Fotoproteção Oral

Fotoproteção Oral
Polypodium leucotomos
Reduz o Eritema, o Número de Sunburn Cells e Células
Epidérmicas Proliferativas, a Infiltração dos Mastócitos
Dérmicos e os Dímeros de Ciclobutano Pirimidina após a
Radiação UV (1)
Table of Contents
Extrato
de
Polypodium
leucotomos
administrado via oral reduz a lesão da pele
humana induzida pela exposição à UV..... 03
Administrado por via oral, o extrato de
Polypodium leucotomos protege a pele do
dano
causado
pela
exposição
UV..............04
Polypodium
05
“... as biópsias obtidas da pele tratada
com PL demonstraram menos sunburn
cells, dímeros de ciclobutano pirimidina,
células epidérmicas proliferativas e
infiltração dos mastócitos dérmicos
.............................03”
leucotomos.........................
Propriedades........................................
05
Mecanismo de ação ..............................
05
Indicação.............................................
05
Posologia..............................................0
5
Contraindicações..................................05
Formulário 1........................................ 06
Letter to the Doctor
Este Cosmetic Paper tem como objetivo
apresentar os resultados de um estudo
que pesquisou o efeito fotoprotetor da
administração
oral
do
extrato
antioxidante
natural
Polypodium
leucotomos. Segundo os resultados, a
administração reduz o eritema, o número
de sunburn cells e número de células
epidérmicas proliferativas, a infiltração
dos mastócitos dérmicos e os dímeros de
ciclobutano pirimidina após a radiação
UV.
Formulário
Overview
2.........................................07
A exposição
cutânea à radiação UV
Referências
Bibliográficas......................
08
pode causar deposição do material elastótico,
redução de colágeno e aumento da expressão das metaloproteinases (MMPs).
Polypodium leucotomos possui propriedades antioxidante, anti-inflamatória e
Apendix.......................................................09
fotoprotetora (3).
J Dermatol Sci. 2003 Jun;32(1):1-9.
Extrato de Polypodium leucotomos Administrado Via Oral
Reduz a Lesão da Pele Humana Induzida Pela Exposição à UV.
Middelkamp-Hup MA, Pathak MA, Parrado C, Goukassian D, Rius-Diaz F, Mihm MC,
Fitzpatrick TB, Gonzalez S.
Wellman
Laboratories
of
Photomedicine,
Department
of
Dermatology,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
J Am Acad Dermatol. 2004 Dec;51(6):910-8.
Embasamento: a radiação UV
induz a lesão na pele humana. A
proteção
cutânea
por
agentes
fotoprotetores promove benefícios
substanciais.
Objetivo: foi investigado o efeito
fotoprotetor da administração oral
de extrato de um antioxidante
natural Polypodium leucotomos (PL).
Métodos:
um
total
de
9
participantes sadios, com fototipo II
e III, foi exposto às doses variáveis da radiação UV sem ou após a administração
oral de PL (7,5 mg/kg). 24 horas após a exposição à radiação a reação eritematosa
foi avaliada e foram obtidas as biópsias das peles não tratadas e tratadas com PL.
Resultados: uma redução significativa do eritema foi encontrada na pele tratada
com PL (P < ,01). Histologicamente, as biópsias obtidas da pele tratada com PL
demonstraram menos sunburn cells (P < ,05), dímeros de ciclobutano pirimidina (P
< ,001), células epidérmicas proliferativas (P < ,001) e infiltração dos mastócitos
dérmicos (P < ,05). Foi observada uma tendência de preservação das células de
Langerhans.
Conclusão: administração oral de PL, um agente quimiofotoprotetor sistêmico
eficaz, promove proteção da pele significativa frente à radiação UV.
