Download Palestra Prof. Leandro Medeiros

FOTOPROTEÇÃO
ORAL
Prof. Leandro Medeiros
Farmacêutico e doutorando em Inovação Terapêutica | UFPE
Coordenador da pós-graduação em fitoterapia na prática multidisciplinar | IDE Cursos
Coordenador do núcleo de pós-graduação em farmácia | IDE Cursos
Membro do Grupo de Trabalho em Fitoterapia | CRN6
Secretário-geral | CRF-PE
Fotoproteção oral
@prof_leandromedeiros
CONTEXTUALIZAÇÃO
Fotoproteção oral
@prof_leandromedeiros
Considerações iniciais
sobre os fotoprotetores orais
•
Suplementos nutricionais que possuem o
objetivo reduzir a agressão provocada
pela exposição da pele à radiação UV
•
Não são capazes de impedir a inflamação,
mas são úteis na redução da intensidade
do fotodano, fotocarcinogênese e
fotoenvelhecimento
•
Atuam potencializando a resposta
antioxidante, colaborando com o sistema
antioxidante exógeno
Gonzalez et al., 2015
Fotoproteção oral
@prof_leandromedeiros
Do que são compostos os
fotoprotetores orais?
Vitamina A
Vitamina C
Vitamina E
Ácidos graxos essenciais
Nicotinamida
Selênio, Zinco, Manganês
Compostos
bioativos isolados
de plantas
Carotenóides
Polifenóis
Terpenóides
Organossulfurados
Taninos
Alcalóides
Compostos
bioativos isolados
de animais
Carnosina
Coenzima Q10
Nutrientes
Gonzalez et al., 2015
Mukthar et al. 2009 pub Talor and Blair, 2009
Fotoproteção oral
@prof_leandromedeiros
cytochrome P450 family, cyclooxygenases, and lipoxygenases. All possible sources of ROS, the whole
anti-oxidative system of the skin as well as all cellular damages are summarized in Figure 1.
Mecanismos de agressão
oxidativa cutânea
Richter et al., 2015
Figure 1. Schematic of the interplay between different ROS sources and the anti-oxidative
@prof_leandromedeiros
Fotoproteção oral
systems in the skin. All ROS sources discussed in this manuscript are exemplified in black
NUTRIENTES E COMPOSTOS BIOATIVOS
COM USO POTENCIAL EM FOTOPROTEÇÃO
Análise das evidências
Fotoproteção oral
@prof_leandromedeiros
Tomato soup
Vegetable juice
Watermelon
Canned, condensed
Processed
Red, fresh
9.77
17.47
11.48
3.99
7.28c
4.10a
245 g
240 mL (∼250 g)
280 g
a USDA
1998. USDA-NCI Carotenoid Database for U.S. Foods. Nutrient Data Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville
Human Nutrition Research Center, Riverdale, Maryland.
b Source: From Ref. 10.
c Source: From Ref. 12.
d Source: From Ref. 13.
Carotenóides
With very few exceptions, lycopene from natural
plant sources exists in the all-trans form, which is the
most thermodynamically stable configuration (20–22). As
a polyene, lycopene readily undergoes cis–trans isomerization. As a result of the (11) conjugated carbon–carbon
double bonds in its backbone, lycopene can be theoretically arranged in 1056 different geometric configurations
(Fig. 2). Although a large number of geometric isomers
are possible for lycopene, Pauling (23) and Zechmeister
•
(20) have found that only certain ethylenic groups of a
lycopene molecule can participate in cis–trans isomerization reactions because of steric hindrance. Interconversion of isomers is thought to take place with exposure to
thermoenergy, absorption of light, or by involvement in
specific chemical reactions. Cis isomers of lycopene have
chemical and physical characteristics distinctly different
from those of their all-trans counterpart. Some of these
differences include lower melting point, decreased color
Grupo de mais de 700 moléculas presentes em
espécies vegetais, com função de fotossíntese
OH
HO
α-carotene
zeaxanthin
Carotenos
HO
β-carotene
β-cryptoxanthin
OH
HO
all-trans lycopene
lutein
Figure 1
Fotoproteção oral
Oxicarotenos
Representative structures of common carotenoids.
@prof_leandromedeiros
Betacaroteno
Doses de 25 mg/dia de betacaroteno isolado, ou
como uma mistura de carotenóides, durante 12
semanas, reduz o eritema cutâneo pós-exposição
UV, em indivíduos sensíveis ao sol.
