the cell surfaces. Annals of clinical microbiology and antimicrobials 11, 21, doi:1476-0711-11-21 [pii]
10.1186/1476-0711-11-21 (2012).
121 Morais, M., Moreira, L., Feas, X. & Estevinho, L. M. Honeybee-collected pollen from five Portuguese Natural Parks: palynological origin, phenolic content, antioxidant properties and antimicrobial activity. Food and Chemical Toxicology 49, 1096-1101, doi:S0278-6915(11)00029-9 [pii]
10.1016/j.fct.2011.01.020 (2011).
122 Almeida-Muradian, L., Pamplona, L. C., Coimbra, S. l. & Barth, O. M. Chemical composition and botanical evaluation of dried bee pollen pellets. Journal of food composition and analysis 18, 105-111 (2005).
123 Hansen, M. The healing power of pollen and other products form the beehive, propolis, royal jelly and honey. (Thorsons, 1979).
124 Mărghitaş, L. A. et al. In vitro antioxidant capacity of honeybee-collected pollen of selected floral origin harvested from Romania. Food Chemistry 115, 878-883 (2009).
125 Gebara, E. C., Lima, L. A. & Mayer, M. Propolis antimicrobial activity against periodontopathic bacteria. Brazilian Journal of Microbiology 33, 365-369 (2002).
126 Cook, N. & Samman, S. Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. The Journal of Nutritional Biochemistry 7, 66-76 (1996).
127 Garcia, M., Pérez-Arquillue, C., Juan, T., Juan, M. & Herrera, A. Note. Pollen analysis and antibacterial activity of Spanish honeys. Food Science and Technology International 7, 155-158 (2001).
128 Proestos, C., Chorianopoulos, N., Nychas, G. J. & Komaitis, M. RP-HPLC analysis of the phenolic compounds of plant extracts. investigation of their antioxidant capacity and antimicrobial activity. Journal of Agricultural and Food Chemistry 53, 1190-1195, doi:10.1021/jf040083t (2005).
129 Almaraz-Abarca, N. et al. Variability of antioxidant activity among honeybee-collected pollen of different botanical origin. Interciencia 29, 574-578 (2004).
130 Balch, P. A. Prescription for Nutritional Healing: The A-to-Z Guide to Supplements. (Avery, 2002).
131 Carpes, S. T., Begnini, R., Alencar, S. M. d. & Masson, M. L. Study of preparations of bee pollen extracts, antioxidant and antibacterial activity. Ciência e Agrotecnologia 31, 1818-1825 (2007).
132 Broadhurts, C. L. Bee product: medicine from the hive. Nutrition science news 4, 366-368 (1999).
133 Freire, K. R. et al. Palynological origin, phenolic content, and antioxidant properties of honeybee-collected pollen from Bahia, Brazil. Molecules (Basel, Switzerland) 17, 1652-1664, doi:10.3390/molecules17021652 (2012).
134 Campos, M. G. et al. Pollen composition and standardisation of analytical methods. Journal of Apicultural Research 47, 154-161 (2008).
135 Campos, M., Frigerio, C., Lopes, J. & Bogdanov, S. What is the future of Bee-Pollen. Journal of ApiProduct and ApiMedical Science 2, 131-144 (2010).
136 Rzepecka-Stojko, A. et al. Polyphenols from bee pollen: Structure, absorption, metabolism and biological activity. Molecules (Basel, Switzerland) 20, 21732-21749, doi:molecules201219800 [pii]
10.3390/molecules201219800 (2015).
137 Baltrušaitytė, V., Venskutonis, P. R. & Čeksterytė, V. Antibacterial activtiy of honey and beebread of different origin agaist Staphylococcus aureus and S. epidemidis. Food Technology and Biotechnology 45, 201-208 (2007).
138 Erkmen, O. & Ozcan, M. M. Antimicrobial effects of Turkish propolis, pollen, and laurel on spoilage and pathogenic food-related microorganisms. Journal of medicinal food 11, 587-592, doi:10.1089/jmf.2007.0038 (2008).
139 Graikou, K. et al. Chemical analysis of Greek pollen - Antioxidant, antimicrobial and proteasome activation properties. Chemistry Central Journal 5, 33-33, doi:10.1186/1752-153x-5-33 (2011).
140 Nakamura, K. et al. Bactericidal activity and mechanism of photoirradiated polyphenols against Gram-Positive and -Negative Bacteria. Journal of Agricultural and Food Chemistry 63, 7707-7713, doi:10.1021/jf5058588 (2015).
141 Cushnie, T. T. & Lamb, A. J. Antimicrobial activity of flavonoids. International Journal of Antimicrobial Agents 26, 343-356 (2005).
142 Tichy, J. & Novak, J. Detection of antimicrobials in bee products with activity against viridans streptococci. The Journal of Alternative and Complementary Medicine 6, 383-389 (2000).
143 Abouda, Z., Zerdani, I., Kalalou, I., Faid, M. & Ahami, M. The antibacterial activity of Moroccan bee bread and bee-pollen (fresh and dried) against pathogenic bacteria. Research Journal of Microbiology 6, 376 (2011).
144 Kačániová, M. et al. Antimicrobial activity of bee collected pollen against Clostridia. Lucrari Stiintifice : Zootehnie si Biotehnologii 47, 362-365 (2014).
145 Kacániová, M. et al. The antimicrobial activity of honey, bee pollen loads and beeswax from Slovakia. Archives of Biological Sciences 64, 927-934 (2012).
146 Mohdaly, A. A. A., Mahmoud, A. A., Roby, M. H. H., Smetanska, I. & Ramadan, M. F. Phenolic extract from propolis and bee pollen: Composition, antioxidant and antibacterial activities. Journal of Food Biochemistry 39, 538-547, doi:10.1111/jfbc.12160 (2015).
