Active Beauty

Mangixyl™
The microbiome-friendly
sebum harmoniser
Crafted by green fractionation
 Focus on
the product

Sebum protects the skin

Sebum is a sophisticated oily complex made up of several classes of lipids: triglycerides, free fatty acids, wax and esters and
squalene which are secreted by the sebaceous glands attached to the hair follicles.

Essential to the health of our skin, sebum has key benefits:

▶ it contributes to the hydration of the epidermis,
▶ it contributes to the suppleness and softness of the epidermis,
▶ it balances the skin microflora.

Sebum overproduction (oily skin) has social impacts

An overexpression of sebum makes the skin appear greasy and promotes the development of blackheads or pimples.
Oily skin can lead to the development of a prone to acne condition.

The important quantity of lipids on the skin creates shininess,

70%
which causes aesthetic discomfort, generating a possible loss
of self-confidence and social isolation.
of consumers
To fight against the visible appearance of oily skin, applying are bothered
mattifying powders in order to adsorb sebum is a solution but by oily skin in
it requires many applications during the day, and the amount of their daily life
product to apply is often visible on the face.

Strategy to replace retinoic acid for sebum reduction

The biological pathways of sebum production is modulated in sebocytes through several nuclear receptors families such as
PPARs, and retinoids specific receptors such as RARs and RXRs.
Indeed, retinoic acid is a very efficient anti-sebum active, yet it modifies the structure of the sebaceous glands leading to dry
skin and it is usually not allowed in cosmetic application due to its intrinsic toxicity.
Mangixyl™
It is therefore necessary to design safer sebum-controlling active ingredients, Barrier function C. acnes impact and
being 100% from natural origin and capable of targeting the same biological improvement Microbiome protection

pathways as pure retinoic acid with guaranteed efficacy. Sebum production

Mangixyl™, the microbiome-friendly

natural sebum harmoniser
Cytoplasm

Mangixyl™ is an active ingredient discovered during the bio-guided Lipids production

fractionation of mango leaves, originating from a responsible, traceable RAR RXR
Nucleus

and sustainable sourcing in Burkina Faso.

PPARγ RXR
Inhibition of gene
Mangixyl™ interacts with some specific receptors of the retinoic acid and transcription

PPARγ-regulated genes pathway and decreases in vitro, ex vivo and in vivo

the synthesis of lipids on all ethnicities. Sebocyte

Additional clinical data showed efficacy against prone-to-acne skin Sebaceous gland

and on the regulation of scalp sebum, while balancing the microbiome.

 Sustainable
& responsible
sourcing

An active ingredient supporting local communities

The mango leaves (Mangifera indica L. Anacardiaceae) are collected
in Burkina Faso (Africa) in close collaboration with the Association
Bendia, located in the Koro Village.

Based on volunteering, this association is a women-led initiative,

offering them employment depending on their age: young women
manage the harvest of leaves and older women take care of the
selection of leaves, then of the drying and stirring steps.

This activity has contributed to improve the daily lives of the

workers, who now have daily access to healthy food in a canteen
and to drinkable water. The purchase price has been granted to
ensure a continuous development for the Koro Village.

Responsibly sourced with full traceability

Association Bendia organises a 100% traceable collection and manages all the steps of the production of dry mango leaves
of particular quality.

To preserve the biodiversity and avoid any disruption of trees’ natural cycle, the harvest is done after the fruiting period
and the wet season following good harvesting practices: only 10% max of leaves per tree are collected and the crop is
done manually, only at eye level.

An active 100% qualified by phytoexperts

The supply of mango leaves coming from Burkina Faso is carefully controlled by our ID Pack protocol,
for a complete authentication of the in-coming raw material. This involves macroscopic and
microscopic analysis of the leaves, DNA analysis and phytochemicals fingerprinting with HPTLC
and HPLC.

A bioguided fractionation of the leaves allowed to complete

the analytical characterization of four main phytomarkers
in Mangixyl™ which act in synergy on the skin: mangiferin,
iriflophenone-3C-β-glucoside, maclurin-3C-β-glucoside and Mangiferin Iriflophenone-3C-β-glucoside
penta-O-galloyl-glucoside.

