Ceramides (ceramides) are natural lipids that, together with fatty acids and cholesterol, form the lipid barrier layer of the skin. They play a critical role in cell membranes, acting as signaling molecules. The amount and composition of ceramides directly affect the processes of division, growth, aging and dying of skin cells.

The term “ceramides” comes from the Latin word “cerebrum,” which means “brain” and is correctly pronounced “cerebrum.” In this regard, we can say for sure that it is more correct to say “ceramides” and not “ceramides”, as many are accustomed to.

Ceramides can be found on labels under the following names:

1. Ceramide NS;
2. Ceramide EOP;
3. Ceramide PC-102 (Hydroxypropyl Bislauramide MEA);
4. Ceramide PC-104 (Hydroxypropyl Bispalmitamide MEA);
5. Ceramide PC-108 (Hydroxypropyl Bisstearamide MEA);
6. Ceramide 1, 2, 3, III, 6-II and up to 9 (but not 5).

Our skin constantly needs moisture, which means it needs to somehow retain it inside itself. This function is carried out through its own extracellular matrix, which normally should contain about 50% ceramides, 25% cholesterol and 15% free fatty acids. And ceramides play an important role in this process. They are also signaling molecules that set the timing of cell death. In addition, ceramides also act as a natural defense against dangerous microorganisms and pollution.

The highest content of ceramides is observed in the stratum corneum, that is, on the surface of the skin. Normally, ceramides should make up approximately 40% of all lipids in the stratum corneum, but, alas, this figure does not last forever.

With age, the amount of ceramides in the skin decreases, and this is one of the reasons for increasing age-related dry skin. In addition, aggressive cleansers that disrupt lipid balance, as well as medications, for example, to lower cholesterol levels, also lead to dryness. In theory, the latter should reduce lipid levels only in the blood, but in reality their intake also affects the skin.

Also, the amount of ceramides decreases during extreme diets. The fact is that a certain amount of essential fatty acids must be present in the diet. If there are not enough of them, then this negatively affects the condition of the skin: dryness and flaking appear.

Why are ceramides added to cosmetics?

It has already been said above that the amount of ceramides in the skin decreases with age. For this reason, cosmetics manufacturers include them in their products, as they good way enriching the skin with ceramides to restore the lipid barrier of the skin.

By the way, we recommend paying attention to the cream with ceramides from Armorique. It perfectly heals damaged skin areas and restores the lipid barrier. An excellent product for restoring skin after peeling, mesotherapy and other intensive procedures.

At what age should you start using products with ceramides?

IN at a young age Cosmetics with ceramides should be used only by those who have impaired lipid barrier integrity. Mature skin a priori needs additional ceramides, so it is better to use cosmetics with them rather than without them.

Ceramides (ceramides)- natural lipids (fats), which are the main structural components of the external structure of the skin. Along with other lipids such as cholesterol and its esters, fatty acids, ceramides prevent water loss through the epidermis, which can lead to dry skin.

Ceramides are listed on labels under the following names: Ceramide NS, Ceramide EOP, Ceramide PC-102 (Hydroxypropyl Bislauramide MEA), Ceramide PC-104 (Hydroxypropyl Bispalmitamide MEA), Ceramide PC-108 (Hydroxypropyl Bisstearamide MEA), Ceramide 1, 2, 3, III, 6-II and so on until 9 (except 5).

Why are ceramides needed?

The skin as a barrier system inhibits the transport of moisture through its own extracellular matrix, which has a unique composition: ~50% ceramides, ~25% cholesterol and ~15% free fatty acids. Ceramides are essential for capacitating and retaining moisture in the skin, as well as regulating a number of cellular functions. Natural ceramides, for example, act as signaling molecules, “giving” cells the time of death. They also serve as a barrier against bacteria and environmental contaminants.

Cells in the outer layer of skin - the surface of the epidermis - are the richest source of ceramides. Ceramides, fatty acids and cholesterol work together in the stratum corneum to prevent water loss and keep skin hydrated and elastic. Ceramides make up about 40% of all lipids in the stratum corneum, however, unfortunately, this figure does not last forever.

Ceramides: aging and destruction

Unfortunately, ceramide levels decline with age. This is one of the reasons why our skin becomes drier as we get older. Harsh cleansers can also disrupt lipid balance, which further leads to dry skin. Some medications, such as statins (drugs for lowering cholesterol levels), also have a negative effect on this factor: they can reduce the lipid content not only in the blood, but also in the outer layer of the epidermis.