PMID: 15583582 [PubMed - indexed for MEDLINE]
Administrado Por Via Oral,
o Extrato de Polypodium leucotomos,
Protege a Pele do Dano Causado Pela Exposição UV
(1)
Com objetivo de avaliar o efeito fotoprotetor da administração oral de um extrato
com propriedade antioxidante, os cientistas norte-americanos de Wellman
Laboratories of Photomedicine, Department of Dermatology, da Faculdade de
Medicina de Harvard, conduziram um estudo em 9 participantes sadios com pele
fotótipo II e III. Os participantes foram expostos às doses variáveis da radiação
UV sem ou após a administração oral:
9 participantes sadios com pele
fototipo II e III
Sem suplementação
Polypodium leucotomos
7,5 mg/kg
Exposição à radiação UV
Resultados:
 O eritema (avaliado 24 h após a
exposição) foi significativamente menor no
grupo tratado com Polypodium leucotomos
(P < ,01);
 As biópsias obtidas do grupo tratado com
Polypodium leucotomos demonstraram
menos sunburn cells, células epidérmicas
proliferativas, infiltração dos mastócitos
dérmicos e dímeros de ciclobutano
pirimidina;
 Foi observada também uma tendência de preservação das células de
Langerhans.
J Am Acad Dermatol. 2004 Dec;51(6):910-8.
Polypodium leucotomos
Extrato de Polypodium leucotomos, uma planta do tipo samambaia, é um fotoprotetor
oral com propriedade antioxidante potente. Estudos recentes demonstraram que na
composição desse extrato estão presentes os ácidos ferúlico, caféico, vanílico, pcumárico e clorogênico (2).
Propriedades




Fotoprotetor (1-4);
Antioxidante (1-3);
Anti-inflamatório (3);
Reduz o eritema, o número de sunburn cells, e células
epidérmicas proliferativas, a infiltração dos mastócitos
dérmicos e os dímeros de ciclobutano pirimidina após
a radiação UV (1).
Mecanismo de Ação
O extrato de Polypodium leucotomos é um potente
antioxidante devido a presença de compostos fenólicos.
Segundo o estudo publicado no Journal of Photochemistry and Photobiology. B,
Biology 2006 Mar 1;82(3):173-9. Epub 2006 Jan 4. a aplicação tópica do extrato
de Polypodium leucotomos inibe a fotopolimerização do ácido trans-urocânico
(fotoprotetor natural localizado no estrato córneo) induzida pela radiação UVA e UVB (4).
Indicação
(1)
Fotoproteção cutânea por via oral.
Posologia
A dose administrada no estudo publicado no Journal of the American Academy
of Dermatology 2004 Dec;51(6):910-8. foi de 7,5 mg/kg (1).
A dose recomendada pelo fabricante do Heliocare® (um produto comercializado),
IVAX Laboratories, Inc, Dermatology Division é de 240 mg/dia (5).
Contraindicações
Os dados indicam que Polypodium leucotomos aumenta os efeitos de digitalis,
sendo contraindicado para os pacientes sob tratamento com essa droga (6).
Formulário 1
Polypodium leucotomos (1)
Tratamento Oral
J Am Acad Dermatol. 2004 Dec;51(6):910-8.
Polypodium leucotomos
Polypodium leucotomos 50:1___240 mg - Reduz o eritema, o número de
(5)
sunburn cells e células epidérmicas
proliferativas, a infiltração dos
mastócitos dérmicos e os dímeros
de ciclobuitano pirimidina após a
radiação UV (1).
240 mg do extrato 50:1 ao dia.
Fotoprotetores
Fotoprotetor FPS 30 ”in vivo” qsp _________50 g
Aplicar conforme orientação médica.
Formulário 2
Outros Fotoprotetores Orais
Proc Soc Exp Biol Med. 2000 Feb;223(2):170-4.
1. Beta-caroteno - Dose Inicial
Beta-caroteno _______________30 mg* - Promove a proteção da pele contra
a formação de eritema UV-induzido .
Tomar 1 cápsula ao dia, pela manhã.
