Neurocosmetics in Skincare—The Fascinating World of Skin–Brain Connection: A Review to Explore Ingredients, Commercial Products for Skin Aging, and Cosmetic Regulation
Abstract
:1. Introduction
Skin and Brain: A Psychobiological Concept
2. A Brief Overview: From Cosmetology and Cosmetic Functions to Neurocosmetics
- Anti-aging action: this refers 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 action: this includes ingredients that can capture and inactivate free radicals at the skin level, reducing the “oxidative stress”;
- Anti-wrinkle action: this concerns ingredients that counteract the onset of wrinkles;
- Depigmenting action: this includes ingredients that lighten the skin color;
- Eudermic action: this considers ingredients that invoke a feeling of wellbeing when applied on the skin;
- Eutrophic action: this refers to substances that nourish the skin and improve its appearance;
- Soothing, anti-redness action: 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 action: this refers to ingredients with eutrophic properties, promoting cell regeneration, and providing the necessary elements for skin development and maintenance over time;
- Toning, “lifting” action: 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 [1].
3. The Neurocosmetics
3.1. Towards Neurocosmetics and How to Understand It: A More in-Depth Insight about Skin Innervation and Neurotransmitters
3.2. Neurocosmetics, the Cosmetic of Neurotransmitters: The Brain and Skincare
- Directly on the cutaneous nervous fiber endings [9], as modulators of the neurotransmitter release [14]. Examples are the botulinum-like peptides that encourage facial musculature relaxation to obtain wrinkle-smoothing, and peptides that inhibit neurons, mainly used to make hypersensitive skin less reactive towards environmental stimuli (temperature changes, air humidity, smog, etc.) [9];
3.2.1. Feelings of Pleasantness and Wellbeing vs. Neurocosmetics
Psychocosmetics
Neurosciences
- Cellular Neurosciences study the behavior of nervous cells in vitro; these related experiments are usually performed by manufacturing companies on neurocosmetic functional ingredients;
- Behavioral Neurosciences study the cognitive (thoughts, memories, and other mental processes) and affective (emotions, feelings, and mood) behavior of individuals [11].
Neuroscience Applications in the Cosmetic Field
- Vital parameters such as heart activity recorded with ECG [64], respiratory activity/frequency, salivary samples for monitoring cortisol release [65,66] (i.e., the decrease in cortisol secretion in saliva after the use of a soothing cream should be observed) [56,67], thermography related to cutaneous blood flow (i.e., when blushing, etc.), the evolution of facial skin temperature under stress [64], and the electrical current perception threshold (CPT); the hyperexcitability of nerve endings (Aβ) increases with age, in which a threshold increase indicates a reduction of unpleasant excitability, (i.e., an improved state of wellness…) [64];
4. Neurocosmetic Ingredients
4.1. Neurocosmetic Ingredients for Combating Skin Stress
4.1.1. Skin Stress and the Stress Pathway: The Role of Cortisol
- 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);
Neurocosmetic Ingredients for Rebalancing Cortisol Levels in the Skin
4.1.2. “Neuro-Relaxing” Anti-Aging Ingredients
The β-Endorphins: A Strategy for Skin Wellness
Discovering Neurocosmetic Ingredients from Plant Extracts
4.1.3. Neurocosmetics as a Strategy to Combat Inflammatory Responses Related to Skin Stress
4.1.4. Intriguing Hints about Sleep-Related Beauty: The Melatonin Receptor MT1
4.2. Neurocosmetic Ingredients for Sensitive Skin
4.2.1. Neuro-Sensitization of the Skin
The Molecular Basis of Sensitive Skin: TRPV-1-Mediated Neuroinflammation
4.2.2. Providing Solutions for Sensitive Skin: Neurocosmetic Ingredients
4.2.3. Providing Solutions for Sensitive Skin: “Coolant” Neurocosmetic Ingredients
An Insight about the Skin Sensation: Warm and Cold Receptors
4.2.4. Soothing Neurocosmetic Products on the Market
4.3. Neurocosmetic Ingredients for Skin Aging
- Intrinsic (chronological) aging or chrono-aging.
- Extrinsic aging
4.3.1. Physiological and Morphological Characteristics of Aged Skin
4.3.2. Skin Neuro-Aging and Neurocosmetic Ingredients
- The protection of nerve cells in the epidermis by providing good support for other skin cells;
- The maintenance of good barrier function in order to improve skin hydration (in the epidermis, nervous cells could stimulate the activity of keratinocytes, enhancing the barrier function that, in turn, causes hydrated and protected skin);
- The firming of skin by preserving the lipolytic activity in adipocytes. In the hypodermis, nervous cells stimulated the adipocytes’ lipolytic activity, which decreases with aging. By protecting nerve cells, good skin firmness is ensured [290].
Rethinking Skin Aging by Modulating Senescence Marker Proteins: The Case of Progerin
Cell Communication Supports by Stimulating POMC-Related Receptor Expression
A Strategy to Combat Dark Spots and Skin Stress
The Youth Proteins: KLOTHO and FOXO
4.4. Biomimetic Peptides
4.4.1. Topical Peptides and Their Skin Permeability
- The physicochemical properties of the substance (pKa, molecular size, stability, binding affinity, solubility, and partition coefficient);
- The time necessary for the permeation;
- The integrity, thickness, and components of the skin, and the cutaneous metabolism;
- The site, area, duration of application, and local depot at the site of application.
- Molecular weight of less than 500 Da;
- Moderate log of partition coefficient octanol/water between 1 and 3;
- Melting point less than 200 °C;
- Reasonable aqueous solubility (>1 mg mL−1);
- Zero or few polar centers.
