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Active Beauty

Neurophroline™
Overall skin stress control
By Soliance technology
Focus on
the product

Skin and brain: same origin - shared functions


Through evolution, the human body has acquired both a central nervous system (brain) and a peripheral nervous system
(nerves and sensors including skin) which enable it to react to its environment and to survive.
Indeed, the brain and the skin originate from the same embryologic tissue, the ectoderm that differentiates to form
neurectoderm (the future brain) and the epidermis.

The skin and the brain are constantly communicating to synchronize external and internal “danger” signals by means of
cytokines, chemokines, electric impulses, and hormones.

Cortisol: a key hormone in stress response


Stress is defined as an external factor that disrupts homeostasis. In a stressful situation, our body responds by liberating
a flush of stress hormones including adrenaline and cortisol, that will result in a fight response (positive reaction to stress
and adaptative reaction). Because our body cannot keep this state for long periods of time, a feedback mechanism returns
the body to normal physiological conditions (elimination of stress hormones and their consequences), thus maintaining
homeostasis. 1,2

Cortisol release is mediated by the brain through the hypothalamus pituitary adrenal gland axis in a cascade reaction. As the
skin and brain share the same origin, skin cells are able to produce cortisol in response to external stress factors.

In case of prolonged exposure to stress (such as mechanical or chemical aggressions, pollution, smoke, sleep deprivation, UV
exposure), skin cells do not stop producing cortisol which breaks down skin homeostasis, leading to redness (inflammation),
and a visible tired look.3

Neurophroline™: biological skin stress inhibitor


Neurophroline™ has been discovered in the wild indigo (Tephrosia purpurea), a native Indian plant used in the Ayurvedic
tradition for its benefits on skin. A specific extraction from the seeds of this plant has been performed to obtain a condensate
enriched in specific sugars including stachyose and ciceritol.4

This exclusive extract has demonstrated its unique biological


capabilities to:

▶ Break down the cortisol production by skin cells


▶ Activate the release of a natural calming neuropeptide
acting on mood
▶ Improve visibly skin tone in only two weeks, proving a fast
action to control stress in skin

1
J Invest Dermatol. 2015 Jun;135(6):1469-71
2
Int J Psychophysiol. 2015 Jun;96(3):169-75
3
J Invest Dermatol.2001 Aug;117(2):309-17
4
J. Nat. Prod., June 23, 2015, 78 (7), pp 1609–1617
Biological
activity

Regulation of cortisol production (in vitro)


Cortisol is produced by keratinocytes in the skin as an 160

instantaneous answer to a stress factor. Normal human Cortisol


140
***
keratinocytes were treated with Neurophroline™ at 0.5%
production 120 -33%*
(pg/ml)
and 1% over 2 hours, and 1µM of cortisone to quantify the
100
-70%**
80 **
release of cortisol. 60

40
Results: Neurophroline™ acts very fast (2 hours) as it 20

inhibits up to -70% of cortisol production by keratinocytes 0


Untreated HNK + HNK + HNK +
at 1%, and -33% at 0.5%. HNK Cortisone Cortisone + 0.5% Cortisone + 1%
Neurophroline™ Neurophroline™

*** p<0.001 Student’s t-test


** p<0.01 Student’s t-test
* p<0.05 Student’s t-test

Stimulation of β-endorphin production (in vitro)


Normal human keratinocytes were incubated for 24 hours +163%*
Beta-endorphin 100
with Neurophroline™ at 0.0025% and 0.0125%. Dibutyryl production
90
(pg/ml)
AMPc was used as a positive control to stimulate beta- 80 +105%*
endorphin release. The amount of beta-endorphin released 70
60
by the cells was quantified by ELISA technic.
50
40
Results: Neurophroline™ significantly stimulates the 30

production of beta-endorphin by skin cells, a natural 20


10
relaxing and pain-relief peptide, up to +163%.
0
Untreated HNK + 0.0025% HNK + 0.0125% HNK + 2m M
HNK Neurophroline™ Neurophroline™ dibutyryl AMPc
* p<0.05 Student’s t-test
Biological
activity

Instant stress regulation (in vitro)

1. Global activation of anti-stress genes (transcriptomic)

Normal human keratinocytes and fibroblasts were incubated with Neurophroline™ at 1% during 24 hours. The mRNA
expression of genes involved in skin homeostatis was quantified by q-RT-PCR.