147 MĂRGĂOAN, R. A. et al. Antimicrobial activity of bee pollen ethanolic and methanolic extracts on Staphylococcus aureus bacterial strain. Bulletin of the University of Agricultural Sciences and Veterinary Medicine 72, 78-80 (2015).
148 Khider, M., Elbanna, K., Mahmoud, A. & Owayss, A. A. Egyptian honeybee pollen as antimicrobial, antioxidant agents, and dietary food supplements. Food Science and Biotechnology 22, 1-9 (2013).
149 Pascoal, A., Rodrigues, S., Teixeira, A., Feás, X. & Estevinho, L. M. Biological activities of commercial bee pollens: Antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food and Chemical Toxicology 63, 233-239 (2014).
150 Koc, A. N. et al. Antifungal activity of the honeybee products against Candida spp. and Trichosporon spp. Journal of medicinal food 14, 128-134, doi:10.1089/jmf.2009.0296 (2011).
151 Özcan, M., Ünver, A., Ceylan, D. A. & Yetisir, R. Inhibitory effect of pollen and propolis extracts. Food/Nahrung 48, 188-194 (2004).
152 Nogueira, C., Iglesias, A., Feás, X. & Estevinho, L. M. Commercial bee pollen with different geographical origins: A comprehensive approach. International Journal of Molecular Sciences 13, 11173-11187, doi:10.3390/ijms130911173 (2012).
153 Bogdanov, S. Bee venom: composition, health, medicine: a review. Peptides 1 (2012).
154 Lee, G. & Bae, H. Bee venom phospholipase A2: Yesterday’s enemy becomes today’s friend. Toxins 8, 48 (2016).
155 Ali, M. Studies on bee venom and its medical uses. International Journal of Advancements in Research & Technology, 1, 1-15 (2012).
156 Schumacher, M. J., Schmidt, J. O., Egen, N. B. & Dillon, K. A. Biochemical variability of venoms from individual European and Africanized honeybees (Apis mellifera). Journal of Allergy and Clinical Immunology 90, 59-65 (1992).
157 Ferreira Junior, R. S. et al. Africanized honey bee (Apis mellifera) venom profiling: Seasonal variation of melittin and phospholipase A(2) levels. Toxicon : official journal of the International Society on Toxinology 56, 355-362, doi:10.1016/j.toxicon.2010.03.023 (2010).
158 Banks, B. E. C. & Shipolini, R. A. in Venoms of the Hymenoptera: Biochemical, Pharmacological and Behavioural Aspects (ed T. Piek) (Academic Press, 1986).
159 Danneels, E., Van Vaerenbergh, M., Debyser, G., Devreese, B. & de Graaf, D. Honeybee venom proteome profile of Queens and winter bees as determined by a mass spectrometric approach. Toxins 7, 4468 (2015).
160 Fennell, J. F., Shipman, W. H. & Cole, L. J. Antibacterial action of melittin, a polypeptide from bee venom.
Experimental Biology and Medicine 127, 707-710 (1968).
161 Han, S. M. et al. Antibacterial activity and antibiotic-enhancing effects of honeybee venom against methicillin-resistant Staphylococcus aureus. Molecules (Basel, Switzerland) 21, 79, doi:10.3390/molecules21010079 (2016).
162 Gauldie, J., Hanson, J. M., Rumjanek, F. D., Shipolini, R. A. & Vernon, C. A. The peptide components of bee venom. European Journal of Biochemistry 61, 369-376 (1976).
163 Benton, A. W. & Morse, R. A. Venom toxicity and proteins of the genus Apis. Journal of Apicultural Research 7, 113-118 (1968).
164 Boutrin, M. C., Foster, H. A. & Pentreath, V. W. The effects of bee (Apis mellifera) venom phospholipase A2 on Trypanosoma brucei brucei and Enterobacteria. Experimental parasitology 119, 246-251, doi:10.1016/j.exppara.2008.02.002 (2008).
165 Leandro, L. F. et al. Antimicrobial activity of apitoxin, melittin and phospholipase A(2) of honey bee (Apis mellifera) venom against oral pathogens. Anais da Academia Brasileira de Ciencias 87, 147-155, doi:10.1590/0001-3765201520130511 (2015).
166 Mollay, C. & Kreil, G. Enhancement of bee venom phospholipase A2 activity by melittin, direct lytic factor from cobra venom and polymyxin B. FEBS Letters 46, 141-144, doi:http://dx.doi.org/10.1016/0014-5793(74)80354-6 (1974).
167 Mollay, C., Kreil, G. & Berger, H. Action of phospholipases on the cytoplasmic membrane of Escherichia coli. Stimulation by melittin. Biochimica et Biophysica Acta - Biomembranes 426, 317-324, doi:http://dx.doi.org/10.1016/0005-2736(76)90340-0 (1976).
168 Choi, J. H. et al. Melittin, a honeybee venom derived antimicrobial peptide, may target methicillin resistant Staphylococcus aureus. Molecular Medicine Reports 12, 6483-6490 (2015).
169 Dosler, S., Karaaslan, E. & Alev Gerceker, A. Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria. Journal of Chemotherapy, 1973947815Y0000000004, doi:10.1179/1973947815y.0000000004 (2015).
170 Al-Ani, I., Zimmermann, S., Reichling, J. & Wink, M. Pharmacological synergism of bee venom and melittin with antibiotics and plant secondary metabolites against multi-drug resistant microbial pathogens. Phytomedicine 22, 245-255, doi:10.1016/j.phymed.2014.11.019 (2015).