4.4.2. Delivery Systems for Peptides
4.4.3. Neurotransmitter-Affecting Peptides
- Pentapeptide-3 (Vialox) is a synthetic peptide derived from snake venom, which acts at the postsynaptic membrane level by following a tubocurarine-like mechanism of action [301,335,344,348]. It is a competitive antagonist of the nicotinic acetylcholine membrane receptor [21,403]. Indeed, it prevents the release of sodium ions (Na+) required for the depolarization and contraction of muscle fibers, leading to muscle relaxation [21,335,336]. Less frequent contractions of muscles result in thinner lines. Softened wrinkles and reduced skin roughness were observed during in vivo and in vitro studies performed for testing this product; the results showed that, after 28 days of twice-daily use, wrinkle depth was reduced by about 49% [21,335];
- Vanistryl®, commercialized by Galena and Lipotec [404], is a complex of the bioactive peptides acetyl tripeptide-30 citrulline and pentapeptide-18 [110,404]. If acetyl tripeptide-30 citrulline is a signal peptide [301,335,336], conversely, pentapeptide-18 is a neurotransmitter inhibitor peptide [335,336,348,405]. These peptides are used in formulations for wrinkle smoothing, and act synergistically, when applied to the skin, to modulate muscular tension and inhibit matrix metalloproteinases (MMPs) [110,406]. Vanistryl® protects the connective tissue from degradation, and rebuilds ECM and dermal components, conferring to skin the integrity and elasticity needed. Furthermore, it exhibits wound-healing and smoothness effects, and reduces skin tension. In vivo skin surface studies (tightness and drying), color studies, and skin elasticity analysis were performed to demonstrate a visible attenuation of stretch marks when Vanistryl® is used [110,404,406].
4.4.4. Botulinum Neurotoxin: The First Neurotransmitter Inhibitor Anti-Wrinkle Ingredient
4.4.5. Topical Peptidomimetic Ingredients as Alternatives to Botox
- Acetyl hexapeptide-3 and -8—synthetic peptides that, by mimicking the portion of SNAP-25, compete with it for the SNARE complex—were the first Botox-like ingredients brought to market by LIPOTEC, with the trade name Argireline® [425,426]. When this analog peptide replaces SNAP-25, the SNARE complex is destabilized, and the release of acetylcholine is inhibited, resulting in muscle contraction being significantly reduced [334,337,353,354]. It was scientifically demonstrated that Argireline® is a safe, effective anti-wrinkle ingredient [337,352,427], particularly suitable for eye care product formulation [345,354]. The results derived from clinical tests showed a wrinkle depth reduction of up to 16.9% within 15 days, and up to 27% within 30 days [395,396]. For performing these tests, a cream containing 10% Argireline® was applied twice daily around the eyes by women aged 44. Moreover, when a cream containing 2% Argireline® was applied in the periorbital area by women aged 35–45, a reduction in wrinkle volume (up to 20.6%) and length (up to 15.9%) was observed within 7 days. An improvement of the skin tone and the presence of fewer wrinkles are the final visible benefits [303,334,335,402];
- Inyline® peptide (Acetyl Hexapeptide-30) by LIPOTEC uses a novel cosmetic approach to reduce muscle contraction and expression wrinkles. It targets the agrin/MuSK post-synaptic pathway, behaving as a competitive antagonist of MuSK (muscle-specific kinase) at the agrin-binding site [428], inactivating the formation of the agrin/MuSK complex and preventing acetylcholine receptor (AChR) clustering—a requirement for triggering muscle contraction [330,429,430,431]. Agrin is a proteoglycan involved in the organization of the basement membrane architecture [432,433]. A specific form of agrin, released by motor neurons, was mainly studied for developing skeletal muscle fibers; it represents a signal for maintaining the acetylcholine receptors’ aggregation, ensuring the neuromuscular junction (NMJ)’s assembly [434,435]. In detail, the agrin, produced by the growing ends of motor neuron axons, binds to MuSK—a tyrosine kinase receptor required for the formation of the neuromuscular junction [429,430,435,436]. In vitro and in vivo experiments were performed to assess the ability of Inyline® to attenuate expression lines. During in vivo tests, 20 female volunteers aged 41–50 applied a cream containing 5% Inyline® peptide solution to the crow’s feet area twice daily for 28 days. The obtained results showed that the treatment decreased wrinkle depth by 14.9% [437];
- BONT-L Peptide Solution (palmitoyl hexapeptide-19) is a synthetic Botox-like peptide [438] by INFINITEC [334], able to inactivate SNAP-25 by inhibiting the formation of the SNARE protein complex [439,440]. As a result, the release of acetylcholine into the synaptic cleft is prevented [440]. Moreover, an in vivo study on 15 volunteers who used a 5% cream applied twice daily showed a reduction in periorbital area micro-reliefs of 38% in 28 days [334];
- Acetyl octapeptide-3, marketed as Snap 8 by LIPOTEC [441], is an elongated sequence of Argireline peptide [303,442]. This analogy allows Snap 8 to mimic SNAP-25 in order to compete effectively in the SNARE complex, obtaining a significant inhibitory effect. It is promoted as the “next-generation” Botox alternative. When used in a 10% cream applied twice a day for 28 days, a reduction in wrinkle depth around the periorbital area of up to 63% was observed [334,336,441,442,443].
- Pentapeptide-18 (Leuphasyl) by LIPOTEC mimics the physiological mechanism of enkephalins and, by blocking calcium channels in the neuron, inhibits catecholamine and acetylcholine release [21,301,405,445]. As a consequence, the inhibitory G-protein-coupled receptor activation occurs with a decrease in the neuronal cell’s excitability, preventing the neurotransmitter release [336]. Its Botox-like effects and its safe efficacy were demonstrated, observing the reduction in the depth of fine lines and wrinkles. Moreover, other interesting properties include its hydration ability and improvement of skin firmness and tone [301,445,446]. Recently, another aspect was also explored, widening pentapeptide-18 (Leuphasyl)’s cosmetic qualities. Park et al. (2020) modified the commercial anti-aging pentapeptide-18 by substituting the N-terminal L-tyrosine with D-tyrosine, or adding L/D-tyrosine at the C-terminus. The role in the melanogenesis process was clearly demonstrated, particularly in the case of Leuphasyl peptide analogs containing C-terminal D-tyrosine, adding whitening properties to a remarkable anti-aging cosmeceutical [446]. It was also well proven that pentapeptide-18, when in the presence of acetyl hexapeptide-3, shows a synergistic effect [110,301,334]. Many studies showed that a cream containing 5% Leuphasyl with 5% Argireline caused a reduction of wrinkles in the periorbital area from 25% to 47% within 28 days [334,402];
- Acetyl dipeptide-1 cetyl ester (Calmosensine™), by SEDERMA—a synthetic replica of the naturally occurring peptide in the body—provides an in vitro Botox-like activity for the reversible inhibition of muscle contractions [334,447]. More specifically, it stimulates the release of pro-endorphins by keratinocytes, leading to the stimulation of relaxation messengers in the skin [334]. As a whole, Calmosensine™ prevents the onset of wrinkles and expression lines by relieving muscular tensions [334,447]. Furthermore, Calmosensine™ plays an important role in modulating the cutaneous perception of unpleasant sensations—such as heat—improving skin comfort, as confirmed by in vivo studies [303,448]. Another important cosmetic property of the active acetyl dipeptide-1 cetyl ester is its ability to significantly upregulate epidermal barrier genes, as shown by the results in the work of Khmaladze et al. (2020). [449] Moreover, acetyl dipeptide 1 cetyl ester can significantly reactivate elastogenesis by upregulating some of the most important dermal genes associated with skin wrinkling, such as alpha-1 type I collagen, decorin, lysyl oxidase-like 1, and fibrillin-1. Additionally, it showed interesting anti-glycation activity and promoted proteasomal activity. Thus, acetyl dipeptide 1 cetyl ester is a promising active compound for skincare formulations, especially if an improved barrier function is essential [449].