Keratinocytes Fibroblasts
Fold 10 Fold 18
expression expression

8
14

10
4

2 6

0
Control HMOX1 NQO1 IL1A ABCA12 LL37 KLK5
2
-2
Control HMOX1 NQO1 NQO2 FTL MT2A TXNRD1
-4 -2

Genes Name / Function Function Genes Name / Function Function


HMOX1 Heme Oxygenase Anti stress - anti oxidation
HMOX1 Heme Oxygenase Anti stress - anti oxidation
NADPH Quinone Reduction of oxidative stress,
NQO1
dehydrogenase 1 detoxification NADPH Quinone Reduction of oxidative stress,
NQO1/2
IL1A Interleukin 1-alpha Inflammation dehydrogenase 1 /2 detoxification
ATP binding cassette Skin barrier and epidermis FTL Ferritin Detoxification of iron
ABCA12
transporter differentiation
Antimicrobial peptide,
LL37 LL37 cathelicidin MT2A Metallothionein Detoxification of heavy metals
protection against infections
Maturation of LL37 peptide, Control of redox system,
KLK5 Kalikrein 5 TXNRD1 Thioredoxin reductase
epidermis differentiation homeostasis

Results: Neurophroline™ significantly stimulates the expression of the genes involved in the skin cells’ homeostasis
(***p<0.001 Students’ t-test, for all markers), and more precisely of:

▶ HMOX1, the major cellular response to stress factors, ▶ Skin barrier marker,
▶ NQO1, the main answer to oxidative stress, ▶ Anti-inflammatory marker,
▶ Iron and heavy metal detoxification, ▶ Redox homeostasis marker.
▶ Antimicrobial markers,
Biological
activity

2. Activation of major anti-stress proteins (proteomic)

Normal human keratinocytes and fibroblasts were Keratinocytes


incubated with Neurophroline™ at 1% during 24 or 48 HMOX1 NQO1
% expression 3500 % expression 250
hours. vs untreated vs untreated
condition 3000 *** *** condition 200
2500 *** ***
The level of expression of the heme oxygenase 1 and 150 *** ***
2000
of the NADPH quinone dehydrogenase, the two main 1500
*** 100
proteins involved in stress response, were quantified by 1000
50
ELISA assay. 500

0 *** 0
24H 48H 24H 48H
Celastrol and Sulforaphane were used as positive
Fibroblasts
control.
HMOX1 NQO1
% expression 500 % expression 250
Results: Neurophroline™ at 1% significantly vs untreated *** vs untreated
condition 400 condition 200
stimulates the expression of the major proteins ***
300 *** ***
involved in cellular stress response in both 150

keratinocytes and fibroblasts : up to 3000% for *** **


200 100 *
HMOX1 and 200% for NOQ1. 100 50

0
0
***p<0.001 ANOVA & Dunnett comparison 24H 48H 24H 48H
**p<0.01 ANOVA & Dunnett comparison
*p<0.05 ANOVA & Dunnett comparison Celastrol 500 nM Sulforaphane 3µM Neurophroline™ 1%

Visible expression of anti-stress markers in the epidermis (ex vivo)


The action of Neurophroline™ on HMOX1 and NQO1 proteins production was evaluated on human reconstructed epidermis
(RHE). RHE were topically treated during 2 days with Neurophroline™ at 1% in a placebo formula, with the placebo alone, or
with positive controls (celastrol or sulforaphane). RHE were sampled and analyzed by immunofluorescence to quantify the
amount of HMOX1 and NQO1 expressed. Placebo Celastrol 750 nM Neurophroline™ 1%

Results: Neurophroline™ at 1% significantly


HMOX1
stimulates the expression of HMOX1 up
to +888%, and NQO1 up to +528% in the
+695%# +888%*
epidermis in only 2 days.
Placebo Sulforaphane 3µM Neurophroline™ 1%
*p<0.05 compared to placebo Student’s t-test

#p<0.05 compared to control Student’s t-test


NQO1

+324% +528%*
Efficacy

Clinical efficacy on volunteers with stressed skin (polluted air)


The clinical efficacy of Neurophroline™ was evaluated in a double Air pollution by PM10 (µg/m3) (1)
blind test versus placebo under dermatological control. Twenty four 80

70
volunteers aged 40 to 67 years old took part in the study (average age:
60
53 ± 2years).
50

