Cosmeceuticals represent a marriage between cosmetics and pharmaceuticals. Like cosmetics, cosmeceuticals are topically applied, but they contain ingredients that influence the biological function of the skin. Cosmeceuticals improve appearance, but they do so by delivering nutrients necessary for healthy skin. Cosmeceuticals typically claim to improve skin tone, texture, and radiance, while reducing wrinkling. Cosmeceuticals are the fastest-growing segment of the natural personal care industry.[1] Consumers are always interested in maintaining a youthful appearance, and as the global population's median age increases, this market is increasingly expanding.

Cosmeceuticals are not subject to review by the Food and Drug Administration (FDA), and the term cosmeceutical is not recognized by the Federal Food, Drug, and Cosmetic Act. Although cosmetics and cosmeceuticals are tested for safety, testing to determine whether beneficial ingredients actually live up to a manufacturer's claims is not mandatory. In general, vitamins, herbs, various oils, and botanical extracts may be used in cosmeceuticals, but the manufacturer may not claim that these products penetrate beyond the skin's surface layers or that they have druglike or therapeutic effects. For cosmetic labels, no division between active ingredients and other ingredients is required; they are all listed together.

The most important botanicals pertaining to dermatologic uses, such as cosmeceuticals, include teas, soy, pomegranate, date, grape seed, pycnogenol, horse chestnut, German chamomile, curcumin, comfrey, allantoin, and aloe; only green and black tea, soy, pomegranate, and date have been studied to the extent that clinical trials for the treatment of parameters of extrinsic aging have been published.[2] Few botanical-based cosmeceuticals have uses that are supported by evidence-based science.

Top antiaging creams currently on the market were evaluated. These included Rosmarinus officinalis, Vitis vinifera (grape seed extract), citronellol, Limonene, Oenothera biennis (evening primrose), Glycyrrhiza glabra (licorice extract), Aframomum angustifolium seed extract, diosgenin (wild yam), N6 furfuryladenine (kinetin), and ergothioneine.[3] Randomized controlled trials are still needed, although some ingredients may have a scientific basis for their use.

Chemoprevention by oral or topical use of dietary or pharmacologic agents to inhibit or reverse the development of cancer is a possibility.[4] Potential cosmeceutical agents in this category include green tea, grape seed extract, vitamin E, and beta-carotene.

Some ingredients, like peppermint oil, are used in cosmeceuticals, personal hygiene products, foods, and pharmaceutical products for both flavoring and fragrance properties; these may produce an allergic contact dermatitis.[5]

The convergence of cosmetics and foods, so-called nutricosmetics, refers to oral supplementation of nutrients, marketed mainly for antiaging effects, ie, reducing wrinkles by fighting free radicals generated by solar radiation. Nutricosmetics include antioxidants such as carotenoids (beta-carotene, lycopene, lutein, zeaxanthin, and astaxanthin) and polyphenols (anthocyanidins, catechins, flavonoids, tannins, and procyanidins).[6]

Men have special skin care influenced by facial shaving and attendant irritation.[7] Maintaining hair softness and facial hydration postshaving may require moisurizers containing glycerine and be improved by ingredients such as niacinamide.

Also see Cosmetics.


The cutaneous permeability barrier is localized in the stratum corneum interstices and is mediated by the lamellar bilayers enriched in cholesterol, free fatty acids, and ceramides. Formulations containing skin-identical lipids have been suggested to facilitate a cascade of physiologic events in keratinocytes, normalizing damaged skin. When applied to the skin for an extended period, water can cause the excretion of cytokines. These proinflammatory molecules induce edema, vasodilation, and frank inflammation; therefore, water alone may alter both the structure and the function of the skin under some conditions. By the same token, moisturizers that make the stratum corneum softer and more pliant by increasing its hydration could be considered cosmeceuticals.

Intact protein-rich corneocytes, surrounded by the lamellar intercellular lipids, provide waterproof barrier protection for the body, damage to which can be treated by a variety of externally applied substances, such as ceramides, hyaluronic acid, licorice extracts, dimethicone, petrolatum, and paraffin wax.[8] Orange roughy (Hoplostetbus atlanticus) oil may be comparable to petrolatum in those with dry skin.[9]

A multilamellar vesicular emulsion ceramide – containing liquid cleanser and moisturizing cream plus fluocinonide cream 0.05% was found to reduce eczema duration, clearance time, and symptoms compared with a bar cleanser plus fluocinonide cream 0.05% in the treatment of mild-to-moderate eczema.[10]


Retinoids are possibly the most prevalent cosmeceuticals in the market. Retinoids are vitamin A derivatives present in all living organisms either as preformed vitamin A or as carotenoids. Vitamin A (retinol) is the prototype of all other retinoids and is necessary for proper growth, bone development, and integrity of mucosal and epithelial surfaces. In vitamin A deficiency, the eyes and the skin are severely affected. The conjunctiva and the cornea develop metaplasia and keratinization, leading to night blindness. The skin develops follicular hyperkeratosis or phrynoderma. The hyperkeratotic follicular papules are usually clustered around bony prominences, such as the elbows and the knees, but in severe deficiency, the papules can be found throughout the entire skin surface.

Early civilizations recognized the benefits of vitamin A in treating and healing night blindness with diets rich in liver. In the 1930s, the clinical manifestations of vitamin A deficiency were recognized, and the idea to use vitamin A in the treatment of skin diseases was initiated. The advent of synthetic analogs of vitamin A in the 1970s brought new interest into their biological activity, especially on the skin. Since then, vitamin A and its derivatives have been useful in the treatment of many skin disorders, including ichthyosis, acne, and psoriasis. A great amount of research has concentrated on its use as an antiaging compound as well as its use for other cutaneous disorders; therefore, today, vitamin A is recognized as comprising a magnitude of biological effects far beyond those on the cornea.

Vitamin A and its derivatives have 2 main functions: they act as antioxidants, and they activate specific genes and proteins. As antioxidants, they protect cells from oxidative damage by 3 different mechanisms: (1) scavenging peroxyl radicals, (2) quenching singlet oxygen, and (3) triplet-state sensitizers. Vitamin A also exerts a hormone-like effect on the skin, activating specific genes through nuclear receptors. The receptors bind to target sequences called hormone response elements on DNA and activate gene transcription. Retinoic acid receptors (RARs) bind all-trans retinoic acid, and retinoic X receptors (RXRs) bind 9-cis retinoic acid. Vitamin A and its derivatives inhibit lipid peroxidation; increase levels of alpha-tocopherol (vitamin E); and activate growth factors, oncogenes, keratins, and transglutaminases.

Histologically, vitamin A and its derivatives induce epidermal thickening, increase mitoses, differentiate keratinocytes, and reduce the number of sebocytes. The dermis shows increased amounts of glycosaminoglycans (GAGs) and anchoring fibrils. Structural changes underlying the cosmetic benefits include correction of epidermal atrophy, deposition of new collagen, generation of new vessels, and enhancement of mitogenesis. This enhanced mitogenesis promotes the shedding of melanin-laden keratinocytes, resulting in bleaching and subsequent depigmentation. The ability of topical tretinoin to improve the appearance of aged and photo-damaged skin by reducing wrinkles, decreasing laxity, bleaching hyperpigmented spots, and bringing about a smoother surface have been well studied and documented. Further remedial qualities of retinoids remain to be elucidated.

Importantly, the effectiveness of the non – FDA-approved cosmetic retinoids has been studied. Clinical and histological evidence suggests structural changes induced by excessive sun exposure can be partially reversed by the use of topical retinoids, such as retinaldehyde. They have been used for the treatment of photoaged skin with demonstrated beneficial clinical and histological effects.[11, 12] Because clinical correlates of these in vitro findings are not entirely convincing, with most studies being poorly constructed, the utility of these preparations for their stated uses is regarded by many authorities as marginal at best.

Hydroxy Acids

Hydroxy acids are likely the second most available cosmeceutical, and in low concentrations, they are found in mass-marketed cosmetic formulation. Hydroxy acids are organic carboxylic acids classified into alpha hydroxy acids (AHAs) and beta hydroxy acids (BHAs) according to their molecular structure.