A presença da Vitamina E (500 UI) no grupo 2 não gerou
diferença significativa na redução do fotoeritema.
Houve redução significativa da contagem de células de
Langerhans em ambos os grupos em ambos os estudos
Stahl et al., 2000
Stahl et al., 2003
Fotoproteção oral
@prof_leandromedeiros
Betacaroteno
286
Wolfgang Köpcke and Jean Krutmann
Estimates with 95% confidence intervals (CI)
•
•
Doses de até 180 mg/dia,
podem aumentar a proteção
contra queimaduras solares
Efeitos observados com, no
mínimo, 10 semanas de
suplementação
Favors Control
Study name
Favors Carotene
SMD
95% CI
06-Garmyn
-0.112
[-1.171,0.948]
07-Gollnick
0.597
[-0.485,1.678]
09-Heinrich
1.339
[0.453,2.224]
10-Lee
2.303
[1.225,3.38]
11-Mathews
0.397
[-0.349,1.143]
12-McArdle
0.00
[-0.98,0.98]
15-Stahl
1.191
[0.128,2.254]
0.802
[0.201,1.403]
(z = 2.6159 , p = 0.0089 )
Pooled (random effects)
-2
0
1
2
-1
Standardized Mean Difference (SMD)
3
4
Std diff in means
Figure 1. Forest plot for meta-analysis of b-carotene supplementation vs placebo on sunburn protection.
Fotoproteção oral
3
10
2
1
9
15
7
(Table 4). Under these conditions, the fixed and t
model effects showed very similar and significant
contrast to the first meta-analysis, however, the d
supplementation was no longer a significant mode
able (P = 0.1064).
Köpcke and Krutmann , 2008
DISCUSSION
This meta-analysis indicates that b-carotene suppl
of humans is effective in providing protection a
@prof_leandromedeiros
Betacaroteno
116
Johnson and Russell
β-Carotene
15′
14′
12′
10′
8′
8′CHO
10′CHO
8′COOH
10′COOH
12′CHO
12′COOH
14′COOH
CHO
Retinal
COOH
CH2OH
Retinol
Retinoic Acid
Figure 1 !-Carotene conversion to vitamin A (retinal, retinol, and retinoic acid). Central cleavage by carotene monooxygenase or CMOI between bonds 15 and
15′ forms retinal directly. A second cleavage enzyme (CMOII) cleaves !-carotene excentrically at the 9′ –10′ position. Cleavage at other bonds forms apocarotenals
(CHO). Apocarotenals may be oxidized to apocarotenoic acids (–COOH), which could form retinoic acid. Apocarotenals may be oxidized to apocarotenoic acids
(–COOH), which could form retinoic acid.
Johnson & Russel, 2010
Fotoproteção oral
Compared with carrots (a source of !-carotene),
@prof_leandromedeiros
!-carotene is given in the absence of fat, no detectable
Betacaroteno
Ensaios pré-clínicos mostram
ação pró-oxidante potencial em
fibroblastos (aumento de heme
oxigenase [HO-1])
Efeitos fotoprotetores do
betacaroteno podem não ocorrer
em todos os indivíduos
Ar ch ives of Bioch em ist r y a n d Bioph ysics
Vol. 389, No. 1, Ma y 1, pp. 1– 6, 2001
doi:10.1006/a bbi.2001.2313, a va ila ble on lin e a t h t t p://www.idea libr a r y.com on
MINIREVIEW
UV Light, Beta-carotene and Human Skin—Beneficial and
Potentially Harmful Effects
H a n s K. Biesa lski 1 a n d Ut e C. Ober m u eller -J evic
Departm en t of B iological Ch em istry an d N u trition , Un iversity of H oh en h eim , Fru w irth strasse 12,
70593 S tu ttgart, Germ an y
Received Sept em ber 7, 2000; pu blish ed on lin e Apr il 6, 2001
Fotoproteção oral
h ypot h esized in t h e 1950s (4). La t er , be
fou n d t o pr even t en dogen ou s (ch lor op
n ou s ph ot osen sit iza t ion in ba ct er ia , a
pla n t s (5). Mor eover , bet a -ca r ot en e
t r ea t ed wit h h em a t opor ph yr in (6) a n d
in g fr om ph ot osen sit ivit y t o visible lig
or a l a dm in ist r a t ion of bet a -ca r ot en e h
fu l t ool for t h er a py in pa t ien t s wit h er
Basu-Modak
t opor ph yrand
ia (E P PTyrrell,1993
) 2 (8). Th is h a s lea d t
