Elucidation of one cause of rough skin caused by irritation due to humidity difference

Discovered the effect of improving the production of acylceramide, which is important for the barrier function of the skin, in "Tea leaf extract"

news release

January 11, 2022

FUJIFILM Corporation (Headquarters: Minato-ku, Tokyo, President and CEO: Sadaichi Goto) has elucidated one of the causes of rough skin caused by stimuli caused by a decrease in humidity (hereinafter referred to as humidity difference stimuli). We also found that tea leaf extract has an effect of promoting the expression of acylceramide-producing enzyme, which is an important barrier-related factor in the stratum corneum.

Results of this research

It is known that skin that has been stimulated by humidity difference becomes sensitive and prone to inflammation. In this research, we have found the possibility of new skin care that leads to "skin that is not irritating" by supplementing the production of acylceramide, which is important for the barrier function of the skin. We will apply the results of this research to the development of cosmetics. This research will be presented at the "142nd Annual Meeting of the Pharmaceutical Society of Japan" to be held at the Nagoya Congress Center from March 25, 2022.

Research background

While many people suffer from skin problems caused by changing seasons and putting on and taking off masks, little research has been done on the mechanism by which such changes in the environment cause rough skin. Therefore, we focused on the "humidity difference" that occurs at the turn of the season and when putting on and taking off the mask, and worked on research to clarify the effect on the skin.

Human skin consists of the epidermis and dermis, and the uppermost layer of the epidermis contains the stratum corneum, which is composed of stratum corneum cells and intercellular lipids. Approximately 50% of the intercellular lipids in the stratum corneum are composed of ceramide and acylceramide, which form a lamellar structure ^{* 2} that is stacked in layers to exert the barrier function ^{* 3} of the skin. In particular, acylceramide has the function of regularly aligning ceramides and preparing them into a strong structure, and is known as an important factor for maintaining barrier function (Fig. 1). Since acyl ceramide has low solubility and is easy to crystallize, it was difficult to efficiently permeate between stratum corneum cells, but we use our unique nanotechnology to stably disperse "human acyl ceramide" in nano size. Successful. We have confirmed that this ingredient restores the lamellar structure and improves the barrier function of the skin ^{* 4} .

[Fig. 1] Skin barrier function and ceramide

The regular alignment of ceramide and acylceramide with the intercellular lipids in the stratum corneum maintains the barrier function of preventing the evaporation of water from the skin and the invasion of external factors.

Details of this research result

1. Development of humidity control culture equipment

Biological samples such as cells and epidermis models are usually cultured in high humidity (around 90% RH ^{* 5} ) to prevent evaporation of the medium components required for culture. Until now, most of the experiments in which the epidermis model was exposed to low humidity and cultured were performed by using a desiccant or removing the humidifying vat of the incubator, and strict humidity control was not performed. .. This time, we have developed a humidity control culture device that can produce air adjusted to any humidity by mixing dry air and saturated water vapor (Fig. 2). By using this device, it has become possible to specify an arbitrary humidity and time, and to incubate the epidermis model by exposing it to humidity-controlled air.

FIG. 2 is a humidity control culture device.

The humidity control culture device and culture plate are removable, and the culture cup of the epidermis model is inserted into the device for use. Air adjusted to any humidity can be supplied to the stratum corneum side of the epidermis model.

2-1. Demonstrated that the moisture content and barrier function of the stratum corneum are reduced by the humidity difference stimulus.

We verified the effect of humidity difference stimulus on the skin using a humidity control culture device. As a result of changing the epidermis model from high humidity (90% RH) to low humidity (30% RH) and culturing, it was found that the water content of the stratum corneum decreased (Fig. 3). In addition, it was confirmed that the TER value, which is an index of the barrier function inside the skin, decreased (Fig. 4), and that foreign substances easily invaded the inside of the skin from the outside (Fig. 5), demonstrating that the barrier function decreased. .. It is thought that the skin that has been stimulated by the difference in humidity will have a reduced amount of water, making it easier for external substances such as bacteria to invade.