A dose pode ser progressivamente aumentada em 30 mg, a cada 8 semanas, de
30 mg para 90 mg.
* Segundo o estudo publicado no Proc Soc Exp Biol Med. 2000 Feb;223(2):170-4., a dose inicial
administrada foi de 30 mg de carotenoides/dia, sendo 29,4 mg de β-caroteno+0,36 mg de αcaroteno+traços de outros carotenoides na forma de óleo vegetal.
J Nutr. 2003 Jan;133(1):98-101.
2. Beta-caroteno
Beta-caroteno _______________24 mg
- Promove a proteção da pele contra
a formação de eritema UV-induzido
(1,2)
.
Tomar 1 cápsula ao dia, pela manhã..
Referências Bibliográficas
1. Middelkamp-Hup MA, Pathak MA, Parrado C, Goukassian D, Rius-Diaz F, Mihm
MC, Fitzpatrick TB, Gonzalez S. Oral Polypodium leucotomos extract
decreases ultraviolet-induced damage of human skin. Wellman Laboratories
of Photomedicine, Department of Dermatology, Massachusetts General Hospital,
Harvard Medical School, Boston, MA 02114, USA.
J Am Acad Dermatol. 2004 Dec;51(6):910-8.
2. Gombau L, Garcia F, Lahoz A, Fabre M, Roda-Navarro P, Majano P, AlonsoLebrero JL, Pivel JP, Castell JV, Gomez-Lechon MJ, Gonzalez S. Polypodium
leucotomos extract: antioxidant activity and disposition. Advancell, 46009
Valencia, Spain.
Toxicol In Vitro. 2006 Jun;20(4):464-71. Epub 2005 Nov 2.
3. 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.
Departments
of
Biology
and
Chemistry/Biochemistry,
Georgian Court College,
Lakewood,
NJ,
USA.
[email protected]
J Dermatol Sci. 2003 Jun;32(1):1-9.
4. Capote R, Alonso-Lebrero JL, Garcia F, Brieva A, Pivel JP, Gonzalez S.
Polypodium
leucotomos
extract
inhibits
trans-urocanic
acid
photoisomerization and photodecomposition. R&D Department, Industrial
Farmaceutica Cantabria, C Arequipa 1 EDIF Ofic 5 planta, IFC, 28043 Madrid,
Spain.
J Photochem Photobiol B. 2006 Mar 1;82(3):173-9. Epub 2006 Jan 4.
5. Heliocare, IVAX Laboratories, Inc, Dermatology Division
6.
Kalawalla
extract,
disponível
em:
http://www.raintree.com/brochures/Kalawalla-extract.pdf, acessado em: 24/05/2007
7. Katiyar SK. Skin photoprotection by green tea: antioxidant and
immunomodulatory effects. Department of Dermatology, University of Alabama
at Birmingham, Birmingham, AL 35294, USA. [email protected]
Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42.
8. JUN (V-Jun sarcoma virus 17 oncogene homolog (avian)), disponível em:
http://atlasgeneticsoncology.org/Genes/JUNID151.html, acessado em 25/04/2007
Apendix
J Am Acad Dermatol. 2004 Dec;51(6):910-8.
Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin.
Middelkamp-Hup MA, Pathak MA, Parrado C, Goukassian D, Rius-Diaz F, Mihm MC, Fitzpatrick TB,
Gonzalez S.
Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA 02114, USA.
BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral
photoprotective agent would have substantial benefits. Objective We investigated the photoprotective
effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL).
METHODS: A total of 9 healthy participants of skin types II to III were exposed to varying doses of
artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after
exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PLtreated and untreated skin. RESULTS: A significant decrease in erythema was found in PL-treated skin
(P < .01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P < .05),
cyclobutane pyrimidine dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast
cell infiltration (P < .05). A trend toward Langerhans cell preservation was seen. CONCLUSION: Oral
administration of PL is an effective systemic chemophotoprotective agent leading to significant
protection of skin against UV radiation.