t h a t bet a -ca r ot en
e m igh t a1999
lso h a ve pr
Jones,
t ies in n or m a l skin a n d t h u s pr even t
Over exposu r e t o su n ligh t pr ovokes
r ea ct ion wh ich clin ica lly m a n ifest s it s
Ch r on ic exposu r e t o su n lea ds t o pr em
(“ph ot oa gin g”) a n d in cr ea ses t h e r isk o
S o la r ra d ia tio n is o n e o f th e m o s t im p o rta n t e n v iro n m e n ta l s tre s s a g e n ts fo r h u m a n s k in , c a u s in g s u n bu rn ,
p re m a tu re s k in a g in g , a n d s k in c a n c e r. B e ta -c a ro te n e
is d is c u s s e d to p ro te c t a g a in s t p h o to o x id a tiv e s tre s s
a n d th u s p re v e n t s k in d a m a g e . Th o u g h be ta -c a ro te n e
h a s be e n s u c c e s s fu lly u s e d a g a in s t p h o to s e n s itiv ity in
p a tie n ts w ith e ry th ro p o ie tic p ro to p o rp h y ria , its be n e fi c ia l p o te n tia l in n o rm a l s k in is s till u n c e rta in . A
n u m be r o f e x p e rim e n ta l s tu d ie s in d ic a te p ro te c tiv e
e ffe c ts o f be ta -c a ro te n e a g a in s t a c u te a n d c h ro n ic
m a n ife s ta tio n s o f s k in p h o to d a m a g e . Ho w e v e r, m o s t
c lin ic a l s tu d ie s h a v e fa ile d to c o n v in c in g ly d e m o n s tra te its be n e fi c ia l e ffe c ts s o fa r. N e v e rth e le s s , in ta k e
o f o ra l be ta -c a ro te n e s u p p le m e n ts be fo re s u n e x p o -
@prof_leandromedeiros
Betacaroteno
Ar ch ives of Bioch em ist r y a n d Bioph ysics
Vol. 389, No. 1, Ma y 1, pp. 1– 6, 2001
doi:10.1006/a bbi.2001.2313, a va ila ble on lin e a t h t t p://www.idea libr a r y.com on
Parece não reduzir
ocorrência de quetarose
solar ou câncer de pele
associado à exposição
solar
MINIREVIEW
UV Light, Beta-carotene and Human Skin—Beneficial and
Potentially Harmful Effects
H a n s K. Biesa lski 1 a n d Ut e C. Ober m u eller -J evic
Departm en t of B iological Ch em istry an d N u trition , Un iversity of H oh en h eim , Fru w irth strasse 12,
70593 S tu ttgart, Germ an y
Received Sept em ber 7, 2000; pu blish ed on lin e Apr il 6, 2001
Fotoproteção oral
S o la r ra d ia tio n is o n e o f th e m o s t im p o rta n t e n v iro n m e n ta l s tre s s a g e n ts fo r h u m a n s k in , c a u s in g s u n bu rn ,
p re m a tu re s k in a g in g , a n d s k in c a n c e r. B e ta -c a ro te n e
is d is c u s s e d to p ro te c t a g a in s t p h o to o x id a tiv e s tre s s
a n d th u s p re v e n t s k in d a m a g e . Th o u g h be ta -c a ro te n e
h a s be e n s u c c e s s fu lly u s e d a g a in s t p h o to s e n s itiv ity in
p a tie n ts w ith e ry th ro p o ie tic p ro to p o rp h y ria , its be n e fi c ia l p o te n tia l in n o rm a l s k in is s till u n c e rta in . A
n u m be r o f e x p e rim e n ta l s tu d ie s in d ic a te p ro te c tiv e
e ffe c ts o f be ta -c a ro te n e a g a in s t a c u te a n d c h ro n ic
m a n ife s ta tio n s o f s k in p h o to d a m a g e . Ho w e v e r, m o s t
c lin ic a l s tu d ie s h a v e fa ile d to c o n v in c in g ly d e m o n s tra te its be n e fi c ia l e ffe c ts s o fa r. N e v e rth e le s s , in ta k e
o f o ra l be ta -c a ro te n e s u p p le m e n ts be fo re s u n e x p o -
h ypot h esized in t h e 1950s (4). La t er , be
fou n d t o pr even t en dogen ou s (ch lor op
n ou s ph ot osen sit iza t ion in ba ct er ia , a
pla n t s (5). Mor eover , bet a -ca r ot en e
tDarlington
r ea t ed wit h h emet
a t opor
yr in (6) a n d
al.,ph 2003
in g fr om ph ot osen sit ivit y t o visible lig
