Effect of honey and its major royal jelly protein 1 on cytokine and MMP-9 mRNA transcripts in human keratinocytes

Institute of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia.
Experimental Dermatology (Impact Factor: 3.76). 10/2009; 19(8):e73-9. DOI: 10.1111/j.1600-0625.2009.00994.x
Source: PubMed


Honey has been used since ancient times as a remedy in wound healing. However, even though the results from randomized clinical trials document that honey accelerates wound healing, no study dealing with its influence on human skin cells (epidermal keratinocytes and dermal fibroblast) has been performed. We demonstrate that keratinocytes, which are known to be involved in wound healing, are responsible for elevated production of mediators including cytokines (TNF-alpha, IL-1beta and TGF-beta) and matrix metalloproteinase-9 (MMP-9) after incubation with honey. Real-time PCR was performed for the quantification of mRNA level of selected cytokines and MMP-9. Furthermore, we show that the increased level of MMP-9 in the epidermis following incubation with honey leads to degradation of type IV collagen in the basement membrane. These data indisputably demonstrate that honey activates keratinocytes and support the findings that honey may accelerate wound healing process.

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    • "This view was initially supported by a fi nding that the MRJP1 protein can be specifi cally degraded by serine proteases, generating a substantial number of MRJP1-related peptides [Rossano et al., 2012]. However, the degradation products of MRJP1 were also shown to have immune-stimulatory activities [Majtan et al., 2006; Tonks et al., 2003] and cell growth stimulatory activity [Watanabe et al., 1998; Kamakura et al., 2001; Majtan et al., 2009]. "
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    ABSTRACT: There is increasing evidence that protein complexation by honey polyphenols is changing honey structure and function. This relatively less investigated fi led of honey research is presented in a context of known mechanism of formation of the stable polyphenol-protein complexes in other foods. At a core of these interactions lies the ability of polyphenols to form non-covalent and covalent bonds with proteins leading to transient and/or irreversible complexes, respectively. Honey storage and thermal processing induces non-enzymatic oxidation of polyphenols to reactive quinones and enables them to form covalent bonds with proteins. In this short review, we present data from our laboratory on previously unrecognized types of protein-polyphenol complexes that differed in size, stoichiometry, and antioxidant capacities, and the implications they have to honey antioxidant and antibacterial activities. Our intent is to provide a current understanding of protein-polyphenol complexation in honey and also some new thoughts /hypotheses that can be useful in directing future research.
    Polish Journal of Food and Nutrition Sciences 04/2015; 65(2):71-80. DOI:10.1515/pjfns-2015-0030 · 0.64 Impact Factor
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    • "Fir honeydew honey contains the flavonoids apigenin and kaempferol, which inhibited TNF-a-induced production of matrix metalloproteinase (MMP)-9 from keratinocytes (Majtan et al., 2013). In contrast, Acacia honey stimulated keratinocytes to release MMP9, together with TNF-a, IL-1b and TGF-b (Majtan et al., 2010). Manuka honey, and to a lesser extent kanuka and rewarewa contain the anti-microbial methyl glyoxal, which modifies the apalbumins, endowing them with an ability to inhibit phagocytosis by macrophages (Bean, 2012). "
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    ABSTRACT: Here we determined whether immunostimulatory plant-derived arabinogalactan proteins (AGPs) and the honeybee-derived protein apisimin are present in varieties of New Zealand honey. Apisimin is a protein of unknown function secreted from the glands of honeybees into Royal Jelly, forming a complex with apalbumin1 capable of stimulating lymphocyte proliferation. AGPs were abundant in kanuka honey with lesser amounts in manuka, kowhai and clover honeys, but absent from Royal Jelly. Apisimin was present in all honeys, as well as Royal Jelly. We report that apisimin shares with honey AGPs the ability to stimulate the release of TNF-α from blood monocytes. Further, it synergizes with AGPs to enhance the release of TNF-α, via a mechanism not involving the formation of a complex with AGPs. In summary, this study provides evidence that AGPs and apisimin are commonly present in different floral varieties of honey, and hence contribute to their immunostimulatory properties.
    Food Chemistry 02/2015; 168:34–40. DOI:10.1016/j.foodchem.2014.07.007 · 3.39 Impact Factor
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    • "In addition to its antibacterial activity, immunmodulatory effects of honey have been described. Honey stimulates the release of inflammatory cytokines from monocytes [44], mRNA expression of TGF-β as an wound-healing promoting cytokine is upregulated [45]. Propolis does not have a high cytotoxicity against periodontal ligament cells [46]. "
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    ABSTRACT: Honey has been discussed as a therapeutic option in wound healing since ancient time. It might be also an alternative to the commonly used antimicrobials in periodontitis treatment. The in-vitro study was aimed to determine the antimicrobial efficacy against Porphyromonas gingivalis as a major periodontopathogen. One Manuka and one domestic beekeeper honey have been selected for the study. As a screening, MICs of the honeys against 20 P. gingivalis strains were determined. Contents of methylglyoxal and hydrogen peroxide as the potential antimicrobial compounds were determined. These components (up to 100 mg/l), propolis (up to 200 mg/l) as well as the two honeys (up to 10% w/v) were tested against four P. gingivalis strains in planktonic growth and in a single-species biofilm. 2% of Manuka honey inhibited the growth of 50% of the planktonic P. gingivalis, the respective MIC50 of the German beekeeper honey was 5%. Manuka honey contained 1.87 mg/kg hydrogen peroxide and the domestic honey 3.74 mg/kg. The amount of methylglyoxal was found to be 2 mg/kg in the domestic honey and 982 mg/kg in the Manuka honey. MICs for hydrogen peroxide were 10 mg/l - 100 mg/l, for methylglyoxal 5 - 20 mg/l, and for propolis 20 mg/l - 200 mg/l. 10% of both types of honey inhibited the formation of P. gingivalis biofilms and reduced the numbers of viable bacteria within 42 h-old biofilms. Neither a total prevention of biofilm formation nor a complete eradication of a 42 h-old biofilm by any of the tested compounds and the honeys were found. Honey acts antibacterial against P. gingivalis. The observed pronounced effects of Manuka honey against planktonic bacteria but not within biofilm can be attributed to methylglyoxal as the characteristic antimicrobial component.
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