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Sytenol®A
Skin protection
Sytenol®A for Skin Protection
Extended life-span, more spare time and excessive exposure to UV radiation from sunlight or tanning devices, especially in the
Western population, has resulted in an ever increasing demand to protect human skin against the detrimental effects of
UV-exposure. It is well-known that UV light acts directly on nucleic acids or indirectly via reactive oxygen species, resulting in
altered redox balance, activation of repair processes, and altered gene expression in skin. Sunscreens - the current gold standard of
photo-protection - are useful, but their skin protection ability is inadequate against UV-induced skin damage. The most severe
consequence of photo-damage is skin cancer. Less severe photo-aging changes result in wrinkling, scaling, dryness, and uneven
pigmentation consisting of hyper- and hypo-pigmentation. Sytenol® A in combination with photostable broad-spectrum sunscreen
provides a solution to skin protection and treatment.
Product Information
Trade Name
Sytenol® A
INCI Name
Bakuchiol
CAS #
10309-37-2
ELINCS
N/A
Harmonized Tariff #
29071190
Appearance
Yellow viscous liquid
Assay (GC)
95% (w/w) min Bakuchiol content
Solubility
Highly miscible with a wide range of hydrophobic emmolients and solubilizers
Suggested use
0.25 to 1%
Storage
Store in original, sealed container at +10 to +30 0C; Avoid light & heat
Patent status
Covered by multiple US and world-wide patents
Safety Data:
REACH-ready safety profile available upon request
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No skin irritation & No skin sensitization (HRIPT) at 2 and 5% dilution in corn oil
No eye irritation (In-vitro; alternate to Draize methodology)
Non-genotoxic in the in-vitro micronucleus assay in human lymphocytes
Non-mutagenic based on TA98 in Salmonella typhimurium Reverse Mutation Assay
Passes aquatic toxicity tests (short-term, Zebra fish & Daphnia magna); Fresh water single cell green alga & biodegradability
Regulatory Status:
USA:
Allowed for personal care applications
Europe:
Up to 1 Ton annual use requires no REACH registration
Rest of the World:
Allowed for use in most Asian, South American and African countries
Consult your regulatory authority for any restrictions this product may have for
use in your country
Sytenol® A Protects Skin from UV-induced Damage
Erythema: Cause & Consequences:
Erythema, the most familiar manifestation of UV radiation exposure, occurs in a biphasic manner. UVA
mediates the early part of this reaction, known as immediate pigment darkening (IPD) and lasts for about
half-hour. Delayed erythema, a function primarily of UV-B dosages, begins 2-8 hours after exposure
and reaches a maximum in 24-36 hours, with erythema, pruritius, and pain in the sun-exposed areas.
A dose of UVB radiation sufficient to induce erythema in human skin results in the formation of about 20
photoproducts per 106 nucleotides.
qCyclooxygenase (COX)-dependent prostaglandin E2 (PGE2) is a mediator of UVR-induced erythema
qPhospholipase A2 (PLA2) is a rate limiting step in the generation of leukotrienes and prostaglandins. PLA2 synthesis occurs only when skin is exposed to UV doses that are sufficient to cause erythema
qDNA may be a chromophore for erythema. Pyrimidine dimerization in transcriptionally active DNA is a key contributor to UV-induced erythema and inflammation
qNitric oxide (NO) is also a contributor to the UV erythema response. NO is produced in the skin by NO synthase that can combine with superoxide to form peroxynitrile, a highly reactive oxidant and mediator of
erythema and cause of tissue injury.
Protocol: Human Clinical Study
Sytenol®A
Sytenol®A
SUMMARY
Treated & irradiated site with 1% Sytenol® A lotion:
Showed practically no changes in L, a and b-values and
ITA0 (average of 10 subjects)
n Conclusion: Protection of skin against
UV-induced erythema/inflammation
Untreated & irradiated site: Showed statistically
significant differences in L-, a- and b-values and ITA0
(average of 10 subjects)
n Conclusion: No protection; Significant skin
erythema/inflammation under UV-exposure
*Statistically significant; p < 0.001
Sytenol® A Provides Skin Protection by Quenching Radicals & Non-radicals and by
Up-regulating Antioxidant Defense System
Sytenol® A is a Broad-Spectrum Antioxidant
Sytenol® A Up-regulates Antioxidant Defence Genes
Antioxidant Defense Gene Expression
Glutathione peroxidase 3 precursor/ Extracellular glutathione peroxidase(GPX3): Protect organism from oxidative damage. Reduce lipid hydroperoxides --> alcohols and hydrogen
peroxide --> water
Glutathione S-transferase theta -1 (GSTT1): Involved in the
detoxification of endogenous compounds, such as peroxidised
lipids, as well as the metabolism of xenobiotics
Glutathione S-transferase P 1(GSTP1): Same as above
NAD(P)H dehydrogenase [quinone] (NQO1):This protein’s enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species.