Diet also plays a role. If the diet lacks essential fatty acids (especially omega acids), this will inevitably affect the natural skin barrier by reducing local immunity and loss of moisture. A certain amount of fat in the diet is essential for healthy skin, so it's not surprising when people experience dry, flaky skin after extreme diets.

What are ceramides in cosmetics?

It is clear that ceramides and other lipids are important for retaining moisture and preventing dry skin. That's why some skin care product manufacturers add ceramides to skin care formulas - this is a good way to replenish ceramides lost during the aging process and as a result of damage to the skin's lipid barrier.

Ceramides in cosmetics as “additional” fats help restore the skin and its hydrolipid mantle. Ceramides in skin care products are different types lipids that are embedded in the cell membrane of the epidermis. There are nine different types of ceramides, which are usually labeled with numbers from 1 to 9.

To increase the activity of ceramides in cosmetics and their ability to penetrate deep into the epidermis, they are sometimes combined with absorption intensifiers (introduced into transdermal systems). Ceramides in cosmetics can also be included in liposomes, special bubbles that easily penetrate the skin. Liposomes themselves, as transdermal systems, can also serve a therapeutic function: they are often made from milk fats, which also help nourish the skin.

Ceramides, cholesterol and fatty acids play a role in maintaining the skin's ability to retain moisture. This is why it is so important to replenish cholesterol and fatty acids along with ceramides, nourishing the skin with appropriate products to maintain a balance identical to the natural ratio of fats in the hydrolipid mantle. Effective means just maintain the appropriate ratios of all these lipids.

Who can benefit from ceramides in cosmetics?

As is already clear, products with ceramides are needed primarily for people with dry, flaky and damaged skin. Ceramides may also be useful in the treatment of some skin diseases, including eczema and psoriasis: people with eczema or psoriasis have less ceramides in the stratum corneum of the epidermis of the skin compared to people with normal skin. Thus, with the help of care cosmetics that contain ceramides, you can improve the condition of allergic skin diseases.

For best results, dermatologists recommend using a mild liquid cleanser that is non-irritating and non-drying, along with a moisturizing or nourishing cream, which contains ceramides and other essential lipids. There are even detergents with ceramides that cleanse the skin so gently that it prevents the inevitable loss of lipids in the process - this is an excellent choice for people with dry or aging skin, as well as patients with eczema or psoriasis.

Natural or synthetic ceramides

Natural ceramides are extremely unstable substances, the production process of which is labor-intensive and expensive ($2,000-$10,000/kg). In addition, many natural ceramides are extracted from nervous system cattle, which raises the question of the risk of infection with prion viruses (“mad cow disease”). Also, natural ceramides can provoke excessive cell apoptosis, which synthetic analogues do not do.

Thus, in cosmetic formulas, synthetic ceramides, mainly of plant origin, are often used instead of natural ones. Although “pseudoceramides” are harmless and work in the same way as natural ones, they have one significant drawback - they do not penetrate the skin as well as natural ceramides. However, their permeability is significantly improved if synthetic ceramides are integrated into liposomes.

Cosmetics with ceramides (ceramides)

You can find ceramides in a variety of products - nourishing and moisturizing creams and masks, eye creams, cleansers, sunscreens, lip glosses, lipsticks and foundations. Virtually every brand produces such products, so cosmetics with ceramides can be found in any segment. Ceramides are also added to some hair care products, particularly conditioners, where they bind to the hair cuticle and repair it, making it less porous.

All EU and US dermatological associations classify ceramides as safe cosmetic ingredients - they do not irritate the skin and actually relieve irritation and itching associated with skin dehydration. In general, cosmetics containing ceramides are beneficial for people with all skin types, they are safe to use and generally do not cause irritation, allergies or inflammation.

The cosmetic market offers a huge number of different anti-aging products with tempting promises. But which ones really work? There are not many ingredients in anti-aging cosmetics whose positive effects have been scientifically proven. Among them are ceramides. What's special about them?

Protective film

There are few representatives of the fair sex who have never heard of ceramides, but few know about the true properties and their importance in the fight against aging. Ceramides, or in scientific terms - ceramides (ceramide) - special lipid molecules consisting of fatty acids and amino alcohol. They are an important part of the cell membrane. Their name is derived from the Latin "cera", which means "wax". And, indeed, with the help of these molecules, a fatty waterproofing barrier is formed in the upper layers of the skin, which allows you to retain moisture and restore the natural barrier of the skin.

As we age, our skin gradually loses ceramides and cannot produce them in the same quantity. This leads to dry skin, wrinkles, and even some types of dermatitis. Newborn babies, especially premature babies, are born with a special wax-like coating of skin that prevents their skin from losing moisture. It is called vernix caseous lubricant, consisting mainly of ceramides.