AHAs range from simple aliphatic compounds to complex molecules. Many are derived from natural sources and are often referred to as fruit acids. The different AHAs include the following: glycolic acid, lactic acid, citric acid, mandelic acid, malic acid, and tartaric acid. Lactobionic acid, a newer AHA, may have advantages over the others.[13]

AHAs have been shown to decrease the signs of aging. The skin appears smoother and more uniform. The likely cause of these changes is the property of AHAs to enhance epidermal shedding. Some claim that AHAs increase the synthesis of GAGs, improve the quality of elastic fibers, and increase the density of collagen. Scientific evidence to support such claims is still incomplete and controversial.

BHAs are aromatic compounds. Salicylic acid is the reference BHA; it has dermolytic properties and helps in various xerotic and ichthyotic disorders. Other BHAs include 2-hydroxy-5-octanoyl benzoic acid, also known as beta-lipohydroxyacid (B-LHA), and tropic acid.

Despite their popularity, the exact mechanisms of action of hydroxy acids remain unknown and are largely controversial; however, at least one aspect of its biological activities may be attributed to the inherent acid strength of the compounds. Studies show that AHAs may increase sensitivity to UV radiation and that sunscreen application may be advisable when these products are used.


The skin is frequently exposed to a constant assault of endogenous and exogenous damaging agents. Agents such as UV radiation, drugs, air pollutants, and heat and/or cold are continually challenging the protective character of the skin. In addition to these external insults, the skin also has to cope with endogenous mitogens, most importantly reactive oxygen species (ROS) and other free radicals. These species are continuously produced during physiological cellular metabolism. To counteract the harmful effects of ROS, the skin is equipped with an antioxidant system to maintain equilibrium between the pro-oxidants, or damaging agents, and the antioxidants, or protective agents; these antioxidants intervene at different levels in the protective process.

Vitamin C

Vitamin C (L-ascorbic acid) is essential for life. Since its discovery in the 1930s, much work has been undertaken to elucidate its mechanisms of action. The roles of vitamin C are numerous. Vitamin C is necessary for the hydroxylation of procollagen, proline, and lysine. Deficiency results in purpura, keratotic follicles, and bleeding gums. Vitamin C is a water-soluble antioxidant that clenches free radicals and regenerates vitamin E. It is an important regulator of collagen expression stimulating its synthesis. Studies have shown that vitamin C levels on the skin are severely depleted after UV irradiation and that, histologically, vitamin C improves and normalizes the changes caused by photodamage. Thus far, however, studies on vitamin C have been few, and information about its effect in vivo is lacking.

Vitamin C has been used effectively to stimulate collagen repair, thus diminishing some of the effects of photoaging on skin. However, vitamin C is easily degraded by heat and light, which along with its high acidity, presents certain challenges for use in a multipurpose skin care formulation. A recently introduced synthetic collagen fraction offers greater stability and compatibility, along with improved efficacy.

Ascorbigen, a skin-permeable form of vitamin C, may have anticarcinogenic effects.[14] However, the underlying mechanisms regarding its potential antiaging and ultraviolet-protective properties have not been fully elucidated.

Vitamin E

Vitamin E (alpha-tocopherol) is the major lipophilic antioxidant in plasma, membranes, and tissues. The term vitamin E collectively refers to 8 naturally occurring molecules (4 tocopherols and 4 tocotrienols), all of which exhibit vitamin E activity. Its major role is generally considered to be the arrest of chain propagation in lipid peroxidation by scavenging lipid peroxyl radicals, hence protecting the cell membrane from destruction. Vitamin E topically applied before UV irradiation has been shown to reduce erythema, edema, sunburn cells, immunosuppression caused by sunlight, and DNA adduct formation. Palm oil esters-in-water nanoemulsions with vitamin E have been formulated as potential nanocosmeceuticals.[15]


Panthenol, the alcohol analog of vitamin B-5, is a water-soluble humectant commonly found in various commercial skin creams, lipsticks, lotions, and hair preparations. It is stable in the presence of oxygen and light but unstable in the presence of acids, bases, and high temperatures. Panthenol is converted in the skin to pantothenic acid, which is an important component on coenzyme A essential for normal cellular metabolism.

Lipoic acid

Lipoic acid is a unique free radical protector. It is fat and water soluble. Once lipoic acid crosses the cell membrane, it is broken down into dihydrofolic acid, which is also an antioxidant. Alpha lipoic acid also recycles other key antioxidants, such as vitamin C, vitamin E, and glutathione.


Ubiquinone, also known as coenzyme Q, is a lipid-soluble quinone derivative that is present in the mitochondria and is used to generate adenosine triphosphate (ATP), enhancing energy. It has been shown to decrease peroxidation of the low-density lipoproteins better than vitamin E.


Niacinamide (nicotinamide) is a basic amide that is a member of the vitamin B complex. It is used in the prophylaxis and treatment of pellagra. Niacinamide does not induce the peripheral flush that accompanies therapy with nicotinic acid. It is one of the newest vitamins in the marketplace. In vitro studies have shown anti–tumor activity on keratinocytes and suppression of UV-B photocarcinogenesis. The main reason for its surge in popularity is its stability. Niacinamide is stable in the presence of oxygen, acid, and high temperatures, and it is inexpensive to formulate. Most of its known effects are the result of increased epidermal turnover and exfoliation. Topical kinetin and niacinamide have been found to exert a synergistic antiaging cutaneous effect in people in the Republic of China.[16]


Topical preparations containing dimethylaminoethanol (DMAE) have been touted for their ability to improve skin firmness and to lift sagging skin. DMAE has been used as a dietary supplement and is associated with improving mental function and enhancing physical performance due in part to its ability to increase the neurotransmitter responsible for stimulating muscles. DMAE is able to diminish the cross-linking of proteins that occurs during aging, probably acting as a free-radical scavenger. It also increases the activity of these enzymes in a dose-dependent manner only in the particulate fractions glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase.

Spin traps

Free radical spin traps are species that react with reactive free radicals to produce fairly stable, unreactive free radicals, thus blocking the free radicals from damaging cellular components. Note the following:


Melatonin, a hormone secreted by the pineal gland, is known to have antimutagenic and oncostatic actions. This beneficial action of melatonin has been explained in terms of its ability to scavenge free radicals and to augment the activities of antioxidant enzymes. It has been shown to suppress UV radiation–induced erythema.


Catalase, an enzyme present in almost all cells of the human body, catalyzes the decomposition of hydrogen peroxide to water and oxygen. High amounts of this enzyme in the skin can impart antioxidative activity.


Glutathione is a tripeptide of glutamic acid, cysteine, and glycine. It is found in all active animal tissue. It is fundamental as an antioxidant, and significantly decreased amounts of glutathione are found after UV exposures.

Superoxide dismutase

Superoxide dismutase (SOD) is an enzyme that destroys superoxide (a highly ROS). SOD is a large molecule and has difficulty penetrating deep into the skin. In theory, once in the lower epidermis and dermis, SOD should decrease UV erythema and damage and act as an excellent antioxidant.


Kulkarni and colleagues have developed a water-soluble fennel extract with measurable peroxidase activity. In vitro studies have shown far better consumption of oxygen than tocopherol, and they have also shown antibacterial activity.


Resveratrol and polydatins are glucopyranosides found in many fruits and vegetables, the highest concentrations being found in grape skins, which synthesize these compounds in response to exposure to UV-A and UV-B and fungal pathogens. Biologic activities of these glucopyranosides include potent free radical scavenging activity, with cardioprotection and neuroprotection and inhibition of lipid peroxidation similar to that seen with vitamins C and E.

Drinking red wine in moderation has been linked with a reduced risk for lifestyle-related diseases such as cardiovascular disease and cancer, encouraging evaluation of resveratrol. In vivo evidence indicates it has protective effects in stress and disease models.[17]


Polyphenolic compounds (eg, catechins, flavonols, thioflavins, thearubigins), also known as epicatechins, are antioxidant in nature. These compounds, tested against human keratinocyte cells stressed by UV-B irradiation, showed high antioxidative properties. Many laboratories have shown that topical treatment or oral consumption of polyphenols inhibits chemical- or UV radiation–induced skin tumorigenesis in different animal models. It possesses anti-inflammatory activity. One of the major and most chemopreventive constituents responsible for the biochemical or pharmacologic effects is -epigallocatechin-3-gallate (EGCG) found in green tea. Genistein, the isoflavone found in soybeans, and pycnogenol, an extract of the bark of French maritime pine (Pinus pinaster), has been shown to significantly prolong tumor latency and to decrease tumor multiplicity with a potent ability to scavenge free radicals.


