SkinCeuticals C E Ferulic - 1 oz.
Introducing C E Ferulic – with Ferulic Acid, a new antioxidant that enhances the already synergistic benefits of C+E – neutralizing free radicals, building collagen, and providing improved antioxidant protection. C E Ferulic delivers an unprecedented 8x photoprotection against environmental damage.
C E Ferulic is a revolutionary topical antioxidant combination that provides an unprecedented eight-times the skin’s natural photoaging protection against damage caused by environmental exposure. More protection is important. It means healthier and more youthful looking skin. Culminating more than 10 years research and testing, SkinCeuticals latest antioxidant breakthrough doubles performance of the original synergistic combination antioxidant, C+E. the addition of ferulic acid has transformed the already powerful combination into a super anti-aging serum with unmatched results.
Why is this important?
Recent studies reveal that we may no be as protected as we think.
• Sunscreens only block 55% of free radicals, leaving your skin vulnerable to damaging, age-accelerating free radicals
• People don’t apply enough sunscreen to achieve full SPF. Real life application of an SPF 20 sunscreen yields an SPF of only 3 or 4
• Most skincare products use a fraction of the active ingredients tested in the laboratory
C E Ferulic is supported by published scientific data – all produced using the same formula we make available to you, tested in the same way you use it.
How to Use:
Once daily using fingertips, apply 4-5 drops of C E Ferulic to face, neck and chest.
Key Ingredients
L-ASCORBIC ACID (VITAMIN C)
• The body’s most important water-soluble antioxidant
• Inhibits UVA and UVB radiation-induced damage
• Photoprotective capabilities
• Promotes collagen synthesis
• Anti-inflammatory properties
ALPHA-TOCOPHEROL (VITAMIN E)
• The body’s most important lipid, or fat-soluable, antioxidant with significant antioxidant functions, especially in cell membranes and lipoproteins
• Photoprotective capabilities
• Helps to protect the cellular membrane from free radical damage
• Improves the skin’s water binding abilities
• Anti-inflammatory properties
FERULIC ACID
• Ubiquitous plant antioxidant
• Neutralizes free radicals known as “superoxide,” “hydroxyl radical” and “nitric oxide.”
• Suppresses radiation-induced oxidative reactions
• Acts synergistically with other antioxidants, improving their potency
• Absorbs UV (approved sunscreen in Japan)
• Anti-inflammatory properties
• Easily absorbed by the skin
A Topical Antioxidant Solution Containing Vitamin C, Vitamin E, and Ferulic Acid
Prevents Ultraviolent Radiation-Induced Caspase-3 Induction in Skin
Lin, F-Y, Monteiro-Riviere, N.A., Grichnik, J.M. Zieliknskin, J.E., and Pinnell, S.R.
Duke Univ., Durham, NC, NC State Univ., Raleigh, NC, Zielinski Laboratory, Inc., San Diego, CA
Introduction
Sunlight and pollution generate oxidative stress in skin leading to skin cancer and photoaging changes. Antioxidants in skin interact to protect the tissue by neutralizing reactive oxygen species (Podda and Grundmann-Kollmann, 2001). Broad spectrum sunscreens are widely used to protect skin from sunlight but at optimal application only 55% of the free radical generation is blocked (Haywood et al., 2003). Topical application of antioxidants when properly formulated .for optimal percutaneous absorption, supplement skin's antioxidant reservoir to provide additional protection.
We have previously demonstrated that 15% L-ascorbic acid and 1 % a-tocopherol formulated at pH lower than 3.5 to allow percutaneous absorption provide synergistic photoprotection when applied topically to skin (Lin et al., 2003). We have demonstrated that this combination protects skin fourfold against UV- induced erythema, cellular damage as measured by sunburn cells, and thymine dimer formation.
We have recently sought to improve this formulation by adding chemically defined low molecular weight antioxidants to improve stability of this solution. We have determined that addition of 0.5% ferulic acid improves stability of L-ascorbic acid and doubles photoprotection to solar-simulated radiation after topical application (Lin et aI, J Invest Dermatol122, A148, 2004). In this study, we report that UV-induced apoptosis of skin cells is mediated by caspase-3 and its downstream mediator caspase- 7 and topical application of a solution containing 15% L-ascorbic acid, 1 % a- tocopherol and 0.5% ferulic acid protects against this activation.
