Microsoft word - alm i - wi - wi – skin health, ageing & cosmoceuticals.doc
ALM I – Dermatology WI – Skin Health, Ageing & Cosmoceuticals
Please read the following article titled “Efficacy and safety of innovativecosmeceuticals”
Clinics in Dermatology (2008) 26, 367–374
Efficacy and safety of innovative cosmeceuticals☆
Xing-Hua Gao, MDa, Li Zhang, MDa, Huachen Wei, MDb, Hong-Duo Chen, MDa,⁎
aDepartment of Dermatology, No. 1 Hospital of China Medical University, Shenyang, ChinabDepartment of Dermatology, The Mount Sinai Medical Center, New York, USA
Abstract The research and development of cosmeceuticals is booming in recent years. Many substances,either from botanical, animal, or chemically synthesized sources, are tested or investigated as the activeingredients in cosmeceuticals. The interactions between cosmeceuticals and skin are complex,depending on the specific composites in cosmeceutical products, condition of the skin or general healthstatus of a subject, and the environment where the action occurs. As such, careful preclinical or clinicalevaluation of efficacy and safety is a prerequisite for the development of a specific cosmeceuticalproduct. This article reviews some of the ingredients that are currently in use or might be potentialcandidates in cosmeceuticals of different categories. 2008 Elsevier Inc. All rights reserved.
are irritability to the skin, contact dermatitis, photosensitiv-ity, comedogenicity, hair and nail damage, hyper- or
The term cosmeceutical was first introduced by Albert
hypopigmentation, infectivity, carcinogenicity, and even
during a meeting about 20 years ago. It is a
systemic adverse effects. The research and development of
category of cosmetic products claimed to have biologically
cosmeceuticals, especially the composite active ingredients,
active ingredients with medicinal or druglike benefits.
should be based on their clarified sources, structures,
Furthermore, they satisfy the needs of beauty and health.
interactive mechanisms with the skin, and, most importantly,
Many substances, either chemically synthesized or extracted
their efficacy and safety on the targeted components of skin.
from plants or animals, can be used as functional ingredients.
Here we review some of the cosmeceuticals with different
Nowadays, many cosmetic products with biologically active
categories of functions, with special focuses on their
ingredients have been developed and marketed, though there
are discrepancies about their regulations and approvals bythe government.
Cosmeceuticals are intended to carry out their functions as
protection, whitening, tanning, antiwrinkling, deodorants,antiaging, and nail and hair care. Cosmeceuticals may,
however, cause some unwanted problems. The common ones
The number and amount of melanocytes, as well as the
type and distribution of melanin in the skin, are the main
☆ This article was supported by the Program for New Century Excellent
factors to determine the color of skin. The synthesis of
Talents in University (NCEP-04-0287).
melanin pigment is completed by a series of oxidative
Corresponding author. Tel.: +86 24 83282642; fax: +86 24 83282633.
reactions, along which tyrosinase is the key enzyme.
0738-081X/$ – see front matter 2008 Elsevier Inc. All rights reserved.
Tyrosinase converts tyrosine to dihydroxyphenylalanine
citric acid, mixed fruit acid, triple fruit acid, sugar cane
(DOPA) and then to dopaquinone; dopaquinone autooxidates
extract, and so on. Primarily, lactic acid and glycolic acid are
to dopachrome and, finally, to dihydroxyindole or dihydrox-
the most widely studied forms of AHAs because they have a
yindole-2-carboxylic acid to form eumelanin (black-brown
molecular size that allows effective penetration into the top
pigment). Dopaquinone can also be converted to cysteinyl
layers of skin. α Hydroxy acids have been used for years in
DOPA or glutathione DOPA and subsequently form
chemical peels. It is generally assumed that AHAs at
pheomelanin (yellow-red pigment). The etiology of hyper-
concentrations of 4% to 15% are not effective for inhibiting
pigmentation includes postinflammatory hyperpigmentation,
melanin production. Rather, it is believed that they can
pregnancy, drugs, photosensitizing agents, UV light, or
accelerate cell turnover rates and exfoliate the stratum
systemic diseases (eg, Addison's disease, liver disease,
corneum. Other research, however, has shown that lactic and
pituitary tumors). There are many pigmentary disorders that
glycolic acids can indeed inhibit melanin production in
pose cosmetic problems in humans. Melasma, freckles, and
addition to their actions as an exfoliant on skin.There are
aging spots are among the most common ones.
