Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen‐induced phototoxic reactions as well as depletion of Langerhans cells in human skin

Abstract

Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P < 0.01), MED (P < 0.001) and MPD (P < 0.001). After oral administration of PL, MED increased 2.8 +/- 0.59 times and MPD increased 2.75 +/- 0.5 and 6.8 +/- 1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.

Polypodium leucotomos Extract Decreases UV-Induced Cox-2 Expression and Inflammation, Enhances DNA Repair, and Decreases Mutagenesis in Hairless Mice

“…34 PL has also been shown to reduce phototoxicity by decreasing inflammation (acute sunburn and depletion of Langerhans cells) and photoaging in both humans and an animal model. 35,36 In addition, PL has been reported to prevent the loss of cell viability (apoptosis) and proliferation induced by UVA. 37 Moreover, PL has also been proven to reduce inflammation through down-regulation of tumor necrosis factor-␣.…”

Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

“…21,22 The possibility that reactive oxygen species-associated effects are responsible for PUVA-induced effects such as immune suppression is supported by the observation that the antioxidative polypodium leucotomos extract has been shown to inhibit PAF production 23 and several types of UV and/or PUVA-induced immunological alterations, such as depletion of antigenpresenting Langerhans cells in human skin. 24 Moreover, the isoflavone genistein, a specific inhibitor of tyrosine kinase, has been shown to inhibit chemical carcinogeninduced reactive oxygen species and PUVA-induced photodamage, including inflammatory skin changes such as dermal neutrophilic and lymphocytic infiltration. 25 We observed that ex vivo PUVA-treated and UVAtreated PC but not unirradiated PC induced immune suppression in a dose-dependent manner (Figure 1c).…”

“…Two to three mice per treatment group were sacrificed before and at various time points (24,48,72,120, and 360 hours) after PUVA exposure. Approximately 1 cm 2 of dorsal skin was excised per mouse, fixed immediately in 4% buffered formaldehyde, processed routinely, and sectioned at 5 m for hematoxylin and eosin (H&E) staining.…”

“…Two to three mice per treatment group were bled at various time points (24,48,72, and 120 hours) after PUVA exposure. Serum levels of IL-10 were measured by Opteia mouse IL-10 ELISA kit (Pharmingen, San Diego, CA), according to the manufacturer's instructions.…”

Sunscreens and Antioxidants as Photo-protective Measures: An update

“…It also possesses regenerative skin properties, and prevents UVBinduced photo-aging [19,20]. * Fernblock, an extract obtained from the fern Polypodium leucotomos, inhibits UVB and PUVA therapy-induced erythema in vivo [21]. It is a potent antioxidant and has shown immunemodulating capability and inhibition of pro-inflammatory cytokines, such as TNF-α or IL-6 [22].…”