A riddle for chemists

If you remember the chemistry, ceramides are a long chain with a sphingoid base associated with a fatty acid. By the way, “sphingoid bases” (also included in chemical composition intercellular lipids) are named after the Sphinx because chemists for a long time could not understand their “mysterious structure.” These bases were first discovered in brain fluid.

Sphingoids make up approximately half of the ceramides. Thus, ceramides are not a pure substance and their composition can vary depending on the fatty acids with which they are combined. There are at least nine different types of ceramides derived from natural way. In addition to natural ceramides, there are also phytoceramides, pseudoceramides and synthetic ceramides. How not to get confused in them?

Natural ceramides formed on the skin by combining a fatty acid with a sphingoid base;
Phytoceramides derived from phytosphingosine (a special type of sphingosine found in yeast, plants and some mammalian tissues);
Pseudoceramides are lipids that have similar properties to ceramides, but with a different structure. Most of them are obtained artificially;
Synthetic ceramides created in laboratories in the likeness of natural ceramides.

There is no need to hide the fact that ceramides used in skin care products are mostly synthetic. Natural ceramides (from plant and animal cells) may often be found in low concentrations. Products with them are much more expensive. But for the effectiveness of the product, it is not the origin of the ceramides that is important, but their correct structure.

Ceramides are designated differently on labels:

According to international nomenclature (INCI), the serial number from the table is simply assigned;

- according to the Motta system, a three-letter designation is used, where the first and second letters are the types of fatty acid amide, the third is the type of base;
- less often the name and origin of ceramides are fully spelled out in Latin.

Not everything is so smooth

According to the results of several studies, when ceramides were taken orally in capsules at 20-40 mg per day for three weeks, the skin's protective barrier noticeably improved, especially in those with dry skin, and transepidermal water loss decreased. However, the effect of capsules with ceramides on the condition of the entire body and, in particular, digestion has so far been little studied and is not approved by all nutritionists and doctors.

Scientists are much more confident about the topical use of ceramides in various cosmetics. It’s even better if these substances are combined with other fat-containing components in a certain ratio. The optimal mixture consists of 50% ceramides, 25% cholesterol and 15% free fatty acids. It is the one that best helps retain moisture in the skin from the inside.

There are still many gaps in the research on these substances, and there are many ceramides that can be used in combination with other components. And it’s not a fact that they will be truly effective. Sometimes, for simple skin problems, ceramides can be replaced with regular Vaseline, but lipid molecules penetrate the skin from the inside and give longer-lasting results. Despite such controversial issues, ceramides are still very beneficial for the skin. Their properties are best revealed in the correct ratio with cholesterol and fatty acids (3:1:1).

Cosmetologists advise starting your acquaintance with ceramides by purchasing inexpensive means, gradually raising the bar in search of the most suitable composition.

Ceramides or ceramides (from Latin cerebrum, “brain”) are a type of lipids (fats). They are the main structural element of the hydrolipid layer of the skin, necessary for protection against aggressive external factors and prevention of moisture loss.

When there is a lack of ceramides, the skin's protective barrier is destroyed © iStock

One of the main functions of ceramides is construction; they fill the intercellular space. If there is a shortage or poor quality of ceramides, the integrity of the skin's natural shield will be disrupted. It is not difficult to predict the sad consequences.

1. 1

   Dehydration Left without cover, the moisture will begin to evaporate.

2. 2

   Dryness When cells cannot retain moisture, the skin begins to experience thirst and an unpleasant feeling of tightness.

3. 3

   Irritation and inflammation Ceramides protect the skin from the penetration of toxins, heavy metals, exhaust gases, viruses and bacteria.

In addition to protecting the skin from the “bad environment,” ceramides have another important function - signaling. They are the ones who give a sign when it’s time for old cells to die and for new ones to be born.

Ceramides: aging and destruction

The lipid balance in the skin can be disrupted due to external and internal circumstances.

Age. Unfortunately, over time, the epidermis loses the ability to synthesize ceramides, which leads to dry skin - one of the main problems of mature skin.

Incorrect care. Too aggressive, incorrectly selected cleansers damage the lipid layer. The result is dehydration.

Extreme weather conditions. Frost and sun, biting wind, excessively cold or dry air can break through the skin's protective system and cause dryness, itching and redness.

Lack of fatty acids in the diet. Yes, the skin does not like it when we eat incorrectly, and does not hide it. Dryness and sensitivity are the price to pay for strict dietary restrictions and a lack of “good” fats in the diet.