4.4.6. Plant Extract Alternatives to Botox
4.4.7. In Silico Designed Botox-Like Peptides
5. Anti-Aging Neurocosmetic Formulations on the Market
- Suitable for mature skin types, Bo2Look Therapy MD estetic serum, elixir, and wrinkle relaxer are formulated with the patented neuropeptide XEP™-018 [478,479]. The latter is a non-invasive anti-aging ingredient alternative to Botox, indicated for smoothing mimic wrinkles by relaxing facial muscles [480]. The main component of this formulation is the Mu-conotoxin CnIIIC, a synthetic biomimetic peptide inspired by that of venomous marine cone snail (Conus consors) [442,480,481,482,483]. This peptide blocks both voltage-gated sodium channels (Nav 1.4) and nicotinic acetylcholine receptors (nAChR), performing its action as a neuromuscular transmission modulator [442,480,483,484,485,486]. It instantly relaxes expression wrinkles when used for formulating a cosmetic product, giving a smooth skin appearance. In fact, in vivo studies conducted on 33 volunteers using a product containing 3% XEP-018 showed a visible reduction in wrinkle depth and rugosity 2 h after a single application [480,483,487];
- NEURO GABA&NANA THERAPY MD serum, cream, peel, and neuro gaba lift mask consist of a combined lifting and peeling instant treatment that contains GABA (gamma-aminobutyric acid) and NANA (N-acetyl-5-neuraminic acid) neurotransmitters, and lactic acid [488]. The smoothing of furrows and improvement of skin tension (“freezing effect”), immediate filling of wrinkles (“plumping effect”), and skin moisturization (“hydro effect”) are the ensured visible effects. When low- and high-molecular-weight hyaluronic acid is added, it deeply and long-lastingly moisturizes the skin, fills wrinkles, and makes the skin firm and flexible [489].
- Biomimetic Therapy PRO line is an intense home care treatment for mature skin types that prevents and reduces the signs of aging. This product, thanks to the presence of Progeline™, Adipofill’in™, and hyaluronic acid, is proposed for the loss of defined face contour, skin laxity, and drooping eyelids. It improves skin elasticity and flexibility, firms, and lifts wrinkles [504].
6. Neurocosmetics: What about Regulation?
- Product type;
- Application site;
- Cosmetic purpose.
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Company/ Supplier | Product | Functionality Category | INCI | In Vitro/Ex vivo | In Vivo | Preservatives | Use Level | Formulation/ Processing | Features |
---|---|---|---|---|---|---|---|---|---|
Neurocosmetic ingredients for combating skin stress | |||||||||
Provital Group | Agascalm | Skin protection. | Propanediol (and) glycerin (and) Agastache mexicana flower/leaf/stem extract. | Inhibition and release of chemokines (up to 104% in vitro). Reduction of the LKB protein degradation preventing the release of NF-κB, responsible for the transcription of proinflammatory agents; migration of the transcription factor NF-κB to the nucleus (up to 70% in vitro). | Skin redness reduction (−10%); vasodilation decrease (−30%); skin hydration improvement (+6%), TEWL (−13%). | None | 1–3% | Liquid; water-soluble. | Vascular tonicity improvement; restoration of the barrier function for moisturized skin; skin radiance enhancement and skin tone improvement. Suitable for sensitive skin. |
Givaudan | Betaphroline | Body sculpting. | Aqua/water (and) butylene glycol (and) Tephrosia purpurea seed extract (and) phenoxyethanol. | Stimulation of β-endorphin release; adenylate cyclase activation; G3PDH inhibition; glycerol release. | Pain relief and improvement in the wellbeing of stomatodynia patients (oral application) (10%, D30; panelists’ evaluation. | Phenoxyethanol | 2–8% | Liquid; water-soluble. | Neurocosmetic and body shaping. |
Mibelle Biochemistry | Happybelle-PE | Skin conditioning; anti-aging; antioxidant. | Happybelle-PE (standard version): lecithin (and) Vitex agnus-castus extract (and) glycerin (and) ascorbyl tetraisopalmitate (and) tocopherol (and) olus oil/vegetable oil (and) cyclodextrin (and) alcohol (and) aqua/ water. Happybelle O (oil-soluble version): Vitex agnus-castus extract (and) Helianthus annuus (sunflower) seed oil. | Stimulation of cell activity; increase in type I and III collagen (in vitro). | Increase in skin hydration and firmness; decrease in wrinkle depth. | None | 1–2% | Liquid; water-soluble. | Reduction of fine wrinkles and deeper lines; stimulation of collagen production; improvement in skin radiance; plumping and lifting effects. |
Provital Group | Happy Skin | Anti-aging; antioxidant. | Glycerin (and) aqua/water, (and) Rhodiola rosea root extract (and) phenoxyethanol (and) potassium sorbate. Liposoluble version: Helianthus annuus (sunflower) seed oil (and) Rhodiola rosea root extract (and) Rosmarinus officinalis (rosemary) leaf extract. | Protection from free-radical-induced damage. | Increase in endorphin levels; enhancement of skin appearance. | Phenoxyethanol (and) potassium sorbate. No preservatives in the liposoluble version | 0.2–2.0% | Liquid; water-soluble. | Recommended to formulate facial, body, and hair care products. |
Givaudan | Neurophroline | Skin protection. | Aqua/water (and) propanediol (and) Tephrosia purpurea seed extract. | Inhibition of stress hormone cortisol release; stimulation of β-endorphin production; global activation of antistress genes (transcriptomic on keratinocytes and fibroblasts); activation of antistress proteins HMOX1 and NQO1 (proteomic on keratinocytes and fibroblasts); increase in HMOX1 and NQO1 expression in the epidermis (ex vivo). | Efficacy on stressed (polluted air) skin: skin luminosity improvement; skin redness reduction; improvement of global skin color (when used at 2%); dark eye circle reduction. | None | 0.1–2% | Liquid; water-soluble. | Overall skin stress control. |