Several recent studies have shown that cysteine derivatives can protect against the negative effects of UV exposure. In particular, N- acetylcysteine (NAC) is shown to be an effective protector against UV-B–induced immunosuppression, to modulate the expression of some oncogenes and tumor suppressor genes, and to increase the amounts of intracellular glutathione. Glutathione is known to be critical in protecting the body's cells against oxidative stress; however, taking glutathione itself does not raise the levels of glutathione in the blood as effectively as taking its precursor n-acetyl-cysteine (NAC).


Allantoin promotes cell proliferation, aiding in the healing process. Allantoin has long been known to enhance the effectiveness and desirability of cosmetic creams and lotions by its action as a skin protectant. Allantoin has been incorporated into shampoos, lipsticks, shaving creams, suntanning products, bath foams, hair gels, baby powders, and various aerosol preparations. It has also been used in topical pharmaceutical markets. Most recently, allantoin has been used in various dental preparations, such as toothpaste and mouthwash. Allantoin has been called a cell proliferant, an epithelization stimulant, and a chemical debrider. It is said to clean away necrotic tissue, hastening the growth of new healthy tissue.


Furfuryladenine (Kinerase) is a natural plant growth factor that retards the aging process in plants. Cut leaves dipped in a solution that contains furfuryladenine remain green, while untreated leaves turn brown. It is marketed as the natural evolution of anti-aging treatment with similar effects in vitro on human skin cells as that in plants, helping to slow and reverse alterations that naturally occur in the cell-aging process.

Uric acid

In the past, uric acid was generally looked upon as merely an end product of purine metabolism. More recently, uric acid has become increasingly recognized as an important biological antioxidant. Scientific studies have demonstrated that uric acid is a potent physiological antioxidant, playing a major role in both extracellular defense mechanisms and intracellular defense mechanisms. Although the precise biochemical mechanism is not completely determined, uric acid appears to have a sparing action in plasma ascorbate, probably by complexing transition metals, such as iron and copper.


Carnosine (beta-alanyl-L-histidine) is a physiological dipeptide that can rejuvenate senescent cultured human fibroblasts. Carnosine has been shown to contain antioxidant, free radical- and metal ion–scavenging activities.

Depigmenting Agents

Hyperpigmentation, the most common and distressing condition afflicting a large subset of the population, requires dermatologists to familiarize themselves with cosmeceutical skin-lightening agents and corrective camouflage formulations.[18] Combination agents with sunscreen are often the most effective treatment available.

Hyperpigmentation is the result of an increased amount of melanin in the epidermis, the dermis, or both. This pigmentary change can be divided into 2 pathophysiologic processes: melanocytosis (increased number of melanocytes) and melanosis (increased amount of melanin). Depigmenting agents work best when melanosis or melanocytosis is restricted to the epidermis. Other methods of depigmentation being used are chemical peels.

Patients with Fitzpatrick skin types I-III benefit from local pigment lightening for the treatment of hormonally induced melasma and postinflammatory hyperpigmentation caused by acne and trauma, whereas those with Fitzpatrick skin types IV and darker may also seek therapy for pigmentary changes that occur around the eyes, in the intertriginous areas, following dermatitis, or with acne and trauma.[19] The criterion standard dermatologic agent for skin lightening had been hydroquinone, until its safety was questioned, which has encouraged use of alternative agents such as retinoids, mequinol, azelaic acid, arbutin, kojic acid, aleosin, licorice extract, ascorbic acid, soy proteins, and N -acetyl glucosamine.

Depigmenting agents can be divided into several groups:

Phenolic compounds include the following:

Nonphenolic compounds include the following:

Combination formulas include the following:


A phenolic thioether, N- acetyl-4-S- cysteaminylphenol is a another type of depigmenting agent. It claims to be more stable and less irritating to the skin than HQ and is specific to melanin-synthesizing cells. A monophenol compound tert-butyl-4-hydroxyanisole (mequinol) has been studied in the treatment of solar lentigines and related hyperpigmented lesions. The topical combination product containing 2% 4-hydroxyanisole/0.01% tretinoin solution (Solage) is well tolerated and superior to either active component.

Vitamin C

Vitamin C (L-ascorbic acid) and its derivatives are believed to act as reducing agents on melanin intermediates. They block the oxidative chain reaction from tyrosine/dihydroxyphenylalanine (DOPA) to melanin at various points.

Kojic acid

Kojic acid (5-hydroxy-2-[hydroxymethyl]-4-pyrone), a fungal metabolic product, has been increasingly used as a skin-depigmenting agent in skin care products marketed in Japan since 1988. Kojic acid inhibits tyrosinase activity; this finding has been attributed to its ability to chelate the copper required by tyrosinase.


Arbutin, or hydroquinone-beta-D-glucopyranoside, consists of HQ bound to glucose; arbutin is a naturally occurring beta-D-glucopyranoside derivative of HQ. Arbutin can inhibit melanogenesis by affecting the activity of tyrosinase rather than by killing melanocytes and decreasing the synthesis of melanin. Arbutin executes its activity by mimicking the amino acid tyrosine, the usual substrate of tyrosinase.

Azaleic acid

Azaleic acid (AZA) is a dicarboxylic acid originally isolated from Plasmodium ovale. It has been reported to have depigmenting effects, while showing no significant activity on normal skin. AZA is believed to selectively inhibit tyrosinase in hyperactive melanocytes.

Paper-mulberry compound

The compound 5-(3-2,4-[dihydroxyphenyl]propyl)-3,4-bis (3-methyl-2-butenyl)-1,2-benzenediol from paper-mulberry root bark has been shown to inhibit mushroom tyrosinase, to scavenge free radicals, and to depigment UV-induced hyperpigmentation in guinea pigs. Studies in humans show no irritation or sensitization.

Chemical peeling agents

Chemical peeling has become an established technique in treating cutaneous hyperpigmentation. Chemical peeling agents include glycolic acid, resorcinol, and salicylic acid.

Chemical compounds

Kligman's formula consists of 5% hydroquinone (HQ), 0.1% tretinoin, and 0.1% dexamethasone in hydrophilic ointment.

Pathak's formula consists of 2% HQ and 0.05-0.1% tretinoin.

Westerhof's formula consists of 4.7% N -acetylcysteine (NAC), 2% HQ, and 0.1% triamcinolone acetonide.

Other Cosmeceuticals


Because of the awareness of the environmental damage caused by industrialization, a trend has developed to use products with natural ingredients. No other ingredient can serve this purpose as well as botanicals. Botanicals are now part of every product in the market from cosmetics to soft drinks. Avocado, banana, lemon, and other similar botanicals are listed on thousands of labels. They exert their purported effects through the mechanisms of antioxidants, AHAs, BHAs, and other unclear properties.

Some examples of botanicals include chamomile, which inhibits the release of histamine and has anti-inflammatory properties, and ginseng, which stimulates the biosynthesis of proteins, RNA, and lipids. Ginkgo biloba extract was found to locally induce SOD and to catalase enzyme activity in the epidermis after topical application as well as to systemically increase the activity of both enzymes in the liver, the heart, and kidneys. Curcumin found in curry has anti-inflammatory activity by inhibiting leukotriene formation, inhibiting platelet aggregation, and stabilizing neutrophilic lysosomal membranes. Glycyrrhizin found in licorice roots inhibits proinflammatory activities of prostaglandins and leukotrienes. Capsaicin inhibits substance P, a peptide transmitter of the inflammatory process. Aloe vera has been shown to accelerate wound healing and to protect and soothe the skin.


Hyaluronic acid (HA), or hyaluronan, is the prototype of all other GAGs. Studies have demonstrated that decreased amounts are present in aged skin and that topically applied HA accelerates wound repair. Other studies have noted epidermal regeneration after the application of low molecular weight HA.


Lipolysis is mediated, in part, by beta-adrenergic receptors, which induces fat breakdown, and alpha2-adrenergic receptors, which inhibits fat breakdown. Agents that bind to these receptors may hypothetically serve a therapeutic effect on cellulite. Beta-adrenergic stimulators include theobromine, theophylline, aminophylline, caffeine, isopropylarterenol hydrochloride, and epinephrine. Alpha2-adrenergic inhibitors include yohimbine, piperoxan, phentolamine, and dihydroergotamine.



Papain, an enzyme found in the papaya fruit, chemically digests intercellular bonds. Papain has been studied in the treatment of hypertrophic scars, and it can be used to exfoliate keratotic skin.