Creams with ceramides are suitable for any skin type © iStock

The role of ceramides in cosmetics

Products with ceramides come to the rescue in cases where the skin, for one reason or another, suffers from a lack of its own lipids. Ideally, the ceramides included in the cream should freely integrate into the hydrolipidic layer of the epidermis, filling the “gaps”, and thus restore the integrity of the protective skin barrier.

Indications for use

Cosmetics with ceramides are universal and suitable for any skin type. But there are cases when creams with ceramides are vital.

Sensitive skin

It is characterized by a weakened lipid barrier, and cosmetics with ceramides can alleviate its condition, protect and prevent a reaction to negative external factors.

Dry skin

Its main problem is a permanent lack of lipids, and in particular ceramides. Creams containing them are able to seal moisture and retain it in the skin.

Aging skin

Suffers from a lack of fat for obvious reasons, which include, for example, a decrease in the synthesis of its own lipids.

Skin after procedures

Creams with ceramides are indicated after salon peelings and dermabrasion procedures. After these manipulations, the skin requires rapid restoration of the hydrolipid mantle.

Problem skin

Despite the increased oiliness, she can also benefit from ceramides in order to establish the process of normal cell exfoliation and avoid the effect of over-dried skin as a result of treatment.

Lack of ceramides can lead to dryness and flaking © iStock

What are ceramides in cosmetics?

The skin synthesizes 9 different ceramides; only a few of their analogs are used in beauty products.

In cosmetic formulas, ceramides are usually combined with other lipids - cholesterol, fatty acids, amino acids. In such an environment, they work with increased efficiency.

Natural and synthetic ceramides

For cosmetic needs, ceramides of natural and synthetic origin are used. There is a common belief that synthetic, so-called pseudoceramides, are much inferior in quality and effect to their natural prototype. However, there is no scientific data to confirm or refute this claim yet.

Tools Overview

Considering the above, it is not surprising that ceramides are in demand as a cosmetic ingredient and appear in creams for a wide variety of purposes.

Cosmetical tools with ceramides for skin with different needs

Cosmetics with ceramides

Name	Ingredients	Action	Indications
Triple lipid restore 2:4:2, skinceuticals	high lipid content: 2% ceramides, 4% cholesterol, 2% Omega 6-, 9-fatty acids	Corrects signs of aging, increases lipid levels, moisturizes.	aging skin, dry, dehydrated
Corrective cream for problem skin against imperfections and post-acne Effaclar Duo (+), La Roche-Posay	lipo-hydroxy acid, prokerad – patented ceramide	Helps reduce inflammation and prevents hyperpigmentation in the post-acne area.	problematic skin with inflammatory elements
Moisturizing anti-stress fluid for the face Skin Rescuer, kiehl's	squalane, mannose, shea butter, five types of cramides	Soothes, restores, reduces redness.	sensitive, irritated skin prone to redness
Serum for a youthful look Liftactiv serum 10 eye & Lashes, vichy	hyaluronic acid, ceramides, reflective particles	Improves the condition of the skin around the eyes and eyelashes.	wrinkles around the eyes, thin weakened eyelashes
Multi-active night gel-oil visionnaire nuit, lancôme	seaweed, jasmonic acid derivatives, vegetable oils, ceramides	Moisturizes, softens, restores the surface of the skin.	tired, dehydrated skin, dull complexion, uneven texture

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Ceramides and skin

The main task of our skin is to protect the body from external aggression (biological, chemical, physical) and help in maintaining inner world, or, as doctors say, homeostasis. The evolution of the skin in humans as a biological species inhabiting planet Earth, their formation from the moment of conception to birth, renewal and restoration throughout life and, of course, structural uniqueness and functioning - everything is subordinated to the solution of this vital task.

Today, much is known about the structure and operation of the skin barrier, and this knowledge is successfully used for the benefit of humans. In this publication, we will touch upon one of the interesting, complex and important aspects related to skin permeability and its barrier function. Almost nothing passes through intact skin, and this is an indispensable condition for maintaining the integrity of our body. This is true both for substances that come into contact with the skin from the outside and for those that are inside. It is the skin, and specifically its stratum corneum, that protects us from moisture loss. How the stratum corneum copes with this task became known in the late 90s of the last century, and these ideas brought experimental and practical dermatology to a new level and laid the foundation for the development of the modern concept of prevention and correction of skin problems and treatment of skin pathologies.