Green
et ofal.,
or a l a dm
in ist r a t ion
bet a1999
-ca r ot en e h
fu l t ool for t h er
a
py
in
pa
t
ien
t s wit h er
Frieling,
2000
2
t opor ph yr ia (E P P ) (8). Th is h a s lea d t
t h a t bet a -caBiesalski,
r ot en e m igh t a2001
lso h a ve pr
t ies in n or m a l skin a n d t h u s pr even t
Over exposu r e t o su n ligh t pr ovokes
r ea ct ion wh ich clin ica lly m a n ifest s it s
Ch r on ic exposu r e t o su n lea ds t o pr em
(“ph ot oa gin g”) a n d in cr ea ses t h e r isk o
@prof_leandromedeiros
Betacaroteno
Não existe UL estabelecida para o betacaroteno
Suplementação de 20 mg/dia foi associado
positivamente sobre o aumento da incidência de câncer
de pulmão e próstata em fumantes
Lepalla, 2000
Bjelakovic, 2007
Fotoproteção oral
@prof_leandromedeiros
microfibrillar network and dietary
supplementation gives partial protection.
Representative photomicrographs of fibrillin-1
staining of presupplemented skin at baseline
(unirradiated) (a) and 24 h post-UVR
(b) showing a truncated fibrillin-rich
microfibrillar network following UVR (arrows
indicate the presence of microfibrils). This
remodelling was offset by dietary
supplementation with both olive oil
[unirradiated (c), irradiated (d)] and tomato
paste with olive oil [unirradiated (e),
irradiated (f)]. Scale bar, 50 lm.
Licopeno
Postsupplementation,
olive oil
Postsupplementation,
tomato paste
Consumo de 55 g de molho de tomate
(equivalente a 16 mg de licopeno)
Redução das concentração
deradiation
MMP-1
Fig 5. Acute ultraviolet
(UVR)
induces matrix metalloproteinase (MMP)-1
(p = 0,04)
expression and this is abrogated by dietary
supplementation with tomato paste.
Representative photomicrographs of MMP-1
staining of presupplemented skin at baseline
(unirradiated) (a) and 24 h post-UVR (b)
showing an induction of this enzyme. This
induction was partially offset by dietary
supplementation with tomato paste
[unirradiated (c), irradiated (d)]. The arrows
highlight positively stained cells. Scale bar,
50 lm.
Unirradiated
Manteve as concentrações de
objective erythemal measurements
fibrilina-1
(a)
(b)
(c)
(d)
Postsupplementation,
tomato paste
compared with the visual
assessment of the MED. An MED is derived using an interval
scale of UVR change, meaning that small alterations in erythemal sensitivity may go undetected, while erythema measurements provide a more sensitive tool in assessing the impact of
potentially protective agents. The degree of protection
observed would not provide clinically useful protection against
sunburn erythema, but indicates some abrogation of UVRinduced effects on skin.
Fotoproteção oral
Irradiated
Presupplementation
Aumentou a deposição de procolágeno tipo I (p = 0,05)
Reduziu concentrações de reação de
cadeia de polimerase (p = 0,01)
(f)
(e)
through transcription factor AP-1, which in turn is activated
through UVR-induction of MAP kinase signalling pathways.34
We have demonstrated that a single UVR dose increased MMP1 expression in the dermis before supplementation, consistent
with previous studies.30 Following tomato paste supplementaRizwan et al., 2011
tion there was inhibition of UVR-induced MMP-1 expression
in the dermis, whereas the control (olive oil alone) did not
effect change. This inhibitory effect of tomato paste on UVR
induction of MMP-1 was@prof_leandromedeiros
accompanied by a small increase in
Licopeno
Doses de 8 a 16 mg/dia, na
forma de suplemento ou
como produtos derivados
do tomate, por 12 semanas,
podem gerar proteção
contra queimaduras solares.
