Clinical Applications of Polypodium leucotomos (Fernblock®) in Oncodermatology

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Angeles Juarranz	--	3169	2023-07-18 11:16:59	\|
2	format correct	Conner Chen	Meta information modification	3169	2023-07-21 03:52:14	\|

Clinical Applications of Polypodium leucotomos (Fernblock®) in Oncodermatology

This entry is adapted from the peer-reviewed paper 10.3390/life13071513

Exposure to sun radiation leads to higher risk of sunburn, pigmentation, immunosuppression, photoaging and skin cancer. In addition to ultraviolet radiation (UVR), recent research indicates that infrared radiation (IR) and visible light (VIS) can play an important role in the pathogenesis of some of these processes. Detrimental effects associated with sun exposure are well known, but new studies have shown that DNA damage continues to occur long after exposure to solar radiation has ended. Regarding photoprotection strategies, natural substances are emerging for topical and oral photoprotection. In this sense, Fernblock^®, a standardized aqueous extract of the fern Polypodium Leucotomos (PLE), has been widely administered both topically and orally with a strong safety profile. Thus, this extract has been used extensively in clinical practice, including as a complement to photodynamic therapy (PDT) for treating actinic keratoses (AKs) and field cancerization.

Polypodium leucotomos Fernblock® photoprotection

1. Introduction

Photoprotection is the first-line prevention strategy to avoid the development of skin cancer and premature aging. Ultraviolet radiation (UVR) promotes skin cancer by inducing DNA damage, triggering inflammatory processes and causing immunosuppression and plays part in premature aging through alterations in extracellular matrix network and remodeling. Most of these detrimental effects are mainly mediated by generation of reactive oxygen species (ROS) and the consequent oxidative stress. Adoption of specific behaviors (such as wearing protective clothes, hats and sunglasses, and avoiding excessive sun exposure) and the use of topical sunscreens are the most common measures to counteract the harmful effects of UVR. Although traditional sunscreens are a critical component in all photoprotective regimens, they have limitations (inadequate application and need for frequent reapplication, short half-life, lack of photostability and insufficient protection against all wavelengths, among others) and have also increasingly been questioned for their safety and their impact on the environment ^[1]^[2]. In this sense, photoprotection can be provided not only by topical sunscreens but also by oral administration of substances (such as polyphenols, carotenoids and other antioxidants) that are being identified as systemic photoprotection agents in humans ^[2]. A well-known photoprotective agent is the standardized aqueous extract from the leaves of the fern Polypodium leucotomos (PLE or Fernblock^® (trademark name)). Polypodium leucotomos (PL) is a fern of the Polypodiaceae family, genus Phlebodium, native to Central and South America, where it has had a historical role in traditional medicine, especially for the treatment of skin diseases. A standardized aqueous extract from the leaves of the fern PL (PLE), rich in polyphenols and specifically in phenolic acids, has been developed to exploit the photoprotective properties of the plant and to provide a steady phenolic content. This extract was introduced as Fernblock^® in Europe in the year 2000, both in topical and oral forms, and is currently available in more than 26 countries, including the U.S., as a dietary supplement, since 2006.

Phenolic compounds identified in PLE are 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid (protocatechuic acid), 4-hydroxy-3-methoxybenzoic acid (vanillic acid), 3,4-dihydroxycinnamic acid (caffeic acid), 4-hydroxycinnamic acid (p-coumaric),3-methoxy-4-hydroxycinnamic acid (ferulic acid), 4-hydroxycinnamoylquinic acid and five chlorogenic acid isomers ^[3]. Of these, ferulic and caffeic acids are the most potent antioxidants. However, it is important to note that González et al. demonstrated in 2018 that there were significant differences between different PL extracts which could be attributed to the specific plant part used, the method of extraction and the plant’s origin and growth conditions. Generally, extracts from the leaves are more potent and yield more meaningful outcomes. Nonetheless, this research also suggested that other moieties, whether antioxidant or not, may have a critical role in the function of these extracts as dietary supplements with antiaging and antioxidant properties ^[4]^[5]. As mentioned earlier, this extract is rich in polyphenols and specifically in phenolic acids and has been developed to exploit the photoprotective properties of the PL fern and to provide a steady phenolic content. Its solid mechanism of action, its success in clinical trials, and the increased social interest in natural substances, such as polyphenols, have placed PLE as an interesting photoprotective, antioxidant and anti-inflammatory option (Figure 1). In this regard, numerous studies have been carried out to prove the role of the aqueous PLE in photoprotection, which have been summarized by many authors ^[6]^[7].