Deoxyribonucleic acid (DNA) repair enzymes

UV-B radiation–induced cyclobutane pyrimidine dimers in the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that contribute to photocarcinogenesis. Lotions containing bacteria-derived DNA repair enzymes, and photolyase-containing liposomes have been shown to reduce the incidence of cancerous and precancerous lesions. When the bacterial DNA repair enzyme T4 endonuclease V is intracellularly delivered, it increases the rate of repair of sunlight-induced DNA damage in human cells.

Yarosh et al[20] showed that the topical application of a DNA repair enzyme to sun-damaged skin lowered the rate of development of actinic keratoses and basal cell epitheliomas during 1 year of treatment. Topical application of photolyase-containing liposomes to UV-B–irradiated skin and subsequent exposure to photoreactivating light decreased the number of UV-B radiation–induced dimers by 40-45%. Photolyase-induced dimer repair completely prevented UV-B radiation–induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that the topical application of bacterial DNA repair enzymes might be effective in dimer reversal, leading to immunoprotection and a decrease in photocarcinogenesis.

Growth factors

Growth factors are sold over the counter as a serum or cream for wound healing and antiaging. The efficacy of these compounded substances are not validated.

Epidermal growth factor

Epidermal growth factor (EGF) is found in bodily fluids. When EDG is bound to the epidermal growth factor receptor (EGFR), it stimulates epidermal growth and differentiation. It has been used in the treatment of burns and excision wounds, where it accelerates re-epithelization.

Transforming growth factor

Transforming growth factor (TGF) stimulates normal skin growth and cellular growth and repair. TGF exerts positive regulatory effects on the accumulation of the body's extracellular matrix proteins. TGF is also a mediator of fibrosis (repair tissue formation) and angiogenesis (development of new blood cells), and it promotes the healing of wounds.


Hormonal creams claim to be the most effective means to stop or slow the aging process by reversing the loss in tone and elasticity of the skin. Confirmatory evidence of this claim is yet to be published.


Some studies have shown anti-aging effects of estrogens. One investigation found that after 6 months of applying 0.01% estradiol and 0.3% estriol compounds, the elasticity, firmness, wrinkle depth, and pore sizes of the skin were markedly improved. On immunohistochemical analysis, significant increases of type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. Also, no systemic adverse effects were noted. However, better studies are needed before these agents are routinely used for their anti-aging effects.


Progesterone creams are being marketed as formulations that reverse the chemical changes that occur in collagen with aging and that normalize the immune system. Some manufacturers' claims also state that progesterone cream heals skin conditions, such as acne, psoriasis, rosacea, seborrhea, and keratoses. Other manufacturers claim that progesterone creams are a topical supplement for women who experience symptoms relating to premenstrual syndrome (PMS), menopause, or osteoporosis. None of these claims is supported by well-designed studies.


Topical application is quickly becoming the preferred method of testosterone administration. Theoretically, when topically applied, testosterone bypasses the stomach and the liver and does not cause an undesirable rise in estrogen. Manufacturers claim that testosterone creams have many benefits, such as memory enhancement, antidepressant effects, increased resistance to stress, and the ability to treat disorders associated with hypogonadism (eg, increased storage of fat, shrinkage of muscle mass). Recent studies have shown that testosterone gel applied to the skin once daily restored blood levels of the hormone in men with hypogonadism.

Growth hormone

Growth hormone (GH) and its mediator insulin-like growth factor-1 (IGF-1) are responsible for many effects on growth, development, immunity, and metabolism. Produced and secreted by the anterior pituitary gland in the brain, GH is released in pulses in response to signals from the hypothalamus. GH exerts anabolic effects throughout the body, favoring the growth of tissues, bones, and muscles. Studies have shown that the aging population has lowering levels of GH in the body, with resultant decreased lean body mass, fat deposits, immunity, and overall energy.

Botulinum A exotoxin

Botulinum A exotoxin is a neurotoxin produced by the bacterium Clostridium botulinum. This toxin is now being used by cosmetically oriented specialists for the treatment of a large variety of movement-associated wrinkles on the face and neck. As a simple and effective nonsurgical procedure, the injection of botulinum toxin A seems to be an effective method of eliminating crow's feet and wrinkle lines that are on the upper third of the face and producing temporary browlift. This form of temporary chemical denervation compliments the cosmetic practitioner's armamentarium. In addition, the use of botulinum toxin to block sympathetic innervation of eccrine sweat glands is proving to be valuable in treating hyperhidrosis of the axillae, palms, and soles.


Microcollagen pentapeptides

Fibroblasts in aged tissue produce less collagen than those in younger skin, but their capability to produce collagen is still present. Fibroblast collagen production has been reported to be stimulated by a pentapeptide fragment of the collagen molecule.

At the carboxyl-terminal end of the collagen molecule is a fragment that has been identified as a participant in the regulation of its own synthesis. Lys-Thr-Thr-Lys-Ser pentapeptide is a potent stimulator of collagen and fibronectin synthesis, which are­ both important components of the interstitial matrix.

Copper peptides

The copper-dependent lysyl oxidase (LO) plays a critical role in the biogenesis of connective tissue matrices by cross-linking the extracellular matrix proteins collagen and elastin. Levels of LO increase in many fibrotic diseases, while expression of the enzyme is decreased in certain diseases involving impaired copper metabolism.

Within the past decade, the gene encoding LO has been cloned, facilitating investigations of the regulation of expression of the enzyme in response to diverse stimuli and in numerous disease states. Transforming growth factor-beta, platelet-derived growth factor, angiotensin II, retinoic acid, fibroblast growth factor, altered serum conditions, and shear stress are among the effectors or conditions that regulate LO expression. Since the production of both collagen and elastin is reduced in aging skin and in skin exposed to ultraviolet light, copper peptides may be able to help produce new collagen and hence repair aged skin.

Antimicrobial agents

The use of antimicrobial agents in cosmetics and related toiletries has been rampant in recent years. It is increasingly found in baby oils, creams, and lotions to help prevent and control impetigo and milia; in deodorants, to inhibit microbial decomposition of perspiration; and in various scalp preparations, to inhibit microorganisms that are associated with seborrheic dermatitis.


This is the latest rage in the arsenal of antibacterial chemicals, included in detergents, dishwashing fluids, soaps, deodorants, cosmetics, lotions, creams, and even toothpaste. Triclosan (2, 4, 4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antimicrobial agent, routinely used in various personal care products. It is also incorporated into polymers through melt-mixing, with the aim of providing persistent antibacterial action on the surface of the polymer.


Chlorhexidine is effective against a wide range of gram-negative and gram-positive vegetative bacteria, yeasts, dermatophyte fungi, and lipophilic viruses. It is inactive against bacterial spores except at elevated temperatures.

Povidone iodine

This compound is soluble in water, forming a golden brown solution. Like iodine, the solution of the iodine complex is bactericidal and fungicidal. However, unlike solutions of iodine, it does not stain. The antiseptic action of povidone-iodine solutions is due to the available iodine present in the complex.

PCMX (para-chloro-meta-xylenol)

PCMX is effective against both gram-positive and gram-negative bacteria and fungal and yeast microorganisms. PCMX has been tested as safe for use in long-term wound care and is more effective on a broader range of microorganisms than the other antiseptics.

Hydrogen peroxide

In solution, hydrogen peroxide provides mechanical cleansing and some debridement of wounds by its effervescent action; however, it can cause ulceration of newly formed tissue and can create granulomas. It is toxic to fibroblasts and, therefore, should never be used as an aftercare solution for wounds.

Antidandruff preparations

Most preparations for the treatment of dandruff largely depend on antimicrobial agents for their therapeutic effect. One leading antidandruff lotion is a combination of benzethonium chloride and N- trichloroethyl mercapto-4-cyclohexene-1,2-dicarboximide. Biphenamine hydrochloride provides an excellent bacteriostatic antifungal property and local anesthetic action.

Zinc pyrithione

Zinc-2-pyridine-thiol-1-oxide is one of the most widely used antimicrobial agents, while lauryl isoquinolinium bromide and bislauryltrimethylammonium polythionate are 2 other popular agents. In addition to their antiseborrheic properties, 2,2'-thiobis-4-chlorophenol and diiodohydroxyquin also exhibit antiseptic qualities.


