Polypodium leucotomos extract inhibits trans-urocanic acid photoisomerization and photodecomposition

https://doi.org/10.1016/j.jphotobiol.2005.11.005Get rights and content

Abstract

In this report, we demonstrate a possible molecular mechanism by which a hydrophilic extract of the leaves of the fern Polypodium leucotomos (Fernblock®, PL) blocks ultraviolet (UV)-induced skin photodamage. The extract inhibits UVA and UVB light induced photoisomerization of trans-urocanic acid (t-UCA), a common photoreceptor located in the stratum corneum, and also blocks its photodecomposition in the presence of oxidizing reagents such as H2O2, and titanium dioxide (TiO2). PL protects in vitro human fibroblasts from UV-induced death as well. These results suggest the potential of employing the PL extract as a component of sunscreen moistures in order to prevent photodecomposition of t-UCA, to inhibit UV-induced deleterious effects of TiO2 and to protect skin cells and endogenous molecules directly involved in skin immunosurveillance.

Introduction

trans-Urocanic acid (t-UCA) is a major ultraviolet (UV)-absorbing component produced from histidine metabolism, present in the stratum corneum, that possesses photoprotective and free radical scavenger properties [1]. Its molecular mechanism of photoprotection includes the absorption of UV photons which induces its change to cis-UCA and also produces non-photoprotective species [2]. However, the presence of endogenous amount of H2O2 and the use of photocatalytic compounds like TiO2 in sunscreen preparations, can lead the formation of hydroxyl radicals and reactive oxygen species (ROS) under UV radiation [3], [4], [5], [6]. The later are involved in the inactivation of different enzymatic systems, required for the cutaneous integrity and the formation of t-UCA oxidative breakdown metabolites which are involved in skin inmunosuppression mechanism [7], [8], [9], [10].

We have described previously the beneficial effect of an hydrophilic extract of Polypodium leucotomos (Fernblock®, heretofore referred as PL) in preventing acute sunburn and acute PUVA (psoralen + UVA)-induced phototoxic skin reactions in human subjects and minimizing photoaging changes in mice [11], [12], [13], [14], [15]. PL also inhibits the formation of ROS induced by UV light [16] and possess anti-inflammatory properties [17].

In this work, we study the capacity of PL to reduce the photoisomerization and the photoxidative breakdown of t-UCA. Furthermore, we have found that PL treatment of in vitro irradiated cells protect against UV-induced cell death, thus postulating this extract as a useful tool to minimize photoinduced cell damage by direct irradiation and UV-induced ROS generation and oxidant damage.

Section snippets

Cells and reagents

Human primary fibroblasts were obtained from clinical samples of healthy volunteers as described elsewhere, and were cultured in DMEM medium supplemented with 10% FCS at 37 °C in 5% CO2 atmosphere. Human erythrocytes were collected from peripheral blood of healthy volunteers. Hydrophilic extract of P. leucotomos (PL) was prepared as follow. Dry P. leucotomos leaves were extracted employing water at 55 °C as solvent, allowing recirculation until the sample reached a plateau of antioxidant activity

PL inhibits UVB- and UVA-induced trans-UCA isomerization

To investigate whether PL interferes the t-UCA isomerization molecular mechanisms implicated in photoimmunosuppression, we assayed its ability to block the UV-mediated photodecomposition of trans-UCA. An in vitro assay showed that UVB irradiation induces the formation of cis-UCA (Fig. 1A). The amount of cis-isomer formed is dose-dependent, increasing exponentially from 0 to 10 J cm−2 and reaching a plateau thereafter (Fig. 1A). When irradiation of t-UCA with 4.8 J cm−2 UVB light occurs in the

Discussion

Recently, it becomes clear that UV exposure induces skin immunosuppression [24] due to depletion of immune cells such as Langerhans cells [25], and/or isomerization of trans-urocanic acid (t-UCA) [10]. t-UCA suffers a reaction of isomerization upon exposure to UV light, yielding the cis-isomer, which is inactive in terms of photoprotection [26] and seems to mediate at least partially immunosuppression. Our results clearly show that PL efficiently inhibits UV-induced photoisomerization of t-UCA,

Acknowledgments

The authors wish to thank Rosario Castilla for expert technical assistance and Dr. Miguel Vicente-Manzanares for editorial preparation of the manuscript. This work was partially supported by research grant of IFC. SG is a consultant of IFC.

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      The fern Polypodium leucotomos (synonyms Phlebodium aureum (L.) J. Sm., Polypodium aureum L.) is endemic to the Americas where it has been use ornamentally (North America) and as a traditional medicine for skin conditions (Central America) [1]. More recently, a phenolic-rich standardized aqueous extract of the leaves of P. leucotomos—Fernblock®—has been investigated in preclinical and clinical studies for its photoprotective effects secondary to anti-inflammatory, immunomodulatory, antioxidant, and other mechanisms of action and has demonstrated both mechanistic potential and/or preclinical [2–14] and clinical efficacy [15–23]. Because of the potential for use by humans as a functional antioxidant ingredient in foods and dietary supplements, we previously conducted a battery of toxicological studies to investigate the potential health hazards of Fernblock® [24].

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      Phenolic compounds identified in Fernblock® are 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, 4-hydroxy-3-methoxy-benzoic acid (vanillic acid), 3,4-dihydroxycinnamic acid (caffeic acid), 4-hydroxycinnamic acid (p-coumaric acid), 3-methyoxy-4-hydroxicinnamic acid (ferulic acid), 4-hydroxycinnamoyl-quinic acid, and five isomers of chlorogenic acid and account for approximately 1% (w/w) of the extract's dry weight. ( Garcia et al., 2006) This PLE has been the subject of multiple clinical and preclinical studies demonstrating its mechanistic potential and photoprotective utility (Garcia et al., 2006; Gombau et al., 2006; Zattra et al., 2009; Mulero et al., 2008; Janczyk et al., 2007; Middelkamp-Hup et al., 2004a, 2004b; Aguilera et al., 2013; Ahmed et al., 2013; Alonso-Lebrero et al., 2003; Caccialanza et al., 2007, 2011; Capote et al., 2006; Gonzalez et al., 2000; Gonzalez and Pathak, 1996; Gonzalez et al., 1997; Middelkamp-Hup et al., 2007; Philips and Gonzalez, 2013; Philips et al., 2003; Rayward et al., 1997; Reyes et al., 2006; Rodriguez-Yanes et al., 2014, 2012) and is marketed throughout the world for various skin-related applications. It has been demonstrated to significantly reduce skin damage from exposure to ultraviolet radiation (Middelkamp-Hup et al., 2004a, 2004b; Aguilera et al., 2013; Gonzalez et al., 1997) and provide therapeutic benefits in the management of photodermatoses, (Tanew et al., 2012) vitiligo, (Middelkamp-Hup et al., 2007; Reyes et al., 2006) and psoriasis. (de las Heras et al., 1997)

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