Figure 1. The graphical summary highlights the latest relevant studies concerning Fernblock^®, represented by the image of the fern, and examines their implications for its clinical application. The image includes abbreviations such as MAPK (mitogen-activated protein kinase), AK (actinic keratosis), NRF2 (nuclear factor erythroid-2-related factor 2), and CPDs (cyclobutane pyrimidine dimers), which correspond to specific molecular pathways or biomarkers related to Fernblock^® and its effects. Created with BioRender.com.

2. Oncodermatology

In the field of oncology, a recent review by Calzari et al. (2023) elucidates the ways in which PLE functions and assesses its applications in oncodermatology, with reference to both in vitro and in vivo research ^[8]. However, this review is not the only one, as the trend in recent years has been to publish literature reviews demonstrating the photoprotective effects of PLE, thereby confirming its therapeutic potential against various types of cancerous growths. Alongside these reviews, there have been seven experimental studies, four of which were clinical and three preclinical, which can be found summarized in Table 1.

Accordingly, a wide range of earlier studies are recognized as crucial references that have significantly advanced our understanding of the potential of Fernblock^® in the field of cancer prevention in both mice and humans. PLE inhibited UVR-mediated DNA damage and mutagenesis through a double mechanism that consisted of prevention of cyclobutane pyrimidine dimer (CPDs) accumulation and reduction of 8-OH-dG and H2Ax, thus preventing oxidative damage ^[4]. Also, PLE decreased UVA-dependent mitochondrial DNA damage by reducing common deletions (CD) ^[9]. In vitro and in vivo studies suggest that PLE may have a role in the treatment of UV-induced skin inflammation and cancer, probably due to its antioxidant and p53-activating properties ^[10]. It is important to note that the extracellular matrix (ECM) provides structural integrity to the tissue and is remodeled during skin aging/photoaging and cancer. In vitro experiments showed that PLE directly inhibited the enzymatic activity and expression of MMPs in melanoma cells and fibroblasts and stimulated the expression of tissue inhibitors of metalloproteinases (TIMPs) in melanoma cells, reducing melanoma cell growth and ECM remodeling ^[11]^[12]. Also, clinical studies shown that PLE reduces epidermal cell proliferation and the number of cyclin D1- and PCNA-positive epidermal cells caused by UVR exposure ^[13]^[14]. In relation to the process of cancerization, previous research has shown that taking oral PLE supplements following PDT can improve AK clearance and reduce recurrence as compared to PDT alone ^[15].

However, three recent studies have been conducted to determine the effectiveness of PLE in the context of cancerization not only by oral administration but also by topical administration. The first of them investigated the effectiveness of a new medical device (NMD) in treating the field cancerization in 30 patients with Aks after PDT. The NMD contained a complex of DNA-repair enzymes, UV-filters and Fernblock^®, while the control group received a standard sunscreen (SS). The study utilized clinical, dermoscopic, reflectance confocal microscopy (RCM) and histological evaluations to assess the outcomes and found that after six and twelve months of treatment, the SS group showed a significant increase in the number of AKs compared to the NMD group. The NMD group also showed a significant reduction in the extension and grade of atypia compared to the SS group. Histopathological evaluation showed an improvement in keratinocyte atypia grade in all groups after six months of PDT, but p53 expression was significantly lower in the NMD group at twelve months compared to the SS group. Overall, the NMD was well-tolerated with no serious adverse events reported ^[16]. Another recent prospective clinical study evaluated the effectiveness of the same formulation in individuals with AK who underwent cryotherapy. The evaluation involved measuring changes in the AKASI score (Actinic Keratosis Area and Severity Index) and utilized non-invasive line-field confocal-optical coherence tomography (LC-OCT) analysis. The findings revealed that the use of the sunscreen containing DNA-repairing enzymes and PLE significantly reduced the AKASI score after 3 and 12 months treatment compared to the control group. Consequently, the study concluded that the PLE-based sunscreen considerably improved AKASI score among individuals receiving cryotherapy treatment ^[17]. Finally, a recent prospective, multicenter, randomized controlled trial was conducted to compare not only the effectiveness of a sunscreen with Fernblock^® vs. one without but also the impact of oral photoprotection for managing AKs in elderly individuals with severe actinic damage. The group that received both topical sunscreen with Fernblock^® and Fernblock^® oral supplementation showed the most significant improvements in AK and field cancerization parameters compared to control group (which used a standard topical sunscreen). These results suggest that combining oral and topical photoprotection leads to superior clinical and anatomical outcomes ^[18]. In summary, these studies provide evidence to suggest that both oral and topical PLE could be utilized as an adjuvant treatment option for field cancerization. However, it is necessary to conduct further research in order to validate its effectiveness when compared to established and widely accepted medications considered to be the gold standard.

