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Crocus - Crocus Chrysanthus

CROCUS STEM CELLS

CROCUS STEM CELLS (CROCUS CHRYSANTHUS)

The crocus is a resilient flowering plant and the universal emblem of youth. Crocus stem cells can release skin growth factors, promote collagen and elastin production, and refine skin texture. Their plumping and firming effects fill in wrinkles and provide instant results.

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How does it work?

STUDY #1: MIMICKING THE ACTIVITY OF NATURAL GROWTH FACTORS IN THE DERMIS

Our active ingredient was developed from the Crocus Chrysanthus bulb extract. Crocus Bulb Extract has been shown to stimulate keratinocytes to secrete growth factors that could enhance the synthesis of matrix proteins in the dermis. Its activity on fibroblasts was comparable to the one of the transforming growth factors (TGF-β) which activates the synthesis of ECM proteins (collagen and elastin). Crocus Bulb Extract thus has a growth factor-like activity in the dermis.

STUDY #2: GROWTH FACTOR-LIKE ACTIVITY

Gene expression analysis conducted on fibroblasts incubated with the test products for 24h showed that:

• Secretions of untreated keratinocytes (coming from a 50 year old donor) had a pro-aging effect on fibroblasts (control). This resulted in a reduced expression of elastin and lysyl oxidase-like 2 (LOXL-2), an enzyme required for elastic fiber formation.

Crocus Bulb Extract, when applied directly to the fibroblasts, had no effect or a slight pro-aging effect on these cells.

• As expected, TGF-β had an anti-aging effect on fibroblasts as it led to a strongly increased expression of elastin and LOXL-2.

• Secretions of keratinocytes treated with Crocus Bulb Extract had a strong anti-aging effect comparable to the TGF-β's one.

S-346 / © Mibelle AG Biochemistry 2008

STUDY #3: STIMULATION OF CTGF IN FIBROBLASTS

During the previously described study, the gene expression coding for the connective tissue growth factor (CTGF) was also analyzed in fibroblasts after 24h and 72h of incubation with the different test products. CTGF stimulates the production of collagen by fibroblasts and is significantly reduced in aged skin.

Secretions of untreated keratinocytes showed an aging effect by significantly reducing CTGF expression. However, here also, secretions of keratinocytes treated with Crocus Bulb Extract had a similar effect to TGF-β and led to an increased expression of CTGF.

This indicates that the stimulatory effect of Crocus Bulb Extract on the synthesis of matrix proteins is due to the compounds secreted by the keratinocytes when they are first treated with Crocus Bulb Extract.

Crocus Bulb Extract can thus reverse the aging process by stimulating the communication between keratinocytes and fibroblasts in aged skin.

S-364 / © Mibelle AG Biochemistry 2008

STUDY #4: STIMULATION OF GROWTH FACTORS IN KERATINOCYTES

Gene array analysis conducted on keratinocytes showed that Crocus Bulb Extract increased the expression of growth factors playing an important role in keratinocyte growth, tissue repair and communication between the epidermis and the dermis

• Fibroblast growth factor 5 (FGF-5)
• Fibroblast growth factor 7 (FGF-7)
• Connective tissue growth factor (CTGF)
•Insulin-like growth factor binding protein 6 (ILGFBP6)

Thus, the anti-aging effect of Crocus Bulb Extract relies on the stimulation of the keratinocytes to release growth factors. And these growth factors are able to enhance the synthesis of matrix proteins in the dermis as shown in the previous steps of the study.

S-358 / © Mibelle AG Biochemistry 2008

STUDY #5: MATRIX REJUVENATION AFTER 2 WEEKS OF TREATMENT

A cream containing 0.4% Crocus Bulb Extract was applied twice daily to the inner side of the forearm of a 53 year old woman whilst her other forearm was treated with the corresponding placebo.

Analysis of skin matrix was performed using a two-photon microscope. This innovative non-invasive 3D technique visualizes deeper skin structures. It is based on the principle that infrared laser irradiation can cause autofluorescence of some molecules (eg elastin) or second harmonic generation (eg collagen).

Collagen and elastin were visualized before and after 2 weeks of treatment and their content was measured in the papillary dermis and in the upper part of the reticular dermis. Results showed, already after two weeks' treatment, that Crocus Bulb Extract increased the content of the two main skin structure components compared to the placebo:

• by more than 115% for
• collagen by more than 25% for elastin

S-374 / © Mibelle AG Biochemistry 2008

STUDY #6: FIRMING EFFECT AFTER 2 WEEKS OF TREATMENT

20 women aged from 36 to 65 (average: 47.1) applied a cream containing or not 2% Crocus Bulb Extract twice daily for 28 days to the inner side of their forearms. The firmness of their skin was determined using a cutometer.

Results showed that Crocus Bulb Extract significantly increased skin firmness:

• by more than 11% after 14 days

• by almost 13% after 28 days

Crocus Bulb Extract thus offers a rapid firming effect to the skin

S-352 / © Mibelle AG Biochemistry 2008

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