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Here comes the sun: The role of polypodium leucotomos extract

DII small banner By Warren R. Heymann, MD
Aug. 9, 2017

Polypodium leucotomos Extract
Ultraviolet (UV)B response. Changes in biomarkers of UV radiation exposure before and after Polypodium leucotomos extract (PLE). A, Stained nuclei for cyclobutane pyrimidine dimers (CPD), Ki67, proliferating cell nuclear antigen (PCNA), and cyclin D1. B, Sunburn cells and cytoplasmic staining for cyclooxygenase-2 (COX-2). Representative photomicrographs. (Original magnifications: ×20.)
Credit: JAAD
It’s the time of year when patients ask “What sunscreen should I use?” After recommending broad-spectrum sunscreens that are water-resistant to 80 minutes, I try to steer the conversation analogizing sun protection to driving. You wouldn’t just rely on an airbag to protect you — you need to be awake, sober, not distracted (no texting!), wear your seat belt, and have a car in good working order. Sunscreen is just part of the story — patients need to avoid the midday sun, wear hats and appropriate clothes, and seek shade. It is the rare person that uses the right amount of sunscreen with appropriate reapplications. Any easy to use adjunctive agent that can assist in photoprotection would be most welcome. Does Polypodium leucotomos extract (PLE) qualify?
PLE is a powerful antioxidant due to its high content of phenolic compounds, including chlorogenic acid, coumaric acid, vanillic acid, and ferulic acid, the latter two displaying the most potent inhibition of oxidation in vitro (1). According to Parrado et al, PLE is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of the activator protein (AP1), NF-κB, and protection of natural antioxidant enzyme systems. At the cellular level, PLE decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PLE reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PLE decreases UV radiation-induced cell proliferation. PLE also prevents common deletions mitochondrial DNA damage induced by UVA, and matrix metalloproteinase (MMP-1) expression induced visible light and infrared radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging. (2)
Kohli et al conducted a study that was designed to objectively evaluate the molecular and photobiologic effects of oral administration of Polypodium leucotomos extract (PLE). Twenty-two subjects with Fitzpatrick skin phototype I to III were enrolled. On day 1, subjects were irradiated with visible light, ultraviolet (UV) A1, and UVB (using 308-nm excimer laser). Evaluation was done immediately and 24 hours after irradiation. On days 3 and 4, irradiation and evaluation process was repeated after ingestion of only 2 doses of PLE. Clinical assessments and colorimetry data showed a decrease in UVB-induced changes in 17 of 22 subjects post-PLE administration; histologic findings demonstrated such a decrease in all 22 subjects. The authors concluded that PLE can potentially be used as an adjunctive agent to lessen the negative photobiologic effects of UVB. (3)
Adverse reactions to PLE are minor and may include mild episodic fatigue, bloating, and headaches (1). No evidence of mutagenicity was observed in a bacterial reverse mutation test or in vitro mammalian chromosomal aberration test nor was any genotoxic activity observed in an in vivo mouse micronucleus test (4). The package insert from PLE states that “there are no known side effects”. The dosing is one 240 mg capsule each morning with a recommendation of ingesting it 30 minutes prior to sun exposure and a second capsule a few hours later.

PLE is derived from a South American fern known as “calaguala” and has also been reported to benefit patients with atopic dermatitis, vitiligo, psoriasis, and polymorphous light eruption, in addition to its effect on photodamage and carcinogenesis. (1).

We all have our personal approaches for health maintenance — mine is 30 minutes of exercise daily, atorvastatin, and baby aspirin. Over the past several years I have been suffering from “anti-oxidant fatigue” as there have been so many products touted for innumerable conditions. After preparing this commentary, however, I started taking PLE when outdoors. With a history of melanoma, how could I resist? I look forward to the day when I can sing the Beatles’ lyric — Here comes the sun and I say it’s all right (enjoy the link https://youtu.be/U_O1QKQCsGs).

1. Berman B, et al. Polypodium leucotomos – An overview of basic investigative findings. J Drugs Dermatol 2016; 15: 224-8.
2. Parrado C, et al. Fernblock (Polypodium leucotomos extract): Molecular mechanisms and pleiotropic effects in light-related skin conditions, photoaging and skin cancers, a review. Int J Mol Sci 2016 Jun: 17(7), pii: E1026. doi: 10.3390/ijms17071026.
3. Kohli I, et al. The impact of oral Polypodium leucotomos extract on ultraviolet B response: A human clinical study. J Am Acad Dermatol 2017; 77: 33-41.
4. Murbach TS, et al. A comprehensive toxicological safety assessment of an aqueous extract of Polypodium leucotomos.(Fernblock). Food Chem Toxical 2015; 86: 328-41.

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