Human Nutrition a
Research Com
Supplementation with !-Carotene
or a Similar Amount of Mixed
Carotenoids Protects Humans from
UV-Induced Erythema
(Manuscript received 27 August 2002. Initial review completed 13
September 2002. Revision accepted 10 October 2002.)
Ulrike Heinrich, Christine Gärtner,* Mathilde Wiebusch,
Olaf Eichler,†1 Helmut Sies,†1 Hagen Tronnier
and Wilhelm Stahl†2
Institut für Experimentelle Dermatologie, Universität WittenHerdecke, D-58455 Witten, Germany, *Cognis Deutschland GmbH
& Co. KG, Nutrition and Health, D-40551 Düsseldorf, Germany
and †Institut für Physiologische Chemie I and BiologischStahl et al.,2001
Medizinisches Forschungszentrum, Heinrich-Heine-Universität
Düsseldorf, D-40001 Düsseldorf, Germany
Stahl et al.,2003
Aust et al., 2005
Fotoproteção oral
ABSTRACT Carotenoids are useful oral sun protectants,
and supplementation with high doses of !-carotene protects against UV-induced erythema
formation. We com@prof_leandromedeiros
pared the erythema-protective effect of !-carotene (24
Licopeno
Uso do licopeno parece ser
seguro em doses de até 120 mg/
dia, por até 1 ano
Maioria dos trabalhos avaliando
seu potencial terapêutico em
hiperplasias de próstata
(benignas ou malignas)
ADULT UROLOGY
PHASE I-II PROSPECTIVE DOSE-ESCALATING TRIAL OF
LYCOPENE IN PATIENTS WITH BIOCHEMICAL RELAPSE OF
PROSTATE CANCER AFTER DEFINITIVE LOCAL THERAPY
PETER E. CLARK, M. CRAIG HALL, LESTER S. BORDEN, JR, ANTONIUS A. MILLER,
JENNIFER J. HU, W. ROBERT LEE, DIANA STINDT, RALPH D’AGOSTINO, JR, JAMES LOVATO,
MICHELLE HARMON, AND FRANK M. TORTI
ABSTRACT
Objectives. To report a prospective trial of lycopene supplementation in biochemically relapsed prostate
cancer.
Methods. A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating,
Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily
supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific
antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary
endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics,
and the toxicity/tolerability of this regimen.
Results. A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median
serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of
patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1
patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at
3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and
90 mg/day were similar, with additional elevation only at 120 mg/day.
Conclusions. Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well
tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued
by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible
Clark et al.,2006
Fotoproteção oral
@prof_leandromedeiros
Camellia sinensis
Planta rica em
polifenóis da família
das catequinas
No Brasil, há grande
variabilidade
padronizações de
extratos à base de
Camellia sinensis
Fotoproteção oral
OH
OR2
OH
OH
OH
O
HO
OH
B
O
HO
A
R2
C
OH
OR1
OH
Epicatechin: R1=R2=H
Epigallocatechin: R1=H; R2=OH
Epicatechin-3-gallate: R1=Galloyl: R2=H
Epigallocatechin-3-gallate: R1=Galloyl: R2=OH
O
O
HO
OR1
OH
Theaflavin: R3=R2=H
Theaflavin 3-gallate: R1=Galloyl; R2=H
Theaflavin: 3′-gallate: R1=H: R2=Galloyl
Theaflavin: 3,3′-digallate: R1=R2=Galloyl
Fig
body fat (45%
clearly establish the efficacy of tea@prof_leandromedeiros
in the prevention of
crease), and i
cardiovascular disease.
Camellia sinensis
As catequinas podem
reduzir a lesão ao DNA
induzida por UVA/UVB
Modelos em animais
indicam que o extrato
reduz a lesão oxidativa
cutânea, inflamação
cutânea e hiperplasia
epidermal associada à
radiação UV
Elmets et al.,2001
Katiyar, Ahmad, Mukhtar, 2000
Fotoproteção oral
@prof_leandromedeiros
statistically significant difference between active and placebo
(P = 0.62; Figure 4). Similarly, no statistically significant difference between treatment groups was found after multiple
imputation or per-protocol analyses.
