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Photo: Takayuki/Shutterstock.com
Photo: Takayuki/Shutterstock.com

Age may bring wisdom, but it also brings less desirable things. 

As the years pass, ageing manifests itself on our skin as wrinkles, crow’s feet, and pigment spots. 

To regain a more youthful and vibrant look, consumers have traditionally tried to moisturise and smooth out the former two. But there is now growing awareness that a homogeneous skin tone is even more important for a youthful look than wrinkles and crow’s feet. 

BASF’s DN-Aura is a 100 percent natural active ingredient extracted from leaves of the Vietnamese Lansium domesticum tree. This active ingredient shrinks and lightens pigment spots on the skin through epigenetic action – mitigating a major sign of ageing in the process. 

A major  sign of ageing accelerated by sunlight and pollution 

Pigmentation irregularities of the face, décolleté area and hands are universally undesirable among men and woman, of all skin types, across all regions. However, they are hard to avoid: more than 90% of Caucasian people over the age of 50 have pigment spots on exposed areas of skin such as the face, shoulders, and the backs of hands1. Asian skin types are even more affected. In Chinese women, for example, pigment spots appear more frequently and earlier in life – and the number of spots is of 20 times more importance to them compared to French Caucasian women2

UV exposure is a major factor contributing to the formation of pigment spots. An observational study showed that Japanese women from Kagoshima, on the south-western tip of Kyushu island, have a significantly higher degree of facial hyperpigmentation than women from the north-eastern city of Akita, which is further away from the equator and therefore receives less UV radiation3. New studies show that environmental factors such as traffic-related air-pollution accelerate the formation of pigment spots: In China, an increase of 20 µg/m3 in coarse particular matter (PM10) was associated with 16% more pigment spots on the cheeks4,5.   

How pigmentation works

So, how can people turn the clock back – or at least regain a youthful complexion? First, it is important to understand how skin pigmentation occurs. Pigmentation is a natural tanning process that involves the production of melanin by melanocyte cells and subsequent melanin distribution throughout the epidermis. Tyrosinase is a key enzyme involved in melanin synthesis. With ageing, UV exposure and environmental factors often cause an overproduction of tyrosinase, triggering the appearance of pigment spots6,7. Therefore, one way to tackle pigment spots is to control tyrosinase production. 

Several studies have demonstrated the implication of epigenetic mechanisms in the pigmentation process in animals (e.g. alpaca, mice, etc.), but few studies have associated microRNA (miRNA) with pigment spots in humans. 

Our company’s experts therefore investigated whether the modulation of miRNAs – short nucleic acid molecules – could be used in melanin regulation. 

fig. 1: miR-490-3p action on skin pigmentation
fig. 1: miR-490-3p action on skin pigmentation

Modulating an essential gene

In an internal study, our experts discovered the miR-490-3p molecule to be an epigenetic target that “silences” tyrosinase expression. This miRNA, which controls tyrosinase production in melanocytes, is inhibited by UVB radiation, a major environmental factor triggering an increase of pigment spots in the skin (fig. 1).

To stimulate this “tyrosinase gene silencer”, our company developed DN-Aura*, an epigenetic solution to shrink and lighten pigment spots on the skin. This active ingredient is a natural extract from the leaves of Asia’s Lansium domesticum, also known as langsat – a tree that is highly valued for its tasty native fruits and the antioxidant properties of several parts of the plant8. The extract is standardised in plant dry matter and available as a preservative-free powder.

fig. 2: Quantification of miR-490-3p expression by Q-RT-PCR in human melanocytes after 24 hours with or without treatment with DN-Aura
fig. 2: Quantification of miR-490-3p expression by Q-RT-PCR in human melanocytes after 24 hours with or without treatment with DN-Aura

Remarkable in-vitro effects

In vitro, our researchers demonstrated that our natural extract is capable of regulating melanin synthesis through an epigenetic pathway on three different levels: the miRNA miR-490-3p; the enzyme tyrosinase; and the pigment responsible for skin colour, melanin.