In an attempt to improve the stability of this antioxidant formulation, we have surveyed a number of low molecular weight, chemically pure coantioxidants. Ferulic acid at a concentration of 0.5% provided the best combination of stability and cosmetic elegance. Ferulic acid is a ubiquitous plant antioxidant. (Figure 1) (Graf, 1992; Kikuzaki et al., 2002). It is important in plant cell wall and lignin synthesis. Although this compound is found only in plants, it has characteristics that may provide useful antioxidant protection for skin. It has solubility in both hydrophilic and lipophilic environments. Its phenolic nucleus and extended side chain conjugation allows it to readily form a resonance stabilized phenoxy radical which accounts for its strong radical- scavenging effects. In addition, it absorbs ultraviolet light initiating phenoxy radical formation leading to cis-trans isomerization. The phenoxy radical can participate in free radical scavenging (Graf, 1992). In this study, we demonstrate that 0.5% ferulic acid improves the chemical stability of a solution of 15% L-ascorbic acid and 1 % alpha-tocopherol. In addition, topical application to skin of the ferulic acid stabilized formulation markedly increases photoprotection against solar-simulated radiation.
Methods
15% L-ascorbic acid and 1 % dl-a-tocopherol (C+E, SkinCeuticals, Garland, TX); 15% L-ascorbic acid, 1 % dl-a tocopherol and 0.5% trans ferulic acid in an aqueous vehicle; 0.5% trans ferulic acid alone were applied (500 ul) daily for 4 days to a 7.5xl0 cm patch of skin. On day 4, solar-simulated ultraviolet radiation, filtered through a WG295 Schott selective UVB band-high pass filter to filter wavelengths less than 295 nm was administered in triplicate to treated and untreated control skin, 2x -lOx MED at 2x MED intervals (lx MED=40 mJ/cm2). Twenty four hours later irradiated and nonirradiated control skin was biopsied, and portions were frozen in liquid nitrogen and formalin-fixed. For western blotting, cell protein was extracted from freeze-fractured skin and electrophoresed in 12 % SDS-polyacrylamide gel, transferred to PVDF membranes and probed for activated caspase-3 or 7 with human cleaved- caspase- 3, or cleaved-caspase-7 antibody (Cell Signaling Technology, Inc). These antibodies were used for imunohistochemistry on formalin-fixed tissue. Western blots were standardized for application by determining a-tubulin levels. ('Santa Cruz Biotechnology, Inc). Results are expressed as mean +/- standard deviation (n=3).
Results
Figure 1 reveals the erythema in skin generated by the solar simulator and the eightfold protection afforded by the ferulic acid-stabilized solution of vitamins C and E. Figure 2 reveals progressive activation of caspase-3 by increasing amounts of solar-simulated radiation. Figure 3a reveals protection by antioxidant solutions of activation of caspase-3 by 4x and 8x MEDs of solar-simulated radiation. Figure 3b shows relative quantification of antioxidant protection of 4x MEDs of solar-simulated radiation. With 8x MEDs of radiation (Figure 3c), protection of vitamin C, E and ferulic acid is almost complete and is better than vitamin C and E or ferulic acid alone. Figure 4a shows activation of caspase- 7 by 4x and 8x MED of solar- simulated radiation and protection by antioxidant solutions. Figure 4b shows relative protection with antioxidant solutions and Figure 4c reveals virtually complete protection by vitamins C, E and ferulic acid. Figure 5 shows immunohistochemistry of activation of caspase-3 by 4x MED of solar-simulated light. Activation occurs in both epidermis and dermis (Figure 5a-5c); in epidermis, activation is particularly strong in the basal layer. Ferulic acid alone (5d) and vitamins C+E (5e) provide partial protection but vitamins C, E and ferulic acid (Sf) provides virtually complete protection.
Discussion
In this study we demonstrate that solar-simulated radiation activates caspase-3 in skin leading to apoptosis of skin cells. Activation occurs through a pathway involving caspase- 7. These effects occur in both epidermis and dermis. Activation can be partially prevented by 0.5% ferulic acid alone or by an aqueous formulation containing 15% L-ascorbic acid and 1 % a-tocopherol. A solution containing the combination of 15% L-ascorbic acid, 1 % a-tocopherol and 0.5% ferulic acid provides virtually complete protection.
Although the mechanisms of action of the additive effects of ferulic acid are unknown, they may be related to the relatively unique antioxidant effects of hydroxycinnamic acids (Rice-Evans et al., 1996; Graf, 1992; Kikuzaki, et al. 2002).
References
1. GrafE: Antioxidant potential of ferulic acid. Free Rad Bioi Med 13:435-448 (1992).
2. Haywood R, Wardman P, Sanders R, Linge C: Sunscreens inadequately protect against ultraviolet-A-induced free radicals in skin: implications for skin aging and melanoma? ] Invest DerrnatoI121:862-868 (2003).