PMID: 15583582 [PubMed - indexed for MEDLINE]
Toxicol In Vitro. 2006 Jun;20(4):464-71. Epub 2005 Nov 2.
Polypodium leucotomos extract: antioxidant activity and disposition.
Gombau L, Garcia F, Lahoz A, Fabre M, Roda-Navarro P, Majano P, Alonso-Lebrero JL, Pivel JP, Castell
JV, Gomez-Lechon MJ, Gonzalez S.
Advancell, 46009 Valencia, Spain.
The extract of the fern Polypodium leucotomos (PL, Fernblock) is an oral photoprotectant with strong
antioxidative properties. Recent studies to determine its chemical composition have shown 4hydroxycinnamic
acid
(p-coumaric), 3
methoxy-4-hydroxycinnamic
acid
(ferulic), 3,4dihydroxycinnamic acid (caffeic), 3-methoxy-4-hydroxybenzoic acid (vanillic) and 3-caffeoilquinic acid
(chlorogenic) to be among its major phenolic components. No conclusive data are available, however,
on the H2O2-scavenging capacity of these compounds, or on their absorption and metabolism
following their oral intake. In the present work, their antioxidative capacity was assessed by the
luminol/H2O2 assay, their absorption studied using Caco-2 cells to resemble the intestinal barrier,
and their metabolism investigated using cultured primary rat hepatocytes. The antioxidant capacity of
PL components increased in a concentration-dependent manner, with ferulic and caffeic acids the
most powerful antioxidants. The apparent permeability results correspond to a human post-oral
administration absorption of 70-100% for all tested substances. Coumaric, ferulic and vanillic acids
were metabolized by CYP450-dependent mono-oxygenases and partially conjugated to glucuronic acid
and sulfate. These phenolic compounds may contribute to the health benefits afforded by this oral
photoprotectant.
PMID: 16263237 [PubMed - indexed for MEDLINE]
J Dermatol Sci. 2003 Jun;32(1):1-9.
Predominant effects of Polypodium leucotomos on membrane integrity,
lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1
in ultraviolet radiation exposed fibroblasts, and keratinocytes.
Philips N, Smith J, Keller T, Gonzalez S.
Departments of Biology and Chemistry/Biochemistry, Georgian Court College, Lakewood, NJ, USA.
[email protected]
BACKGROUND: Polypodium leucotomos has been reported to have antioxidant, anti-inflammatory and
photoprotective properties. Exposure of skin to ultraviolet (UV) radiation can lead to deposition of
excessive elastotic material, reduction in collagen, and increased expression of matrix
metalloproteinases (MMPs). OBJECTIVE: The goal of this research was to determine the effects of P.
leucotomos in the absence or presence of UVA or UVB radiation on membrane damage, lipid
peroxidation, and expression of elastin and MMP-1 in fibroblasts and keratinocytes, respectively.
METHODS: Fibroblasts and keratinocytes, respectively, were irradiated by a single exposure to UVA
(0.6, 1.8 or 3.6 J) or UVB radiation (0.75, 2.5 or 7.5 mJ), and then incubated with, or without, P.
leucotomos (0.01, 0.1 and 1%) and examined for membrane damage, lipid peroxidation, expression
of elastin (protein levels) and MMP-1 (protein levels or MMP-1 promoter activity). RESULTS: UV
radiation did not significantly alter membrane integrity, lipid peroxidation or MMP-1 expression, but
increased elastin expression. P. leucotomos significantly improved membrane integrity, inhibited lipid
peroxidation, increased elastin expression, and inhibited MMP-1 expression in both fibroblasts, and
keratinocytes. The effects of P. leucotomos predominated in the presence of UVA or UVB in both
fibroblasts and keratinocytes, respectively, with the exception of inhibition of MMP-1 protein levels in
fibroblasts only in combination with UV radiation. CONCLUSION: Lower concentration of P.
leucotomos (lower than 0.1%), may be beneficial in preventing photoaging by improving membrane
integrity and inhibiting MMP-1, without increasing elastin expression. Higher concentration (greater
than 0.1%) of P. leucotomos may reverse the loss of normal elastic fibers associated with intrinsic
aging.
