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Beauty is now more than skin deep — the emergence of cosmeceuticals

Ever wonder if the beauty products that line the shelves in pharmacies really work? Hamde Nazar et al look at various anti-ageing products and examine their actions

Cosmeceuticals are cosmetic products with biologically active ingredients which claim to have medical or drug-like benefits, including anti-ageing effects. This article will look at the structure of the skin and at the components that are most closely implicated in the appearance of aged skin. We will also highlight current marketed topical ingredients and therapies used to bring about improvements in the aesthetic appearance of the facial skin. 

The science of skin

Collagen, an abundant protein, is the main structural component of the skin. It plays a key role in providing the structural scaffolding for cells, tissues and organs. In the face, collagen makes up 75 per cent of the skin and the presence of healthy collagen levels gives the skin its strength and durability, and is responsible for a smooth, plump and youthful appearance. Dermal fibroblasts make precursor molecules called pro-collagen, which is converted into collagen. The regulation of collagen production is under the control of the cytokine transforming growth factor-ß, which promotes collagen production,1 and a transcription factor, activator protein-1, which inhibits collagen production and up-regulates collagen breakdown by up-regulating enzymes called matrix metalloproteinases (MMPs).2

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Generation of reactive oxygen species (ROS) is also thought to play a major role in the ageing process. The free radical theory of ageing purports that ageing is a result of a lifetime accumulation of oxidative damage to cells resulting from excess ROS produced as a consequence of aerobic metabolism.3

Intrinsically aged skin (chronologically aged skin) is thin, relatively flattened, dry and unblemished, with some loss of elasticity and age-related loss of architectural regularity. General atrophy of the extracellular matrix is reflected by a decrease in the number of fibroblasts. Reduced levels of collagen and elastin with impaired organisation are primarily because of decreased protein synthesis affecting types I and III collagen in the dermis, with an increased breakdown of extracellular matrix proteins.4

Although the skin possesses extremely efficient antioxidant activities, during ageing ROS levels rise and antioxidant activities decline. The ROS are necessary in multiple mitogen-activated protein kinase pathways (pathways involved in directing cellular responses to stimuli) and the induction of AP-1, in turn, up-regulates expression of matrix-metalloproteinases, providing a plausible mechanism for the increased collagen degradation in aged human skin.5,6

Extrinsic skin ageing is primarily due to solar ultraviolet radiation and partly to other factors, such as infrared light, smoking and air pollutants.7

As well as depleting cellular antioxidants, exposure to UV radiation results in the production of ROS and the induction of AP-1, which causes increased MMP production, with subsequent increased breakdown of collagen.5,7 Increased breakdown and decreased production of collagen are the cornerstones of photo-ageing. Each UV insult induces a wound response with subsequent imperfect repair, leaving an invisible “solar scar”. Repetitive UV insults over a lifetime eventually lead to development of a visible wrinkle.8

The behaviour of skin during the ageing process and its response to extrinsic harmful affects have been widely studied and has been the focus within the cosmetic industry for decades in the search for topical ingredients, injectable substances or resurfacing treatments that increase the production or longevity of collagen. 

Prevention

The primary approach to preventing photoageing is by sun avoidance, the use of protective clothing and the proper use of sunscreen. Sunscreen use reduces the level of DNA damage and protect sun-exposed skin from erythema.9 The broad-spectrum properties of a sunscreen, as well as sun protection factor (SPF), play an important role in skin protection against ultraviolet A and ultraviolet B radiation.10

Heliocare Advanced Anti-ageing UV protection provides a high level UVA and UVB protection in a range of formulations with SPF 50. The formulation uses an extract from Polypodium leucotomos, a fern originating in Central America. It is originally an aquatic plant, which adapted to life on land, developing its own natural protective mechanisms against UV radiation and has been used for centuries in the treatment of dermatological conditions. Most of its beneficial effects are related to its antioxidant and ROS scavenging capability. It has also shown to be a protector during exposure to ROS and UV and may also contribute to the healing and regeneration of the skin that is required post-exposure.11

Lipid nanoparticles are being investigated as vehicles to enhance the skin penetration and prolongation of traditional UV protectants such as titanium oxide. Once enclosed in these solid carriers the achieved penetration and retention of the sunscreens have been improved compared with the standard oil-in-water emulsions.12,13

Therapy

On a molecular level, topical retinoids (chemical compounds that are chemically related to vitamin A) have been demonstrated to inhibit UV-induced inflammation mediated by AP-1. All-trans retinoic acid (carboxylic acid form of vitamin A) also acts to inhibit induction of the c-Jun protein (a precursor of AP-1) by UV radiation, thereby preventing increased MMPs that cause dermal damage.14,15 Clinical improvement occurs after several months of application. In addition, skin conditions continued to improve with application duration of at least 10–12 months. Clinical results are reversible after cessation of therapy and therefore long-term treatment three to four times a week is recommended to maintain clinical benefits.16

Retinol

SkinCeuticals Retinol is a refining cream with pure retinol that helps stimulate cell regeneration and build collagen to diminish the appearance of fine lines, wrinkles, and age spots from both intrinsic and photoageing. This cream should be used for advanced treatment of pre-conditioned skin.