Regarding melanoma, Aguilera et al. (2013) also investigated the protective role of oral administration of PLE in patients at risk of malignant melanoma (MM) and in the interaction between MC1R polymorphisms and the cyclin-dependent kinase (CDK) inhibitor 2A gene (CDKN2A) status with MED 25–50%. Among patients with familial MM, those individuals with mutations in CDKN2A and/or MC1R had greater differences regarding the response to treatment with PLE ^[19]. According to these results, the authors indicated that patients with higher UVR sensitivity (lower basal MED) would benefit the most from oral PLE treatment. These results are intriguing, and thus studies with long-term PLE administration in patients with a high risk of developing MM would be important to expand and confirm these data. No recent clinical studies have been reported in this field that confirm the effectiveness of PLE in preventing melanoma. However, there are new pre-clinical studies which help uncover new mechanisms of action in relation to this matter (Table 1). Within the scope of the latest in vitro studies, three principal works have been incorporated to the scientific approach. The first one explores the potential of a dietary supplement containing sulforaphane (SFN) and Fernblock^® extract, in terms of its antioxidant, antineoplastic and antiaging properties. The study analyzed the impact of SFN/FB combination on MMPs, ROS production, and IL-1β secretion in human normal keratinocytes. The combination of these actives was found to be more effective than each on its own in inhibiting melanoma cell migration in vitro, MMP-1, -2, -3 and -9 production, inflammasome activation and IL-1β secretion. Moreover, when used in normal keratinocytes with a pro-inflammatory stimulus like TNF-α, SFN/FB was more efficient in inhibiting MMP-1 and -3 production and IL-1β secretion than SFN or FB alone. Based on these results, the authors suggested that SFN/FB-based supplements could be used as potential preventive measures against skin aging and as adjuvants in the treatment of advanced melanoma ^[20].

The second work represents an important step forward with respect to understanding the mechanisms involved in DNA damage, and in particular the formation of dark CPDs. Initially discovered by Premi el al (2015), this recent work performed by Portillo-Esnaola et al. (2021) confirms that UVA radiation triggers DNA damage in melanocytes even hours after sun exposure has ended due to increased production of nitrogen reactive species (NO•, O2− and ONOO−), which is linked with the increased formation of CPDs and dark-CPDs. UVA-induced significant dark-CPD formation was observed as soon as 3 h after exposure and the highest peak of dark-CPD formation was obtained 24 h after exposure. However, pre-treatment with Fernblock^® (0.3–0.75 mg/mL) was found to reduce the production of these reactive species and the formation of dark-CPDs due to its antioxidant and scavenging properties. We now understand that PLE not only prevents sunlight-induced DNA damage but also offers protection against it even after exposure to solar irradiation. This suggests that Fernblock^® could be a promising candidate to complement traditional sunscreens in providing long-lasting skin protection against dark-CPD formation formed after irradiation ^[21]^[22].

