Review Article

The Anti-Inflammatory and Antibacterial Action of Nanocrystalline Silver and Manuka Honey on the Molecular Alternation of Diabetic Foot Ulcer: A Comprehensive Literature Review

Table 3

Modes of action of manuka honey.

NumberAuthorsNature of studiesMajor findings on antibacterial action

Physical property
[76]M. D. Mandal and S. Mandal, 2011ReviewOsmotic effect can draw water from bacteria and dehydrate them
[77]Molan, 2001ReviewAcidity (pH 3.2–5.5) can inhibit the growth of most microorganisms

Active ingredient
[78] Adams et al., 2008In vitroHigh concentrations of MGO ranged from 38 to 828 mg/kg as compared with non-MH
[79]Mavric et al., 2008In vitroMGO ranging from 38 to 761 mg/kg can inhibit E. coli and S. aureus at 1.1 mM
[80]Atrott and Henle, 2009In vitroMGO ranged from 189 to 835 mg/kg and was directly responsible for the antibacterial property
[81]Kwakman et al., 2011In vitroGlycoside of methyl syringate called “Leptosin” correlated positively with antibacterial activity
[82]Kato et al., 2012In vitroOther than MGO, cationic and noncationic compounds contributed to antibacterial activity

Mechanism of action
[83]
[84]
Henriques et al., 2010
Jenkins et al., 2011
In vitroHoney-treated cells fail to proceed cell division and separation
(i) S. aureus(ii) MRSA
[85]Roberts et al., 2012In vitroExtensive cell lysis on P. aeruginosa at MIC 12% (w/v) after 60 minutes of exposure to MH
[86]Packer et al., 2012In vitroRibosomal function on S. aureus interfered including protein synthesis, the metabolic process, and transcription
[87]Maddocks et al., 2012In vitroInhibition of the binding of Streptococcus pyogenes to fibronectin and the development of biofilm
[88]Kronda et al., 2013In vitroLimit P. aeruginosa to capture iron and impede its growth

Bactericidal activity on different microorganisms
[89]Cooper et al., 1999In vitroStreptococcus pyogenes
[90]Cooper et al., 2002In vitroPseudomonas species
[91]Hammond and Donkor, 2013In vitroClostridium difficile
[81]Kwakman et al., 2011In vitroMRSA, Bacillus subtilis, E. coli, P. aeruginosa
[87]Maddocks et al., 2012In vitroStreptococcus pyogenes
[92]Cooper et al., 2002In vitroVancomycin-resistant Enterococci
[93]French et al., 2005In vitroAntibiotic-resistant strains of coagulase-negative Staphylococci

NumberAuthorsNature of studiesMajor findings on anti-inflammatory action

Active ingredient
[94]Chan et al., 2013In vitroPinobanksin, pinocembrin, luteolin, and chrysin are the major flavonoids found in MH; low levels of quercetin and galangin were also detected
[95]Raso et al., 2001In vitroQuercetin and galangin inhibit the expression of COX-2 and iNOs in a concentration-dependent manner
[96]Cho et al., 2004In vitroChrysin suppresses the activity of proinflammatory enzymes
[97]Tonks et al., 2007In vitro5.8-kDa component isolated from MH stimulates the proinflammatory cytokines TNF-α and IL-1β and the anti-inflammatory cytokines IL-6 via toll-like receptor (TLR) 4
[98]Tomblin et al., 2014In vitroPhenolic content is directly correlated to the anti-inflammatory activity of MH through a TLR1/TLR2 signalling pathway

NumberAuthorsNature of studiesMajor findings on anti-inflammatory action

Mechanism of action
[99]Henriques et al., 2006In vitroThe formation of free radicals such as hydroxyl radicals are inhibited and contribute to resolving chronic inflammation
[100]Tonks et al., 2003In vitroProinflammatory cytokines TNF-α and IL-1β as well as anti-inflammatory cytokine IL-6 from monocytes are stimulated
[47]van den Berg et al., 2008In vitroROS production and scavenge superoxide anions are inhibited
[101]Bean, 2012In vitroThe proinflammatory cytokine TNF-α and the anti-inflammatory cytokines IL-10 and IL-1 and the growth factors PDGF and TGF-β are upregulated
ROS production by phagocytosis is downregulated
[102]Leong et al., 2012In vitro
Animal study
The production of superoxides by neutrophil decreased
Leukocyte infiltration and odema in the mice model decreased