Neurocosmetics – How cutaneous nervous system impacts accelerated aging and tissue regeneration

Cortisol plays a complex role in skin health with effects ranging from positive to negative depending on exposure context and duration. It is triggered by stress, air pollution, blue light and various other factors.

Prolonged exposure leads to inflammation, accelerating skin aging by damaging collagen and elastin fibers. It can cause breakouts and adversely affect the skin barrier by reducing ceramide production, crucial for maintaining hydration and preventing water loss. This is definitely the hormone we want to keep under control, and at its lowest levels.

Beta-endorphin, on the other side – a neuropeptide produced in the skin – exerts anti-inflammatory effects, reducing redness and swelling associated with inflammation. It stimulates keratinocyte proliferation and migration, expediting wound healing and enhancing overall skin health. It increases the production of natural moisturizing factors, improving skin hydration and preventing dryness.

Now, envision the prospect of reducing cortisol levels by up to 80% and increasing beta-endorphin levels fourfold… Are you there yet? Can you see it? Then welcome in the world of LAST.

The most innovative approach to functional skincare

The term „neurocosmetics” was first officially used in 2007, during the annual meeting of North American Society of Cosmetic Chemists. It is based on the approach known as NICE (Nervous, Immune, Cutaneous and Endocrine systems) and Traditional Chinese Medicine. It develops the concept that both brain and skin may be influenced by the ingredients that activate many processes of cellular protection and regeneration, either soothing or stimulating, reducing inflammatory and unwanted reactions or modulating certain receptors (p.e. defensive cellular nets) – in consequence accelerating or slowing down the pace of the aging process. “Neurocosmetics are nontoxic, bioactive topical products that contain ingredients designed to work at a neurological level, and not elsewhere” – Vito Rizzi.

Multidimensional spectrum of neurocosmetics’ activity

Neurocosmetics aim to preserve, over time, the physiological and functional skin characteristics of the area where they are applied. Following the complex research by V. Rizzi, J. Gubitosa, P. Fini, P. Cosma published in Cosmetics 2021, the broad, multidimensional spectrum of neurocosmetics’ activity, can be divided into different types of action:

• Anti-aging: referring to all ingredients that – via different pathways – combat the skin aging processes, preventing and fighting the signs of aging, revitalizing senescent skin, promoting the elimination of toxins, improving microcirculation, and reducing the number and the depth of wrinkles;
• Antioxidant: ingredients that capture and inactivate free radicals at the skin level, reducing the “oxidative stress”;
• Anti-wrinkle: ingredients that counteract the onset of wrinkles;
• Depigmenting: ingredients that lighten the skin color;
• Eudermic: ingredients that invoke a feeling of wellbeing when applied on the skin;
• Eutrophic: this refers to substances that nourish the skin and improve its appearance;
• Soothing, anti-redness: exhibited by ingredients able to soothe pain and reduce skin redness in cases of mild inflammation, counteracting irritation, and bringing relief to stressed skin;
• Regenerating: ingredients with eutrophic properties, promoting cell regeneration, and providing the necessary elements for skin development and maintenance over time;
• Toning, “lifting”: this concerns ingredients that restore skin tone and firmness by acting at both the epidermis and dermis levels, encouraging the typical turgor of young and healthy skin.

Raising beta-endorphin level in skin

Beta-endorphin is a peptide neurotransmitter produced in the central nerve system, where it causes an analgesic effect. It reliefs pain, produces euphoria, reduces stress and strengthens the immune system. By acting on the central and peripheral opioid receptors, β-endorphins inhibit the transmission signals via nervous cells from the source of the pain (nociceptor) to the spinal cord. Thus, endorphins, due to their connections with the brain’s “pleasure centers”, generate euphoric feelings when binding to the opiate receptors. Moreover, β-endorphins also bind their receptors to immune system cells; they seem to be involved in the fine-tuning of the immune response.