Antimicrobial substances, such as hexachlorophene, aluminum phenolsulfonate, and zinc peroxide, as well as various quaternaries, such as cetyltrimethylammonium bromide, alkyldimethylbenzylammonium chloride, and diisobutylphenoxyethyldimethylbenzylammonium chloride, have been used in antiperspirant and deodorant formulations.

Tyrothricin and neomycin have also been used in deodorant formulations. Studies have shown that neomycin alone or in combination with aluminum chlorhydroxide produces effective odor suppression, along with a significant increase in gram-negative organisms. Its effectiveness as a deodorant is essentially attributed to its exceptional suppression of gram-positive organisms.

Trichlorocarbanilide is a high-duty, wide-spectrum bacteriostatic agent also used in deodorants. It has lasting safe and stable bactericidal effect. It also has high effects on inhibiting and killing gram-positive, gram-negative bacteria, fungus, saccharomycetes, and virus.

Other antimicrobial preparations

Several diverse chemical substances are used in the therapy for various fungal infections, including fatty acids and their derivatives (eg, zinc, calcium, alkanolamine undecylenates), phenolics (4-halothymols), halogenated quinolines (iodochlorhydroxyquin), quaternary ammonium salts (hexadecamethylenebis-isoquinolinium chloride), and sulfur and sulfur compounds (zinc ethylene bis -dithiocarbamate). Phenol and polyphenol derivatives that are used in cosmetic formulations include hexylresorcinol, p- chloro-m- xylenol, o- phenylphenol, and chlorothymol. Quaternary ammonium compounds that are used in cosmetic formulations include benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, and cetyltrimethylammonium bromide.

Topical anesthetics and antipruritics

Specific local anesthetic agents are often found in a variety of topical drugs and toiletry products, such as hand and scalp lotions, foot preparations, and aftershave products, to relieve local discomfort and to reduce pruritus. The anesthetic agents are also found in formulations designed to be useful in diaper dermatitis, sunburn, and acne vulgaris.

Ethyl aminobenzoate

Ethyl aminobenzoate (benzocaine) has been a widely used local anesthetic; however, the increasing incidence of sensitization has prompted the introduction of noncaine anesthetics.

Benzyl alcohol

In creams, lotions, and ointments, benzyl alcohol at a 2% level provides effective local anesthetic effects and preservative qualities.

Diperodon hydrochloride

Diperodon hydrochloride and monohydrate are piperidine compounds in the class of N- substituted aminobenzenes. At approximately a 1% level, they provide local anesthetic effects and antipruritic actions.

Pramoxine hydrochloride

Pramoxine hydrochloride, which is reportedly more potent than cocaine, is used in topical preparations at concentrations of about 1%; however, the monohydrate salt is often preferred in some applications because it is not alkali sensitive, it is more soluble with various solvents, and it may avoid certain color changes or darkening in products that contain hydrochloride-sensitive components. Specific local anesthetic agents, such as benzocaine, pramoxine, and diperodon, exert their effects on mucous membranes and abraded, broken, or irritated cutaneous membranes. They are not effective on unbroken skin.


Menthol and related cooling compounds are widely used in products that range from common cold medications to toothpastes, confectionery, cosmetics, and pesticides. Menthol affects the nerve endings to provide a cooling antipruritic action.


Topical application of capsaicin is thought to deplete substance P from local sensory nerve terminals. In experiments on human skin, inflammation was induced by injection of substance P (SP) or histamine intradermally, UV irradiation, nonimmunologic contact urticaria, tuberculin reaction, contact allergens, and benzalkonium chloride with or without capsaicin pretreatment. The flare response to SP and histamine was suppressed by capsaicin pretreatment, whereas the wheal was enlarged. Interestingly, capsaicin pretreatment enhanced the responses to all other inflammatory agents.

Varicose vein sclerosing agents

Sclerosing agents can be subdivided in different groups depending on their mechanism of action.

Cleaning solutions

These types of sclerosants provoke damage of the endothelium by attacking the lipids of the membrane, thereby causing cell damage and inflammation. Sclerosing agents belonging to this group include polidodecanol (Aethoxysclerol), the sodium tetradecyl sulfate (Sotradecol), sodium morrhuate, and ethanolamine oleate (Ethamolin). Aethoxysclerol is a local anesthetic and is therefore painless and probably the most effective.

Osmotic solutions

These solutions work by dehydrating the endothelial cell by osmosis, until their destruction. Substances that belong to this group include hypertonic saline and Sclerodex (10% NaCl, 25% dextrose, 1% phenethyl alcohol).

Hair removal agents

Depilatory agents

The standard chemical depilatory agents, available in gels, creams, lotions, aerosols, or roll-on forms, are the salts of thioglycolic acid (sodium thioglycolate or calcium thioglycolate) that were patented in the 1930s for dehairing cattle hides. Thioglycolate depilatories work by hydrolyzing and disrupting disulfide bonds of hair keratin, causing the hair to break in half and allowing the hair to separate from the skin.

Hair loss treatments

Pinacidil, P-1075, cromakalim, and nicorandil

The opening of intracellular potassium channels is a common mechanism of action for a set of antihypertensive drugs that includes the hair-growth-inducing agent minoxidil. As demonstrated by minoxidil studies, potassium channel openers (PCOs) influence hair growth. Correlative studies demonstrate that a series of PCOs, including pinacidil, P-1075 (an active pinacidil analog), cromakalim, and nicorandil, maintain hair growth in cultured follicles.

Cysteine and arginine

High sulfur proteins are cysteine-rich proteins synthesized during the differentiation of hair matrix cells, and they form hair fibers in association with hair keratin intermediate filaments. Trichohyalin (THH) is a major structural protein of the inner root sheath cells and medulla layer of the hair follicle and, to a lesser extent, of other specialized epithelia made from the conversion of arginine to citrulline.

Saw palmetto (Serenoa repens)

Saw palmetto seems to work locally at the actual site of hormone binding to receptors on cells. It apparently stops or at least reduces the receptor binding of androgens. It also locally inhibits 5-alpha reductase and 3-ketosteroid reductase, the enzymes that are involved in converting testosterone to the more potent DHT. Green tea has been associated with higher levels of sex hormone-binding globulin (SHBG). SHBG is a molecule that binds with high affinity to testosterone. Testosterone bound to SHBG is not bioactive and cannot bind to androgen receptors or be converted into DHT. Green tea may also have an effect on the type I 5 alpha reductase enzyme.

Scar management

Differentiating hypertrophic scars from keloids can be challenging. Key points that must be kept in mind are first, that scars can range between the ones that become hypertrophic in the first few months and then completely resolve with no treatment, and the more severe hypertrophic scars that become disfiguring and permanent. Keloids may not recur for 6 months to as long as 2 years after surgery.

Silicone gel sheeting

Silicone gel sheeting has been a widely used clinical management option for hypertrophic scars and keloids since the early 1980s. The mechanism of action of silicone gel sheeting is unknown. Temperature differences of as small as 1°C, as found under silicone gel sheeting, can have a significant effect on collagenase kinetics and may alter scarring. Silicone itself has never been found in significant amounts in scars treated with sheeting so a direct chemical effect is unlikely. Others believe that static electricity generated by silicone gel sheeting induces a polarization of scar tissue that results in involution. Occlusion of scars by silicone gel sheeting might alter cytokine levels, which in turn would have an effect on scar remodeling.

Adhesive microporous hypoallergenic paper tape

The application of adhesive microporous hypoallergenic paper tape after surgery has been shown to be successful. The mechanism of benefit is unknown, but it may in part be mechanical (pressure therapy) and/or occlusive.

Miscellaneous compounds in scar management

These include the following:


The use of cosmeceuticals has drastically risen in recent years. This significantly increases the armamentarium of the clinician in improving the treatment of skin conditions. However, at times, claims of effectiveness lack convincing evidence, thus the industry is challenged to provide convincing evidence of the effectiveness of these compounds.

Finally, remember that while the effectiveness of the non–FDA-approved cosmetic retinoids has been studied and clinical and histological evidence suggests structural changes induced by excessive sun exposure can be partially reversed by the use of topical retinoids, clinical correlates of these in vitro findings are not entirely convincing. Most studies are poorly designed, and many authorities regard the utility of these preparations for their stated uses as marginal at best.


Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Disclosure: Nothing to disclose.


Santiago A Centurion, MD, Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey

Disclosure: Nothing to disclose.

Specialty Editors

Andrea Leigh Zaenglein, MD, Associate Professor of Dermatology and Pediatrics, Department of Dermatology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center

Disclosure: Nothing to disclose.