According to the views accepted in the modern scientific world, the stratum corneum is similar to brickwork, where the role of bricks is played by corneocytes - absolutely impenetrable horny scales through which diffusion of substances is impossible. Horny scales are held together by intercellular “cement” - a lamellar structure, which is an alternation of lipid layers (membranes) parallel to each other, between which there is a thin layer of water. This structure is often called the lipid barrier of the skin in the scientific literature, and it is this structure that serves as the main permeability barrier and regulates the passage of substances through the stratum corneum. Understanding how the lipid barrier is formed, what it consists of, and how it functions provides ample opportunities in terms of regulating skin permeability - this is important when applying cosmetics and medicines. Modern developments of dermatotropic drugs and the development of programs for skin care and restoration are carried out taking into account the structure and condition of the skin barrier.

The most important component of the lipid barrier of the stratum corneum is ceramides - in the body, these amazing lipids are found in the myelin sheaths of neurons in the brain, where they were first discovered and which is why they got their name (from the Latin cerebrum - brain). Ceramides form the basis of the lipid matrix - they account for half (50 mol%) of all lipids. Another common component is cholesterol (free and ester-bound) - 30-35 mol%). The remaining lipids are free fatty acids. (Such a unique quantitative and qualitative lipid composition is characteristic only of the stratum corneum. In the membranes of living cells - external (plasma) and internal, surrounding organelles - the key component is phospholipids, and cholesterol occupies only a few percent.

Ceramides: chemical structure and nomenclature

Ceramides, together with sphingomyelin, glycosphingolipids and phosphosphingosides, belong to the group of sphingolipids. In the case of ceramides, one of the fatty acid residues is atypically attached through an amide bond to the corresponding base (amino alcohol). From a chemical point of view, the diversity of ceramides is due to the many possible options connections of two structural units - a polar “head” (sphingosine base) and a hydrophobic “tail” (fatty acid). The following sphingosine bases (amino alcohols) are involved in the formation of ceramides: sphingosine, phytosphingosine, b-hydroxysphingosine and dihydrosphingosine. A fatty acid chain (“tail”) is attached to the base different lengths(from 16 to 28 carbon atoms in increments of two atoms - depending on the type of ceramide).

A distinctive feature of some skin ceramides is their unique chemical structure, which is not found in ceramides of other body tissues. The most interesting example is O-acylated ceramides, which have long acyl chains with a terminal hydroxyl group. This group may remain unchanged or may be ethyrified with linoleic acid or a-hydroxy acids. In addition, hydroxyceramides can form a chemical bond with proteins (due to this, the lipid barrier is attached to the horny envelopes of corneocytes). These chemical features underlie the ability of ceramides to form a compact and dense structure of the stratum corneum. Any impact that destroys such bonds involving ceramide molecules or other components of the intercellular “cement” causes transepidermal loss of moisture and facilitates the penetration of potentially harmful exogenous substances into the body.

At least 11 classes of ceramides have been identified, numbered according to their thin layer chromatography fraction number (higher number corresponds to higher ceramide polarity). Later research led to the emergence of a new, systematic classification, in which the class number is replaced by a letter designation, from which the chemical structure of ceramide is clear. The last letter in the designation corresponds to the sphingosine base:

S - sphingosine;

P - phytosphingosine;

N - b-hydroxysphingosine;

DS - dihydrosphingosine.

This is preceded by a letter indicating the type of fatty acid residue:

N - non-hydroxyl acid;

A - a-hydroxy acid;

O - sh-hydroxy acid.

Ceramides are a subclass of lipid molecules, the simplest type of sphingolipids, consisting of sphingosine and a fatty acid. Ceramides are an important lipid component of the cell membrane. Ceramide is involved as a precursor molecule in the synthesis of sphingomyelin. In the cell, ceramides play the role of not only a membrane element, but also a signaling molecule. They are involved in cellular processes such as cell differentiation, cell proliferation and apoptosis.

If a fatty acid attached through an ester bond is found in the ceramide structure, the letter E is placed before the designation. In the stratum corneum of the skin there are ceramides designated according to this nomenclature as: EOS, NS, EOP, NR EOH, AS, NH, AP, NDS, ADS and AN. In addition, the two ceramides that form covalent bonds are designated OS and OH. Ceramides EOS, EOH and EOP contain linoleic acid attached to the terminal hydroxyl group, and α-hydroxy acids through an ester bond. Each ceramide differs in the structure of the sphingosine base or the length of the fatty acid chain.

Ceramides as the basis of intercellular “cement”

Intercellular lipids account for about 15% of the dry weight of the stratum corneum of the skin. As mentioned above, lipids are a mixture of ceramides (about 50 mol%), cholesterol and its esters (30-35 mol%) and free fatty acids (about 15 mol%). This proportion is important for the normal functioning of the barrier, and its change is fraught with disruption of the water balance of the stratum corneum, which is clinically expressed in the development of dry skin (read more about dry skin in the article) with all the ensuing consequences.