The third study, performed by Gallego-Rentero et al. (2022) is related to DNA damage induced by photopollution. The interaction of UVA radiation with environmental pollutants, specifically those of a polycyclic aromatic hydrocarbon (PAH) nature such as benzo[a]pyrene (BaP), produces what is known as photopollution. BaP acts as a photosensitizer and upon absorption of UVA radiation it causes increased cell damage in vitro and tumorigenicity in mice even at non-toxic concentrations. Thus, the study evaluated the protective effect of Fernblock^® against the combination of pollution and UVA radiation in human keratinocyte and mouse melanocyte cell lines. This preclinical study demonstrated the efficacy of Fernblock^® in preventing changes in cellular structure, viability, oxidative stress, and DNA damage. These findings provide strong evidence that Fernblock^® induces the priming of cells, rapidly promoting the activation of repair mechanisms and efficient elimination of oxidized derivatives that appear in the nuclear DNA as a result of sequential exposure to BaP and UVA light ^[23].

In order to enhance photoprotection, it is crucial to explore innovative methods that move beyond conventional measurements of minimal erythema dose (MED). The first evaluation focuses on demonstrating the clinical impact of assessing the immunomodulatory and preventive effects of DNA damage through in vivo studies. Thus, Schalka and Donato (2019) clinically evaluated the efficacy of an SPF 90 sunscreen with PLE in protecting against sun-induced skin damage vs. the same formulation without PLE. The presence of PLE provided additional protection, further reducing erythema, pigmentation, DNA damage, collagen breakdown and immunosuppression vs. placebo ^[24]. One of the most significant findings from this study is the marked reduction of p53 in skin areas protected with SPF 90 sunscreen containing Fernblock^® indicating reduced DNA alteration. These findings were completed by Aguilera et al. (2021), who conducted an in vitro study that analyzed the impact of Fernblock^® as a part of topical sunscreen in protecting the skin from photoimmunosuppression and other detrimental biological effects caused by exposure to UV radiation. In addition to the biological activity demonstrated in previous studies, the UV absorption properties of PLE provide an additional booster effect to topical sunscreens, increasing SPF and UVAPF and enhancing protection against not only erythema and permanent pigment darkening reaction but also against immunosuppression ^[25].

Regarding xeroderma pigmentosum (XP), data has shown that PLE reduces UVR-induced COX-2 levels, at least in part through activation of p53, and decreased epidermal cell proliferation induced by UVR in a mouse model ^[10]. A case report on XP treatment demonstrated the efficacy of a topical film-forming medical device containing a DNA-repair enzyme, photolyase (Repairsomes^®) and very high protection UV filters in preventing the growth of skin cancer lesions in patients with XP ^[26].

Finally, it is worth highlighting the recent findings of Lacerda et al. (2023) in the field of oral cancer prevention. Their study demonstrated that PLE has the ability to suppress oral cancer cell growth in vitro in SCC-9, SCC-15 and SCC-25 cell lines and prevent tumor development in vivo in mice with induced oral carcinogenesis. A decrease in the expression of Ki67 and PCNA proliferating markers as well as in N-cad (Cdh2), Vim and Twist markers related to migration was observed in tongue tissues. Therefore, PLE may have a beneficial effect on immune and inflammatory responses related to oral tumors and could be a promising natural therapeutic approach for preventing and treating oral cancer due its immunomodulatory activity ^[27].

Table 1. This table provides a summary of the scientific articles published in the last five years in the field of oncodermatology, specifically highlighting the references to, and conclusions about, PLE treatment.

