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Page 2 of 9 Torres et al. Plast Aesthet Res 2020;7:57 I http://dx.doi.org/10.20517/2347-9264.2020.87

exposure to UVR, reactive oxygen species (ROS) are generated in the skin, which result in oxidative
stress. This contributes to acute UV-induced erythema (i.e., photoinflammation) and tanning through
[1]
upregulation of cyclooxygenase-2 (COX-2), which is involved in early inflammation . With chronic UVR
exposure, the formation of photoproducts and ROS can lead to DNA damage, while at the same time cause
downregulation of tumor suppressor genes. This allows cells to continue replicating while genetic mutations
[1]
go unrepaired resulting in cancer formation (i.e., photocarcinogenesis) . ROS in the skin can also activate
proteins which play an important role in photoaging through blockage of collagen gene transcription,
[1]
inhibition of collagen synthesis, and overexpression of enzymes that break down collagen .

Photoprotection against UV and visible light is one preventative health strategy to reduce the negative
effects of electromagnetic radiation. Historically, photoprotection has been achieved through topical routes.
Photoprotection strategies include behavioral modifications such as seeking shade while outdoors, wearing
photoprotective clothing including hats and sunglasses, as well as applying sunscreen on otherwise exposed
[2,3]
skin sites .

Sunscreens are the most widely recognized means of photoprotection by the public; however, they do have
several limitations. These include the need for regular reapplication and lack of efficacy due to under-
application (i.e., not applying sufficient amounts). More recently, the ecological safety and potential
human toxicity of organic sunscreens, such as oxybenzone and octinoxate, have raised concerns among
[3,4]
dermatologists and the general public . However, there is limited evidence of direct toxic effects of
organic sunscreens in humans and coral reef species. Nevertheless, inorganic-based sunscreens - namely,
zinc oxide and titanium oxide-based sunscreens - have been recommended as an alternative for those
[4,5]
concerned about the potential health and environmental impact of organic sunscreens . In addition,
alternative photoprotective methods have gained increased interest as adjunct protection against UVR and
visible light exposure.

Systemic photoprotection has been used in conjunction with topical photoprotection. It may be
[6]
administered either subcutaneously or orally. Examples include vitamins, minerals, polyphenols,
carotenoids, and α-melanocyte stimulating hormone analog, as well as various plant-based agents that have
been reported to yield photoprotective and anti-photocarcinogenic properties. These agents act through
[7]
their antioxidant, anti-inflammatory, and immunomodulatory effects . The focus of this article will be to
review evidence-based systemic and topical botanicals as photoprotective agents.

BOTANICALS WITH PHOTOPROTECTIVE PROPERTIES
Polypodium leucotomos extract
Polypodium leucotomos is a tropical fern belonging to the family Polypodiaceae. It is native to Central and
South America where it has been used traditionally to treat various skin diseases including psoriasis and
atopic dermatitis [1,7,8] . At this time, Polypodium leucotomos extract (PLE) is the most well studied botanical
[9]
photoprotective agent. It is commercially available worldwide as an over-the-counter oral supplement .
While there are many different preparations of PLE, most of the studies reported in peer-reviewed literature
have been done with Fernblock® (Cantabria Labs, Madrid, Spain). PLE has antioxidant, anti-inflammatory,
[1,7]
immunomodulatory, tumor suppressive, and anti-aging properties . These qualities are mainly attributed
to the fern’s high polyphenol content, which is obtained from the leaves. Polyphenols are the most
abundant class of antioxidants present in plant-based food and beverages. The polyphenols present in
PLE are p-coumaric acid, chlorgenic acid, vanillic acid, caffeic acid, and ferulic acid. Of these, the most
[1]
powerful antioxidants are ferulic and caffeic acids . It must be emphasized that the concentration of these
constituents can vary depending on the PLE preparation. Accordingly, the different PLE preparations may
[10]
vary in term of their photoprotective ability. This was demonstrated in a study by Gonzalez et al. , where
the photoprotective activity of six different PLE preparations (including Fernblock®) were tested in vitro.