hans cells, and cutaneous photoaging due to disruption of the
extracellular matrix.4 Clinically, UV radiation possesses both
pro-inflammatory and anti-inflammatory effects. Its pro-inflammatory
effects include induction of photodermatoses and
photoaggravated skin diseases, and acceleration of cutaneous
photoaging, whereas the anti-inflammatory effects include increased
susceptibility to photocarcinogenesis.
PLE has been shown to act at the molecular and cellular levels
to inhibit UV induced photodamage. Its chemical composition
includes phenolic compounds such as p-coumaric, ferulic,
caffeic, vanillic and chlorogenic acids, potent ROS inhibitors,
which demonstrate significant antioxidant, anti-inflammatory,
and photoprotective activity after systemic absorption.5,6 Specifically,
PLE inhibits Th1 proinflammatory response via Th1
cytokines IL-2, IL-6, IFN-γ, TNF-α, which may explain the use of
PLE in Th-1 mediated inflammatory phenomena such as psoriasis.
7 PLE has also been shown to decrease UV-induced mast
cell infiltration, leading to a reduction in neovascularization, tumor
growth, and cutaneous elastosis7.PLE also has a beneficial
effect in cutaneous photoaging and sun-damaged skin8, as it
has been shown to preserve cytoskeletal structure in human fibroblasts
and their proliferative capacity after exposure to UVA
radiation, as well as improve cell membrane integrity, increase
elastin expression, inhibit lipid peroxidation and MMP-1 expression
in fibroblasts and keratinocytes.9 Its photoprotective
properties are due to its inhibition of UVA and UVB induced
photoisomerization and photodecomposition of trans-urocanic
acid (t-UCA), which is a major UV-absorbing component in the
stratum corneum.10 It also decreases the formation of sunburn
cells, cyclobutane pyrimidine dimers, proliferation of epidermal
cells, and preserves Langerhans cells after UV exposure.11
Effects of PLE on Photoaging and Skin Cancer
The studies are summarized in Table 1. It has been shown
that pre-treatment with PLE may prevent UVA-induced skin
photodamage by preventing UVA-dependent mitochondrial
damage.12 Results from a pilot study conducted by Villa et
al,12 suggest that pre-treatment with oral PLE may prevent
the increase of common deletion (CD) following UVA exposure.
CD is a 4977 base pair long mitochondrial DNA whose
deletion is thought to be induced by chronic UVA radiation
and is found in UVA-damaged skin, hence associated with
photoaging.13 In this study, ten healthy patients received
UVA exposure (2 and 3 times each patient’s MED-A values)
combined with pre-treatment with either two 240mg of PLE
or placebo. PLE was administered 8 and 2 hours prior to
UVA exposure. The authors found that, although there was
no significant histologic difference in skin after UVA exposure
between the two groups, there was a difference with
regard to increase in the common deletion, with the placebo
group showing a higher increase in CD values than the PLE
group. Specifically, the PLE group had less of an increase in CD levels compared to the placebo group as the UVA dose
was increased. This effect, however, did not reach statistical
significance, which could be due to the small sample size.
Another potential mechanism for protective effect of PLE in
photocarcinogenesis is via activation of tumor suppressor
p53 gene and inhibition of molecular marker COX-2, which is
induced by UV exposure and involved in mutagenesis. Both
effects have been demonstrated in a mouse model.14
In another study, Aguilera et al,15 investigated the effect of PLE
in patients who were at a high-risk for skin cancers; the study
included patients with history of melanoma, family history of
melanoma, or atypical mole syndrome. The authors assessed
MED-B in these patients before and after administration of 1080
mg of oral PLE, and found a statistically significant increase in
MED-B values after treatment with oral PLE, with each subject
serving as its own control. Of note, 720 mg of oral PLE was
administered in three doses (240 mg every 8 hours) and then
single doses of 360 mg of oral PLE given 1 day and 3 hours,
respectively, prior to exposure to UVB. The authors also found
that an increase in MED-B was noted in patients with darkercolored
eyes and in those with a lower base-line MED-B. They
concluded that these two characteristics were independent factors
in predicting a better response to oral PLE.
PLE and Photodermatoses
Demonstration of photoprotective properties of PLE has lead
to the investigation of oral PLE for the treatment of immunologically-
mediated photodermatoses, including polymorphous
light eruption (PMLE), solar urticaria, chronic actinic dermatitis,
actinic prurigo, and subacute cutaneous lupus erythematosus
(SCLE) (Table 1).
In a study by Caccialanza et al,16 26 patients with PMLE and two
patients with solar urticaria unresponsive to other topical and
systemic therapy were given a daily dose of 480 mg oral PLE, in
two divided doses, starting fifteen days prior to sun exposure.
Patients were then asked to rate their response to sun exposure.
The authors found that 80% of participants reported a positive
response with oral PLE; specifically, 49% reported improvement
and 31% reported normalization of response to photoexposure
after treatment with oral PLE. The two patients with solar urticaria,
however, did not show any response to the PLE.
A follow-up study by Caccialanza et al,17 with a larger sample
size (53 with PMLE and 4 with solar urticaria) and identical
protocol confirmed similar results.17 They found a statistically
significant (P<0.05) benefit from administration of oral PLE for
treatment of PMLE. Of note, 73.68% of participants reported a
positive response, of which 43.86% noted improvement and
29.82% had normalization. Three out of the four patients with
solar urticaria did not show improvement. They found no adverse
reactions from the use of oral PLE.