Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review

Abstract

Healthier life styles include increased outdoors time practicing sports and walking. This means increased exposure to the sun, leading to higher risk of sunburn, photoaging and skin cancer. In addition to topical barrier products, oral supplementations of various botanicals endowed with antioxidant activity are emerging as novel method of photoprotection. Polypodium leucotomos extract (PL, commercial name Fernblock(®), IFC Group, Spain) is a powerful antioxidant due to its high content of phenolic compounds. PL 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 AP1 and NF-κB and protection of natural antioxidant enzyme systems. At the cellular level, PL decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PL reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PL decreased UV radiation-induced cell proliferation. PL also prevents common deletions mitochondrial DNA damage induced by UVA, and MMP-1 expression induced Visible Light and Infrared Radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging.

Keywords: DNA; Polypodium leucotomos extract; antioxidant; immunosuppression; infrared (IR); oral; photoaging; photocarcinogenesis; photoprotection; ultraviolet (UV) radiation; visible light (VIS) radiation.

Figure 1

Polypodium leucotomos (PL) extract’s anti-UV effects: (A) decreases pro-inflammatory mechanisms of UV radiation include ROS-induced lipid peroxidation; (B) decreases UV-induced DNA damage; (C) increases the expression of active p53; (D) inhibits UV-induced Cox-2 enzyme levels; (E) reduces UV-induced nuclear transcription factors AP-1 and NF-κB; (F) reduces MMPs production; (G) decreases inflammation and vasodilation; and (H) inhibits skin immunodepression. Black arrows indicate increased/decreased effects due to UVR. ROS, reactive oxygen species; mtDNA, mitochondrial DNA; UV, ultraviolet; ECM, extracellular matrix; CPD, cyclobutane pyrimidine dimers; MMP, matrix metalloproteinase; MAPK, mitogen-activated protein kinases; AP-1, activator protein-1; NF-κB, nuclear factor kappa beta; TGF-β, transforming growth factor-β.; COX, cyclooxygenase enzymes; PGE2, prostaglandin E2; TNF-α, tumor necrosis factor-α; iNOS, isoforms of nitric oxide synthase; RANK, receptor activator of nuclear factor kappa-B; RANKL, receptor activator of nuclear factor kappa-B ligand.

Figure 2

Tested anti IR–VIS effects of Polypodium leucotomos (PL) extract: (A) ultraviolet radiation (UV), visible light (VIS), and infrared radiation (IR) depth penetration in the skin; and (B) main PL effects reflect its capacity to decrease MMP-1 upregulation induced by cutaneous exposure to IR–VIS. Black arrows indicate increased/decreased effects due to IR–VIS.