Ceramides as precursors are synthesized in special organelles of granular keratinocytes, called lamellar granules (or Odland granules). Analysis of the lipid content of the granules showed that they contain mainly phospholipids and sphingolipids (glycosphingolipids and sphingomyelin), which are subsequently modified into ceramides and free fatty acids. The main process of formation of lamellar structures occurs at the border of the granular and stratum corneum of the skin. Two important enzymes work here - phospholipase A2 and B-glucocerebrosidase, which catalyze the breakdown of ceramide precursors and the formation of the final form of intercellular “cement”. For the correct occurrence of this process, a certain water content and the acidity value of the medium (pH) are very important. Phospholipase A2 has maximum activity at neutral pH, while other enzymes prefer a more acidic environment. Water is important for the functioning of all enzymes, so the barrier function of the stratum corneum can be impaired in conditions of prolonged dehydration of the stratum corneum, which is observed in some pathologies (psoriasis, xerosis) and in cases where the skin is often exposed to detergents.

Many works have been devoted to the study of the structure of the stratum corneum and lipid matrix. According to one of the most popular models, the intercellular “cement” has a mosaic structure and consists of two characteristic zones: the “crystalline” zone is practically impermeable to water; it is divided by small sections of a “liquid crystal” zone, which allows water to pass through much better. Due to this organization, the intercellular “cement” has a certain permeability to water, high plasticity and resistance to mechanical stress. The mosaic nature of the lipid matrix is ​​supported, among other things, by the fact that the ceramides included in its composition are heterogeneous and are represented by several classes with different physicochemical and structural features. Each type of ceramide plays a different role. Thus, ceramide 1 (EOS), a fundamental component of intercellular cement, is responsible for cross-linking corneocytes with matrix lipids, and its deficiency is one of the main causes of many dermatoses.

Cosmetics based on ceramides (for example,) are especially recommended for restoring skin after damaging aesthetic procedures (including), as well as for caring for dry skin with a damaged barrier. It is a wonderful example of introducing fundamental knowledge into practice and embodies corneotherapeutic approaches that are becoming increasingly popular among dermatologists and cosmetologists.

Ceramides as cell cycle regulators

So, ceramides are the main element of the lipid barrier, but, as further research has shown, they perform not only a structural function, but are also a regulator of some important processes occurring in skin cells. Ceramides act like second messengers in the cell cycle. Thus, they play a significant role in apoptosis - programmed cell death, affecting cell proliferation and differentiation. The “vector” of this influence depends on the specific type of ceramide and can be multidirectional for different compounds: in some cases it is stimulation, in others it is inhibition.

The biological activity of ceramides on the cell cycle has been confirmed experimentally: by adding exogenous ceramides and sphingomyelin to keratinocyte cell cultures, their effect on cell proliferation and differentiation has been demonstrated. Two short-chain synthetic ceramides C2 and C6, two natural ceramides 3 and 6A, as well as sphingomyelin were taken. Keratinocytes were incubated in a medium containing 0.5; 1; 5 and 10 µM of the test substance. All ceramides studied, except sphingomyelin, inhibited cell proliferation. Ceramide C2 turned out to be the most active - at a concentration of 10 µM it inhibited DNA synthesis by 60%. Natural ceramides showed only a small effect on proliferation rates.

Ceramides for pregnant women and embryo development

Ceramides are required for embryo formation. Ceramides play a key role in the transformation of a clump of stem cells into a full-fledged embryo. Scientists at the University of Georgia, working under the direction of Dr. Erhard Bieberich, found that in the early stages of embryonic development, ceramides accumulate in the apical zone of cells directed into the cavity, helping to form the poles of the embryo. Polarity is necessary for cell differentiation and the transformation of a sphere consisting of undifferentiated cells into a structured embryo. According to Bieberich, at the very beginning we are clumps of stem cells, but literally within 24 hours some of the cells die, and some form a hollow sphere with an inner layer (primitive endoderm), which gradually turns into an embryo, and an outer layer (primitive ectoderm ), supporting the development of the embryo.

Ceramides perform several functions in both developing and mature organisms: in particular, they are the main structural elements of the skin barrier and serve as precursors in the synthesis of the protective sheath of nerve cells - myelin. Recently, scientists have received more and more evidence that, in addition to structural ceramides, they perform a number of signaling functions. In an earlier study, Bieberich's group showed that ceramide, in a complex with the PAR-4 protein, is involved in the elimination of unnecessary cells during brain development. The results of the latest work indicate that ceramides concentrated in the apical zone of cells attract proteins that ensure the formation of polarity and trigger a cascade of reactions with their participation.