Fold Change vs Control
Sytenol® A Protects Skin via Multi-factorial Oxidative Pathways
Literature Data
q Inhibits mitochondrial lipid peroxidation [H Haraguchi et al., Planta Med, 66(6):569-571, 2000]
q Protects mitochondrial respiratory enzyme activities against both NADPH-dependent
and dihydroxyfumarate-induced peroxidation injury [H Haraguchi et al., Planta Med, 66(6):569571, 2000]
q Prevents NADH-dependent and ascorbate-induced mitochondrial lipid peroxidation; Protects
human red blood cells against oxidative haemolysis; Protects biological membranes against various
oxidative stresses [H Haraguchi et al., Phytother Res, 16(6):539-44, 2002]
q Inhibits the expression of inducible nitric oxide synthase gene via the inactivation of nuclear
transcription factor-kappaB in RAW 264.7 macrophages [HO Pae et al., Intl Immunopharmacol,1
(9-10):1849-55, 2001]
q Inhibits lipid peroxidation induced by Fenton-reaction, [S Adhikari et al., Chem Res Toxicol,
16:1062-1069, 2003]
q Induces caspase-3-dependent apoptosis through the activation of JNK, followed by Bax
translocation into mitochondria in rat liver myofibroblasts [EJ Park et al., Eur J Pharmacol, 559
(2-3):115-123, 2007]
Sytenol® A Protects Skin by Inhibiting Glucose Oxidase Activity
% Reduction in Glucose Oxidase Activity
Assayed in vitro with the
Amplex® Red Glucose/Glucose
Oxidase Assay Kit (Invitrogen,
cat. #A22189)
q
nGlucose oxidase converts
glucose to glucono-d-lactone with
the release of H2O2
+ Iron --> Reactive
Oxygen Species --> Oxidative stress
to skin (Fenton reaction)
nH2O2
Sytenol® A Provides Skin Protection
by Down-regulating Pro-inflammatory Genes and Enzymes
Sytenol® A Down-regulates Pro-inflammatory Genes (DNA microarray study)
Pro-inflammatory gene expression
Cyclooxygenase-1 (Prostaglandin G/H synthase precursor)(PTGS1/
COX-1): Prostaglandin biosynthesis; Acts both as a dioxygenase and
as a peroxidase
Phospholipase A-2-activating protein (PLAA): Eicosanoid synthesis,
release of neutrophil lysosomal enzymes and superoxide and on RBC
hemolysis
Cytosolic phopholipase A2 (PLA2G4A): Catalyzes hydrolysis of
membrane phospholipids to release arachidonic acid which is
subsequently metabolized into eicosanoids
Prostaglandin E2 receptor EP2 subtype (PTGER2): Inflammatory
reaction via the EP2 receptor through its regulation of TNF-alpha and
IL-6 Prostaglandin E2 receptor EP4 subtype (PTGER4): Inflammatory
reaction via the EP4 receptor through its regulation of TNF-alpha and
IL-6
Prostaglandin dehydrogenase 1(HPGD):
Degrades PGF2a and
PGE2 (cause inflammation) and converts to hydroxy metabolites
(anti-inflammatory)
Fold change vs Control
Sytenol® A Inhibits Pro-inflammatory Enzymes
Literature Data
Phopholipase A2 inhibitor: Weak inhibitor of Phospholipase A2,
but dose-dependently inhibits Leukotriens B4 and Thromboxane B2; Topical
administration inhibited TPA-induced ear edema and myeloperoxidase activity
and also reduced PGE2 content in arachidonic acid acid-induced response [ML
Fernandiz et al.,J Pharm Pharmacol, 48:975–980, 1996]
q
iNitric Oxide Synthase (iNOS) inhibitor: Inhibits expression of iNOS
mRNA through the inactivation of transcription factor -kB [HO Pae et al., Intern
Immunopharmacol, 1(9-10), 1849-1855, 2001
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New Sytheon Data
Cyclooxygenase inhibitor: ~40% reduction in COX-2 inhibition with 50
µg/ml Sytenol A; Assayed in-vitro using a kit from Cayman Chemical; Determined
COX-2 activity at 590 nm with BioRad 3550-UV microplate spectrophotometer
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Sytenol®A Provides Skin Protection by Inhibiting Elastase Gene
Expression
Elastase breaks down elastin, an elastic fiber that, together with Collagen determines the mechanical
properties of connective tissue. Sytenol®A also has a moderate inhibitory activity against Collagenase
(MMP-1), which is responsible for degrading Collagen I. The major component of extracellular matrix is
Collagen, a support system for the survival of each and every cell in the body.