Seppic | Sepicalm S WP | Protective agent; soothing agent; skin conditioning agent; skin moisturizing agent; sensorial modifier. | Sodium cocoyl amino acids (and) sarcosine (and) potassium aspartate (and) magnesium aspartate. | +48% production of ß-endorphins; Targets the key inflammation pathway (NF-κB): −32% of IL-6/-16% of IL-8; −78% of free radical induction (superoxide anion); −80% elastase inhibition; −100% hyaluronidase inhibition; −80% lipoxygenase inhibition. | Benefits on volunteers: skin water content is increased for up to 5 h after application (+15%); −7.4% redness after mechanical abrasion; −25% redness after solar erythema; −46% stinging sensation in 10 s. | None | 3% | Liquid; water-soluble. | Increased skin comfort for sensitive skin; suitable for sensitive skin. |
Seppic | Sepicalm VG WP | Skin lightening agent; soothing care agent. | Sodium palmitoyl proline (and) Nymphaea alba flower extract. | Double skin lightening action: inhibition of inflammatory pigmentation induced by cutaneous stress, and modulation of gene expression in the basal pigmentation (MIC1, MITF, tyrosinase) after 16 h. | Benefits on volunteers: 90% lighter skin; 91% more radiant; 94% lighter spots; 73% smaller spots. | None | 3% | Liquid; amphiphilic. | Suitable for sensitive skin. |
Neurocosmetic ingredients for sensitive skin | |||||||||
Rahn | Defensil SOFT | Anti-aging; anti-inflammation; anti-redness; antistress; couperose; soothing. | Propanediol (and) Albatrellus ovinus extract (and) citric acid. | Affinity to TRPV1 (in vitro); Functionally blocks the TRPV1 receptor (in vitro); Neuron-driven inflammation (in vitro) counteraction. | Reduction of skin discomfort and irritation; protection from heat stress and soothing of hyperalgesic skin; prevention of IR-induced barrier damage (in vivo). | None | 1–3% | Liquid; water-soluble. Processing: incorporation at temperatures < 50 °C. | Increase in the overall tolerance of the skin to irritants; prevention of the sensitization of TRPV1 receptors by blocking serotonin receptors; prevention of IR-aging by protecting from IR-induced heat stress. |
Givaudan | Mariliance | Skin protection. | Aqua/water (and) propanediol (and) Rhodosorus marinus extract. | Reduction of TRPV1 expression; inhibition of the expression of IL-1α, NRG, and NGF R, and reduction of NGF production; reduction of IL-1α synthesis; penetration of Mariliance in emulsion and validation of the results observed in vitro on IL-1α production (ex vivo). | Reduction of skin sensitivity (3%). | None | 1–3% | Liquid; water-soluble. Processing: incorporation at the end of the formulation under stirring or homogenization; can be heated for a short time < 80 °C. pH usage range: 2.0–10.0. | Neuro-soother; calming, anti-tightening. |
Lucas Meyer Cosmetics | Neutrazen | Soothing agent. | Water (and) butylene glycol (and) dextran (and) palmitoyl tripeptide-8. | Biomimetic of neuromediator (POMC) :reduction of the consequences of substance P release; inhibition of the release of IL-1-induced IL-8 production (in vitro). | Reduction of sensitive skin symptoms related to cutaneous neurogenic inflammation. | None | 0.3–2.5% | Liquid; water-soluble; colorless; pH usage range: 5.2–7.2. | Designed to prevent and reverse signs of neurogenic inflammation (redness and swelling); calms and soothes irritated skin caused by UV, immune reactions, and mechanical stress; helps to maintain and restore a normal skin sensitivity threshold; suitable for sensitive and intolerant skin. |
Givaudan | Ocaline PF | Skin protection. | Maris aqua (and) aqua/water (and) Cucurbita pepo seed extract (and) potassium sorbate (and) phenoxyethanol (and) citric Acid. | Inhibition of the mast cells degranulation (ex vivo) and histamine release induced by substance P. | Preventive effect on sensitive skin/stinging test (5%); soothing of irritated skin (10%, 60 min, 180 min, 24 h). | Potassium sorbate (and) phenoxyethanol | 3–10% | Liquid; water-soluble. | Prevention of sensitive skin by a neurocosmetic approach. |
Givaudan | Ocaline XP | Skin protection. | Maris aqua (and) aqua/water (and) Cucurbita pepo seed extract (and) citric acid (and) benzyl alcohol (and) potassium sorbate. | Inhibition of the mast cells’ degranulation (ex vivo). | Preventive effect on sensitive skin/stinging test (5%); soothing of irritated skin (10%, 60 min, 180 min, 24 h). | Benzyl alcohol (and) potassium sorbate | 3–10% | Liquid; water-soluble. | Prevention of sensitive skin by a neurocosmetic approach; soothes away neurogenic inflammation. |
Mibelle Biochemistry | Pinolumin | Antioxidant; energizing; radiance; anti-redness; whitening. | Standard version: Pinus cembra wood extract (and) alcohol (and) pentylene glycol (and) aqua/ water; Alcohol-free powder version, twofold concentrated: Pinus cembra wood extract (and) maltodextrin (and) aqua/water. | Inhibition of neuroinflammation (in vitro); inhibition of the function of TRPV1 (in vitro); anti-inflammatory activity: inhibition of the release of proinflammatory mediators (CGRP, IL-8, and PGE2) (in vitro); protection of collagen by inhibiting the UVA-induced MMP-1 production (in vitro). | Visible anti-redness effect; reduction of color irregularities; overall improvement of skin tone evenness. | None | 2% | Liquid; water-soluble. Incorporation: For cold processes, dissolve Pinolumin into the aqueous phase. In hot/cold processes, add during the cooling phase below 40 °C. Thermostability: temperatures of up to 40 °C for a short time will not affect the stability of Pinolumin. | Calms sensitive and irritated skin; visibly reduces redness and age spots; protects from the effects of environmental stress; suitable for sensitive skin. |