3. Lin JY, Selim MA, Shea CR, Grichnik JM,
Omar MM, Monteiro-Riviere NA, Pinnell SR: UV photoprotection by combination topical antioxidants vitamin C and vitamin E. ] Arner Acad DerrnatoI48:866-874 (2003).
4. Podda M, Grundmann-Kollmann M: Low molecular weight antioxidants and their role in
skin ageing. Clin Exper DerrnatoI26:578-582
(2001). ..
5. Rice-Evans CA, Miller NJ, Paganga G: Structure- antioxidant activity relationships of flavonoids and phenolic acids. Free Rad Bioi Med 20:933- 956 (1996).
6. Kikuzaki H, Hisamoto M, Hirose K, Akiyama
K, Taniguchi H: Antioxidant properties of ferulic acid and its related compounds. Agri Food Chern 50:2161-2168 (2002).
This study was supported in part by a research grant R43 AR 050302-01 from the National Institutes of Health.
Dr. Pinnell is a consultant for SkinCeuticals (Garland, TX).
Dr. Zielinski is President of Zielinski Research (San Diego, CA).
Ferulic Acid Stabilizes a Topical Solution Containing
Vitamins C+E and Doubles it's Photoprotection for Skin
Lin J.Y., Lin, F-Y., Burch, J.A., Gupta, R., Grichnick, J.M., Monteiro-Riviere, N.A., Zielinski, J., and Pinnell, S.R.
Chang Gung Memorial Hospital, Taipei, Taiwan, Duke Univ., Durham, NC, NC State Univ., Raleigh, NC, Zielinski Research, San Diego, CA
Introduction
We previously demonstrated that topical antioxidants,
when properly formulated to maximize percutaneous
absorption, can supplement the antioxidant reservoirs of
skin and provide meaningful photoprotection (Lin et al.,
2003). Thus, 15% L-ascorbic acid and 1% a-tocopherol
formulated at pH lower than 3.5 to allow percutaneous
absorption provide synergistic photoprotection when
topically applied to skin. We have demonstrated that
this combination protects skin fourfold against photo-induced
erythema, cellular damage as measured by
sunburn cells, and thymine dimer formation.
In an attempt to improve the stability of this antioxidant
formulation, we have surveyed a number of low
molecular weight, chemically pure coantioxidants.
Ferulic acid at a concentration of 0.5% provided the best
combination of stability and cosmetic elegance. Ferulic
acid is a ubiquitous plant antioxidant. (Figure 1) (Graf,
1992; Kikuzaki et al., 2002). It is important in plant cell
wall and lignin synthesis. Although this compound is
found only in plants, it has characteristics that may
provide useful antioxidant protection for skin. It has
solubility in both hydrophilic and lipophilic
environments. Its phenolic nucleus and extended side
chain conjugation allows it to readily form a resonance
stabilized phenoxy radical which accounts for its strong
radical-scavenging effects. In addition, it absorbs
ultraviolet light initiating phenoxy radical formation
leading to cis-trans isomerization. The phenoxy radical
can participate in free radical scavenging (Graf, 1992).
In this study, we demonstrate that 0.5% ferulic acid
improves the chemical stability of a solution of 15%
L-ascorbic acid and 1% a-tocopherol. In addition,
topical application to skin of the ferulic acid stabilized
formulation markedly increases photoprotection against
solar-simulated radiation.
Methods
15% L-ascorbic acid and 1% dl-a-tocopherol {C+E,
SkinCeuticals, Garland, TX); 15% L-ascorbic acid,
10% dl-a-tocopherol and 0.50% trans ferulic acid in
an aqueous vehicle; and 0.50% trans ferulic acid alone
were tested. Chemical stability was determined by
high pressure liquid chromatography after heating at,
45°C for one month. To test photoprotection, each
formulation, (500 ul) was applied daily for 4 days to
a 7.5xl0 cm patch of skin. On day 4, solar-simulated
ultraviolet radiation (UVR), filtered through a WG295
Schott selective UVB band-high pass filter to filter
wavelengths less than 295 nm was administered in
triplicate to treated and untreated control skin, 2X –l0X
MED at 2XMED intervals (IX MED = 40 mJ/cm2).
Twenty-four hours later, areas were photographed
with polarizing filters and enlarged photographs were
measured by colorimeter to determine erythema. Skin
was biopsied and sunburn cells were enumerated in
sections of hematoxylin and eosin- stained skin. When
photodamage is extensive, it is difficult to precisely
identify a sunburn cell. in the presence of epidermal
necrosis. For analysis, whenever sunburn cells could not
be accurately identified, an upper limit of 35 sunburn
cells/mm was used. Results are expressed as mean +/- standard deviation (n = 6). The P values were calculated
by Student t test. Thymine dimers were detected in
formalin-fixed skin by reaction with anti thymine dimer
antibody.