When ceramide synthesis was artificially suppressed, polarizing proteins did not accumulate in the apical zone, cells died, and endoderm formation did not occur. The restoration of ceramide synthesis completely normalized all processes. The authors plan to undertake a detailed study of the functions of ceramides in mature cells. They suggest that disturbances in its synthesis can lead to cells losing direction in the tissue structure and to their malignancy. There are also diseases in which a large number of cells die as a result of triggering the self-destruction mechanism (apoptosis). Perhaps the reason for this is an increase in the level of ceramides inside the cells. To study the localization and concentration of ceramides in cells, scientists have already developed antibodies that specifically bind to these lipids and allow them to be visualized and quantified.

"Cementing" properties of ceramides

Over the past few years, a number of studies have been conducted regarding the topical application of ceramides and other components of the intercellular lipid “cement”. The main interest of the researchers was the effect of these compounds on the barrier function of the skin. The barrier properties of the skin are assessed by its ability to prevent the evaporation of water from the body. We have already said that the main restraining structure is the stratum corneum. However, it is not a 100% barrier, and normally some amount of water constantly evaporates through the skin. Water slowly seeps through the intercellular spaces of the stratum corneum from the inside to the outside and, upon reaching the surface, evaporates into the atmosphere. This process is called transepidermal water loss (TEWL), and with any damage to the stratum corneum, the level of TEWL increases.

The TEWL index is used to assess the ability of local drugs to restore the barrier properties of the stratum corneum. The work studied the properties of two emulsion preparations (like lamellar emulsions): one contained only ceramides 3 and 3V (a semi-synthetic analogue of natural ceramides), the other contained their combinations with ceramide b, phytosphingosine, cholesterol and linoleic acid. The study involved 12 women aged 22-24 years. Before using the drugs, the stratum corneum was damaged by treatment with a surfactant (sodium lauryl sulfate, SLS) or a non-polar solvent (acetone). Long-term (24 hours) contact with SLS caused a change in the structure of the intercellular “cement” - the skin responded to this by increasing the TEWL index. Application of acetone led to the “washing out” (extraction) of lipids in the stratum corneum of the skin, which also damaged the stratum corneum and increased TEWL. Application of an emulsion, which contained both ceramides, led to an insignificant decrease in TEWL and an increase in skin hydration in areas where “damaging” agents were applied - a surfactant and a non-polar solvent. Much best effects was achieved using the second drug: its use reduced TEWL by 20% and increased the moisture content of the stratum corneum by 10%.

Many skin barrier dysfunctions are associated with a decrease in ceramide content or significant changes in their proportions. Hence, local application The “right” mixture of ceramides and other lipids found in the stratum corneum can improve barrier function. In particular, it has been shown that the systematic application of a specially formulated mixture of ceramide, cholesterol and free fatty acids restores the impaired function of the intercellular “cement” and significantly increases the moisture content of the stratum corneum (more on skin hydration). What is interesting: when each of the components of the drug was used separately or even in paired combinations, no effect was observed. Moreover, in these cases, regeneration even slowed down, and only a three-component mixture in the correct proportion accelerated the regeneration of the barrier. Based on these results, it can be concluded that all three compounds - ceramides, cholesterol and free fatty acids - are essential for skin barrier function.

Topical application of a mixture of physiological lipids of the stratum corneum and semi-synthetic ceramide 3 was also effective, especially in the case of various dermatoses (contact dermatitis (CD), allergic contact dermatitis (ACD) or atopic dermatitis (AD)) - study results (duration 4 or 8 weeks) this was confirmed in 580 patients with one of these pathologies.

As a substitute for ceramides in last years Their analogues began to be used more and more widely. The properties of pseudoceramides are close to those of natural substances, and in some cases they are an almost ideal replacement for ceramides. Ceramides applied to the skin are able to restore defects in the intercellular structure caused not only by aging or exogenous factors (including such cosmetic procedures, such as peeling, dermabrasion, mesotherapy), but also skin diseases, such as atopic dermatitis or psoriasis. The restorative effect is especially pronounced when using mixtures in which ceramides are combined with other components of the intercellular “cement” of the stratum corneum - cholesterol and free fatty acids.