reports that glycolic acid, or glycolic acid with hydroqui-
Hydroquinone, with a phenol structure, is well known for
none, is highly effective in reducing the pigment in melasma
its suppressive effect on melanin synthesis. Topical hydro-
There have been, however, accumulating reports
quinone in 2% to 4% concentrations, alone or in combination
on adverse effects of cosmetics containing AHA. They
with tretinoin 0.05% to 0.1%, has been successfully used for
include severe redness, swelling, blistering, burning, itching,
years in treating melasma.The problem with hydroquinone
discoloration, and increased photosensitivity. The side
use is that it can be a skin irritant causing contact dermatitis,
effects are related to the pH and concentration of AHA,
particularly in higher concentrations of 4% or greater, or
vehicles used, and frequency of application.
when combined with tretinoin. Hydroquinone is also an
Kojic acid (5-hydroxy-4-pyran-4-one-2-methyl), a natural
unstable and easily oxidized ingredient in cosmetic formula-
substance produced by fungi or bacteria, such as Aspergillus,
tions. It is, therefore, essential to package it in a
Penicillium, or Acetobacter spp, is present in traditional
nontransparent and airtight container to avoid light and air
Japanese fermented foods. There is convincing evidence, in
exposure. An uncommon adverse effect is exogenous
vitro and in vivo, showing kojic acid to be effective for
ochronosis, characterized by progressive sooty darkening
inhibiting melanin production.Kojic acid is highly
of the skin area exposed to hydroquinone. Derivatives of
effective in reducing the pigment in melasma The
hydroquinone have also shown some promises for lightening
problem with kojic acid is that it is an extremely unstable
skin. For example, arbutin contains a form of hydroquinone
ingredient in cosmetic formulations. Upon exposure to air or
(β-D-glucopyranoside) derived from the leaves of bearberry,
sunlight, it can turn to a strange shade of brown and lose its
cranberry, mulberry, or blueberry shrubs, and in most types
efficacy. Furthermore, some controversial studies have
of pears. Pure forms of arbutin derivatives, such as α-arbutin,
shown that kojic acid has some mutagenic properties, at
β-arbutin, and deoxyarbutin, are considered more potent for
least in some strains of bacteria.A stable derivative of
lightening skin. It was reported that deoxyarbutin effectively
kojic acid, 5-[(3-aminopropyl)phosphinooxy]-2-(hydroxy-
inhibits mushroom tyrosinase in vitro with a Ki that is
methyl)-4H-pyran-4-one (Kojyl-APPA), was synthesized.
10-fold lower than hydroquinone and 350-fold lower than
Kojyl-APPA significantly inhibited tyrosinase activity at
arbutin. In a human clinical trial, topical treatment of
24 hours after treatment in normal human melanocytes. In
deoxyarbutin for 12 weeks resulted in a significant or slight
addition, Kojyl-APPA decreased melanin content to 75% of
reduction in overall skin lightness and improvement of solar
control in melanoma cells and decreased the newly
lentigines in a population of light skin or dark skin
synthesized melanin to 43% of control in normal human
individuals, respectivelyArbutin inhibits melanin synth-
melanocytes. Its permeation through skin increased by about
esis in a dose-dependent mannerSo far, most of the
8 times as compared with kojic acid.Again, there have
research describing arbutin's effectiveness has been done in
been no reports on its clinical usefulness and safety issues.
vitro. Clinical studies are needed to test at what concentra-
Azelaic acid is a naturally occurring saturated dicar-
tion or in what vehicle arbutin is more effective to lighten
boxylic acid originally isolated from Pityrosporum ovale. It
the skin, and what possible hazards it may pose to skin.
is an effective therapeutic agent in treatment of a number of
Another study screened several phenolic derivatives using
skin disorders (eg, acne and rosacea) when applied in a
B16 melanoma cells and found that a biphenyl derivative,
cream or gel at concentrations of 15% to 20%. It can also
2,2′-dihydroxy-5,5′-dipropyl-biphenyl (DDB), down-regu-
inhibit melanin production. A double-blind study with
lated melanin synthesis effectively. DDB down-regulates
329 women showed that 20% azelaic acid cream in
melanin synthesis by inhibiting the maturation of tyrosinase,
conjunction with a broad-spectrum sunscreen yielded 65%
leading to acceleration of tyrosinase degradation.DDB,
good or excellent results against melasma. Over the treatment
thus, might be a potential depigmenting candidate as a
period of 24 weeks, the azelaic acid cream had comparable
cosmeceutical, given careful and sufficient testing and trials.