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Elsevier Royalty Other

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Cristina S. Solis, MS, to the development and writing of this article.


  1. Draelos ZD. The cosmeceutical realm. Clin Dermatol. Nov-Dec 2008;26(6):627-32. [View Abstract]
  2. Thornfeldt C. Cosmeceuticals containing herbs: fact, fiction, and future. Dermatol Surg. Jul 2005;31(7 Pt 2):873-80; discussion 880. [View Abstract]
  3. Cronin H, Draelos ZD. Top 10 botanical ingredients in 2010 anti-aging creams. J Cosmet Dermatol. Sep 2010;9(3):218-25. [View Abstract]
  4. Wright TI, Spencer JM, Flowers FP. Chemoprevention of nonmelanoma skin cancer. J Am Acad Dermatol. Jun 2006;54(6):933-46; quiz 947-50. [View Abstract]
  5. Herro E, Jacob SE. Mentha piperita (peppermint). Dermatitis. Dec 2010;21(6):327-9. [View Abstract]
  6. Anunciato TP, da Rocha Filho PA. Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and cosmeceuticals. J Cosmet Dermatol. Mar 2012;11(1):51-4. [View Abstract]
  7. Draelos ZD. Male skin and ingredients relevant to male skin care. Br J Dermatol. Mar 2012;166 Suppl 1:13-6. [View Abstract]
  8. Draelos ZD. New treatments for restoring impaired epidermal barrier permeability: skin barrier repair creams. Clin Dermatol. May-Jun 2012;30(3):345-8. [View Abstract]
  9. Domoto N, Koriyama T, Chu BS, Tsuji T. Evaluation of the efficacy of orange roughy (Hoplostetbus atlanticus) oil in subjects with dry skin. Int J Cosmet Sci. Aug 2012;34(4):322-7. [View Abstract]
  10. Draelos ZD. The effect of ceramide-containing skin care products on eczema resolution duration. Cutis. Jan 2008;81(1):87-91. [View Abstract]
  11. Stratigos AJ, Katsambas AD. The role of topical retinoids in the treatment of photoaging. Drugs. 2005;65(8):1061-72. [View Abstract]
  12. Serri R, Iorizzo M. Cosmeceuticals: focus on topical retinoids in photoaging. Clin Dermatol. Nov-Dec 2008;26(6):633-5. [View Abstract]
  13. Tasic-Kostov M, Savic S, Lukic M, Tamburic S, Pavlovic M, Vuleta G. Lactobionic acid in a natural alkylpolyglucoside-based vehicle: assessing safety and efficacy aspects in comparison to glycolic acid. J Cosmet Dermatol. Mar 2010;9(1):3-10. [View Abstract]
  14. Wagner AE, Rimbach G. Ascorbigen: chemistry, occurrence, and biologic properties. Clin Dermatol. Mar-Apr 2009;27(2):217-24. [View Abstract]
  15. Teo BS, Basri M, Zakaria MR, Salleh AB, Rahman RN, Rahman MB. A potential tocopherol acetate loaded palm oil esters-in-water nanoemulsions for nanocosmeceuticals. J Nanobiotechnology. Feb 23 2010;8:4. [View Abstract]
  16. Chiu PC, Chan CC, Lin HM, Chiu HC. The clinical anti-aging effects of topical kinetin and niacinamide in Asians: a randomized, double-blind, placebo-controlled, split-face comparative trial. J Cosmet Dermatol. Dec 2007;6(4):243-9. [View Abstract]
  17. Nakata R, Takahashi S, Inoue H. Recent advances in the study on resveratrol. Biol Pharm Bull. 2012;35(3):273-9. [View Abstract]
  18. Badreshia-Bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for women of color. J Drugs Dermatol. Jan 2007;6(1):32-9. [View Abstract]
  19. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. Sep-Oct 2007;20(5):308-13. [View Abstract]
  20. Yarosh D, Klein J, O'Connor A, Hawk J, Rafal E, Wolf P. Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group. Lancet. Mar 24 2001;357(9260):926-9. [View Abstract]
  21. Alam M, Dover JS. On beauty: evolution, psychosocial considerations, and surgical enhancement. Arch Dermatol. Jun 2001;137(6):795-807. [View Abstract]
  22. Albright R, Johnson N, Sanderson TW, Farb RM, Melton R, Fisher L, et al. Pesticide residues in the top soil of five West Alabama counties. Bull Environ Contam Toxicol. Sep 1974;12(3):378-84. [View Abstract]
  23. Arora RB, Kapoor V, Basu N, Jain AP. Anti-inflammatory studies on Curcuma longa (turmeric). Indian J Med Res. Aug 1971;59(8):1289-95. [View Abstract]
  24. Ashcroft GS, Dodsworth J, van Boxtel E, Tarnuzzer RW, Horan MA, Schultz GS, et al. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-beta1 levels. Nat Med. Nov 1997;3(11):1209-15. [View Abstract]
  25. Ashcroft GS, Greenwell-Wild T, Horan MA, Wahl SM, Ferguson MW. Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response. Am J Pathol. Oct 1999;155(4):1137-46. [View Abstract]
  26. Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point. Dermatology. 1997;195(3):248-52. [View Abstract]
  27. Bazzano GS, Terezakis N, Galen W. Topical tretinoin for hair growth promotion. J Am Acad Dermatol. Oct 1986;15(4 Pt 2):880-3, 890-3. [View Abstract]
  28. Bedi MK, Shenefelt PD. Herbal therapy in dermatology. Arch Dermatol. Feb 2002;138(2):232-42. [View Abstract]
  29. Bernstein JE, Parish LC, Rapaport M, Rosenbaum MM, Roenigk HH. Effects of topically applied capsaicin on moderate and severe psoriasis vulgaris. J Am Acad Dermatol. Sep 1986;15(3):504-7. [View Abstract]
  30. Buhl AE, Conrad SJ, Waldon DJ, Brunden MN. Potassium channel conductance as a control mechanism in hair follicles. J Invest Dermatol. Jul 1993;101(1 Suppl):148S-152S. [View Abstract]
  31. Burke BM, Cunliffe WJ. Oral spironolactone therapy for female patients with acne, hirsutism or androgenic alopecia. Br J Dermatol. Jan 1985;112(1):124-5. [View Abstract]
  32. Casado FJ, Nusimovich AD. LMW hyaluronic acid to induce epidermal regeneration. Drug Cosm Ind. 1991;148:30-34.
  33. Chakraborty AK, Funasaka Y, Komoto M, Ichihashi M. Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res. Aug 1998;11(4):206-12. [View Abstract]
  34. Chan AC. Partners in defense, vitamin E and vitamin C. Can J Physiol Pharmacol. Sep 1993;71(9):725-31. [View Abstract]
  35. Chiu AE, Chan JL, Kern DG, Kohler S, Rehmus WE, Kimball AB. Double-blinded, placebo-controlled trial of green tea extracts in the clinical and histologic appearance of photoaging skin. Dermatol Surg. Jul 2005;31(7 Pt 2):855-60; discussion 860. [View Abstract]
  36. Cusan L, Dupont A, Belanger A, Tremblay RR, Manhes G, Labrie F. Treatment of hirsutism with the pure antiandrogen flutamide. J Am Acad Dermatol. Sep 1990;23(3 Pt 1):462-9. [View Abstract]
  37. Draelos ZD. Hydroxy acids for the treatment of aging skin. J Geriatr Dermatol. 1997;5:236-240.
  38. Draelos ZD. New developments in cosmetics and skin care products. Adv Dermatol. 1997;12:3-17; discussion 18. [View Abstract]
  39. Edwards CR, Teelucksingh S. Glycyrrhetinic acid and potentiation of hydrocortisone activity in skin. Lancet. Aug 4 1990;336(8710):322-3. [View Abstract]
  40. Ekoe JM, Burckhardt P, Ruedi B. Treatment of hirsutism, acne and alopecia with cyproterone acetate. Dermatologica. 1980;160(6):398-404. [View Abstract]
  41. Ellis CN, Berberian B, Sulica VI, Dodd WA, Jarratt MT, Katz HI, et al. A double-blind evaluation of topical capsaicin in pruritic psoriasis. J Am Acad Dermatol. Sep 1993;29(3):438-42. [View Abstract]
  42. Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol Surg. Jul 2005;31(7 Pt 2):814-7; discussion 818. [View Abstract]
  43. Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatol Surg. Jul 2005;31(7 Pt 2):827-31; discussion 831. [View Abstract]