CoenzymeQ10

The enzymatic and non-enzymatic antioxidants of the skin are depleted by UV-induced oxidative stress.17 Non-enzymatic antioxidants commonly found within the skin include ascorbic acid, coenzymeQ10 (CoQ10), vitamin E, vitamin C, niacinamide and beta-carotene. Although one would assume that topical application of creams would replenish these lost antioxidants, there are insufficient long-term studies proving the photo-protective properties of topical supplementation. However, recent studies have shown promising results for topical administration of CoQ10 and its ability to penetrate into the viable layers of the epidermis.18 It has been identified that topical application of CoQ10 may inhibit the production of interleukin-6, which is responsible for stimulating fibroblasts in the dermis to up-regulate MMPs production.19 Scientists have also postulated that CoQ10 positively influences on the age-affected anaerobic cellular metabolism that has been observed from skin biopsies of young and old donors by improving mitochondrial function.20 NIVEA Q10 Plus Antiwrinkle Day Cream offers a source of CoQ10 with SPF15 UVA and UVB protection.

Besides the topical application of antioxidants, endogenous photo-protection through dietary micronutrients is becoming more important because the biggest part of cumulative UV-dose is obtained in everyday life without topically applied sunscreens.21 Our understanding is that a range of these vitamins interact synergistically to cause an effect. However, there are no significant long-term studies available on topical antioxidants and supplementation of antioxidants proving photo-protective properties.

Polyphenols

Polyphenols are secondary plant substances consisting of polycyclic aromatic compounds bonded with hydroxyl groups. Several plant phenol compounds, such as green tea, grape seed, pomegranate, resveratrol and others, exhibit anti-inflammatory and antioxidant effects and are capable of modulating several signaling cascades resulting in effective prevention of cellular photo-damage and DNA repair mechanisms. Green tea extract from the leaves of the plant Camellia sinensis has been shown to also reduce photoageing and skin cancer.22,23 It is presumed that the UV-protective effects are due to enhanced interleukin-2-mediated DNA repair.24 Some of these extracts can be administered orally, as well as delivered topically. Garnier Moisture Match is the latest retail product that offers an effective moisturising cream containing naturally derived ingredients, including green tea extract, citrus extract, camellia oil and blue lotus extract, for the treatment of a range of skin types. However, there is scope for a greater range of products combining plant-derived and herbal products with molecular techniques to provide effective anti-ageing benefits.

Innovative therapies

Study results on the cutaneous effects of hormone replacement therapy or topical application of oestrogen have indicated increased elasticity, less severe wrinkling and increased collagen production than the control group.25,26 HRT appears to alter the basic components of the skin resulting in slowing of the ageing process in menopausal women.27 These findings suggest a cosmetic application of hormones could be applied in management of improving the appearance of aged skin.

Growth factors

Growth factors (GFs) and cytokines are known to mediate the complex interactions involved in wound healing. Early studies are showing that GFs relevant to wound healing may induce new collagen, elastin, and glycosaminoglycan formation and mediate angiogenesis. The aim behind harnessing these molecules is stimulation of fibroblasts and subsequent keratinocyte proliferation and resultant collagenesis and remodeling of extracellular matrix.28 A number of products containing a single or combination of growth factor are currently marketed for skin rejuvenation, for example, Neocutis Biocream Bio-restorative Skin Cream.

To date, Sundaram et al29 have claimed to show that topical application of products containing high concentrations of a physiologically balanced mixture of GF appears to reverse the signs of ageing. However, controlled studies of the stimulatory role of GFs have not been published. Since some malignant cells may have receptors for certain GFs, the risks of tumour genesis must be considered. But the concept of a treatment serum containing multiple growth factors, cytokines, peptides and a concentrated blend of antioxidants would be an ideal treatment for the treatment of photo-damaged skin.

The accumulation of DNA damage in the cell is thought to play an important role in the ageing process. Early data of the use of DNA-oligonucleotides (short nucleic acid sequences) on UV-irradiated skin has been shown to stimulate melanogenesis and enhance DNA repair capacity.30 Melanocyte production in the hypodermis (the layer under the skin) results in greater levels of melanin, which is responsible for absorption of UV-B light and reducing its penetration to deeper layers.31 Similar results have been shown by Hadshiew et al where the use of small DNA fragment thymidine dinucleotide induced photoreceptive responses in cultured cells and intact skin.32 Promising results mean there is potential for the development of topical application of nucleic acids in the treatment of photoageing skin.

Conclusion

A range of currently marketed cosmeceutical products have demonstrable anti-wrinkle, anti-ageing and photo-protective affects. The main advantages of these topical therapies are cost-effectiveness, effective photo-protective properties from UVA and UVB radiation, and avoidance of invasive procedures for the consumer. Ongoing research is identifying new ingredients and therapies that target specific processes in the skin ageing process so as to achieve a more tailored and enhanced means to fight the signs of ageing.


Hamde Nazar is a senior lecturer in pharmacy practice at Sunderland Pharmacy School, University of Sunderland.
Abdullah Nazar, BDS, is a general dental practitioner based in Hampshire who undertakes cosmetic dentistry as well as general facial cosmetic procedures, and is a clinical lecturer at King’s College London.
Mahdi Nazar is a doctor at North Cumbria University Hospitals NHS Trust
Correspondence to: Hamde Nazar (email hamde.nazar@sunderland.ac.uk)

Citation: The Pharmaceutical JournalURI: 11135579

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