Volume 37, Issue 2, Page 21 (February 2006)
LESLIE S. BAUMANN, M.D.
DR. BAUMANN is director of cosmetic dermatology at the University of Miami. To respond to this column, or to suggest topics for future columns, write to Dr. Baumann at our editorial offices via e-mail at
Polypodium leucotomos extract, derived from a tropical fern, has been used to treat inflammatory conditions and has also been demonstrated to exhibit immunomodulating activity in vitro and in vivo. This plant extract has shown antioxidant and photoprotective effects against acute UV exposure (Photodermatol. Photoimmunol. Photomed. 1997;13:50–60; Photodermatol. Photoimmunol. Photomed. 1999;15:120–6).
P. leucotomos is found in abundance in the Honduran rain forest as well as throughout the tropics of Central and South America and the Caribbean. Various parts of the fern are used in traditional medicine in these regions for many indications, including tumors, psoriasis, atopic dermatitis, vitiligo, rheumatoid arthritis, and arthritis.
Early evidence supporting the traditional uses of P. leucotomos extract (PLE) was seen more than 20 years ago in 304 psoriasis patients (Med. Cutan. Ibero. Lat. Am. 1983;11:65–72).
In the 1990s, Dr. Thomas Fitzpatrick and his team at Harvard Medical School heard that this substance, when given orally, had utility in the treatment of vitiligo. They tested it and found, to their surprise, that it did not help vitiligo, but when they gave it to patients with vitiligo who were receiving psoralen-UVA (PUVA) treatment, the recipients developed less erythema from the PUVA.
Dr. Fitzpatrick had spent years looking at ß-carotene as a photoprotective agent and found it inadequate, so he was excited to discover that PLE had this capacity. This excitement eventually led to the published studies, making this botanical extract one of the best studied of the antioxidants.
I first heard about P. leucotomos in 2001 at a cocktail party hosted by the American Academy of Dermatology, where Dr. Fitzpatrick told me about his PLE findings. Since then, many studies evaluating this extract have been published.
Investigators evaluated PLE's free-radical-scavenging activity as part of a study of reactive oxygen species and lipid peroxidation. The authors reported that the fern extract exhibited antioxidant, anti-inflammatory, and photoprotective activity against photooxidative stress in vitro and in vivo.
Testing human and guinea pig skin, they showed that the topical application of PLE significantly inhibited the erythemal response induced by UVB, as well as the phototoxic reaction to PUVA after topical or oral administration of a photosensitizer (Photodermatol. Photoimmunol. Photomed. 1996;12:45–56).
The researchers concluded from their results that the apparent photoprotection exhibited by PLE against reactive oxygen species may have potential clinical applications against sunburn and phototoxic reactions. Current research seems to support that conclusion.
In a recent study, researchers evaluated the capacity of oral PLE to reduce the clinical and histologic damage to human skin induced by PUVA treatment. Ten healthy patients with skin types II-III were exposed to PUVA alone and to PUVA with 7.5 mg/kg of oral PLE.
Clinical results showed consistently lower phototoxicity in PLE-treated skin after 48–72 hours, and less pigmentation after 4 months. Histologic results revealed notable differences in PLE-treated skin, with significantly fewer sunburn cells, preservation of Langerhans cells, and reduction in vasodilation and tryptase-positive mast cell infiltration (J. Am. Acad. Dermatol. 2004;50:41–9).
The authors concluded that the PLE conferred significant protection to the skin against the known harmful effects of PUVA. This study was clearly small, but its encouraging results led the team to further investigate the fern constituent.
In research reported later that year by the same group, nine healthy people with skin types II-III were exposed to different doses of artificial UV either without or following oral administration of 7.5 mg/kg of PLE.
At 24 hours after exposure, the investigators evaluated erythematous reactions and obtained paired biopsy specimens from PLE-treated skin and untreated skin. Significantly less erythema was seen in the skin treated with PLE. The biopsy specimens showed fewer sunburn cells, cyclobutane pyrimidine dimers, and proliferating epidermal cells, along with less mast cell infiltration. Signs of Langerhans cell preservation were also noted.
This small study supported the team's earlier findings, as they concluded that oral PLE imparts significant systemic protection to the skin against UV radiation (J. Am. Acad. Dermatol. 2004;51:910–8).
Other evidence buttresses the reports of PLE's photoprotective effect on human cells. A recent in vitro study showed that the hydrophilic PLE efficiently and in a dose-dependent manner preserved human fibroblasts and restored their proliferative capacity when the cells were exposed to UVA.