Oncodermatology
Design	Pathology/Focus	Summary/Outcome	Study Reference
Review	General oncodermatology	This review reports the mechanisms through which Polypodium leucotomos acts to evaluate its uses in oncodermatology with references to in vitro and in vivo studies.	^[8]
Review and book chapter	Continuing medical education about skin cancer and sunscreen use	These reviews provide evidence-based recommendations for the use of sunscreen as a preventive strategy against skin cancer while also considering potential risks and environmental impacts associated with the use of some chemical sunscreen filters. PLE is included as a reference oral sunscreen technology for prevention of photodamage.	^[28]^[29]^[30]^[31]^[32]
Reviews and book chapter	Botanical interventions for photoprotection and skin cancer	These works review the main actives derived from plants with scientific evidence as treatment in photoprotection and offer an overview of cancer and phytotherapy. Specifically, they review the existing literature on the properties of PLE and its potential therapeutic effects in preventing skin damage. These reviews include studies conducted in vitro, in vivo and clinical trials.	^[33]^[34]^[35]^[36]^[37]
Review	Preventive interventions for keratinocyte carcinoma	This manuscript examines the potential of pharmaceuticals, plant-derived phytochemicals and vitamins for preventing keratinocyte carcinoma. One such reference photoprotectant is PLE, which has been shown to inhibit the development of tumors and acute UV-induced damage in humans.	^[38]
Clinical study	Field cancerization	This clinical study suggests that a new medical device treatment containing Fernblock^® (NMD) is a useful treatment method for improving the precancerous field and preventing the development of new AKs.	^[16]
Clinical study	Oral cancer	The findings indicate that PLE has the ability to suppress oral cancer cell growth in vitro and prevent tumor development in vivo. Thus, PLE could be a promising natural therapeutic approach for preventing and treating oral cancer.	^[27]
Preclinical study	Skin cancer markers	This in vitro study suggests that FB could be a promising candidate to complement traditional sunscreens in providing long-lasting skin protection against dark-CPDs formation after irradiation.	^[21]
Preclinical study	Melanoma	This in vitro research suggests that supplements containing sulforaphane/FB could be used to prevent skin aging and help treat advanced melanoma.	^[20]
Preclinical study	Skin cancer induced by photopollution	This preclinical study demonstrates the efficacy of PLE in preventing changes in cellular structure, viability, oxidative stress and activation of the melanogenic signaling pathway caused by exposure to both BaP and UVA light.	^[23]
Actinic keratosis
Review	Actinic keratosis	This review article examines in vitro experiments and clinical trials that utilize evidence-based therapeutic methods before or after photodynamic therapy (PDT). Specifically, the effectiveness of topical treatments and oral supplementation, such as diclofenac, imiquimod and PLE, among others, as well as mechanical-physical treatments, are evaluated.	^[39]
Review	Actinic keratosis	In this article, the authors offer expert opinions and practical insights into the treatment of actinic keratosis and field cancerization using monotherapy or a combination of therapies among which PLE is cited. The primary objective is to achieve improved, quicker and more tolerable clinical outcomes.	^[40]
Review	Actinic keratosis	This review discusses various physical ablative techniques and drug preparations available for treatment. It emphasizes the need for careful evaluation of efficacy, toxicity and tolerability data, as well as practical considerations such as treatment protocols and patient preferences, to achieve maximal adherence and prevent treatment failure. It includes PLE as a chemopreventive treatment tool against the development of AK.	^[41]
Xeroderma pigmentosum
Review	Xeroderma pigmentosum	The purpose of this review is to present the symptoms, diagnosis, and treatment of XP. It also includes oral PLE as a treatment adjuvant due to its chemoprotective, antioxidative, anti-inflammatory and immunomodulatory properties. All these effects have the potential to lessen the phototoxic effects of UVR and thus reduce UVR-induced skin damage and cancer.	^[42]