Mibelle Biochemistry | SensAmone P5 | Skin conditioning. | Pentapeptide-59 (and) hydrogenated lecithin (and) Butyrospermum parkii (shea) butter (and) phenethyl alcohol (and) ethylhexylglycerin (and) maltodextrin (and) aqua/water. | Inhibition of TRPV1 receptor activation (in vitro). | Instant reduction of skin reactivity following a single application; reduction of skin sensitivity. | None | 1–2% | Liquid; water-soluble. | Calms over-reactive skin; minimizes skin’s response to stress; reduces the itching sensation of sensitive skin; suitable for sensitive skin. |
Givaudan | Sensityl | Skin protection. | Water (and) Phaeodactylum tricornutum extract (and) pentylene glycol. | Epigenetic control of inflammation through exosomal communication; genetic control of skin soothing and calming (downregulation of a complete set of genes involved in anti-inflammatory and soothing activities); control of the acute phase of inflammation (reduction of immune cell recruitment); inhibition of immune cell recruitment (significant reduction of dendritic cells) (ex vivo 3%); reduction of proinflammatory signal through IL-8 inhibition (ex vivo 3%); reduction of pain sensation through TRPV1 expression reduction (ex vivo 3%); control of microbial proliferation (ex vivo 3%). | Protection of skin microbiota against sensitive skin conditions (3% vs. placebo), restoration and protection of sensitive skin (3%); improvement of cutaneous reactivity (3%). | Sodium benzoate (and) benzoic acid | 1–3% | Liquid; water-soluble. | Soothing; calming; neuro-soothing; skin microflora rebalancing. |
BASF | Skinasensyl LS 9749 | Soothing agent. | Liquid synthetic tetrapeptide: water (and) glycerin (and) coco-glucoside (and) acetyl tetrapeptide-15. | Binding on the µ-opioid receptor (in vitro); inhibition of the CGRP release by sensory neurons (in vitro). | Increase of the skin’s tolerance threshold. | Sorbic acid | 1–3% | Liquid; water-soluble. Processing: it is incorporated into the finishing process below 50 °C, or at room temperature for cold processing; colorless. | Inhibits the release of the CGRP neuromediator from sensory neurons; increases the skin tolerance threshold; specifically designed to soothe sensitive skin. |
BASF | Skinasensyl LS 9852 | Soothing agent. | Powder synthetic tetrapeptide: mannitol (and) sodium citrate (and) acetyl tetrapeptide-15. | Binding on the µ-opioid receptor (in vitro); inhibition of CGRP release by sensory neurons (in vitro). | Increase of the skin’s tolerance threshold (capsaicin, heat) (in vivo). | None | 0.3–1.0% | Powder; water-soluble; colorless. | Inhibits the release of the neuromediator CGRP from sensory neurons; increases the skin tolerance threshold; specifically designed to soothe sensitive skin. |
Seppic | Sepicalm S WP | Protective agent; soothing agent; skin conditioning agent; skin moisturizing agent; sensorial modifier. | Sodium cocoyl amino acids (and) sarcosine (and) potassium aspartate (and) magnesium aspartate. | +48% production of ß-endorphins; Targets the key inflammation pathway (NF-κB): −32% of IL-6/−16% of IL-8; −78% of free radical induction (superoxide anion); −80% elastase inhibition; −100% hyaluronidase inhibition; −80% lipoxygenase inhibition. | Benefits on volunteers: skin water content is increased for up to 5 h after application (+15%); −7.4% redness after mechanical abrasion; −25% redness after solar erythema; −46% stinging sensation in 10 s. | None | 3% | Liquid; water-soluble. | Increase skin comfort for sensitive skin; suitable for sensitive skin. |
Seppic | Sepicalm VG WP | Skin lightening agent; soothing care agent. | Sodium palmitoyl proline (and) Nymphaea alba flower extract | Double skin lightening action: inhibition of inflammatory pigmentation induced by cutaneous stress, and modulation of gene expression in the basal pigmentation (MIC1, MITF, tyrosinase) after 16 h. | Benefits on volunteers: 90% lighter skin, 91% more radiant, 94% lighter spots, 73% smaller spots. | None | 3% | Liquid; Amphiphilic | Suitable for sensitive skin |
“Coolant” neurocosmetic ingredients for sensitive skin | |||||||||
Givaudan | Evercool Skin | Cooling. | Menthyl PCA (and) Lactamide MEA (and) menthane carboxamide ethylpyridine. | Activation of cooling sensation receptor TRMP8. | Long-lasting cooling effect (2%, 30 min, 60 min, 120 min). | None | 1–4% | Water-soluble; soluble in alcohol; odorless. | Patented combination of Givaudan cooling activities; improved, long-lasting freshness. |
Salvona | HydroSal SalCool | Cooling; delivery systems/carriers. | Propylene glycol (and) hydroxypropyl Cellulose (and) methyl diisopropyl propionamide (and) menthyl lactate (and) ethyl menthane carboxamide (and) phenethyl alcohol (and) caprylyl glycol (and) ethylhexylglycerin. | The release kinetics of the ingredients are optimized and synchronized to result in continuous, long-lasting, enhanced refreshment. | In a consumer perception test, the intensity of the sensation from an aftershave balm containing HydroSal™ SalCool was compared to an aftershave balm containing free menthol at 1% loading: HydroSal™ SalCool lasted twice as long as the freementhol at the same strength. | None | 7.0–15.0% | Water-soluble; compatible with hydro-alcoholic formulations; odorless. Processing: incorporation to the water phase during production, or at the end of the process when the temperature is below 30 °C. | Suitable for sensitive skin; it can be incorporated in skin, lip, scalp, and hair care formulations. |
Neurocosmetic ingredients for skin aging | |||||||||
Lucas Meyer Cosmetics | Adipofill’in | Anti-aging; anti-wrinkle; skin conditioning; delivery systems/ carriers. | Aqua/water (and) propanediol (and) ornithine (and) phospholipids (and) glycolipids. | Activation of HIF-1α; increase in lipid storage in human adipocytes; decrease in fatty acids released from adipocytes. | Lipofilling-like effect; decrease in nasogenian fold depth and skin roughness. | None | 0.5–2% | Liquid; water-soluble; pH usage range: 4.5–6.0. Incorporation/processing: at the end of the formulation (< 40˚C). | Skin smoother, firmer, less tired, plumper and lifted; reduction of nasogenian folds. |