  44. Fulton JE Jr. The stimulation of postdermabrasion wound healing with stabilized aloe vera gel-polyethylene oxide dressing. J Dermatol Surg Oncol. May 1990;16(5):460-7. [View Abstract]
  45. Gendler EC. Topical treatment of the aging face. Dermatol Clin. Oct 1997;15(4):561-7. [View Abstract]
  46. Gensler HL. Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide. Nutr Cancer. 1997;29(2):157-62. [View Abstract]
  47. Ghersetich I, Lotti T, Campanile G, Grappone C, Dini G. Hyaluronic acid in cutaneous intrinsic aging. Int J Dermatol. Feb 1994;33(2):119-22. [View Abstract]
  48. Goodman DS. Vitamin A and retinoids in health and disease. N Engl J Med. Apr 19 1984;310(16):1023-31. [View Abstract]
  49. Greenway FL, Bray GA. Regional fat loss from the thigh in obese women after adrenergic modulation. Clin Ther. 1987;9(6):663-9. [View Abstract]
  50. Griffiths CE. Drug treatment of photoaged skin. Drugs Aging. Apr 1999;14(4):289-301. [View Abstract]
  51. Hamaoka H, Minakuchi K, Miyoshi H, Arase S, Chen CH, Nakaya Y. Effect of K+ channel openers on K+ channel in cultured human dermal papilla cells. J Med Invest. Aug 1997;44(1-2):73-7. [View Abstract]
  52. Hipkiss AR, Brownson C, Carrier MJ. Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev. Sep 15 2001;122(13):1431-45. [View Abstract]
  53. Humbert P. Topical vitamin C in the treatment of photoaged skin. Eur J Dermatol. Mar-Apr 2001;11(2):172-3. [View Abstract]
  54. Idson B. Vitamins of the skin. Cosmet Toilet. 1993;108:79-92.
  55. Jiang H, Yamamoto S, Kato R. Induction of anagen in telogen mouse skin by topical application of FK506, a potent immunosuppressant. J Invest Dermatol. Apr 1995;104(4):523-5. [View Abstract]
  56. Kagan VE, Serbinova EA, Forte T, Scita G, Packer L. Recycling of vitamin E in human low density lipoproteins. J Lipid Res. Mar 1992;33(3):385-97. [View Abstract]
  57. Kagan VE, Serbinova EA, Safadi A, Catudioc JD, Packer L. NADPH-dependent inhibition of lipid peroxidation in rat liver microsomes. Biochem Biophys Res Commun. Jul 15 1992;186(1):74-80. [View Abstract]
  58. Kalyon BD, Olgun U. Antibacterial efficacy of triclosan-incorporated polymers. Am J Infect Control. Apr 2001;29(2):124-5. [View Abstract]
  59. Kang S, Fisher GJ, Voorhees JJ. Photoaging and topical tretinoin: therapy, pathogenesis, and prevention. Arch Dermatol. Oct 1997;133(10):1280-4. [View Abstract]
  60. Katayama K, Armendariz-Borunda J, Raghow R, Kang AH, Seyer JM. A pentapeptide from type I procollagen promotes extracellular matrix production. J Biol Chem. May 15 1993;268(14):9941-4. [View Abstract]
  61. Katiyar SK, Elmets CA. Green tea polyphenolic antioxidants and skin photoprotection (Review). Int J Oncol. Jun 2001;18(6):1307-13. [View Abstract]
  62. Khandpur S, Suman M, Reddy BS. Comparative efficacy of various treatment regimens for androgenetic alopecia in men. J Dermatol. Aug 2002;29(8):489-98. [View Abstract]
  63. Kligman A. The future of cosmeceuticals: an interview with Albert Kligman, MD, PhD. Interview by Zoe Diana Draelos. Dermatol Surg. Jul 2005;31(7 Pt 2):890-1. [View Abstract]
  64. Kligman AM. Hydration injury to human skin. In: Van der Valk PG, Maibach HI. The Irritant Contact Dermatitis Syndrome. Orlando, Fla: CRC Press; 1996:187-90.
  65. Kligman AM. Why Cosmeceuticals?. Cosmet Toilet 1993; 108:39.
  66. Kligman AM, Fulton JE Jr, Plewig G. Topical vitamin A acid in acne vulgaris. Arch Dermatol. Apr 1969;99(4):469-76. [View Abstract]
  67. Kligman LH. Effects of all-trans-retinoic acid on the dermis of hairless mice. J Am Acad Dermatol. Oct 1986;15(4 Pt 2):779-85, 884-7. [View Abstract]
  68. Kligman LH, Kligman AM. Petrolatum and other hydrophobic emollients reduce UV-A-induced damage. J Dermatol Treatment. 1992;3:3.
  69. Kulkarni AP, Chaudhuri J, Mitra A, Richards IS. Dioxygenase and peroxidase activities of soybean lipoxygenase: synergistic interaction between linoleic acid and hydrogen peroxide. Res Commun Chem Pathol Pharmacol. Nov 1989;66(2):287-96. [View Abstract]
  70. Kumar CA, Das UN. Effect of melatonin on two stage skin carcinogenesis in Swiss mice. Med Sci Monit. May-Jun 2000;6(3):471-5. [View Abstract]
  71. Lahti A, Maibach HI. Species specificity of nonimmunologic contact urticaria: guinea pig, rat, and mouse. J Am Acad Dermatol. Jul 1985;13(1):66-9. [View Abstract]
  72. Lee OS, Kang HH, Han SH. Oriental herbs in cosmetics: Plant extracts are reviewed for their potential as cosmetic ingredients. Cosmet Toilet. 1997;112:57-64.
  73. Leung AY, Foster S. Encyclopedia of Common Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: Wiley John & Sons; 1996.
  74. Leyden JJ, Grove GL, Grove MJ, Thorne EG, Lufrano L. Treatment of photodamaged facial skin with topical tretinoin. J Am Acad Dermatol. Sep 1989;21(3 Pt 2):638-44. [View Abstract]
  75. Liao S, Hiipakka RA. Selective inhibition of steroid 5 alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate. Biochem Biophys Res Commun. Sep 25 1995;214(3):833-8. [View Abstract]
  76. Lin SY, Chang HP. Induction of superoxide dismutase and catalase activity in different rat tissues and protection from UVB irradiation after topical application of Ginkgo biloba extracts. Methods Find Exp Clin Pharmacol. Jul-Aug 1997;19(6):367-71. [View Abstract]
  77. Liu M, Wikonkal NM, Brash DE. Induction of cyclin-dependent kinase inhibitors and G(1) prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis. Sep 1999;20(9):1869-72. [View Abstract]
  78. Liu M, Wikonkal NM, Brash DE. UV induces p21WAF1/CIP1 protein in keratinocytes without p53. J Invest Dermatol. Aug 1999;113(2):283-4. [View Abstract]
  79. Loden M, Barany E. Skin-identical lipids versus petrolatum in the treatment of tape- stripped and detergent-perturbed human skin. Acta Derm Venereol. Nov-Dec 2000;80(6):412-5. [View Abstract]
  80. Lyle WG. Silicone gel sheeting. Plast Reconstr Surg. Jan 2001;107(1):272-5. [View Abstract]
  81. Maguire JJ, Kagan V, Ackrell BA, Serbinova E, Packer L. Succinate-ubiquinone reductase linked recycling of alpha-tocopherol in reconstituted systems and mitochondria: requirement for reduced ubiquinone. Arch Biochem Biophys. Jan 1992;292(1):47-53. [View Abstract]
  82. Maibach HI, Johnson HL. Contact urticaria syndrome. Contact urticaria to diethyltoluamide (immediate-type hypersensitivity). Arch Dermatol. Jun 1975;111(6):726-30. [View Abstract]
  83. Marks R, Pearse AD, Walker AP. The effects of a shampoo containing zinc pyrithione on the control of dandruff. Br J Dermatol. Apr 1985;112(4):415-22. [View Abstract]
  84. Matsuda H, Higashino M, Nakai Y, Iinuma M, Kubo M, Lang FA. Studies of cuticle drugs from natural sources. IV. Inhibitory effects of some Arctostaphylos plants on melanin biosynthesis. Biol Pharm Bull. Jan 1996;19(1):153-6. [View Abstract]
  85. Maurer M, Handjiski B, Paus R. Hair growth modulation by topical immunophilin ligands: induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia. Am J Pathol. Apr 1997;150(4):1433-41. [View Abstract]
  86. Merfort I, Heilmann J, Hagedorn-Leweke U, Lippold BC. In vivo skin penetration studies of camomile flavones. Pharmazie. Jul 1994;49(7):509-11. [View Abstract]