A botanical study identified the optimal position of the leaves

in the aerial part of the trees. A selective harvest specification
has been set up following this analysis to supply sun exposed
+29% mangiferin content leaves. Maclurin-3C-β-glucoside
 Mode
of action

Targeting the same transcription factors than retinoids

1. Identification of the inhibition pathway by RT-qPCR (in vitro)

Sebocytes derived from induced pluripotent stem cells from Gene regulation by Mangixyl™
3 different skin origins (Caucasian, Asian and African) were on all origins of sebocytes
cultivated in sebum overproduction conditions. Mangixyl™
Fold change 0
was tested at 0.3% on the cells, and a RT-qPCR analysis has
been run to identify which genes were up or down-regulated, -0.5

and to quantify these variations. -1

#
Results: Mangixyl™ triggers the down-modulation of the genes -1.5

only associated to lipogenesis. On the contrary of known action ***

-2
of retinoids, it does not impact the differentiation of sebocytes *** ***
-2.5
(available data).
FDFT1 (Squalene synthase) DGAT2 (diacylglycerol acyltransferase)
Mangixyl™ can down-regulate the pathway of sebum production
FADS2 (Fatty acid desaturase-2) PPARγ (lipid activated transcription factor)
at different levels: genes coding for enzymes directly involved in
lipid synthesis and genes coding for transcription factors. Unpaired T test vs stimulated condition (AA5): #p<0.1, **p<0.01, ***p<0.001

2. Molecular docking and Inverse molecular docking (in silico)

A bioinformatics calculation has been performed to predict the possible interactions between some key phytomarkers of
Mangixyl™ and proteins (receptors and enzymes) involved in sebum regulation:
▶ a direct molecular docking calculated the interaction between mangiferin and PPARγ receptor,

▶ an inverse molecular docking determined which proteins (receptors/enzymes) from the lipogenesis pathway were able
to interact with benzophenone derivatives, including the phytomarkers of Mangixyl™.

Molecular docking of mangiferin into PPARγ receptor Inverse molecular docking: protein-based approach
Very low Binding energy: -164 +/- 1 kJ/mol Score <7 not considered (not significant), >7 robust and significant. Max =12.

Category Name Iriflophenone-3-C-G Maclurin-3-C-G Consequences

PPARγ 9.5 7.8

Transcription Modulation of
RXRα 7.2 9.0
factor / receptor lipogenesis
PPARδ 7.0 7.2

FAD
8.4 7.5
synthase
Direct impact
on sebum
Squalene
Enzyme 8.5 7.1 production
synthase
pathway
Cholesterol
8.3 7.5
oxidase

This analysis demonstrated that 3 phytomarkers of Mangixyl™ behave like good possible ligands for PPARγ, PPARδ and
RXRα, thereby mimicking the action of retinoids. Those phytomarkers may also act as direct lipogenesis enzymes inhibitors.
 Biological
activity

Reduction of sebum production (in vitro)

Sebocytes were exposed in a 2D culture model to a lipogenic mix Lipogenesis in 2D sebocytes
stimulating sebum overexpression. % of 120
Cells were then treated with one of the following ingredients: stimulated +88%***
control 100
▶ reference (Olumacostat glasaretil, at 1µM), -22%**
▶ Mangixyl™ at 0.3%,
80 -37%*** -40%***
▶ pure mangiferin tested at the same amount as contained in 60 #
Mangixyl™ (5.7µg/ml). 40
The lipids content was measured by Bodipy® fluorescent probe 20
after 7 days.
0
Control Control Reference Mangixyl™ Mangiferin
Results: Mangixyl™ at 0.3% significantly reduces lipogenesis by 0.3%

-40%***, better than the reference. + lipogenic mix (without androgens)

Note: Mangiferin alone shows a good efficacy but lower than Mangixyl™, thereby
demonstrating that it acts in synergy with the other phyto-compounds included in Mangixyl™. Student's t-test: **p<0.01, ***p<0.001