Biosil Technologies | Glistin | Anti-aging; antioxidant | Glutamylamidoethyl indole (and) aqua/water | Neurotrophic effect (NGF-like); neuro-cutaneous messenger; cutaneous neuroprotection: anti-apoptotic effect. | «Antistress» (cutaneous sensitivity). | None | 1% | Liquid; water-soluble; miscible with alcohols and glycols; colorless; pH usage range: 7.0. | Prevention of neurodegeneration. |
Biosil Technologies | Glutrapeptide | Slimming and firming agent; anti-aging; antioxidant. | Pyroglutamylamidoethyl indole (and) butylene glycol. | Enhancement of neurons’ ability to support lipolysis; synergy with caffeine for slimming effect; enhancement of fibroblast contractile ability together with NGF. | Skin appearance, firmness, density, and elasticity improvement after 28 days of treatment; amelioration of cellulite appearance after 28 days of treatment; overall slimming effect up to 4 cm for the arms, 6 cm for the waist, 4 cm for the abdomen, and 3.5 cm for the thighs. | None | 1–5% | Liquid; water-soluble; colorless; pH usage range: 6.0; miscible with alcohols and glycols. | Neuroprotection; neuroslimming; body firming; cell detoxification; prevention of neurodegeneration. |
Codif Technologie Naturelle | Lakesis | Anti-aging; firming. | Caprylic/capric triglyceride (and) Pistacia lentiscus (mastic) gum. | Activation of youth proteins KLOTHO and FOXO; reactivation of cellular detoxification processes; improvement of cellular activity; improvement of type I collagen synthesis by 47%; reactivation of fibrillin synthesis. | Redensification of the dermis; improvement of facial contours. | None | 0.2% | Liquid; liposoluble. Processing: stable up to 80 °C. | Lifting action on the oval face. |
BASF | Neurobiox | Anti-wrinkle; anti-aging; brightening agent. | Water (and) butylene glycol (and) pentylene glycol (and) Achillea millefolium extract (and) xanthan gum. | Improvement of the epidermal thickness (ex vivo); stimulation of epidermal differentiation (ex vivo); stimulation of synthesis: filaggrin, cytokeratin 10, MO-R1, and MC-2R receptors (ex vivo); dose-effect on the gene expression of MC-2R and MOR-1 receptors; effect on the protein synthesis of MC-2R and MOR-1; Stimulation of involucrin gene expression (in vitro). | Pore refining; skin brightening; skin softness; stimulation of epidermal renewal; wrinkle smoothening. | None | 0.5–2% | Liquid; water-soluble; colorless; low-pH tolerant; high-pH tolerant; cation compatible. | Support of cell communication by stimulating the expression of POMC-related receptors; improvement of epidermal differentiation; acceleration of skin renewal; improvement of skin softness, radiance, and visible reduction of the appearance of wrinkles and pores. |
Codif Technologie Naturelle | Neuroguard | Anti-aging; anti-wrinkle. | Glycerin (and) aqua/water (and) hydrolyzed algin | Increase in the production of neuroprotector sAPPα by 87% (in vitro); protects the communication between nerves and fibroblasts from the toxicity of neuro-aging and preserves fibroblasts’ activity (in vitro); protection of the extracellular matrix from the toxicity of neuro-aging (in vitro); protection of the synthesis of collagen and elastin from neuro-aging toxicity (in vitro). | Reduce the volume and area of crow’s feet wrinkles. | Neuroguard P: phenoxyethanol; Neuroguard G: preservative-free. | Neuroguard P: 1.5%; Neuroguard G: 3% | Liquid; Water-soluble; Processing: incorporation at less than 50 °C. | Protection of neurons from neuro-aging; prevention from fibro-aging; decrease in wrinkle depth. |
Codif Technologie Naturelle | Neurolight.61G | Skin lightening. | Glycerin (and) water (and) Pancratium maritimum extract. | Inhibition of POMC expression and intracellular melanin synthesis (in vitro); reduction of the melanocyte dendricity and the synthesis of receptors for substance P (in vitro); inhibition of the effects of substance P on the export of melanin (in vitro); inhibition of the synthesis and export of melanin (in vitro). | Reduction of the surface of the pigment spots; clarification of the pigmentation of dark spots without lightening the pigmentation of the skin. | None | 1.5% | Liquid; water-soluble. | Neurocosmetic treatment of dark spots. |
Lucas Meyer Cosmetics | Progeline | Anti-aging. | Glycerin (and) water (and) dextran (and) trifluoroacetyl tripeptide-2. | Reduction of progerin synthesis; inhibition of MMPs and elastase; increase in syndecans. | Improvement of cutaneous elasticity up to 93%; improvement of cutaneous firmness up to 82%; improvement of cutaneous viscoelasticity up to 42%. | None | 0.5–2% | Liquid; Water-soluble; Odorless; Colorless; pH usage range: 4–6; Processing: incorporation at the end of the formulation at a temperature of < 40 °C. | Exhibition of a remodeling effect and reduction of signs of aging: sagging and wrinkles; lifting effect on jawlines. |
Neurotransmitter-Affecting Peptides | |||||||||
---|---|---|---|---|---|---|---|---|---|
Company/ Supplier | Product | Functionality Category | INCI Name | In vitro/Ex vivo | In vivo | Preservatives | Use Level | Formulation/ processing | Features |
DSM | Vialox | Anti-aging; anti-wrinkle; myorelaxant agent. | Pentapeptide-3. | Competitive antagonist effect towards the acetylcholine receptors coupled with the enkephalin receptor and closure of the calcium channels, leading to muscle relaxation (in vitro); reduction of muscle contractions by 71% within 1 min after treatment, and 58% 2 h later (in vitro). | Decrease in wrinkle size (−49%) and skin roughness (−47%) after 28 days of application. | None | - | Powder; water-soluble. | A topical alternative to muscle relaxing injections; an intensive treatment for fighting expression lines. |