  87. Messager S, Goddard PA, Dettmar PW, Maillard JY. Determination of the antibacterial efficacy of several antiseptics tested on skin by an 'ex-vivo' test. J Med Microbiol. Mar 2001;50(3):284-92. [View Abstract]
  88. Moriwaki Y, Yamamoto T, Higashino K. Enzymes involved in purine metabolism--a review of histochemical localization and functional implications. Histol Histopathol. Oct 1999;14(4):1321-40. [View Abstract]
  89. Motulsky HJ, Insel PA. Adrenergic receptors in man: direct identification, physiologic regulation, and clinical alterations. N Engl J Med. Jul 1 1982;307(1):18-29. [View Abstract]
  90. Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, et al. International clinical recommendations on scar management. Plast Reconstr Surg. Aug 2002;110(2):560-71. [View Abstract]
  91. Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Nutr Cancer. 1998;30(1):21-4. [View Abstract]
  92. Nakagawa M, Kawai K, Kawai K. Contact allergy to kojic acid in skin care products. Contact Dermatitis. Jan 1995;32(1):9-13. [View Abstract]
  93. Olsen EA, Katz HI, Levine N, Shupack J, Billys MM, Prawer S, et al. Tretinoin emollient cream: a new therapy for photodamaged skin. J Am Acad Dermatol. Feb 1992;26(2 Pt 1):215-24. [View Abstract]
  94. Palumbo A, d'Ischia M, Misuraca G, Prota G. Mechanism of inhibition of melanogenesis by hydroquinone. Biochim Biophys Acta. Jan 23 1991;1073(1):85-90. [View Abstract]
  95. Pelle E, Muizzuddin N, Mammone T, Marenus K, Maes D. Protection against endogenous and UVB-induced oxidative damage in stratum corneum lipids by an antioxidant-containing cosmetic formulation. Photodermatol Photoimmunol Photomed. Jun-Aug 1999;15(3-4):115-9. [View Abstract]
  96. Port RB, Paige ML, Berstein JR, Alvarez GR. The 'altered states' foreign body. Am J Dis Child. Oct 1986;140(10):972-3. [View Abstract]
  97. Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med. Apr 2002;8(2):143-52. [View Abstract]
  98. Rattan SI, Clark BF. Kinetin delays the onset of ageing characteristics in human fibroblasts. Biochem Biophys Res Commun. Jun 15 1994;201(2):665-72. [View Abstract]
  99. Rokhsar CK, Lee S, Fitzpatrick RE. Review of photorejuvenation: devices, cosmeceuticals, or both?. Dermatol Surg. Sep 2005;31(9 Pt 2):1166-78; discussion 1178. [View Abstract]
  100. Saulis AS, Mogford JH, Mustoe TA. Effect of Mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg. Jul 2002;110(1):177-83; discussion 184-6. [View Abstract]
  101. Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A. Treatment of skin aging with topical estrogens. Int J Dermatol. Sep 1996;35(9):669-74. [View Abstract]
  102. Shuster S. The aetiology of dandruff and the mode of action of therapeutic agents. Br J Dermatol. Aug 1984;111(2):235-42. [View Abstract]
  103. Silverman AK, Ellis CN, Voorhees JJ. Hypervitaminosis A syndrome: a paradigm of retinoid side effects. J Am Acad Dermatol. May 1987;16(5 Pt 1):1027-39. [View Abstract]
  104. Smith WP. Hydroxy acids and skin aging. Cosmet Toilet. 1994;109:41-48.
  105. Srivastava R. Inhibition of neutrophil response by curcumin. Agents Actions. Nov 1989;28(3-4):298-303. [View Abstract]
  106. Steenvoorden DP, Beijersbergen van Henegouwen GM. Cysteine derivatives protect against UV-induced reactive intermediates in human keratinocytes: the role of glutathione synthesis. Photochem Photobiol. Nov 1997;66(5):665-71. [View Abstract]
  107. Steenvoorden DP, van Henegouwen GM. The use of endogenous antioxidants to improve photoprotection. J Photochem Photobiol B. Nov 1997;41(1-2):1-10. [View Abstract]
  108. Stege H, Roza L, Vink AA, Grewe M, Ruzicka T, Grether-Beck S, et al. Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin. Proc Natl Acad Sci U S A. Feb 15 2000;97(4):1790-5. [View Abstract]
  109. Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH, Afzal M. Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study. Trop Med Int Health. Aug 1996;1(4):505-9. [View Abstract]
  110. Tarcsa E, Marekov LN, Andreoli J, Idler WW, Candi E, Chung SI, et al. The fate of trichohyalin. Sequential post-translational modifications by peptidyl-arginine deiminase and transglutaminases. J Biol Chem. Oct 31 1997;272(44):27893-901. [View Abstract]
  111. Teelucksingh S, Mackie AD, Burt D, McIntyre MA, Brett L, Edwards CR. Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet. May 5 1990;335(8697):1060-3. [View Abstract]
  112. Thiele JJ, Schroeter C, Hsieh SN, et al. The antioxidant network of the stratum corneum. Curr Probl Dermatol. 2001;29:26-42. [View Abstract]
  113. Urbach W. Cosmeceuticals-The future of cosmetics?. Cosmet Toilet. 1995;110:33.
  114. Van Scott EJ, Yu RJ. Alpha hydroxy acids: procedures for use in clinical practice. Cutis. Mar 1989;43(3):222-8. [View Abstract]
  115. Van Scott EJ, Yu RJ. Control of keratinization with alpha-hydroxy acids and related compounds. I. Topical treatment of ichthyotic disorders. Arch Dermatol. Oct 1974;110(4):586-90. [View Abstract]
  116. Van Scott EJ, Yu RJ. Hyperkeratinization, corneocyte cohesion, and alpha hydroxy acids. J Am Acad Dermatol. Nov 1984;11(5 Pt 1):867-79. [View Abstract]
  117. Varani J, Fisher GJ, Kang S, Voorhees JJ. Molecular mechanisms of intrinsic skin aging and retinoid-induced repair and reversal. J Investig Dermatol Symp Proc. Aug 1998;3(1):57-60. [View Abstract]
  118. Vermeer BJ, Gilchrest BA. Cosmeceuticals. A proposal for rational definition, evaluation, and regulation. Arch Dermatol. Mar 1996;132(3):337-40. [View Abstract]
  119. Wallengren J, Moller H. The effect of capsaicin on some experimental inflammations in human skin. Acta Derm Venereol. 1986;66(5):375-80. [View Abstract]
  120. Weber SU, Thiele JJ, Cross CE, Packer L. Vitamin C, uric acid, and glutathione gradients in murine stratum corneum and their susceptibility to ozone exposure. J Invest Dermatol. Dec 1999;113(6):1128-32. [View Abstract]
  121. Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med. Jan 1995;208(1):124-30. [View Abstract]
  122. Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ. Topical tretinoin improves photoaged skin. A double-blind vehicle- controlled study. JAMA. Jan 22-29 1988;259(4):527-32. [View Abstract]
  123. Weiss JS, Ellis CN, Headington JT, Voorhees JJ. Topical tretinoin in the treatment of aging skin. J Am Acad Dermatol. Jul 1988;19(1 Pt 2):169-75. [View Abstract]
  124. Weissmann A, Bowden J, Frank BL, Horwitz SN, Frost P. Antiandrogenic effects of topically applied spironolactone on the hamster flank organ. Arch Dermatol. Jan 1985;121(1):57-62. [View Abstract]
  125. Yamamoto S, Jiang H, Kato R. Stimulation of hair growth by topical application of FK506, a potent immunosuppressive agent. J Invest Dermatol. Feb 1994;102(2):160-4. [View Abstract]
  126. Yamamoto S, Kato R. Hair growth-stimulating effects of cyclosporin A and FK506, potent immunosuppressants. J Dermatol Sci. Jul 1994;7 Suppl:S47-54. [View Abstract]
  127. Zhang L, Lerner S, Rustrum WV, Hofmann GA. Electroporation-mediated topical delivery of vitamin C for cosmetic applications. Bioelectrochem Bioenerg. May 1999;48(2):453-61. [View Abstract]