It was recently confirmed by several research groups – that betaendorphins are produced also in skin cells and do improve it’s appearance. They can not only release the neurotransmitters giving sensation of pleasure, well-being and relaxation but are also involved in accelerating tissue regeneration, redensifying skin and wound healing. They enhance the barrier function of the skin, increase its resistance to stress and in particularly to pollution. While beta-endorphines are usually synthesised in response to physiologic stressors like pain or during exercise – inducing betaendorphin biosynthesis means actually activating it without the external factor.

Our active ingredient derived from the Rhodiola rosea L. root, belonging to the family of Crassulaceae, stimulates the production of ß-endorphins in the skin due to two active compounds: Rosavins (Rosavin, Rosin and Rosarin) as well as Flavonoids and chlorogenic acids.

It induces ß-endorphin biosynthesis by stimulating central and peripheral receptors, thus improving general mood and physical condition (in vitro efficacy). Its antioxidant properties protects against free radicals-induced damage. Lishmanov et al. studied the effects of a Rhodiola rosea treatment by measuring Skin Repair Serum’s levels of ß-endorphin:

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Bigliardi et al. (2002) showed the involvement of the skin’s β-endorphins in communication with peripheral nerve endings. The authors reported that keratinocytes positive for β-endorphin staining are clustered around the terminal ends of afferent C-fibers, which signal the sensations of warmth, cold, or pain to the central nervous system. Moreover, the authors described the β-opiate receptor as being expressed in the dermis and epidermis nerve fibers. It has been supposed that keratinocytes can communicate directly with the nervous system due to the opiate receptor system; hence, this should open potential therapies for skin diseases—for example, atopic dermatitis and psoriasis.

Interacting with cannabinol receptors

The endocannabinoid system (ECS) is a complex system of molecules and receptor sites that influences and regulates a wide range of functions and processes in the central and peripheral nervous systems, including appetite and digestion, chronic pain, inflammation and immune system responses, mood, learning and memory, motor control, reproductive system function, stress, skin and nerve function. The ECS system is comprised of:

• Endocannabinoids- molecules produced in the human body to keep the internal functions running smoothly;
• Endocannabinoid receptors- sites throughout the body where endocannabinoids bind to signal the ECS needs to take action. There are two types of receptors: CB1, found in the central nervous system, and CB2, found in the peripheral nervous system;
• Enzymes- responsible for breaking down endocannabinoids once they have carried out their function.

Both receptors CB1 and CB2 are widely distributed in numerous organs and tissues within the body and have significant signaling and regulatory functions. CB2 activation supports healthy nervous and immune system function, while activating its counterpart (CB1) receptors can modulate mood, memory, or even perception of pain. While binding to the CB1 receptors positively influences many brain functions, research has shown that it may also have some unwanted psychoactive effects. This is why our focus is only on the CB2 receptor. One of our key ingredients – Copaiba oleoresin as well as Patchouli extract – are phytocannabinoids (produced by plant) containing high amounts of beta-caryophyllene, which has been found to bind selectively to CB2 receptors in the body. They are therefore capable of triggering an immune system response that prevents inflammation without the psychotropic effect which mediates the CB1 receptor. It assists with pain management, the digestive system, respiratory system, and overall cellular health. It is also neuroprotective and helps to calm anxiety.

Reducing stress, decreasing cortisol

Stress is the body’s response to a whole range of external and psychological factors that disrupt homeostasis. Pollution, UV radiation, blue light, insufficient sleep, social media, relationships, work-related worries, and the high number of working hours are just some of the everyday modern stressors. Stressful lifestyles have visible impact on the skin. Indeed, as reported in the literature, there are pieces of evidence that psychological stress could encourage some skin diseases—such as acne, psoriasis, dermatitis, or rosacea—or, in other cases, promote hair loss.

Cortisol is the stress mediator, also known as the stress hormone. It’s a steroid hormone, ensuring proper regulation of an organism. Under stressful conditions, cortisol is regulated by both the brain and keratinocytes. In keratinocytes, cortisol synthesis is controlled by two specific enzymes: HSD1 – Cortisol generator and HSD2 – Cortisol repressor.

