INTRODUCTION
Polypodium leucotomos is a species of fern in the family Polypodiaceae. The South American P. leucotomos species is known locally as “calaguala†and extracts of this fern are called “anapsos.†P. leucotomos extracts have been used for the treatment of psoriasis in South America and Spain1 and growing clinical scientific evidence suggests P. leucotomos is also beneficial for the treatment of various skin disorders and conditions including atopic dermatitis,2 vitiligo3 and, because it affords sun protection from ultraviolet radiation, prevention of polymorphic light eruption.4 Its antitumor effects were alluded to nearly 50 years ago.5 Phenolic components of P. leucotomos extract include chlorogenic acid, coumaric acid, vanillic acid, caffeic acid and ferulic acid, the latter two being the most potent inhibitors of oxidation in vitro.6,7 We review the in vivo animal, in vitro human, and human clinical studies performed to help elucidate the actions of and pathways affected by PL.
EXPERIMENTAL EVIDENCE
In Vivo Animal Studies
Strains of hairless albino mice have been developed for studying the harmful effects of UV radiation on the skin8,9; using these animals, numerous studies have demonstrated the beneficial effects of P. leucotomos following skin exposure to ultraviolet light.
In 1999, the antioxidant and photoprotective properties of P. leucotomos extract were demonstrated when applied topically to hairless mice exposed to UVB radiation.10 Compared to untreated mice, P. leucotomos-treated mice showed a significant reduction in the sunburn response and diminished histologic evidence of photoaging damage, including reduced dermal elastosis. Eight weeks after stopping UV exposure, P. leucotomos-treated mice also showed a reduction in the development of skin tumors compared to untreated UV-exposed mice.
A subsequent study showed that P. leucotomos also has beneficial effects when administered orally in a similar hairless mouse model.11 These animals were fed ~300mg/kg/day of P. leucotomos extract or vehicle in their drinking water for 10 days and then exposed to UV radiation and evaluated for cyclooxygenase-2 (Cox-2) expression by Western blot analysis. Upregulation of Cox-2 is associated with UV-induced skin cancer.12,13 Cox-2 levels were 4-times lower in P. leucotomos-fed mice at 48 hours and 5-times lower at 72 hours, compared to vehicle fed mice. Other beneficial effects of feeding P. leucotomos included a significant decrease in UV-induced inflammation including a 60% decrease in neutrophil infiltration into the skin at 24 hours and a 50% decrease macrophages in the skin at 24 and 48 hours.11
Other studies have assessed the ability of P. leucotomos to counteract UV radiation-associated skin cancers. In one study, animals received an oral extract of P. leucotomos (~300 mg/kg) for 5 days prior to UVB (equivalent to 1-1.5 times the minimal erythema dose [MED] and for 2 days afterward. The number of cells positive for the tumor suppressor p53 increased by 63%, proliferating cells decreased by 13% in P. leucotomos treated mice compared to mice that were UV-irradiated but did not receive P. leucotomos. They also had a reinforced network of dermal elastic fibers.14 These animals were observed to have an enhanced the antioxidant plasma capacity that was 30% greater