References

Yeager, D.G.; Lim, H.W. What’s New in Photoprotection: A Review of New Concepts and Controversies. Dermatol. Clin. 2019, 37, 149–157.
Parrado, C.; Philips, N.; Gilaberte, Y.; Juarranz, A.; González, S. Oral Photoprotection: Effective Agents and Potential Candidates. Front. Med. 2018, 5, 188.
García, F.; Pivel, J.P.; Guerrero, A.; Brieva, A.; Martínez-Alcázar, M.P.; Caamaño-Somoza, M.; González, S. Phenolic Components and Antioxidant Activity of Fernblock, an Aqueous Extract of the Aerial Parts of the Fern Polypodium Leucotomos. Methods Find. Exp. Clin. Pharmacol. 2006, 28, 157–160.
González, S.; Lucena, S.R.; Delgado, P.; Juarranz, A. Comparison of Several Hydrophilic Extracts of Polypodium Leucotomos Reveals Different Antioxidant Moieties and Photoprotective Effects in Vitro. J. Med. Plants Res. 2018, 13, 336–345.
Del Rosso, J.Q. Polypodium Leucotomos Extract (PLE): New Study Gives Evidence-Based Insight into Ain’t Nothing Like the Real Thing. J. Clin. Aesthet. Dermatol. 2019, 12, 45.
Parrado, C.; Nicolas, J.; Juarranz, A.; Gonzalez, S. The Role of the Aqueous Extract Polypodium Leucotomos in Photoprotection. Photochem. Photobiol. Sci. 2020, 19, 831–843.
Pourang, A.; Dourra, M.; Ezekwe, N.; Kohli, I.; Hamzavi, I.; Lim, H.W. The Potential Effect of Polypodium Leucotomos Extract on Ultraviolet- and Visible Light-Induced Photoaging. Photochem. Photobiol. Sci. 2021, 20, 1229–1238.
Calzari, P.; Vaienti, S.; Nazzaro, G. Uses of Polypodium Leucotomos Extract in Oncodermatology. J. Clin. Med. 2023, 12, 673.
Villa, A.; Viera, M.H.; Amini, S.; Huo, R.; Perez, O.; Ruiz, P.; Amador, A.; Elgart, G.; Berman, B. Decrease of Ultraviolet A Light-Induced “Common Deletion” in Healthy Volunteers after Oral Polypodium Leucotomos Extract Supplement in a Randomized Clinical Trial. J. Am. Acad. Dermatol. 2010, 62, 511–513.
Rodríguez-Yanes, E.; Juarranz, Á.; Cuevas, J.; Gonzalez, S.; Mallol, J. Polypodium Leucotomos Decreases UV-Induced Epidermal Cell Proliferation and Enhances P53 Expression and Plasma Antioxidant Capacity in Hairless Mice. Exp. Dermatol. 2012, 21, 638–640.
Philips, N.; Smith, J.; Keller, T.; Gonzalez, S. Predominant Effects of Polypodium Leucotomos on Membrane Integrity, Lipid Peroxidation, and Expression of Elastin and Matrixmetalloproteinase-1 in Ultraviolet Radiation Exposed Fibroblasts, and Keratinocytes. J. Dermatol. Sci. 2003, 32, 1–9.
Philips, N.; Conte, J.; Chen, Y.J.; Natrajan, P.; Taw, M.; Keller, T.; Givant, J.; Tuason, M.; Dulaj, L.; Leonardi, D.; et al. Beneficial Regulation of Matrixmetalloproteinases and Their Inhibitors, Fibrillar Collagens and Transforming Growth Factor-β by Polypodium Leucotomos, Directly or in Dermal Fibroblasts, Ultraviolet Radiated Fibroblasts, and Melanoma Cells. Arch. Dermatol. Res. 2009, 301, 487–495.
Kohli, I.; Shafi, R.; Isedeh, P.; Griffith, J.L.; Al-Jamal, M.S.; Silpa-archa, N.; Jackson, B.; Athar, M.; Kollias, N.; Elmets, C.A.; 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.e1.
Middelkamp-Hup, M.A.; Pathak, M.A.; Parrado, C.; Goukassian, D.; Rius-Díaz, F.; Mihm, M.C.; Fitzpatrick, T.B.; González, S. Oral Polypodium Leucotomos Extract Decreases Ultraviolet-Induced Damage of Human Skin. J. Am. Acad. Dermatol. 2004, 51, 910–918.
Auriemma, M.; Di Nicola, M.; Gonzalez, S.; Piaserico, S.; Capo, A.; Amerio, P. Polypodium Leucotomos Supplementation in the Treatment of Scalp Actinic Keratosis. Dermatol. Surg. 2015, 41, 898–902.
