Role of Oral Polypodium Leucotomos Extract in Dermatologic Diseases: A Review of the Literature

February 2014 | Volume 13 | Issue 2 | Original Article | 148 | Copyright © February 2014

Samreen Z. Choudhry MD,a Neal Bhatia MD,b Roger Ceilley MD,c Firas Hougeir MD,d
Robert Lieberman MD,e Iltefat Hamzavi MD,a and Henry W. Lim MDa

aDepartment of Dermatology, Henry Ford Hospital, Detroit, MI
bAssociate Clinical Professor, Harbor-UCLA Medical Center, Los Angeles, CA
cClinical Professor of Dermatology, University of Iowa, Private Practice, West Des Moines, IA
dAtlanta, GA
eThomas Dermatology, Inc. Las Vegas, NV

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.