Galena; Lipotec | Vanistryl | Firming agent; delivery systems/carriers. | Water/aqua (and) caprylyl/capryl glucoside (and) lecithin (and) glycerin (and) Pseudoalteromonas ferment extract (and) acetyl tripeptide-30 citrulline (and) pentapeptide-18 (and) xanthan gum (and) caprylyl glycol (and) potassium sorbate (and) phenoxyethanol. | Inhibition of extracellular matrix (ECM) degradation (in vitro); modulation of acetylcholine release from neuron cell cultures by preventing the entry of Ca2+ into the neuron: attenuation of muscle contraction and relaxation of the muscle tissue surrounding striae (in vitro); increases dermal protein synthesis: type I collagen raised to 128%, type IV to 81%, and elastin to 31%, in 15 days (in vitro); increases fibroblast adhesion (125% in 5 h) and keratinocyte growth (36% after 48 h) (in vitro); enhancement of wound healing effect on keratinocytes (in vitro). | Improvement of the skin surface, dryness, and firmness; decrease in erythema (−18%); attenuation of stretch marks; improvement of the color of stretch marks. | Phenoxyethanol (and) potassium sorbate | 5% | Liquid; Water-soluble. Incompatibilities: oxidants and electrophiles. Processing: Incorporate in the aqueous phase in the final step of the manufacturing process. In the case of emulsion preparation, it should be added once the emulsion is formed. Generally, add at a temperature below 40 °C; pH usage range: 4.0–8.0. | Maintenance and improvement of the dermal structure; regeneration of thethe epidermis, reconstruction of the connective tissue by protecting and boosting dermal proteins; increase in skin elasticity. |
Topical peptidomimetic ingredients as alternatives to Botox | |||||||||
Lipotec | Argireline | Anti-aging; anti-wrinkle; myorelaxant agent. | Aqua/water (and) acetyl hexapeptide-8 (and) caprylyl glycol. | Modulation of SNARE complex formation (in vitro); modulation of catecholamine release in chromaffin cells (in vitro). | Reduction of expression of wrinkles (volume by 20.6% and length by 15.9%) in just 1 week, with a solution of Argireline peptide (2%). | None | Max 10% | Liquid; water-soluble; colorless. Processing: incorporation at the final stage of the manufacturing process, at a temperature below 40 °C.pH usage range: 3.0–6.0. | Reduction of wrinkle depth caused by the contraction of muscles of facial expression, especially on the forehead and around the eyes, after 1 week. |
Lipotec | Argirelox | Anti-aging; anti-wrinkle; myorelaxant agent. | Aqua/water (and) glycerin (and) acetyl hexapeptide-8 (and) pentapeptide-18 (and) citric acid (and) caprylyl glycol. | Modulation of glutamate release (in vitro). | Reduction of expression lines in frontal and periorbital regions, prolonging the effects of BoNT-A even after 6 months. | None | 10% | Liquid; water-soluble. Incompatibilities: oxidants and electrophiles. Processing: incorporation in the aqueous phase of emulsions and gels in the final step of the manufacturing process.When preparing the emulsion, it should be added once the emulsion is formed at a temperature below 40 °C;colorless; pH usage range: 3.0–8.0 | Muscle relaxation by modulating acetylcholine (ACh) release; smoothing effect on expression lines by modulating the SNARE complex and calcium channels; reduction of reappearance of expression lines in the crow’s feet area. |
Infinitec | BONT-L Peptide Solution | Anti-aging; anti-wrinkle; myorelaxant agent. | Water/aqua (and) palmitoyl hexapeptide-19. | SNARE protein complex inhibition by 30%. | A cream containing 5% BONT-L Peptide was tested for 28 days on 15 volunteers; an average reduction of 38% of macro-relief of human skin. | Phenoxyethanol | 3–5% | Liquid; water-soluble. | Muscles’ relaxation by minimizing the release of acetylcholine, and consequent wrinkle reduction, in 4 weeks. |
Infinitec | BONT-L Peptide Powder | Anti-aging; anti-wrinkle; myorelaxant agent. | Dextran (and) palmitoyl hexapeptide-19. | SNARE protein complex inhibition by 30%. | A cream containing 5% BONT-L Peptide was tested for 28 days on 15 volunteers; an average reduction of 38% of macro-relief of human skin. | None | 3–5% | Powder; water-soluble. | Muscles’ relaxation by minimizing the release of acetylcholine, and consequent wrinkle reduction, in 4 weeks. |
Sederma | Calmosensine | Anti-Aging; anti-wrinkle; skin moisturizer; soothing agent; smoothing agent;cooling agent. | Butylene glycol (and) aqua/water (and) laureth-3 (and) hydroxyethyl cellulose (and) acetyl dipeptide-1 cetyl ester. | Stimulation of the release of pro-endorphins by keratinocyte; progressive reduction in muscle contraction, with levels as low as 1 ppm leading to total muscular inhibition within 2 h (in vitro). | Modulation of the cutaneous perception to lessen unpleasant sensations; reduction of the perception of heat. | None | 3% | Liquid; water-soluble. Processing: incorporation at room temperature. | Enhancement of skin comfort; relief of tension to help prevent the onset of wrinkles and expression lines. Suitable for sensitive skin |
Lipotec | Inyline | Anti-aging; anti-wrinkle; myorelaxant agent. | Aqua/water (and) acetyl hexapeptide-30 (and) arginine (and) caprylyl glycol. | Reduction of AChR clustering, a key step in the post-synaptic functionality of the neuromuscular junction (NMJ) (in vitro). | Decrease in wrinkle depth of up to 14.9%. | None | 5% | Liquid; water-soluble. | Attenuation of expression wrinkles. |