40
The clinical test was run during summer time, in skin-stressing
30
conditions as the volunteers where living in an geographical area 20
known to have significant atmospheric pollution (measured in ten air 10

quality control stations around the location of the clinical test during 0

the testing period). 1

9
6

8
4

10
5
3
2

7
n

n
n

n
n

n
io

n
io
io

io

io
io

io

io

io

io
at

at
at

at

at
at

at

at

at

at
St

St
St

St

St
St

St

St

St

St
The volunteers applied twice a day the placebo or the cream containing Air pollution by ozone (µg/m3) (1)
Neurophroline™ at 2% on the most sensitive skin part of their face: 140

under their eyes. The clinical assessment was run for one month. 120

100

Pollution by PM10 and ozone was always very close to the 80

recommended limits and exceeded it at some periods. Therefore the 60

stress was very intense during the testing period. 40

20

0
(1) Source Airpomenia - Tricity location
1

9
6

8
4

10
5
3
2

7
n

n
n

n
n

n
tio

n
tio
io

io

io
io

io

io

tio

io
at

at

at
at

at

at
a

at
a
St

St
St

St

St
St

St

St

St

St

Max Monthly Recommended


per day average WHO max.value

Fast improvement of skin color and luminosity


The visible efficacy of Neurophroline™ was evaluated by measuring L* improvement
the evolution of the L* value (skin luminosity under eyes) with a 3

spectrocolorimeter, as well as the ITA value (skin color) and the a*


2.5
value (skin redness). ***
2
+57%***
1. Recovery of skin luminosity (L* value) 1.5 +103%***
**
Results: Neurophroline™ significantly enhances the skin luminosity
1 ***
of volunteers with stressed skin in 2 weeks, with up to +57% 0.5
*
improvement in one month. 0
D0 - D14 D0 - D28

* p<0.1 ANOVA
** p<0.01 ANOVA Placebo Neurophroline™ 2%
*** p<0.001 ANOVA
Efficacy

2. Improvement of skin color 3. Visible efficacy after 1 month

Pictures of the volunteers were taken after one month of use


Reduction of skin redness (a* value)
of Neurophroline™. The focus is done on the area under eyes
0.6
since it is the most sensitive part of the skin.
0.4
Volunteer 6
0.2

0 D0 D28

-0.2

-0.4

-.06
x2.4**
-.08
*
-1 ***
D0 - D14 D0 - D28

*p<0.05 *** p<0.001 ANOVA


Volunteer 7

D0 D28

Skin color (ITA angle)


10

****
8
+99%**
6 +187%**

4
**** *** Volunteer 13

D0 D28
2
*
0
D0 - D14 D0 - D28

*p<0.05 **p<0.01 ***p<0.001 ****p<0.0001 Students’ t-test

Placebo Neurophroline™ 2%

Volunteer 10

Results: Neurophroline™ shows very rapid results at D0 D28

improving the global skin color around the eye. Skin


redness is significantly reduced by 2.4 times after 28
days, and the skin’s color is significantly improved
by 99% during the same period of time.

Results: Neurophroline™ visibly reduces the signs of


stress/fatigue after one month of use of the product. Dark
circles are amazingly reduced, confirming the fast action of
Neurophroline™ on stress relief.
Summary
Technical information
Suggested INCI: Water, Propanediol, Tephrosia purpurea seed extract

Origin: Vegetal extraction

Preservation: Preservative-free

Appearance: Clear, light yellow liquid

Solubility: Water soluble

Dosage: 0.1-2%

Processing: Can be added at the end of the formulation process


under stirring or homogenizing. Can be heated for a short
time with the water phase of formulation. Formulate at
temperature below 50°C, and final pH below 6.0.

China compliant

Claims
Claims: cortisol release control, anti-stress, anti-aging for
sensitive skins, anti-aging, anti-dark circles

Applications: Anti-aging creams, Nights and day creams fighting stress,


Anti-stress / fatigue creams and serums, Dermocosmetics
products, Eye care products.

Givaudan Active Beauty


17-23 rue de la Voie des Bans
FR-95100 Argenteuil, France

(Induchem AG) Industriestrasse 8a,


CH-8604 Volketswil, Switzerland

(Induchem USA Inc.) 535 Fifth Avenue


New York, NY 10017, United States

global.cosmetic@givaudan.com

The data in this document (“Data”): (i) has been prepared by Soliance in accordance with Soliance’s internal protocols
and procedures; (ii) is provided to Customer for its information and internal use only; (iii) is provided without warranty of
any kind, including, without limitation, any implied warranty of accuracy, merchantability, fitness for particular purpose
or non-infringement of third party intellectual property rights. In no event shall Soliance be liable to Customer or any
third party for any losses, indemnities or damages of any kind (including, without limitation, any and all direct, special,
indirect, incidental, or consequential damages or lost profits or revenues) that may arise out of, or in connection with,
the use of the Data by Customer. Customer is solely responsible for assessing the accuracy and reliability of the Data for
its own purposes (including, without limitation, Customer’s end-use applications), and assumes all risks and liabilities
arising out of or in connection with the use of the Data. LEAFLET-NEUROPHROLINE-04.16-1000 www.givaudan.com