PLE conferred the same photoprotection on the human keratinocyte cell line HaCaT. PLE-treated human fibroblasts were also protected from UV-induced morphologic changes.
The authors concluded that PLE could play an important role in preventing sunburn and skin disorders mediated by UV exposure (J. Photochem. Photobiol. B 2003;70:31–7).
Researchers, citing PLE's antioxidant characteristics and its reported photoprotective effects in vitiligo treatment, set out to assess the photoprotective effects of the topically or orally administered extract. The investigators exposed 21 healthy volunteers—previously untreated or treated with oral psoralens—to solar radiation, and evaluated immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral PLE administration.
They discovered that the extract was effective in both forms, with PLE increasing the UV doses required for IPD, MED, and MPD. An immunohistochemical assessment showed that Langerhans cells received photoprotection from both the topical and oral formulations (Photodermatol. Photoimmunol. Photomed. 1997;13:50–60).
The investigators concluded that PLE should be considered as a possible approach for systemic photoprotection, and may serve as an adjuvant to photochemotherapy and phototherapy, perhaps enhancing the safety and efficacy of PUVA or UVB.
Effects on Cell Expression
Researchers used fibroblasts and keratinocytes to test the effects of PLE—in the presence of UVA or UVB—on membrane damage, lipid peroxidation, and the expression of elastin and matrix metalloproteinase 1 (MMP-1).
The cell samples were separately irradiated with a single exposure of UVA or UVB radiation and then incubated with or without PLE (0.01%, 0.1%, and 1%). Although UV did not significantly influence membrane integrity, lipid peroxidation, or MMP-1 expression, PLE did significantly enhance membrane integrity, inhibit lipid peroxidation, and inhibit MMP-1 expression in both fibroblasts and keratinocytes. Elastin expression was increased by UV radiation and PLE (J. Dermatol. Sci. 2003;32:1–9).
The authors suggested that PLE concentrations less than 0.1% may help combat photoaging by ameliorating membrane integrity and hampering MMP-1 expression without promoting elastin expression, whereas concentrations greater than 0.1% may reverse natural elastic fiber degradation.
Researchers recently showed that PLE partially inhibits the production of cytokines that exhibit a Th1 pattern (IL-2, IFN-?, and TNF-a) in human phytohemagglutinin-stimulated peripheral blood mononuclear cells.
At all doses tested, PLE completely eliminated production of the inflammatory cytokine IL-6. A second experiment by the same laboratory demonstrated that topically applied PLE significantly lessened mast cell infiltration and the angiogenesis promoted by chronic UVB irradiation in hairless albino SKH-1 mice (Anticancer Res. 2000;20:1567–75).
The authors concluded that PLE's moderate inhibition of the immunologic Th1 response accounts for the immunosuppressive, anti-inflammatory, and antioxidant properties previously ascribed to the fern extract. Furthermore, they inferred that the demonstrable inhibitory effect on TNF-a and IL-6 production may account for PLE's inhibition of angiogenesis and protection of human Langerhans cells from depletion initiated by solar irradiation.
They speculated that PLE may be a potential treatment for autoaggressive and inflammatory conditions characterized by aggravated Th1 responses.
Researchers looked at whether topical PLE could prevent or ameliorate cutaneous UVB-induced damage and photoaging in hairless mice. The results showed that mice treated with PLE had significantly reduced skinfold thickness and dermal elastosis, compared with untreated controls.
A reduction was also seen in the number of mice that had skin tumors 8 weeks after cessation of UV exposure (Photodermatol. Photoimmunol. Photomed. 1999;15:120–6).
The investigators concluded that PLE treatment improved or mitigated the histologic damage linked to skin photoaging and reduced UVB-induced skin tumor prevalence in mice.
P. leucotomos extract is available in an oral supplement marketed as Heliocare. It is sold by pharmacists behind the counter but without a prescription. The directions say to take one per day, but I tell my patients to take one per day except on days when they anticipate significant sun exposure, in which case they should take two per day.
Many studies suggest the efficacy of both oral and topical antioxidants in protecting the skin against photodamage (J. Invest. Dermatol. 2005;125:xii-xiii). One study showed that a combination of topical and oral antioxidants has a synergistic effect (Biofactors 2003;18:289–97).
I believe that antiaging regimens should include an oral antioxidant in addition to a topical antioxidant. Long-term studies are required to test this theory.
© 2006 Elsevier Inc. All rights reserved.