Lipotec | Leuphasyl | Anti-aging; anti-wrinkle; myorelaxant agent. | Aqua/water (and) glycerin (and) pentapeptide-18 (and) caprylyl glycol. | Modulation of glutamate release in a neuron cell culture(in vitro). | Decrease in depth of expression wrinkles (−11.64%). | None | 3–10% | Liquid; water-soluble; colorless; pH usage range: 2.0–5.0.Processing: incorporation at the final stage of the manufacturing process at a temperature below 40 °C. | Reduction of wrinkle depth caused by the contraction of muscles responsible for facial expression, especially in the forehead and around the eyes; has a synergistic effect with Argireline. |
Lipotec | Snap 8 | Anti-aging; anti-wrinkle; myorelaxant agent. | Aqua/water (and) acetyl octapeptide-3 (and) caprylyl glycol. | Inhibition of SNARE complex formation (in vitro); modulation of catecholamine release in chromaffin cells (in vitro); modulation of glutamate release in a neuron cell culture (in vitro). | Wrinkle depth reduction (63%). | None | 3–10% | Liquid; water-soluble; colorless. | By reducing muscle contractions, depth of fine lines and expression wrinkles is reduced within one month of treatment. |
DSM | Syn-ake | Anti-aging; anti-wrinkle; smoothing agent. | Glycerin (and) aqua/water (and) dipeptide diaminobutyroyl benzylamide diacetate. | Reversible antagonist of the muscular nicotinic acetylcholine receptor (mnAChR) (in vitro); inhibition of the Na+ uptake at the postsynaptic membrane to attenuate muscle cell contractions (in vitro); mimics/mimic waglerin-1 functionality. | Wrinkle reduction up to 52% after 28 days; measurable smoothing effect on 80% of the volunteers; measurable wrinkle reduction on 73% of the volunteers; reduction of wrinkle depth; smoothing of crow’s feet lines and forehead wrinkles. | None | 1–4% | Liquid; water-soluble. | Reduction of the appearance of mimic wrinkles. |
Infinitec | X50 Myocept | Anti-aging; anti-wrinkle; myorelaxant agent; cosmetic drone. | Powder form: lactic acid/glycolic acid copolymer (and) palmitoyl hexapeptide-52 (and) polyvinyl alcohol (and) palmitoyl heptapeptide-18.Liquid suspension: water/aqua (and) xanthan gum (and) lactic acid/glycolic acid copolymer (and) palmitoyl hexapeptide-52 (and)polyvinyl alcohol (and) palmitoyl heptapeptide-18. Additives: phenoxyethanol (and) caprylyl glycol (and) glycerin (and) glyceryl caprylate (and) phenylpropanol. | Reduction of the entry of calcium into the neuron, and inhibition of the formation of the SNARE protein complex; reduction of the neuronal exocytosis. | −20% wrinkle depth and length reduction in just 4 weeks. | Phenoxyethanol | 1% | Powder/liquid suspension; water-soluble. | Reduction of the expression lines. |
Plant extract alternatives to Botox | |||||||||
Gattefossé | Gatuline Expression | Anti-aging; anti-wrinkle; myorelaxant agent; smoothing agent. | Alcohol (and) water (and) Acmella oleracea extract. | Inhibition of muscle contractions (in vitro). | Smoothing efficacy on crow’s feet wrinkles. | None | 2–5% | Liquid; water-soluble; insoluble in oils; color: yellow to amber; odor: characteristic; pH usage range: 5.0–7.0. Processing: incorporation at cold temperatures. | Improvement of the eye contour by reducing expression lines and wrinkles. |
BASF | Myoxinol | Anti-aging; Botox-like agent. | Hydrolyzed Hibiscus esculentus extract (and) dextrin. | Inhibition of muscle cell contraction; free radical scavenging. | Wrinkle smoothening (1%). | None | 0.5–2% | Powder; water-soluble; insoluble in oils and fats; color: beige to pale yellow; odor: characteristic; pH usage range: 5.0–7.0. Processing: incorporate below 50 °C during the finishing process, or at room temperature for cold processing. | Anti-oxidant; smooths expression lines. |
Codif Technologie Naturelle | Stoechiol | Anti-aging; anti-wrinkle; Botox-like agent. | Caprylic/capric triglyceride (and) Lavandula stoechas | Wrinkle relaxation; stimulation of the division of keratinocytes in the basal layer to restore the density of the epidermis; promotes the production of the lipid cement involved in the restructuring of the stratum corneum. By increasing the expression of the adhesion proteins, Stoechiol increases the formation of inter-corneocyte links, promoting the reorganization of the corneocytes and, therefore, the cohesion of the corneal layer. Immobilization of the wrinkle coupled with a re-densifying and smoothing effect of the epidermis leads to a rapid and lasting reduction in the depth of expression lines. | Immediate anti-age effect from 0.25%. Within just 1 h, the amplitude of the cutaneous relief is smoothed; after 24 h wrinkles are less visible; 7 days after the end of treatment, wrinkles are visibly attenuated. An immediate anti-wrinkle action coupled with a long-term anti-age effect that continues beyond the end of treatment. | None | 0.25% | Liquid; liposoluble. | Reversible and repetitive inhibition of muscle contractions; redensifying and restructuring action on the epidermis; immediate and long-term reduction in the main wrinkle; immediate and long-term smoothing action on the roughness of the skin; decrease in the expression lines (visible within 24 h). |
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Rizzi, V.; Gubitosa, J.; Fini, P.; Cosma, P. Neurocosmetics in Skincare—The Fascinating World of Skin–Brain Connection: A Review to Explore Ingredients, Commercial Products for Skin Aging, and Cosmetic Regulation. Cosmetics 2021, 8, 66. https://doi.org/10.3390/cosmetics8030066
Rizzi V, Gubitosa J, Fini P, Cosma P. Neurocosmetics in Skincare—The Fascinating World of Skin–Brain Connection: A Review to Explore Ingredients, Commercial Products for Skin Aging, and Cosmetic Regulation. Cosmetics. 2021; 8(3):66. https://doi.org/10.3390/cosmetics8030066
Chicago/Turabian StyleRizzi, Vito, Jennifer Gubitosa, Paola Fini, and Pinalysa Cosma. 2021. "Neurocosmetics in Skincare—The Fascinating World of Skin–Brain Connection: A Review to Explore Ingredients, Commercial Products for Skin Aging, and Cosmetic Regulation" Cosmetics 8, no. 3: 66. https://doi.org/10.3390/cosmetics8030066