Lipogenesis inhibition vs retinoic acid on 3 ethnicities (in vitro)

Sebocytes from 3 different ethnicities (Caucasian, Asian and Lipogenesis on 3 ethnicities
African) were cultivated in sebum overexpression conditions. % of 120
***
Cells were then treated with one of the following ingredients: stimulated **
control 100 ***
▶ retinoic acid at 10µM (RA10),
▶ Mangixyl™ at 0.3%. 80
-43% -46%
The lipids are stained by Bodipy® fluorescent probe. 60 *** *
40 -78%
Results: Mangixyl™ at 0.3% shows a significant efficacy better -84% **
-88%
20 -90% *
than retinoic acid on Causasian and Asian sebocytes (up to *
***
-90%*** for Caucasian sebocytes) and an excellent activity on 0
Untreated Untreated Reference Mangixyl™
African sebocytes. RA10 0.3%

+ lipogenesis stimulation (AA5)

Mangixyl™ is a highly potent inhibitor of sebum
overproduction (lipogenesis), with an overall higher efficacy Caucasian Asian African

than retinoic acid. ANOVA multi comparison: *p<0.05, **p<0.01, ***p<0.001

Reduction of the volume of sebaceous glands (ex vivo)

Explants containing sebaceous glands were treated +37% -50%*
with Mangixyl™ at 1% in a lipogenesis stimulated
condition during 7 days.The quantity of lipids and
the volume of the sebaceous glands were assessed,
such as several differentiation markers.

Results: Mangixyl™ at 1% significantly reduces the

quantity of lipids, thus it decreased the 3D volume
of the sebaceous glands by -50%* in only one week,
Untreated Untreated Mangixyl™ 1%
without modification of the glands structure,
unlike known action of retinoids. + lipogenesis stimulation (10% linoleic acid)

Mann Whithey test: *p<0.05

 Clinical
efficacy
Decrease of sebum production
Fast sebum reduction on
all skin types (in vivo)
Three clinical studies have been conducted,
double blind vs placebo, on women volunteers D0
with oily skin from 3 ethnicities: #1 Europe
(15 women), #2 China (20 women), #3 South
Africa (20 women).

The measurement of sebum quantity was

done on cheek and nose area at D0 and D28
x2.2* x1.8# x2.2**
by sebumeter or sebufix apparatus.

The tested product was a cream, applied twice

a day on the face, containing 1% Mangixyl™
D28
for Caucasian volunteers and 2% of active for
Asian and African volunteers.

Results: Mangixyl™ significantly reduces the

quantity of sebum on oily skin in only one
month for all skin ethnicities thus reducing
European native Asian native African native
inaesthetic shininess.
Mann Whitney test vs placebo: *p<0.05
Unpaired student t test vs placebo: #p<0.1; **p<0.01

Improvement of the quality of the skin (in vivo)

Barrier function enhancement Measurement of TEWL
after 28 days
A clinical study has been performed in double blind vs placebo ΔD0D28 4%
TEWL (%)
conditions on a group of 15 European women with oily skin. 2%
2.2%
0%
Volunteers applied twice a day on their face the placebo or a
-2%
cream containing 1% Mangixyl™. -4%
Mangixyl™
-6%
-8% Placebo
The skin quality of the volunteers was assessed by analysing the -10%
barrier function quality (TEWL) using a Tewameter ®. -12%
-14% -12.9%***

Results: While reducing the amount of sebum, Mangixyl™

-14.9%*
significantly improves the skin barrier function (TEWL
decreased by -14.9%*) after 28 days. Paired t student test vs D0
Unpaired t student test vs placebo *p<0.05, ***p<0.001
 Clinical
efficacy

Impacting C. acnes while protecting skin microflora

Prone-to-acne skin is a multifactorial condition, leading to pimples and irritation, and involving:
▶ an excess of sebum production, with modified lipids composition (excess of free fatty acids, triglycerides and squalene),
▶ a colonisation by some strains of C. acnes with specific metabolism including particular lipase activity.
Mangixyl™ has been tested on several factors related to acne.

