A redensified and thicker epidermis in eight weeks

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How to keep an ageless look while staying natural? One of the main beauty secrets is to keep the first shield of our body healthy and young: our epidermis. A young epidermis is dense, thick and its major components are continuously regenerated. This relatively fast process keeps those cells plump and results in youthful and healthy looking skin on the surface.

In literature, it has been proven that loss of innervation influences keratinocytes proliferation and reduces epidermal thickness.1–3 Since there is a link between epidermal thinning and nerve degeneration, boosting skin re-innervation could be a good way to fight against skin ageing in general and epidermis ageing in particular. In this way, we have developed an active ingredient obtained from seeds of Voandzeia subterranea (EpigenistTM). 

In vitro, the capacity of Epigenist to boost neuritogenesis was evaluated in a model of neuron in culture. Then, its efficacy to improve epidermal thickness and quality was appraised on a re-innervated skin model. 

In vivo, the visible and measurable effects on skin were assessed by clinical studies a panel of 20 female Caucasian volunteers, after application on the face. Epigenist was evaluated on its ability to increase epidermal thickness and to improve skin aspect by decreasing roughness.

In the course of research performed on epidermis ageing, we observed that when the skin is no longer innervated, the epidermis loses its volume to reach the aspect of an aged skin. Could cutaneous ageing be explained partially by the decrease of innervation? The scientific results are positive and highlight the major influence of nervous fibres on the formation of a thick and well organised epidermis, characteristic of young skins. 

As there is a link between nerve degeneration and epidermal thinning boosting skin re-innervation could be a good way to fight against skin ageing in general and epidermis ageing in particular. In this way, we have developed an active ingredient obtained from seeds of Voandzeia subterranea (Epigenist, INCI name: Voandzeia Subterranea Seed Extract [and] Maltodextrin). 

Our innovation, Epigenist™, shows the ability to boost the neuritogenesis in the epidermis. When applied on the skin, Epigenist reverses the natural loss with ageing of nervous fibres. Their growth restarts, counterbalancing the passing of time.

With the idea to find an ingredient with rejuvenating power, BASF looked deep into the indigenous lands of Africa. In this region grows a pea: the bambara pea (INCI name: Voandzeia subterranea Seed Extract) cultivated for its nutritional qualities (rich in proteins, vitamins, and mineral salts). This pea also brings the benefit of soil fertility. BASF research has proven that Voandzeia subterranea has interesting  anti-ageing properties for the skin and particularly for the epidermis.

Effect on neuritogenesis (in vitro)

The neuritogenesis was evaluated by the capacity of Epigenist (now referred to as ‘the bambara pea seed extract’) to increase neurite length of PC12 cells in culture (Fig. 1). Neurite length was measured by image analysis on microphotographs taken from PC12 in culture. 

The addition of the bambara pea seed extract at 0.025% in the culture has clearly increased, in a dose dependent manner, the length of the PC12 neurites compared to untreated control culture (neurite length visualised in red by image analysis). In vitro, the bambara pea seed extract contributes to induce neuritogenesis.

 

A new re-innervated skin model

To best apprehend the implication of the innervation on skin, a re-innervated skin model was developed. This model was based on a co-culture of human skin explant from surgical abdomino plasties and primary sensory neurons (PSN) from dorsal root ganglia (DRG).4 A control was performed by culturing a skin explant without PSN. 

After 10 days of co-culture between skin explant and neurons, a dense network of nerve fibres was observed in the culture. In presence of PSN, nerve fibres were present in the human skin explant. The outgrowth of neurites inside the dermis and epidermis was revealed by immunolabelling of a neuron specific protein, the protein gene product 9.5 (PGP9.5) (Fig. 2). Its presence proves that the skin model is suitable to study the effect of an active ingredient on skin innervation.

 

Effect on epidermal thickness (in vitro)

We used the new innervation model to evaluate the effect of the bambara pea seed extract at 0.025% on epidermal thickness over 10 days. A control was performed by culturing a skin explant without PSN. At the end of incubation, a histological study was done on the skin explant. Re-innervation has induced an increase of epidermal thickness compared to the un-innervated skin control. This increase was stressed in presence of the bambara pea seed extract at 0.025% (Fig. 3). 

Due to its properties to boost innervation, the bambara pea seed extract at 0.025% clearly improved epidermal thickness by 28%.

In vivo effect on epidermal thickness and roughness

In vivo studies were conducted on the half face on 20 female volunteers aged from 45 to 55 years. After 56 days of treatment with the bambara pea seed extract versus placebo emulsion, the epidermal thickness (confocal microscopy measurement) and skin roughness (topography analysis of data obtained by fringes projection) were evaluated. 

After 56 days of treatment by the bambara pea seed extract at 0.5% an increase by 10% of the thickness of epidermis measured by confocal microscopy was observed while no evolution of epidermis thickness has been obtained on the placebo treated half face (Fig. 4).

The skin roughness parameters have also been evaluated by topography analysis of the data obtained by fringes projection at the level of the crow’s feet. The considered parameters were: Stm (mean difference between peaks and valleys) and SA (average roughness). 

No effect on the evolution of skin roughness parameters has been observed after 28 days of treatment. On the contrary, after 56 days of treatment, both parameters, Stm and SA, have been significantly reduced for the treatment with the bambara pea seed extract. The diminution represents 4% for each parameter and is significant. No difference between D56 and D0 has been observed for placebo treatment (Fig. 5). 

After 8 weeks with the bambara pea seed extract at 0.5%: the skin surface is smoothed and the wrinkles are reduced comparatively to placebo treatment.

Conclusion

Since epidermal thickness and epidermal nerve ending decrease with ageing, our proposal was to enhance epidermal innervation to fight against epidermal thinning and by consequence to fight against skin ageing. Therefore, we have developed and tested Epigenist obtained from seeds of Voandzeia subterranea. 

We have first demonstrated that Epigenist boosts neuritogenesis with an increase of the neurite length in a culture of neuronal cells. Then, we have tested this extract on re-innervated skin model. After treatment, the epidermis is thicker. 

Finally, Epigenist was tested in a randomised split-face study carried-out on 20 female volunteers. After 56 days of application of the products, an increase by 10% of the thickness of epidermis was observed in the half face treated with the emulsion containing Epigenist, while no evolution of epidermis thickness was obtained on the placebo treated half-face. Visible consequences of this increase of epidermal thickness were an improvement of skin aspect by decreasing roughness; after treatment by Epigenist, the skin surface is smoothed, the wrinkles are reduced comparatively to placebo treatment.

References
1 Hsieh ST, Lin WM, Chiang HY et al. Skin innervation and its effects on the epidermis. J Biomed Sci 1997; 4 (5): 264-8.
2 Huang IT, Lin WM, Shun CT, Hsieh ST. Influence of cutaneous nerves on keratinocyte proliferation and epidermal thickness in mice. Neuroscience 1999; 94 (3): 965-73.
3 Hsieh ST, Lin WM. Modulation of keratinocyte proliferation by skin innervation. J Invest Dermatol 1999; 113 (4): 579-86.
4 Lebonvallet N, Boulais N, Le Gall C et al. Effects of the re-innervation of organotypic skin explants on the epidermis. Exp Dermatol 2012; 21 (2): 156-8.