De Unamuno Bustos, B.; Aguilera, N.C.; Azorín García, I.; Andrino, A.C.; Ros, M.L.; Rodrigo, R.; Vitale, M.; González, S.; Botella Estrada, R. Long-Term Efficacy of a New Medical Device Containing Fernblock ® and DNA Repair Enzyme Complex in the Treatment and Prevention of Cancerization Field in Patients with Actinic Keratosis. J. Clin. Exp. Dermatol. Res. 2019, 10, 499.
Lamberti, A.; Cartocci, A.; Donelli, C.; Cortonesi, G.; Trovato, E.; Milani, M.; Rubegni, P.; Cinotti, E. Prevention Strategies in Patients Affected by Actinic Keratosis of the Head: A 12-Month, Prospective, Assessor-Blinded, Controlled Study with Lesion-Directed Treatment Associated with Medicalized Photoprotection; Longdom Publishing SL: Barcelona, Spain, 2022; Volume 13, p. 5.
Pellacani, G.; Peris, K.; Ciardo, S.; Pezzini, C.; Tambone, S.; Farnetani, F.; Longo, C.; Chello, C.; Gonzalez, S. The Combination of Oral and Topical Photoprotection with a Standardized Polypodium Leucotomos Extract Is Beneficial against Actinic Keratosis. Photodermatol. Photoimmunol. Photomed. 2023, 1–8.
Aguilera, P.; Carrera, C.; Puig-Butille, J.A.; Badenas, C.; Lecha, M.; González, S.; Malvehy, J.; Puig, S. Benefits of Oral Polypodium Leucotomos Extract in MM High-Risk Patients. J. Eur. Acad. Dermatol. Venereol. 2013, 27, 1095–1100.
Serini, S.; Guarino, R.; Vasconcelos, R.O.; Celleno, L.; Calviello, G. The Combination of Sulforaphane and Fernblock® XP Improves Individual Beneficial Effects in Normal and Neoplastic Human Skin Cell Lines. Nutrients 2020, 12, 1608.
Portillo-Esnaola, M.; Rodríguez-Luna, A.; Nicolás-Morala, J.; Gallego-Rentero, M.; Villalba, M.; Juarranz, Á.; González, S. Formation of Cyclobutane Pyrimidine Dimers after UVA Exposure (Dark-CPDs) Is Inhibited by an Hydrophilic Extract of Polypodium Leucotomos. Antioxidants 2021, 10, 1961.
Premi, S.; Wallisch, S.; Mano, C.M.; Weiner, A.B.; Wakamatsu, K.; Bechara, E.J.H.; Halaban, R.; Brash, D.E. Chemiexcitation of Melanin Derivatives Induces DNA Photoproducts Long after UV Exposure. Science 2015, 347, 842–847.
Gallego-Rentero, M.; Nicolás-Morala, J.; Alonso-Juarranz, M.; Carrasco, E.; Portillo-Esnaola, M.; Rodríguez-Luna, A.; González, S. Protective Effect of the Hydrophilic Extract of Polypodium Leucotomos, Fernblock®, against the Synergistic Action of UVA Radiation and BenzoPyrene Pollutant. Antioxidants 2022, 11, 2185.
Schalka, S.; Donato, L.C. Evaluation of Effectiveness of a Sunscreen Containing Polypodium Leucatomos Extract in Reducing the Sun Damage to the Skin. Surg. Cosmet. Dermatol. 2019, 11, 310–318.
Aguilera, J.; Vicente-Manzanares, M.; de Gálvez, M.V.; Herrera-Ceballos, E.; Rodríguez-Luna, A.; González, S. Booster Effect of a Natural Extract of Polypodium Leucotomos (Fernblock®) That Improves the UV Barrier Function and Immune Protection Capability of Sunscreen Formulations. Front. Med. 2021, 8, 684665.
González-Morán, A.; Piquero-Casals, J. Use of a Topical Film-Forming Medical Device Containing Repairsomes® in a Patient with Xeroderma Pigmentosum to Avoid Progression to Skin Cancerization. Clin. Cosmet. Investig. Dermatol. 2020, 13, 677–681.
Lacerda, P.A.; Oenning, L.C.; Bellato, G.C.; Lopes-Santos, L.; de Antunes, N.J.; Mariz, B.A.L.A.; Teixeira, G.; Vasconcelos, R.; Simões, G.F.; de Souza, I.A.; et al. Polypodium Leucotomos Targets Multiple Aspects of Oral Carcinogenesis and It Is a Potential Antitumor Phytotherapy against Tongue Cancer Growth. Front. Pharmacol. 2023, 13, 1098374.