When exposure to stress is prolonged, skin cells do not stop the production of cortisol. Disruption of the HSD1 & HSD2 expression balance by stress quickly increases cortisol synthesis.

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone into biologically active cortisol and, as a result, under conditions of stress, the levels of cortisol in the skin increase – and remain elevated – driving collagen to atrophy and reducing cell growth. In this regard, the breakdown of skin homeostasis takes place, inducing inflammation and a visibly tired look.

Only when a feedback mechanism is established does the body return to normal physiological conditions: the stress hormones and the related consequences are eliminated, restoring homeostasis. This is the field in which neurocosmetics could act.

Cortisol generated through everyday stress disrupts collagen and hyaluronic acid production by fibroblasts, which directly impacts skin’s radiance and hydration.

Slowing down the aging process

Over the years, significant anatomical and physiological changes at the skin level, which progressively decrease skin thickness, elasticity, tone and chromatic uniformity, are observed. Although the aging process is gradual, skin aging times and methods largely depend on individual characteristics. The nature of the main causes that affect aging are genetic and environmental; for this reason, intrinsic aging and extrinsic aging are distinguished, as well described in the literature. Extrinsic aging is age- independent, therefore can be influenced by us – and is associated with many features, including life behaviors, diseases, environmental pollution, and sunlight exposure (photo-aging). In particular, smoking, toxic substances, some drugs and UV rays induce the release of inflammatory mediators, the deactivation of the body’s natural defense systems, and the production of free radicals, with a consequent increase in the tendency for the manifestation of aging skin. Both beta-endorphin and cortisol have a visible impact on skin condition. Managing cortisol levels can prevent some of the negative effects on skin:

• Increased blood sugar levels, which promote “glycation” in the skin, damaging collagen and elastin. As a result, long- term aging and loss of the skin’s ability to fully bounce back are accelerated;
• Due to the strong catabolic effect of cortisol, the degradation of dermal proteins occurs;
• Skin dryness due to the reduction in the production of hyaluronic acid—a natural moisturizer for our skin, associated with an increase in transepidermal water loss (TEWL);
• Increase in the appearance of fine lines and wrinkles, thinning skin, reduced elasticity;
• Less effective skin barrier repair. Furthermore, elevated concentrations of cortisol can disrupt epidermal cohesion.

Neuroactive ingredients at LAST

To influence and enhance particular neurological states, we infuse our formulations with different neuroactive ingredients, carefully combined with key performing substances. This art enables us to develop truly potent mixtures.

In our signature Skin Repair Serum, we used Rhodiola Rosea root extract which is a powerful antioxidant, simultaneously clinically proven to stimulate the production of beta-endorphins (raising their level in skin more than 4 times!). We combined it with Copaiba oleoresin containing large amounts of beta-caryophyllene that interacts with cannabinol receptors in the body, also releasing beta- endorphin, with Frankincense extract used in Ayurvedic and Chinese medicine as well as with Myrrh extract: grounding, balancing, promoting feelings of spirituality during mindfulness practices. Both Frankincense and Myrrh, as well as rosemary leaf extract that we use, have also anti-inflammatory effectiveness while Cassia Angustifolia – an Ayurvedic plant used in eastern medicine for over 1000 years – has clinically proven influence on dealing with stress, rebalancing the cortisol regulators level produced by keratinocytes, restoring the collagen and hyaluronic acid synthesis in fibroblast, as well as increasing hydration and radiance on the skin.

These ingredients are raising Hyaluronic Acid synthesis by +99% and Collagen synthesis by +13%:

Immediate and long-term hydration (ex vivo):

In vitro and ex vivo results:

All this neural activity is completed with a drop of aromatherapeutic neroli – used for relaxation, reducing stress, enhancing mood, vanilla – reducing nervous tension and lemongrass – relieving anxiety, stress and irritability. In the end, you not only look good, thanks to the biomimetic tetrapeptide, vitamins, bioferments or plant alternatives to retinol but you also feel good, experiencing the holistic (both physical and mental) idea of well-being.