PMID: 12788523 [PubMed - indexed for MEDLINE]
J Photochem Photobiol B. 2006 Mar 1;82(3):173-9. Epub 2006 Jan
Polypodium leucotomos extract inhibits trans-urocanic
photodecomposition.
Capote R, Alonso-Lebrero JL, Garcia F, Brieva A, Pivel JP, Gonzalez
R&D Department, Industrial Farmaceutica Cantabria, C Arequipa
Madrid, Spain.
4.
acid photoisomerization and
S.
1 EDIF Ofic 5 planta, IFC, 28043
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.
PMID: 16388959 [PubMed - indexed for MEDLINE]
Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42.
Skin photoprotection by green tea: antioxidant and immunomodulatory effects.
Katiyar SK.
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
[email protected]
Because of a characteristic aroma and health benefits, green tea is consumed worldwide as a popular
beverage. The epicatechin derivatives, commonly called polyphenols, present in green tea possess
antioxidant, anti-inflammatory and anti-carcinogenic properties. The major and most highly
chemopreventive constituent in green tea responsible for the biochemical or pharmacological effects is (-)epigallocatechin-3-gallate (EGCG). Epidemiological, clinical and biological studies have implicated that solar
ultraviolet (UV) light is a complete carcinogen and repeated exposure can lead to the development of
various skin disorders including melanoma and nonmelanoma skin cancers. We and others have shown that
topical treatment or oral consumption of green tea polyphenols (GTP) inhibit chemical carcinogen- or UV
radiation-induced skin carcinogenesis in different laboratory animal models. Topical treatment of GTP and
EGCG or oral consumption of GTP resulted in prevention of UVB-induced inflammatory responses,
immunosuppression and oxidative stress, which are the biomarkers of several skin disease states. Topical
application of GTP and EGCG prior to exposure of UVB protects against UVB-induced local as well as
systemic immune suppression in laboratory animals, which was associated with the inhibition of UVBinduced infiltration of inflammatory leukocytes. Prevention of UVB-induced suppression of immune
responses by EGCG was also associated with the reduction in immunosuppressive cytokine interleukin (IL)10 production at UV irradiated skin and draining lymph nodes, whereas IL-12 production was significantly
enhanced in draining lymph nodes. Antioxidant and anti-inflammatory effects of green tea were also
observed in human skin. Treatment of EGCG to human skin resulted in the inhibition of UVB-induced
erythema, oxidative stress and infiltration of inflammatory leukocytes. We also showed that treatment of
GTP to human skin prevents UVB-induced cyclobutane pyrimidine dimers formation, which are considered
to be mediators of UVB-induced immune suppression and skin cancer induction. The in vitro and in vivo
animal and human studies suggest that green tea polyphenols are photoprotective in nature, and can be
used as pharmacological agents for the prevention of solar UVB light-induced skin disorders including
photoaging, melanoma and nonmelanoma skin cancers after more clinical trials in humans.
PMID: 12871030 [PubMed - indexed for MEDLINE]
Proc Soc Exp Biol Med. 2000 Feb;223(2):170-4.
Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure.
Lee J, Jiang S, Levine N, Watson RR.
Arizona Prevention Center, School of Medicine, University of Arizona, Tucson 85724, USA.
