suppresses the lipopolysaccaride (LPS)-induced production of
nitric oxide in macrophages and was shown to decrease iNOS
mRNA and its protein expression by inhibiting NF-ĸ B/Rel activation.
68 In the inactive state, NF-ê B remains complexed to the
inhibitory protein I- ĸB. However, upon activation by various signals,
NF-ĸB can translocate to the nucleus and bind to the kappa
B motif of the target gene.63 Silymarin has been shown to inhibit
many steps in the NF-ĸB pathway; it blocks TNF alpha and UVinduced
activation of NF-ĸB, translocation to the nucleus and ĸ
B DNA binding and gene expression. Interestingly, the effects
of silymarin on NF-ĸB activation are specific, and do not impact
AP-1 activation. Silymarin can also inhibit the TNF-induced activation
of MAP kinase kinase and c-jun kinase and mitigated
TNF-induced cytotoxicity and caspase activation.69,70
Polyphenols can be obtained through both diet and oral supplementation
but these methods are limited by poor systemic
bioavailability and variability of gut metabolism.16 Supplementing
skin with a topical antioxidant is a more intuitive way of directly
replenishing the skin’s endogenous antioxidants that are depleted
from constant UV exposure.71 Various studies have shown that
there is a greater amount of antioxidants in the epidermis compared
to the dermis as the epidermis is in direct contact with oxidative
stressors. However, due to irradiation damage, antioxidant activity
in the upper layers of the stratum corneum decreases over time.72
Topical polyphenol formulations have been shown to have good
permeability in the stratum corneum, with higher concentrations in
the outermost layer, thereby targeting the site of antioxidant loss.72
In one study evaluating the penetration of polyphenols into the
stratum corneum and underlying tissue, 90% of phenolic content
was retained in the stratum corneum, with only 10% in underlying
tissue. Catechins had greater permeability compared to curcumin
and resveratrol, but this observed effect was greatly impacted by
solubility in the delivery vehicle chosen.71 Passive delivery of polyphenol
extracts is greatly dependent on the formulation, which
affects the permeability of the active agent into deeper skin layers.
The most common delivery agents currently employed are gels or
emulsions, which have shown efficacy for topical polyphenol delivery.
15 As antioxidants are inherently unstable, creation of a stable
formulation has been a challenge.14 Proper investigation into the
optimal concentration and formulation is required for standardization
and maximization of polyphenol delivery to skin.
Endogenous defense mechanisms are inadequate to combat
oxidative stress and therefore dietary and/or topical supplementation
with polyphenols are an important complementary
preventative and therapeutic strategy. These natural agents have
broad anti-inflammatory and anti-oxidative properties, targeting
many different cellular responses to ROS stimulation. Though
most of the evidence for the protective effects of polyphenols are
derived from in vitro and animal studies, epidemiologic studies
do suggest an improvement with polyphenolic supplementation
on cardiovascular markers in particular. Continued research into
bioavailability and function of these agents will help translate
their therapeutic potential to treat clinical disease.
Adam Friedman has been an investigator, consultant, or speaker
for Johnson & Johnson, Amgen, Valeant, Onset, Loreal, and
Salvona. Holly Gunn and Aimee Krausz have not disclosed any
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