The researchers treated a culture of Asian human foreskin melanocytes derived from surgery with DN-Aura at 0.034% and 0.07%, and tested miR-490-3p expression after 24 hours of treatment using quantitative real-time polymerase chain reaction (Q-RT-PCR). As fig. 2 shows, our active ingredient at 0.07% increases the level of miR-490-3p significantly by a factor of 1.4. At the lower dose, results were not significant. 

In separate studies, researchers showed that the extract decreases the level of tyrosinase in a melanocyte culture after 72 hours of treatment at 0.034% by 33%, and decreases the levels of melanin in a co-culture of human melanocytes and keratinocytes after 4 days of DN-Aura treatment at 0.07% by 34%.

In vivo effect on pigment spot surface and melanin content

To prove the efficacy of DN-Aura in vivo, researchers conducted a double-blind, randomised split-face clinical study on 53 female Chinese volunteers living in Guangzhou (also known as Canton, north-east of Hong Kong), a sunny and polluted area in China. Aged 18 to 60, all the women exhibited well-defined pigment spots on each half of the face.

In the study, researchers compared the performance of a cream containing our active ingredient at 0.3% with a placebo and with a benchmark product containing Ascorbyl Glucoside (AA2G) at 2%. After twice-daily application of the creams for 56 days, the researchers measured pigment spot surface area and the total quantity of melanin by image analysis. High-resolution digital photographs were taken in cross-polarised light at baseline and at D56. The anti-pigment-spot effect of our natural extract is characterised by a decrease in both parameters. 

fig. 3: Percentage reduction in pigment spot surface area compared to placebo and benchmark (A) and ­illustrative picture (B) after 56 days of application of DN-Aura on the face vs baseline (D0)
fig. 3: Percentage reduction in pigment spot surface area compared to placebo and benchmark (A) and ­illustrative picture (B) after 56 days of application of DN-Aura on the face vs baseline (D0)

Pigment spot surface area

In a group of 28 participants, DN-Aura at 0.3% significantly decreased pigment spot surface area on the face by 23% (p<0.01) vs baseline (D0) after 56 days. This improvement was significant compared to the placebo (-18%, p<0.05) (fig. 3A). The pigment spot surface area was evaluated in images via grey level analysis, on a defined pigment spot of the face (fig. 3B).

In a second group of 25 participants, DN-Aura significantly decreased pigment spot surface area by 20% (p<0.01) versus baseline, while the benchmark product did not show any effect.

fig. 4: Percentage reduction in pigment spots’ melanin content compared to placebo and benchmark after 56 days of application on the face vs baseline (D0)
fig. 4: Percentage reduction in pigment spots’ melanin content compared to placebo and benchmark after 56 days of application on the face vs baseline (D0)

Easy to process, 100% natural ingredient 

DN-Aura is delivered as a preservative-free, water-soluble powder that is easy to process: Dissolved at 20% w/w in water at room temperature, it is incorporated during final processing below 40°C, or at room temperature for cold processing. 

For cosmetics manufacturers this new active ingredient is a very effective, easy-to-process tool in order to combat a major sign of ageing. Its new mode of action based on epigenetic regulation ensures that pigment spots, perceived by many as an unwelcome nuisance, are dealt with at their root cause, rather than just on the surface. 

* INCI: Maltodextrin (and) Lansium Domesticum Leaf Extract. As a leaf extract, DN-Aura is of 100% natural origin according to ISO 16128 and complies with the COSMOS standard for organic and natural cosmetics. 

Additional information:

AUTHORS:

Corinne Reymermier, R&D project leader, corinne.reymermier@basf.

com, Vincent Bardey, Molecular Biology, vincent.bardey@basf.com Florence

Trombini, Global Strategic Marketing, florence.trombini@

basf.com, Valérie Andre-Frei, R&D Scouting & Communication, valerie.

andre-frei@basf.com, BASF Beauty Care Solutions

www.carecreations.basf.com

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