Excessive exposure to solar radiation, especially ultraviolet A (UVA: 320-400 nm) and ultraviolet B (UVB: 290-320
nm) radiation, may induce UV-carcinogenesis and erythema in the skin. Although the protective effects of
carotenoids against skin lesions are still unclear, beta-carotene has been proposed as an oral sun protectant. The
purpose of this study was to determine the magnitude of the protective effects of oral alpha- and beta-carotene
supplementation for 24 weeks on UVA- and UVB-induced erythema in humans. While being exposed to UVA and
UVB radiation, 22 subjects (11 men and 11 women) were supplemented with natural carotenoids for 24 weeks.
Each day for the first 8 weeks, subjects were given 30 mg of natural carotenoids containing 29.4 mg of betacarotene, 0.36 mg of alpha-carotene, and traces of other carotenoids in vegetable oil. The natural carotenoid dose
was progressively raised by 30-mg increments, at every 8 weeks, from 30 mg to 90 mg. Small areas (1 cm2) of
the skin were exposed to increasing doses of UV light (16-42 mJ/cm2) to determine the minimal erythema dose
(MED). MED was defined as a uniform pink color with well-defined borders. MED readings were obtained by visual
inspection 24 hr postirradiation. Blood samples taken during supplementation were used to determine alpha- and
beta-carotene serum levels and for a lipid peroxidation analysis. During natural carotenoid supplementation, the
MED of solar simulator radiation increased significantly (P<0.05). After 24 weeks of supplementation, serum betacarotene levels were increased from 0.22 microg/ml (95% CI; 0.16-0.27) to 1.72 microg/ml (95% CI;1.61-1.83).
Similarly, alpha-carotene serum levels increased from 0.07 microg/ml (95% CI;0.048-0.092) to 0.36 microg/ml
(95% CI; 0.32-0.40). Serum lipid peroxidation was significantly (P<0.05) inhibited in a dose-dependent manner
during natural carotenoid supplementation. The present data suggest that supplementation with natural
carotenoids may partially protect human skin from UVA- and UVB-induced erythema, although the magnitude of
the protective effect is modest.
PMID: 10654620 [PubMed - indexed for MEDLINE]
J Nutr. 2003 Jan;133(1):98-101.
Supplementation with beta-carotene or a similar amount of mixed carotenoids
protects humans from UV-induced erythema.
Heinrich U, Gartner C, Wiebusch M, Eichler O, Sies H, Tronnier H, Stahl W.
Institut fur Experimentelle Dermatologie, Universitat Witten-Herdecke, Germany.
Carotenoids are useful oral sun protectants, and supplementation with high doses of beta-carotene protects against
UV-induced erythema formation. We compared the erythema-protective effect of beta-carotene (24 mg/d from an
algal source) to that of 24 mg/d of a carotenoid mix consisting of the three main dietary carotenoids, betacarotene, lutein and lycopene (8 mg/d each). In a placebo-controlled, parallel study design, volunteers with skin
type II (n = 12 in each group) received beta-carotene, the carotenoid mix or placebo for 12 wk. Carotenoid levels
in serum and skin (palm of the hand), as well as erythema intensity before and 24 h after irradiation with a solar
light simulator were measured at baseline and after 6 and 12 wk of treatment. Serum beta-carotene concentration
increased three- to fourfold (P < 0.001) in the beta-carotene group, whereas in the mixed carotenoid group, the
serum concentration of each of the three carotenoids increased one- to threefold (P < 0.001). No changes occurred
in the control group. The intake of either beta-carotene or a mixture of carotenoids similarly increased total
carotenoids in skin from wk 0 to wk 12. No changes in total carotenoids in skin occurred in the control group. The
intensity of erythema 24 h after irradiation was diminished in both groups that received carotenoids and was
significantly lower than baseline after 12 wk of supplementation. Long-term supplementation for 12 wk with 24
mg/d of a carotenoid mix supplying similar amounts of beta-carotene, lutein and lycopene ameliorates UV-induced
erythema in humans; the effect is comparable to daily treatment with 24 mg of beta-carotene alone.
PMID: 12514275 [PubMed - indexed for MEDLINE]