Inhibiting C. acnes lipase activity (in vitro) D0 D28

Mangixyl™ showed a 23%* inhibitory action on C. acnes

x2.4* reduction
of porphyrins intensity
lipase activity (Mann whitney test).
+49.5%*
Regulating C. acnes activity on volunteers' skin TG/FFA ratio
evolution
while protecting the Microbiome balance (in vivo) after 28 days
(active vs placebo)
In the double blind versus placebo clinical study performed
on European women with oily skin, the level of porphyrins,
fluorescent metabolites related to C. acnes activity, has been
analysed under VISIA® with UV lamp. Paired t student test vs D0 Wilcoxon test vs D0
Unpaired t student test vs placebo Mann Whitney test vs placebo
Meanwhile, sebum composition and the evolution of their
*p<0.05
skin microbiome has been analysed.

Results: After one month, Mangixyl™ was able to trigger a Relative abundance evolution
significant decrease of porphyrins intensity, expressed as 2.4 Evolution (%) 400%
Drastic evolution of
fold vs placebo, for 80% of volunteers, reflecting the change (D28-D0)/D0 350%
microflora composition
of C. acnes metabolism on the skin of volunteers. 300%
250%
200%
Protection
The sebum quality has been improved by 49.5% though a 150%
353.0%
of microflora
better triglyceride/free fatty acid ratio. 100% composition
50% 36.5%
67.0% 8.1%
0%
Relative abundance evolution of different bacterial genera -18.2% -19.4%
-50%
showed that Mangixyl™ at 1% protected the skin microbiota Placebo Mangixyl™
over time, whereas the placebo group showed a skin dysbiosis.
Staphylococcus Acinetobacter Lawsonella

Reduction of scalp sebum (in vivo) Measurement of sebum D0

quantity after 28 days
ΔD0D28 5%
The sebum-regulating effect of Mangixyl™ has been assessed sebum
1%
variation
on scalp with a rinse-off product (shampoo) in a clinical study (%)
0%

versus placebo. Two groups of 20 women with an oily scalp

-5%
applied either a placebo shampoo or a shampoo containing
1% Mangixyl, every 2 days with 2 applications. At D0 and D28 -10%

the sebum content has been measured on their scalp with a D28
-15%
Sebumeter®.
-20% -19%**
Results: Mangixyl™ induced a significant decrease of the Mangixyl™
quantity of sebum by -20%** compared to placebo after 28 Placebo -20%*
days on scalp. Illustrative photos showed that hair fibres are Wilcoxon test: D28 vs D0
lighter and less greasy than on the placebo. Mann whitney test: Mangixyl™ vs placebo
**p<0.01
Summary
Technical information
INCI: Mangifera Indica (Mango) Leaf Extract (and) Propanediol (and) Water

Origin: Green fractionation

Preservation: None

Appearance: Amber liquid

Solubility: Water soluble

Dosage: 1% to 2%

Processing: Can be added in the water phase at the end of the formulation process
under 40°C and at a pH between 4 and 6.

Claims
Claims: Reduction of sebum production for all skin origins.
Enhancement of the barrier function.
Prone to acne skin correction.
Microbiota protection and rebalancing.
Clean and purify oily scalp.

Applications: Mattifying cream for oily skin

Balancing treatment for combination skin
Daily anti-imperfection gel or cream
Purifying face cleanser
Purifying cleansing gel for the face or body
Make-up remover lotion for oily skin or skin with imperfections
Shampoo or lotion for oily hair

Givaudan Active Beauty Sales Offices

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Givaudan Shanghai Ltd

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Magna House Pudong Zhang Jiang High Tech Park
76-80 Church Street 201203 Shanghai (China)
Staines, TW18 4XR (United Kingdom)
Latin America

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250 rue Pierre Bayle - BP 81218 Av. Engº Billings - 2185, Edificio 31, 1ºAndar - Jaguaré
84911 Avignon Cedex 9 (France) 05321-010 São Paulo - SP (Brazil)

global.cosmetic@givaudan.com
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available on the market. LEAFLET-MANGIXYL-12.22 www.givaudan.com