Results
Stability of L-ascorbic acid was >90% and
dl-a-tocopherol was 100% in the formulation
containing 0.50% ferulic acid. Figure 2 shows the marked
protection against erythema (eightfold) provided by
the ferulic acid-stabilized formulation in comparison
to control, vehicle, ferulic acid alone and vitamins C
and E without ferulic acid. Figure 3a shows colorimeter
readings of the protection provided by each of the
solutions. Colorimetric measurements of combination of vitamins C, E, and ferulic acid were statistically better
than control and vehicle at all MEDs tested; different
from ferulic acid alone at 2x, 6x, and 8xMEDs; and
different combination vitamins C+E at 4x and 6x
MEDs. Sunburn counts (Figure 3b) of combination
of vitamins C, E, and ferulic acid were statistically
different from control and vehicle at all MEDs tested
and different from ferulic acid alone as well as from
the combination of vitamins C+E at 2x, 4x, 6x, and 8x
MEDs. Figure 4 demonstrates dose-response protection
against thymine dimer formation. At 4x MEDs, control
and vehicle-treated skin showed virtually uniform
nuclear fluorescence in both epidermis and papillary
dermis (a). After 8x MEDs ferulic acid-treated (b) and
C+E-treated skin (c) were both; positive but ,skin treated
with C+E+ferulic acid was completely negative (d).
Discussion
Ferulic acid improved stability of ascorbic acid
in aqueous formulations and markedly improved
photoprotection against solar-simulated radiation.
Both effects are apparently related to the antioxidant
properties of ferulic acid. Ferulic acid scavenges hydroxyl
radical, nitric oxide, and superoxide radical (Ogiwara
et al., 2002; Kaul and Khanduja, 1998). Ferulic acid
has been demonstrated to permeate skin when applied
topically and to protect against UVB-induced erythema
(Graf, 1992; Saija et aI., 2000). In addition, topical
application of ferulic acid has been effective for reducing
the number of TPA-induced tumors in mouse skin
(Huang et aI., 1988).
Conclusions
1. 0.5% ferulic acid increased the stability of 15%
L-ascorbic acid and 1 % tocopherol in a solution at
45°C for one month.
2. 0.5% ferulic acid provided eightfold augmentive
photoprotection when combined with 15%
L-ascorbic acid and 1 % a-tocopherol against solar
simulator-induced erythema, cell damage measured
as sunburn cells and thymine dimeriormation.
Reference List
- Graf E: Antioxidant potential of ferulic acid. Free
Radical Biology & Medicine 13:435-448 (1992).
- Huang M'f, Smart RC, Wong C9, Conney AH:
Inhibitory effect of curcumin, chlorogenic acid,
caffeic acid, and ferulic acid on tumor promotion
in mouse skin by 12-0-tetradecanoylphorbol-13-
acetate. Cancer Research 48:5941-5946 (1988).
- Kaul A, Khanduja KL: Polyphenols inhibit
promotional ,phase of tumorigenesis: relevance of
super oxide radicals. Nutrition & Cancer 32:81-85.-(
1998).
- Kikuzaki H, Hisamoto M, Hirose K, Akiyama K, ,
Taniguchi H: Antioxidant properties of ferulic acid
and its related compounds. Journal of Agricultural
& Food Chemistry 50:2161-2168 (2002).
- Lin lY, Selim MA, Shea CR, Grichnik JM,
Omar ~'Monteiro-Riviere NA; Pinnell SR:
UV photoprotection by combination topical
antioxidants vitamin C and vitamin E. Journal of
the American Academy of Dermatology 48:866-874
(2003).
- Ogiwara T, Satoh K, Kadoma Y, Murakami Y,
Vnten S,Atsumi T,Sakagami H, Fujisawa S: Radical
scavenging activity and cytotoxicity of ferulic acid.
Anticancer Research 22:2711-2717 (2002).
- Saija A, Tomaino A, Trombetta D, Deo.pasquale A,
Vccella N, Barbuzzi T, Paolino D, Bonina F: In vitro
and in vivo evaluation of caffeic and ferulic acids as
topical photoprotective agents. International Journal
of Pharmaceutics 199:39-47 (2000).
This study was supported in part by a research grant
R43 AR 050302-01 from the National Institutes of Health.
Dr. Pinnell is a consultant for SkinCeuticals (Garland, TX).
Dr. Zielinski is President of Zielinski Research (San Diego, CA).
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