Camellia sinensis
GREEN TEA CATECHINS A
1.350 mg, 3x/dia, do extrato de
Camellia sinensis (equivalente
a 1.080 mg/dia de catequinas)
não foi superior ao placebo
quanto à redução de
eicosanóides (ácido
hidroxieicosatetraenóico /
PGE2) de neutrófilos e células
T CD3+.
•
t = 12 semanas (n = 50)
Downloaded from ajcn.nutrition.org by guest on April 10, 2016
•
FIGURE 5 UVR-induced PGE2 and 12-HETE production at basel
and
after 12 wk
of supplementation. Mean 1 SEM concentration of
FIGURE 4 UVR-induced neutrophil and T-cell infiltration
at baseline
PGE2 and (B) 12-HETE in suction blister fluid from UVR-exposed
and after 12 wk of supplementation. Representative immunohistochemistry
unexposed skin at baseline and post-supp (n = 20 active; n = 21 placeb
of (A) neutrophils and (B) CD3+ T cells in ultraviolet-exposed
* P , 0.05, **and
P ,unex0.01, and *** P , 0.001 compared with unirradia
skin (Wilcoxon’s
Rank test). MED, minimal erythema dose; PG
posed skin at baseline and post-supp. Mean + SEM number
of (C) Signed
neutroE2; post-supp,
= 22 active;
n = 25 after supplementation; UVR, ultraviolet rad
phils and (D) CD3+ T cells per high-power field (nprostaglandin
tion; 12-HETE, 12-hydroxyeicosatetraenoic acid.
Farrar et al., 2015
Fotoproteção oral
placebo). **P , 0.01 and ***P , 0.001, compared with unirradiated skin
(Wilcoxon’s Signed Rank test). hpf, high-power field; MED, minimal erythema dose; post-supp, after supplementation; UVR, ultraviolet radiation.
16.3 pg/mL; P = 0.35; Figure 5A). Similarly, there was no s
nificant difference in concentration of 12-HETE in UVR-expos
@prof_leandromedeiros
Camellia sinensis
•
Há evidências de benefícios em seres humanos com o
uso tópico de catequinas de C. sinensis, em exposição
UVA/UVB
Elmets et al., 2001
Katiyar et al., 1999
Fotoproteção oral
@prof_leandromedeiros
Pinus pinaster
(Pycnogenol®)
•
Produto padronizado
em 65 a 75% de
procianidinas totais
Fotoproteção oral
@prof_leandromedeiros
Pinus pinaster
(Pycnogenol®)
Pode reduzir a
hiperpigmentação cutânea
Promoveu aumento da DEM
na dose de 1,1 mg/kg, 2x/
dia (4 semanas), com
posterior aumento para 1,66
mg/kg, 2x/dia (4 semanas)
Efeito mediado pela redução da
expressão de NF-kB
Fotoproteção oral
Review
Skin Pharmacol Physiol 2016;29:13–17
DOI: 10.1159/000441039
Received: July 9, 2015
Accepted after revisio
Published online: Octo
French Maritime Pine Bark Extract
(Pycnogenol®) Effects on Human Skin:
Clinical and Molecular Evidence
Susanne Grether-Beck Alessandra Marini Thomas Jaenicke Jean Krutmann
IUF, Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
Key Words
Pycnogenol®
Ni et al., 2001
can
affect human
(for a2001
recent monogra
Saliou
etskinal.,
· Pine bark extract · Pigmentation · Skin barrier Krutmann and Humbert [1]). Initially, m
studies have focused
on the2016
capacity of suc
Grether-Beck
et al.,
Abstract
Nutritional strategies to benefit skin health are of growing
importance. Current approaches mainly involve nutritional
supplements containing antioxidants which were initially
designed to protect human skin against ultraviolet radia-
provide protection against harmful effects
(UV) radiation on human skin. From thes
now generally accepted that oral photoprote
ciple works, although the time kinetics to ac
able photoprotection as well as the magnit
protection that can be achieved markedl
@prof_leandromedeiros
Polypodium leucotomus
Extrato padronizado em
ácidos orgânicos totais
(0,66%), expressos em
ácido caféico e ácido
ferúlico
Estes compostos geram
controle do eritema
fotoinduzido, mecanismos
inflamatórios e suas
respostas celulares
(angiogênese,
fotocarcinogênese e
elastose solar)
Fotoproteção oral
was a
provem
crease
related
flamm
munoh
the im
to pre
As a
compe
would
skin. I
UV li
of PL
Fig. 1 Polypodium leucotomos. The benefits of an aquatic fern
originating in Central America have been used for centuries by Native
given
Americans as an anti-inflammatory agent, which today has applicaangiog
tion, with its natural protective mechanisms against the impact of
reduct
ultraviolet light [3]. Photograph: Copyright Ferndale Laboratories,
elasto
MI, USA; used with permission
Middelkamp-Hup MA., 2004 provem
Bathia, 2015pressi
example, ingenol mebutate gel comes from the Australian
peroxi
plant Euphorbia peplus [1], sinecatechins ointment is a
metall
derivative of the Chinese tea leaves derived from Camellia
atinoc
sinensis [2], and these therapies
and aloe vera, among
@prof_leandromedeiros
p53 g
many others, have been available to dermatologists for
clooxy
antioxidant, immunoregulatory, anti-inflammatory, and
antitumorigenic effects in the context of sunburn, photodermatoses, chronic skin damage, photoaging, and skin cancer
were included (n = 18 of 55). Table 1 cross-references PL
photoprotective effects along with the cellular or molecular
mechanisms involved and the relevant experimental study.