effects to 4% hydroquinone cream with regard to overall
There are many forms and various sources of α hydroxy
rating, reduction in lesion size, and pigment intensity. Severe
acids (AHAs), such as lactic acid, glycolic acid, malic acid,
side effects such as allergic sensitization were not observed
Efficacy and safety of innovative cosmeceuticals
with azelaic Additional research, however, suggests
Magnesium-L-ascorbyl-2-phosphate (MAP) is a stable
that azelaic acid is more irritating than hydroquinone mixed
derivative of ascorbic acid. When used as a 10% cream,
with glycolic acid (source, eMedicine Journal,
MAP showed significant lightening effect in more than half
of patients with melasma and solar lentigines. Furthermore,
acid is an optional candidate for skin lightening if a patient
MAP has been shown to have a protective effect against skin
has acne and postinflammatory hyperpigmentation or has
allergic reaction with hydroquinone.
Alkyl esters of the natural product gentisic acid are also
Retinoids are compounds that have the basic core structure
tyrosinase inhibitors. The smaller esters (eg, methyl and
of vitamin A and its oxidized metabolites, or synthetic
ethyl) were more effeSphingosylphosphorylcholine
compounds that share similar mechanisms of action as
is emerging as a potent signaling-lipid mediator. It
naturally occurring retinoids.Topical retinoids such as all-
significantly inhibits melanin synthesis in a concentration-
trans-retinoic acid (RA), 13-cis-retinoic acid (isotretinoin),
dependent manner, and further, that it reduces the activity
retinol, retinaldehyde, tazarotene, and adapalene have been
shown to improve dyspigmentation of photodamaged skin,
Some amides obtained from coupling p-hydroxycinnamic
including mottling and actinic lentigines. All-trans-retinoic
acid derivatives with phenylalkylamines were also very
acid has been demonstrated to improve melasma and
potent in inhibiting melanin synthesis. The most active
postinflammatory hypermelanosis. Furthermore, RA, in
amides were trans-N-caffeoyltyramine, N-dihydrocaffeoyl-
combination with hydroquinone or 4-hydroxyanisole, or
tyramine, and trans-N-dihydro-p-hydroxycinnamoyltyra-
azelaic acid increases the potency of depigmenting agents for
mine.There have been no studies on what other effects
the treatment of melasma, actinic lentigines, and postin-
these amides have on melanocytes, apart from their strong
flammatory hypermelanosis. There are several possible
mechanisms underlying these effects. All-trans-retinoic acid
Melanin content of the cells was significantly decreased
inhibits melanin synthesis through down-regulation of
by C(2)-ceramide. The tyrosinase activity of cell extracts was
tyrosinase and tyrosinase-related protein 1 expression in
reduced by C(2)-ceramide treatment. In the cell-free system,
melanocytes. All-trans-retinoic acid could also act as a
however, C(2)-ceramide could not suppress tyrosinase,
selective melanocytotoxin in relatively high doses. In
whereas kojic acid directly inhibited tyrosinase. These
addition, RA increases keratinocyte turnover and augments
results suggest that C(2)-ceramide decreases the pigmenta-
melanin loss from the epidermis. The inhibition of glutathione
tion of melanocytes indirectly by regulating tyrosinase.
S-transferase by RA explains its synergistic depigmenting
Furthermore, C(2)-ceramide decreased the protein expres-
action with other melanocytotoxins such as hydroquinone.
sion of microphthalmia-associated transcription factor,
Topical retinoids could irritate the skin causing redness,
dryness, swelling, desquamation, and subjective feelings
Zinc α-2-glycoprotein inhibits melanin production by
B16 melanoma cells via posttranscriptional effects on
A pomegranate extract (PE) from the rind containing 90%
tyrosinase protein. Because zinc α-2-glycoprotein is nor-
ellagic acid showed inhibitory activity against mushroom
mally produced by epidermal keratinocytes, these studies
tyrosinase in vitro, and the inhibition by the extract was
raise the possibility that epidermal-derived zinc α-2-
comparable with that of arbutin. Orally taken PE also
glycoprotein may play a part in normal regulation of melanin
inhibited UV-induced skin pigmentation on the back of
production in vivo.It is interesting to note that endogenous
brownish guinea pigs. The intensity of the skin-whitening
substances might be a potential candidate in a cosmeceutical.
