Latest scientific evidence confirms, that air pollution contributes to premature skin ageing and may even be the primary cause of ageing in some cases. Especially for particulate matter and polycyclic aromatic hydrocarbons (PAHs) negative influence on skin integrity has been shown.
The natural stress-protection molecule Ectoin® is well known to strengthen the skin barrier function, to work against variable stressors such as UVA/UVB radiation, IR-A visible light or allergens, and for its anti-inflammatory activity. This study demonstrates the global protection and prevention efficacy of Ectoin from air pollution induced skin damage. Ectoin® is well suited for topical antipollution products targeting skin pigmentation and accelerated ageing as well as particle stressed and irritated skin.
Beside UV exposure, ambient pollution can be seen as one of the main contributors to premature skin ageing today. In the past years, several epidemiological and mechanistic studies concluded a connection between pollutants and accelerating wrinkles, pigmentation and generally worsening skin conditions. Depending on the level of pollution and pollutant concentration, their nature and the general condition of the skin, the negative effects of air pollution exposure differ. Current research suggests that each individual air pollutant most probably has a specific toxic action on the skin.1 Air pollutants may not only induce skin ageing but are also linked to causing or worsening skin conditions such as acne, atopic dermatitis, eczema and allergic reactions, telangiectasia or even skin cancer.2,3
The first study, showing that particulate matter (PM) may have negative impact on human skin was conducted by Vierkötter et al in 2010. In this epidemiological, crosssectional study with 400 women participating in the evaluation of skin ageing, the association between airborne particle exposure and extrinsic skin ageing, particularly pigment spot formation was shown for the first time.3 The results revealed the strongest association between exposure to soot and the formation of pigment spots. Soot is a mixture of carbon particles covered with polyaromatic hydrocarbons, so called PAHs. PAHs are among the most widespread organic pollutants and are frequently bound to the surface of combustion-derived PM including cigarette smoke.
Air pollution consists of various components, chemical substances and particles. These particles can have different sizes; common classifications are PM10 , PM2.5 , ultrafine particle (UP/UFP) or nanosize particles (UP or PM0.1). PM10 can penetrate into human nasal cavity, PM2.5 in bronchi and pulmonary alveoli, ultrafine particles into the lung tissue and even into the bloodstream. According to the WHO, ultrafine particles constitute over 80% of particulate matter, although their total mass is small in comparison to the mass of larger particles. More than 90% of the world population lives in areas with levels of pollution that are too high.4, 5
Depending on the size and depth of penetration of the particles, the effects on the skin health are different. Skin exposure to PAHs can cause oxidative stress and thus induce melanocyte proliferation, inflammatory diseases and even skin cancer. PAH and PM are known to bind with specificity to the aryl hydrocarbon receptor (AhR), modifying the expression of Cyp1A1 (cytochrome P450, family 1, subfamily A, polypeptide-1) and the release of POMC (pro-opiomelanocortin), MMP1 (matrixmetallopeptidase-1) and IL-6 (interleukin-6) resulting in inflammation, formation of pigment spots, collagen breakdown and wrinkles.1, 6
The clinical relevance of these scientific findings, showing the damaging impact of air pollution on human skin touches upon aspects of both prevention and therapy. Skin care and protection strategies, which do not include pollution protection, may need to be reconsidered.
Ectoin® is a safe and well-studied natural and multifunctional cosmetic active ingredient with global cell protection and repairing properties. It is formulated in numerous anti-ageing as well as sun protection products, where it is used to complete the efficacy of UV-filters on a cellular level. The amino acid derivate is furthermore approved for very sensitive skin conditions and is the main ingredient in medical devices for the treatment of allergies, atopic dermatitis, dry eyes or rhinitis. The use of Ectoin (now referred to by its chemical term ‘ectoine’) on children and infants is shown to be safe.
The stress-protection molecule, so called extremolyte, was discovered in 1985 as the self-defence and survival substance of microorganisms living in a salt lake in Wadi El Natrun (Egyptian desert) under extreme salinity, heat and UV-radiation.7
Ectoine protects and stabilises proteins, enzymes, nucleic acids as well as cell membranes, when applied to human tissues. It restores and stabilises the skin barrier and consequently increases the degree of skin hydration, which can be preserved for 7 days without further treatment.8, 9
Various in vitro, in vivostudies and clinical trials confirm ectoine activity, with regard to protection of Langerhans cells,10 protection from heat/IR-A, UVA/UVB11, 12 and visible light,13 inflammation reduction14 and treatment of atopic dermatitis.15
Furthermore, several clinical studies were conducted with ectoine for the development of an inhalation solution and other medical devices. The inhalation of an ectoine solution by patients suffering from pollution induced COPD resulted in the reduction of lung inflammation.16 Moreover ectoine has been described to act preventive against neutrophilic inflammation induced by environmental nanoparticles and showed a reduction on PM induced exacerbation of allergen sensation.17, 18, 19, 20
The following study will present data, which show that ectoine protects cells against the damaging stress of air pollution and thus prevents pollutant-induced skin ageing like wrinkle and age spot formation.
Methods and results: in vitro study
For thisin vitrostudy fresh human epidermal keratinocytes from female Asian and female Caucasian donors were used. Cells were untreated and pre-treated (24h) with 2 mM ectoine solution. Afterwards, cells were stressed with fine and ultrafine carbon black particles and different surrogates for authentic street particulate matter such as SRM 1650 and SRM 2975 (Table 1).
