| antioxidant |
apo-LF |
relatively
high binding affinity of apo-LF to
Fe2+ and Cu2+ allows reduction of the
prooxidant effect of these ions (Fenton reaction) |
(217, 218) |
| |
holo-LF |
activation of the gene expression of antioxidant markers; overexpression
of antioxidant enzymes |
(219) |
| |
LF–Se |
enhanced activity of antioxidant
enzymes (GPx, GR, GST) within cells and tissues with deficiency
of selenium; selenium is capable of interacting with glutathione and
enables maintaining equilibrium between the oxidant/antioxidant systems |
(220) |
| anticancer |
holo-LF |
potential activator of natural
killer cells inducing apoptosis
cancer cells (MDA-MB-231, MCF-7); modulation
and decrease the expression of inhibitors of apoptotic proteins (surviving); overexpression of Bcl-2 pro-apoptotic proteins (Bax, Bak), mediated in the mitochondrial pathway
of apoptosis |
(35, 221) |
| |
CGA–LF |
LF complex with chlorogenic acid (CGA) inhibited the proliferation of human colon cancer cells (SW480) in a dose dependent manner (the most optimal mixture consists of 100 μM CGA and 200 μM LF); treatment of cancer cells with CGA–LF complexes promote their apoptosis |
(222) |
| |
LF–OA |
treatment of cancer cells (HepG2, HT29, MCF) with lactoferrin–oleic acid complexes (LF–OA) induced
the activation of mitochondria apoptosis pathway, which corresponded
with expression of caspase-3 and pro-apoptic Bax protein; overexpression of p-JKN regulator confirmed the possibility of death receptor-mediated apoptosis pathway |
(223) |
| antibacterial |
apo-LF |
limitation of the availability of iron to microorganisms
resulting
in direct binding of this element in the protein structure contributing
to host defense against pathogens; antibacterial activity of LF against Gram-positive bacteria (S. epidermidis, B. cereus) was greater than against Gram-negative (C. jejuni, Salmonella), which suggests their
higher sensitivity to iron deficiency; direct interactions of LF with
components of microbial cells with lead to increase the permeability
of their membranes resulting in destabilization of structure; prevalence
of basic amino acid in LF sequence provides its high binding affinity
to negatively charged lipopolysaccharides of bacteria membranes; interaction
of LF with LPS caused the inhibition of growth of Gram-negative bacteria resulting in damage to cell; antibacterial activity of
LF can be weakened in presence of some cations (Mg2+ and Ca2+) and anions (HEPES, phosphate, and citrate), which indicates the importance of electrostatic interactions during
binding of LF to bacteria surface; citrate is known as a strong chelator
for ferric ions which will compete with LF for metal binding and consequently
will modify the protein antimicrobial properties; higher antibacterial
activity LF peptides (lactoferricin) in comparison to native protein might be related to less branched
structure which facilitates its interaction with bacteria cell |
(7, 224−228) |
| |
holo-LF |
antibacterial effect of LF (0.1–2.0 mg/mL) against P. aeruginosa was based on the destructive
of biofilm around its cell surface; addition of FeCl3 significantly
decreased antibiofilm effect of LF, suggesting that free ferric ions
may participate in the process of biofilm formation |
(229) |
| |
Ag–LF |
Ag–LF complex showed
germicidal activity against pathogenic bacteria; inhibition of Gram-positive and Gram-negative bacteria (E. faecalis, E. coli, P. aeruginosa, and S. aureus) growth was caused by
the antibiofilm activity of the complex |
(230, 231) |
| antiviral |
bLF |
LF is able interact with viral particles
and also competes
with them for binding to common receptors, avoiding in that way the
adsorption and entering of viruses into the cells; neutralization
of HCV resulting in rapid interactions of virus with bLF occurred
much faster than entering of HCV into the cells; it was reported that
sialic acid as part of LF glycan chain is not involved in these interactions,
but it was reported that desialylated bLF exhibited a higher antiviral
effect against rotavirus compared to native bLF; enhancing of antirotavirus
activity after removing of sialic acid is related to facilitation
of binding of LF with virus; incorporated ferric ion could contribute
to the antiviral activity because holo-LF exerted more effective inhibition of HCV than apo-LF; different activity could be also caused by conformational alterations
that occur in LF structure after metal binding; moreover, LF saturated
with such metals as Fe3+, Mn2+, and Zn2+ was characterized by higher activity against HIV compared to apo-LF |
(126, 151, 232, 233) |
| |
Zn–LF |
antiviral
activity against poliovirus of Zn–LF complex was directly correlated with degree of saturation of LF;
inhibition of viral replication process was based on the binding of LF–metal complex to cell surface and transport
of metal ion across cell membrane that led to interference of virus
maturation |
(234, 235) |
| |
holo-LF |
Fe–LF exhibits
higher anti-HIV activity in T-cell line than other Mn–LF and Zn–LF complexes; as the
authors remarked,
preincubation of cells with protein–metal complex induced more
effective inhibition of HIV infection; Fe–LF may be applied as potential antiviral agent in some diet supplements |
(233) |
| prebiotic |
bLF |
prebiotic
activity of bovine lactoferrin was compared in vitro as well as in fresh cheese samples; it was indicated
that bLF promoted the growth of probiotic bacterial strains (Lactobacillus casei) only in vitro, while their population in fresh cheese samples
was not changed probably because of the presence of psychotropic bacteria |
(236) |
| |
holo-LF |
iron-saturated form
of LF stimulated
the growth of LAB strains (Lactobacillus delbrueckii ssp. bulgaricus, Streptococcusthermophilus) in the yogurt which might be directly related with
chelated metal |
(237) |
| |
Mn–LF |
prebiotic potential of Mn–LF complexes was examined monitoring the
number of Lactobacillus strains (L. plantarum and L. rhamnosus); significant population growth
was observed after 24 h of incubation
of bacterial culture with Mn–LF; the authors related such effect to
manganese uptake which contributes probiotic viability |
(24) |
| anti-inflammatory |
bLF |
LF supplementation reduced the activation of the NF-κB signaling pathway which corresponded
with suppressed expression of pro-inflammatory cytokines (TMF-α, IL-1β) in uterine tissue |
(238) |