uting to UV-induced immunosuppression.3
Antioxidant properties
Studies have demonstrated that irradiation causes activation of endogenous antioxidant systems and increased
glutathione (GSH) consumption to form oxidized glutathione (GSSG). PL has been shown to inhibit glutathione
oxidation in blood and epidermis by allosterically modulating enzymes such as catalase.10,11 In rats treated with
PL, oxidized glutathione (GSSH) levels were decreased in
both non-irradiated and irradiated groups. GSSH levels in
irradiated animals were fourfold lower than in rats that
Polypodium leucotomus
Results
Overview of the effects of ultraviolet radiation on the skin
Systemic UV irradiation can result in acute injuries (i.e.,
erythema, swelling, pain) and long-term damage (i.e.,
Table 1 Polypodium leucotomos photoprotective effects along with the cellular or molecular mechanisms involved. Note that
some mechanisms are interconnected
Protective mechanism
Cellular/molecular level
References
Anti-inflammatory
Reduction of UV-induced macrophage and neutrophil infiltration
Inhibition of UV-induced Cox-2 expression
Blocks TNF-a, iNOS, AP-1, NF-jB
p53 activation
Removal of UV-induced photoproducts and prevents formation of cyclobutan pyrimidine dimers
Enhances natural antioxidant system
Preservation of Langerhans cells and function
Blocks t-UCA photoisomerization and photodecomposition
Preserves cell viability and inhibits cytoskeletal disarray
Inhibits matrix metalloproteinases
2, 5, 12
5
9
5, 11
2, 5, 11
4, 10–13
2, 5, 10, 12, 13
10, 16, 17
1
6
Decrease DNA mutagenesis
Immunoregulation
Cell cycle and cellular integrity
Cox, cyclooxygenase; iNOS, inducible nitric oxide synthase; t-UCA, trans-urocanic acid; TNF, tumor necrosis factor; UV, ultraviolet.
International Journal of Dermatology 2014
ª 2014 The International Society of Dermatology
El-Haj and Goldenstein, 2014
Fotoproteção oral
@prof_leandromedeiros
Outros produtos com evidências
preliminares na fotoproteção oral
•
Punica granatum (romã)
•
Lycium barbarum (goji)
•
Micronutrientes (vitamina E, vitamina C)
Natural Medicines Database, 2016
Fotoproteção oral
@prof_leandromedeiros
CONSIDERAÇÕES FINAIS
Fotoproteção oral
@prof_leandromedeiros
CONSIDERAÇÕES FINAIS
•
Não há evidências de que os suplementos antioxidantes
possam substituir os fotoprotetores orais. É razoável sua
utilização associada aos tópicos.
•
Maioria dos estudos com limitações metodológicas (controle
dietético, amostra pequena)
•
Custos de estudos em seres humanos dificultam sua realização
•
Limitações da legislação sanitária quanto a alegação de uso
nos rótulos de suplementos nutricionais
•
Observações a respeito da biodisponibilidade dos ingredientes
ativos
Biba, 2014
Fotoproteção oral
@prof_leandromedeiros
Obrigado!
Instagram/Periscope: @prof_leandromedeiros
Facebook: @leandro.a.medeiros
E-mail: [email protected]
www.idecursos.com.br
Fotoproteção oral
@prof_leandromedeiros