effect was similar between guinea pigs fed with PE and thosefed with L-ascorbic acid. Pomegranate extract reduced thenumber of DOPA-positive melanocytes in the epidermis ofUV-irradiated guinea pigs, but L-ascorbic acid did not. These
results suggest that the skin-whitening effect of PE wasprobably due to inhibition of the proliferation of melanocytes
The stratum corneum is composed mainly of lipids,
and melanin synthesis by tyrosinase. Further clinical studies
proteins, enzymes, and water. The extracellular lipid
are needed to test its efficacy and safety
membrane of the stratum corneum is composed mainly of
Glabridin was extracted from licorice. It could inhibit
ceramides and its derivatives (40%), cholesterol (25%), and
tyrosinase activity of melanocytes without cytotoxicity, and
free fatty acids (10%-15%), followed by smaller amounts of
it also inhibited UV-B–induced pigmentation and erythema
triglycerides, stearyl esters, and cholesterol sulfate. These
by topical application in a 0.5% There are
lipids are synthesized throughout the epidermis where they
also more potent ingredients extracted from licorice that may
are packaged in lamellar granules and subsequently undergo
become potential depigmenting agents. They include
differentiation and constitute the water barrier. Many factors
glabrene, isoliquiritigenin, glycyrrhisoflavone, and glyas-
could disturb their synthesis pathway, such as essential fatty
perin; all of them could inhibit tyrosinase activity with
acid deficiency, enzyme inhibitors, defective enzymes,
enzyme deficiency, environmental constituents, topically
applied agents, or water content of the stratum corneum.
petrolatum did not show any significant effect, though
High amounts of cholesteryl sulfate, the intercellular cement,
nicotinamide and white petrolatum increased stratum
have been shown to inhibit desquamation. Cornified cell
corneum hydration.Another study showed that a niacina-
envelope, a structure synthesized at late stages of keratino-
mide-containing facial moisturizer improved the stratum
cyte differentiation, is composed of structural proteins,
corneum barrier and, thus, provided a clinical benefit to
including involucrin, loricrin, and the small proline-rich
proteins. The stratum corneum possesses approximately 30%
In xerotic skin, the proteolysis of desmosomes is reduced,
water, which is mainly associated with its elasticity. A
leading to the accumulation of corneocytes on the surface of
healthy stratum corneum contains about 10% tightly held
the skin. Soap-induced xerosis could be ameliorated by the
water. The tightly bound water is closely dependent on the
topical application of exogenous protease, such as bovine
presence of natural moisturizing factor. Natural moisturizing
pancreatic chymotrypsin, papain, and a bacterial protease
factor is composed of amino acids and their metabolites,
from Bacillus licheniformis. Alcalase and optimase, both
which are byproducts formed from the breakdown of
broad specificity alkaline bacterial proteases, were the most
filaggrin. Natural moisturizing factor is found exclusively
efficient ones. Morphological and immunologic analysis of
inside the cells.Perturbation of the aforementioned
bacterial enzyme-treated skin revealed that topically applied
composites in stratum corneum might cause functional
protease specifically induced the degradation of the desmo-
defect and clinical symptoms. Dry skin is one of the
common problems due to defective stratum corneum. It is acondition featured by some subjective or objective denomi-nators, including sensory characteristics with dry, uncomfor-table, itchy, stinging, and tingling sensation; tactile
characteristics with a rough, uneven, and sandlike feeling;and visible characteristics with redness, lackluster surface,
Wrinkle is one of the key features of aging skin, including
dry, white patches, flaky appearance, cracks, and even
photoaging and chronological aging.The exact pathogen-
fissures.In addition, several skin diseases are also
esis of wrinkle is not fully understood yet. Changes in the
featured by dry skin, including atopic dermatitis, ichthyosis,
dermis are most prominent in aged skin. Aged dermis has
and the like. Moisturizers are agents designed to repair the
fragmented elastic fibers, decreased collagen, and dispropor-
damaged stratum corneum to make the stratum corneum
tionate types I and III collagens. At the bottom of a wrinkle,
softer and more pliant by increasing its hydration, resulting
type IV collagen is decreased. Glycosaminoglycans, espe-
in smooth, more supple, and healthier looking skin. More-
cially hyaluronic acid, are decreased. Collagen damage is
over, moisturizers are also designed to act as adjuvant
attributed to several types of collagen-degrading enzymes
treatment option for some dermatologic diseases with feature
known as matrix metalloproteinases (MMPs). Metallopro-
of dry skin. From the view of safety, therapeutic moisturizers
teinases activation can result in production of collagenase,
should be noncomedogenic, devoid of irritant ingredients,
gelatinase, and stromelysin. The degradation of elastins
and compatible with many other therapeutic regimens.