In addition to exvivo experiments, computer modeling of the basic properties of pseudoceramides was carried out in comparison with natural ceramides (EOS, EOP, EON), including the surface area and volume of the molecule, the distribution coefficient between the polar and non-polar phases, etc. The performance of pseudoceramide 14S24 confirmed that it can be used as a replacement for ceramides in the composition of intercellular “cement”. The regenerative properties of pseudoceramide M-palmitoyl-4-hydroxy-1_-proline (Bio 391) were studied. Its effectiveness was compared with emulsions containing ceramide 2 or ceramide 3. After 24 hours of topical skin exposure to 2% SLS, TEWL and skin erythema were recorded, and all three substances had similar effects in reducing skin water loss. To find the optimal therapeutic concentration of pseudoceramide Bio 391, dose-effect relationships were built, and it turned out that moisture loss and skin redness are most effectively reduced at concentrations of 1.0 and 0.5%, respectively. In areas treated with pseudoceramide, TEWL was reduced by 36% compared to placebo (blank) emulsion treatment, and erythema scores were 25% lower compared to controls.

The anti-inflammatory effect of pseudoceramide is an important point. It is known that the regeneration of the skin barrier function is inhibited in the presence of inflammation. When pseudoceramide Bio 391 was used together with HA-bisabolol, a synergistic effect was observed in reducing erythema. Effective reduction of redness was observed with 0.1% pseudoceramide and 0.1% bisabolol.

Currently, natural ceramides are rarely used in dermatotropic preparations. On the one hand, as ingredients they are too expensive, on the other hand, there are a number of technical difficulties when included in recipes. Instead, semi-synthetic or synthetic ceramides are used that are free of these disadvantages. A number of independent studies have confirmed that these compounds are one of the most promising classes of cosmetic ingredients.

An interesting analysis of the fine molecular structure of the intercellular “cement” was carried out using small-angle X-ray diffraction. It turned out that the lipids of the stratum corneum form two crystalline lamellar phases, distinguished by periodicity (6.4 and 13.4 nm). The last phase - called the long period phase (LPP) - is especially important for the operation of the barrier. The FDP is formed by three layers: two wide (5 nm wide) containing ceramides, and one narrow (3 nm) filled with a mixture of ceramides and cholesterol, forming a liquid crystalline phase (“sandwich” model). Consequently, the use in treatment of a mixture of ceramides capable of forming such structures can give very good results in restoring the stratum corneum, which has been confirmed experimentally.

Using wide- and small-angle X-ray diffraction, it was established that the spatial organization of sphingolipids in the mixture EOP/EOS/NP/NS/AP/hexanoylphytosphingosine/hexanoylsphingosine (see Fig. 1) is similar to that observed in intercellular “cement”. Regular local use of such a mixture will allow the delivery of all the substances necessary to restore the skin barrier “in place”, as was shown in experiments in vivo and in vitro using oil-in-water emulsions containing this mixture of lipids. The study measured TEWL, skin hydration and elasticity and recorded changes associated with the use of a sphingolipid mixture compared to a control emulsion (which did not contain sphingolipids). The results were encouraging: TEWL decreased by 4 units, skin hydration increased by 10 units, and skin elasticity increased by 8%. As a result, the mixture of sphingolipids used not only restored the stratum corneum of the skin and increased its hydration, but also increased the elasticity of the skin.

Conclusions about ceramides and their action

Ceramides are key structural elements of the stratum corneum, having a direct effect on skin permeability in both directions and on the “cementation” of corneocytes. Ceramides applied to the skin are able to restore defects in the intercellular structure caused not only by aging or exogenous factors (including cosmetic procedures such as peeling, dermabrasion, mesotherapy), but also by skin diseases such as atopic dermatitis or psoriasis. The restorative effect is especially pronounced when using mixtures in which ceramides are combined with other components of the intercellular “cement” of the stratum corneum. It is important to maintain clear proportions between the individual components of the mixtures, apparently in order to, to one degree or another, reproduce the composition of the intercellular matrix and, consequently, its structure.

Currently, natural ceramides are rarely used in dermatotropic preparations. On the one hand, as ingredients they are too expensive (they are difficult to isolate and obtain in the required industrial quantities), on the other hand, there are a number of technical difficulties when included in formulations. Instead, semi-synthetic or synthetic ceramides are used that are free of these disadvantages. A number of independent studies have confirmed that these compounds are one of the most promising classes of cosmetic ingredients.

Cosmetics based on ceramides are especially recommended for restoring skin after damaging aesthetic procedures, as well as for caring for dry skin with a damaged barrier. It is a wonderful example of introducing fundamental knowledge into practice and embodies corneotherapeutic approaches that are becoming increasingly popular among dermatologists and cosmetologists.