[Fig. 3] Effect of humidity difference stimulation on the water content of the stratum corneum

[Fig. 4] Effect of humidity difference stimulation on the barrier function inside the skin

experimental method

Using a humidity control culture device, change the epidermis model from high humidity (90% RH) to low humidity (30% RH) and incubate for 6 hours. The water content of the stratum corneum and the transepithelial electrical resistance (TER ^{* 6} ) were measured using the epidermis model after culture. The measured values ​​of the epidermis model cultured at 90% RH were set to 100%, and each measured value was shown as a relative value.

result

In the epidermis model stimulated by the humidity difference, the water content of the stratum corneum decreased (Fig. 3). It was also found that the TER value decreased and the barrier function inside the skin decreased (Fig. 4).

[Fig. 5] Effect of humidity difference stimulus on barrier function (prevention of invasion of external factors)

experimental method

Using a humidity control culture device, the epidermis model was changed from high humidity (90% RH) to low humidity (30% RH) and cultured for 48 hours. Fluorescent substances are added to the epidermis model after culturing, assuming foreign substances that invade from the outside. Invasion into the skin was observed.

result

In the epidermis model stimulated by the humidity difference, it was found that more fluorescent substances invaded the skin and the barrier function was reduced.

2-2. Discovered that acylceramide-producing enzymes decrease due to humidity difference stimulation

Next, we examined the effect of humidity difference stimulation on acylceramide, which is important for the barrier function of the skin. As a result of changing the epidermis model from high humidity (90% RH) to low humidity (30% RH) and culturing it, we found that the expression of the acylceramide-producing enzyme ELOVL4 was reduced (Fig. 6).

FIG. 6 shows a decrease in ELOVL4 expression due to humidity difference stimulation.

experimental method

Using a humidity control culture device, the epidermis model was changed from high humidity (90% RH) to low humidity (30% RH) and cultured for 6 hours. The expression level in the epidermis model cultured at 90% RH was set to 100%, and the expression level of ELOVL4 was shown as a relative value.

result

It was confirmed that ELOVL4 was significantly reduced in the epidermis model stimulated by the humidity difference.

From the above results, it was demonstrated that the water content of the stratum corneum and the barrier function decreased in the epidermis model subjected to the humidity difference stimulus. The decrease in ELOVL4 makes it difficult for new acylceramides to be produced, leading to long-term deterioration of moisturizing power and barrier function. We believe that this is one of the causes of rough skin caused by humidity difference stimulation.

3. Discovered the expression promoting effect of ELOVL4 in tea leaf extract

Since the acylceramide-producing enzyme ELOVL4 decreases due to humidity difference stimulation, which leads to a decrease in the barrier function of the skin, we searched for a component that promotes the expression of ELOVL4. As a result, we discovered a new effect of promoting the expression of ELOVL4 in the ingredient "tea leaf extract" derived from oolong tea, which is known for its antioxidant effect (Fig. 7).

FIG. 7: ELOVL4 expression promoting action of tea leaf extract

experimental method

Tea leaf extract is added to epidermal cells at a concentration of 10 ppm. After culturing for 24 hours, cells were collected and the gene expression level of ELOVL4 was measured. The expression level in epidermal cells to which no extract was added was set to 100%, and the ELOVL4 expression level was shown as a relative value.

result

It was confirmed that the gene expression level of ELOVL4 was significantly increased by the tea leaf extract.

In this study, it was demonstrated that the enzyme "ELOVL4", which is important for the production of acylceramide, is reduced by the humidity difference stimulation, the barrier function of the skin is lowered, and that the tea leaf extract has the effect of promoting the expression of ELOVL4. bottom.

In the future, we will utilize the results of this research in the development of cosmetics.

inquiry

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Public Relations Group, Corporate Communication Department, FUJIFILM Holdings Co., Ltd.

Inquiries regarding this research

Fujifilm Healthcare Laboratory Product Development and Brand Promotion Headquarters