González, S.; De Gálvez, M.V.; De Troya, M.; Rodríguez-Luna, A.; Calzavara-Pinton, P. Personalized Medical Photoprotection: Determining Optimal Measures for Susceptible Patient Groups. Open Dermatol. J. 2023, 17, 1–7.
González, S.; Aguilera, J.; Berman, B.; Calzavara-Pinton, P.; Gilaberte, Y.; Goh, C.L.; Lim, H.W.; Schalka, S.; Stengel, F.; Wolf, P.; et al. Expert Recommendations on the Evaluation of Sunscreen Efficacy and the Beneficial Role of Non-Filtering Ingredients. Front. Med. 2022, 9, 790207.
Perez, M.; Abisaad, J.A.; Rojas, K.D.; Marchetti, M.A.; Jaimes, N. Skin Cancer: Primary, Secondary, and Tertiary Prevention. Part I. J. Am. Acad. Dermatol. 2022, 87, 255–268.
Passeron, T.; Lim, H.W.; Goh, C.L.; Kang, H.Y.; Ly, F.; Morita, A.; Ocampo Candiani, J.; Puig, S.; Schalka, S.; Wei, L.; et al. Photoprotection According to Skin Phototype and Dermatoses: Practical Recommendations from an Expert Panel. J. Eur. Acad. Dermatol. Venereol. 2021, 35, 1460–1469.
Sander, M.; Sander, M.; Burbidge, T.; Beecker, J. The Efficacy and Safety of Sunscreen Use for the Prevention of Skin Cancer. CMAJ 2020, 192, E1802–E1808.
Philips, N.; Richardson, R.; Siomyk, H.; Bynum, D.; Gonzalez, S. “Skin Cancer, Polyphenols, and Oxidative Stress” or Coun-teraction of Oxidative Stress, Inflammation, Signal Transduction Pathways, and Extracellular Matrix Remodeling That Mediate Skin Carcinogenesis by Polyphenols. In Cancer; Academic Press: Cambridge, MA, USA, 2021; pp. 439–450.
Araújo Lacerda, P.; Marinho Ottoni Costa, L.; Cuoghi Bellato, G.; Ayaka Yamashita, M.; Lopes-Santos, L.; Augusto, T.M.; Karla Cervigne, N. Perspectives on Cancer and Phytotherapy: An Overview Focusing on Polypodium Leucotomos Therapeutic Properties. J. Cancer Prev. Curr. Res. 2021, 12, 9–18.
Subhadarshani, S.; Athar, M.; Elmets, C.A. Photocarcinogenesis. Curr. Dermatol. Rep. 2020, 9, 189–199.
Bhatia, B.K.; Lim, H.W.; Hamzavi, I.H. Comprehensive Dermatologic Drug Therapy; Wolverton, E.S., Jashin, J., Wu, J.J., Eds.; Elsevier: Amsterdam, The Netherlands, 2020; Volume 23, pp. 263–270.
Zimmerman, C. Herbs for Low-Risk Skin Cancers and Precancers. Altern. Complement. Ther. 2019, 25, 163–166.
Pihl, C.; Togsverd-Bo, K.; Andersen, F.; Haedersdal, M.; Bjerring, P.; Lerche, C.M. Keratinocyte Carcinoma and Photoprevention: The Protective Actions of Repurposed Pharmaceuticals, Phytochemicals and Vitamins. Cancers 2021, 13, 3684.
Piaserico, S.; Mazzetto, R.; Sartor, E.; Bortoletti, C. Combination-Based Strategies for the Treatment of Actinic Keratoses with Photodynamic Therapy: An Evidence-Based Review. Pharmaceutics 2022, 14, 1726.
Piquero-Casals, J.; Morgado-Carrasco, D.; Gilaberte, Y.; Del Rio, R.; Macaya-Pascual, A.; Granger, C.; López-Estebaranz, J.L. Management Pearls on the Treatment of Actinic Keratoses and Field Cancerization. Dermatol. Ther. 2020, 10, 903–915.
Calzavara-Pinton, P.; Calzavara-Pinton, I.; Rovati, C.; Rossi, M. Topical Pharmacotherapy for Actinic Keratoses in Older Adults. Drugs Aging 2022, 39, 143–152.
Leung, A.K.C.; Barankin, B.; Lam, J.M.; Leong, K.F.; Hon, K.L. Xeroderma Pigmentosum: An Updated Review. Drugs Context 2022, 11, 1–17.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Biochemistry & Molecular Biology; Dermatology

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Azahara Rodríguez-Luna

Alicia Zamarrón

Ángeles Juarranz

Salvador González

View Times: 395

Update Date: 21 Jul 2023

Table of Contents

Video Upload Options

Confirm

1. Introduction

2. Oncodermatology

References