After the particle stress, the expression of POMC, MMP1 and Cyp1A1 mRNA was measured in keratinocytes by using real time PCR. POMC, MMP1 and Cyp1A1 are marker genes which can be activated by pollution particles.1
The results in Figure 1 show that fine and ultrafine carbon black particles and diesel particulate matter induced POMC, MMP1 and Cyp1A1 mRNA expression. POMC is known for melanogenesis stimulation in human melanocytes and to cause dark spot formations. It can therefore be used as a marker gene for pigmentation. MMPs play a role in collagenase and elastase breakdown in the extracellular matrix of the dermis and can be used as marker for wrinkle formation. Cyp1A1 mRNA expression induces oxidative stress in humanskin which results in inflammation or cancer.
Ectoine-protected keratinocytes significantly down regulated PM induced overexpression of marker genes. POMC mRNA expression is down regulated in all tested cases by 100% or close to 100%. In addition, ectoine also protected from upregulation of MMP1 and Cyp1A1.
In vivo study
To testin vivothe anti-pollution activity and efficacy of a cream containing the amino acid derivate, a specialised dermatological center in Germany was chosen. The study design (placebo controlled, randomised, double blind) is the most innovative, standardised in vivopollution test method currently available. Six volunteers applied the cream with placebo or 1% ectoine on volar forearm for 5 days twice daily. Furthermore, areas on the volar forearm were tested untreated and unstressed (negative control) as well as untreated and stressed with cigarette smoke (positive control). On day 5, skin was stressed with cigarette smoke as pollutant for 15 minutes to induce oxidative stress to the skin in a standardised pollution chamber system (Fig 2).
The protective activity of the test products was evaluated by analysis of barrier lipid oxidisation levels (measured by malondialdehyde, MDA) of ex vivosamples from the skin surface. MDA results from lipid peroxidation of polyunsaturated fatty acids and is one of the reactive electrophile species that cause toxic stress in skin cells and can therefore be used as a marker for air pollution induced damage.
Five days of cream application with 1% ectoine showed a positive effect. The pollution-induced MDA overexpression was 48% lower compared to placebo and 47% lower compared to untreated but stressed control. A clear trend towards efficacy in protection against pollution induced skin damage was observable.
Summary and discussion
Ectoin strengthens the skin barrier function and is capable to shield the skin from the whole spectrum of air pollution and allergens. This includes clouding metals and PAHs as well as all particle sizes (PM2.5, PM1 , PM0.1 and smaller) for a global, complete and instant protection and prevention of pollution induced skin damage and ageing.
Ectoin forms a so-called ‘Ectoin Hydro Complex’ around skin cells, thus protects the skin at cellular level. Particle induced damage will be prevented and repaired. Air pollution induced expression of POMC, MMP1 and Cyp1A1 in skin cells (Asian and Caucasian) are significantly reduced by Ectoin treatment. The protective activity of Ectoin-containing cream was evaluated in vivoby analysis of barrier lipid oxidisation levels from the skin surface. In conclusion, Ectoin is well-suited for topical cosmetic products for protection against pollution induced skin pigmentation, irritation and ageing.
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5. http://www.who.int/phe/health_topics/ outdoorair/en/, (website accessed on 30.11.2016) 6. Costa C, Catania S, De Pasquale R, Stancanelli R, Scribano GM, Melchini A. Exposure of human skin to benzo[a]pyrene: role of CYP1A1 and aryl hydrocarbon receptor in oxidative stress generation, Toxicology2010; 271(3): 83-6. 7. Galinski EA, Pfeiffer HP, Truper HG. 1,4,5,6Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid. A novel cyclic amino acid from halophilic phototrophic bacteria of the genus Ectothiorhodospira. Eur J Biochem1985 149 (1): 135-9. 8. Graf R, Anzali S, Buenger J, Pfluecker F, Driller H. The multifunctional role of ectoine as a natural cell protectant., Clin Dermatol.2008; 26(4):326-33. 9. Heinrich U, Garbe B, Tronnier H. In vivo assessment of Ectoin: a randomized, vehiclecontrolled clinical trial,Skin Pharmacol Physiol. 2007; 20(4):211-8. 10.BüngerJ,Degwert J,Driller H. The protective function of compatible solute Ectoin on the skin, skin cells and its biomolecules with respect to UV-radiation, immunosupression and membrane damage, IFSCC Magazine 2001 1-6. 11.Bünger J, Driller H. Ectoin: an effective natural substance to prevent UVA-induced premature photoaging, Skin Pharmacol Physiol2004; 17(5): 232-237.
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14.Grether-Beck S, Timmer A, Felsner I, Brenden H, Brammertz D, Krutmann J. Ultraviolet Ainduced signaling involves a ceramidemediated autocrine loop leading to ceramide de novo synthesis, J Invest Dermatol.2005; 125(3): 545-53.
15.Marini A1, Reinelt K, Krutmann J, Bilstein A. Ectoine-containing cream in the treatment of mild to moderate atopic dermatitis: a randomised, comparator-controlled, intraindividual double-blind, multi-center trial, Skin Pharmacol Physiol.2014; 27(2):57-65.
16.Unfried K, Krämer U, Sydlik U, et al. Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals, Int J Chron Obstruct Pulmon Dis.2016; 11(1): 2573—2583.
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