Sytenol®A up-regulates Elastase-specific inhibitory genes [DNA micro-array study]
Gene
Gene Description
PI3
Elastase-specific inhibitor
SERPINB1
Leukocyte elastase inhibitor
Function
Suppresses degradation of
connective tissue components, such as elastin, and
collagen.
Suppresses the development
of solar elastosis and skin
tumors
Fold Change Vs. Control
Sytenol® A
Retinol
+2.7
+2.5
+6.1
+3.8
In-Vitro Elastase Inhibitory Activity: Sytenol®A vs. Retinol
Sytenol® A has a reverse dose-dependency in inhibiting elastase activity
whereas Retinol has a stimulatory activity
Assayed using Calbiochem human
neutrophil elastase (Cat # 324681)
% Reduction in Elastase Activity
& its substrate (Elastase substrate
VIII).
Positive control – El III (Calbiochem
Catalog # 324745) & negative
control water
Elastase inhibitory activity was
determined by quantifying the
absorbance
of
chromophoric
reaction product at 410 nm using
BioRad microplate reader
Sytenol®A Provides Skin Protection by Inhibiting Hypoxia Inducible Factor
1 (HIF-1) [J Biol Chem, 282(22):16413-16422, 2007]
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HIF-1 is a stress inducible transcription factor; triggers during hypoxia such as, in tumor and in ischemic cardiovascular
disease and also in normoxia such as, UV-induced Reactive Oxygen Species generation in keratinocytes
HIF-1 regulates different genes involved in cell survival, apoptosis, cell motility, cytosketal structure, cell adhesion and
energy metabolim
Pro-stimulatory effect on HIF-1 causes photocarcinogenesis
HIF-1 Inhibitory activity of Bakuchiol: IC50 6.1 µM [Tetrahedron Letters, 48(50):8861-8864, 2007]
Sytenol®A Protects the Skin via Multi-factorial Pathways
Sytenol® A clearly shows promise as a new agent that can complement and enhance the
photo-protective effect of currently available sunscreens. In-vitro and studies in humans, Sytenol® A
ameliorates many of the adverse effects of sun-induced skin damage triggered by multiple pathways. It is
a potent broad-spectrum antioxidant, is an effective inhibitor of a wide range of pro-inflammatory genes
and enzymes and has a matrix-degrading metalloprotease inhibitory activity. Sytenol® A has an excellent
safety profile and is a non primary skin irritant and a non primary skin sensitizer as demonstrated by Human
RepeatInsult Patch Test [HRIPT] studies. Topical formulations that include Sytenol® A are likely to lead further
improvements in the way we protect our skin from overexposure to sun.
USA:
315 Wootton Street, Boonton, NJ 07005
www.sytheonltd.com - [email protected]
Disclaimer
The information given and the recommendations made herein are based on our research and literature search
and are believed to be accurate but no guarantee of their accuracy is made. This information is intended to
be helpful, but no warranty is expressed or implied as to the results obtained from use in the formulation,
procedure or products suggested herein. Neither is any permission or recommendation to practice any
invention covered by patent either expressed or implied.
Tel.: +1 973.988.1075
FRANCE:
1ère avenue, 1ère rue, BP 383 06514 Carros Cedex
www.sytheonltd.com - [email protected]
2011 - www.growitgroup.com
Tel.: +33 (0)4.92.08.52.42