A formulation of lactic acid 12% neutralized with
Paeoniflorin (PF), partially purified from roots of Paeo-
ammonium hydroxide and pramoxine hydrochloride 1%
nia lactiflora, protected cells from DNA damage induced by
was tested on dry itchy skin for 7 days. Patients had
UV-B irradiation in cultured normal human keratinocytes
statistically significant improvement in skin surface hydra-
and hairless mouse keratinocytes. It was also revealed that
tion by day 3, with further improvement by day 7, as
0.5% PF-containing formulation reduced facial wrinkles
during an 8-week clinical trial. These results suggest that
Pantothenic acid, a component of coenzyme A, serves as a
the partially purified PF has potent antiaging and anti-
cofactor for a variety of enzyme-catalyzed reactions that are
wrinkle activities, and should be a useful ingredient for
important in the metabolism of carbohydrates, fatty acids,
proteins, sterols, steroid hormones, and porphyrins. The
It was found that Morinda citrifolia fruit extract up-
topical use of dexpanthenol, the stable alcoholic analog of
regulated biosynthesis of type I collagen and glycosamino-
pantothenic acid, improved stratum corneum hydration,
glycans in primary cultures of normal human fibroblasts. 1,4-
reduced transepidermal water loss, and maintained skin
Dihydroxy-2-methoxy-7-methylanthraquinone, an active
ingredient with a type I collagen–stimulating effect, was
A ceramide-dominant physiologic lipid-based emollient
isolated and identified from M. citrifolia fruit. It was
showed satisfactory results in the treatment of childhood
revealed that anthraquinone showed significantly increased
atopic dermatitis, which is featured by dry skin.A
elaboration of type I procollagen C-terminal peptide and
nicotinamide cream containing 2% nicotinamide was tested
glycosaminoglycans, and reduced expression of the collage-
on atopic dry skin over 4 or 8 weeks; white petrolatum was
nase MMP-1 dose dependently in human dermal fibroblasts.
used as control. The results showed that nicotinamide
Furthermore, a nanoemulsion containing anthraquinone
significantly decreased transepidermal water loss, but white
predominantly increased the dermal type I procollagen in
Efficacy and safety of innovative cosmeceuticals
nude mouse skin. These results suggest that anthraquinone
There are 2 distinct types of aging. One is intrinsic aging,
derived from M. citrifolia fruit extract is a good candidate for
which is the natural aging process. The other is extrinsic
aging, which is caused by environmental factors such as
The inner shell of the chestnut has been used as an
repetitive facial expressions, gravity, sleeping positions,
antiwrinkle or skin-firming agent in East Asia. A 70%
smoking, and, above all, exposure to the sunlight. The
ethanol extract from this plant can prevent cell detachment of
commonly seen features of intrinsic aging are fine wrinkles,
skin fibroblasts from culture plates, possibly through
thin and transparent skin, hollowed cheeks and eye sockets,
enhancing the expression of the cell-associated fibronectin
loss of firmness on the hands and neck, sagging, dry skin that
and vitronectin. Scoparone (6,7-dimethoxycoumarin), iso-
may itch, inability to sweat sufficiently, graying hair that
lated from the extract of inner shell of the chestnut, possessed
eventually turns white, and hair loss. Extrinsic factors,
similar properties. These findings underline the usefulness of
especially sun exposure, often act together with the normal
these substances as antiwrinkle/skin-firming agents.
aging process to cause skin aging prematurely. Photoaging is
Dimethylaminoethanol (DMAE) is an analog of the B
the term especially reserved to describe extrinsic aging
vitamin choline and is a precursor of acetylcholine. In a
caused by sun exposure. Photoaging is often featured by age
randomized clinical study, 3% DMAE facial gel applied
spots, spider veins on the face, rough and leathery skin, fine
daily for 16 weeks has been shown to be safe and efficacious
wrinkles that disappear when stretched, loose skin, a blotchy
in the mitigation of forehead lines and periorbital fine
complexion, solar elastosis, actinic keratoses, and skin
wrinkles, and in improving lip shape and fullness and the
cancer. In photoaged skin, the epidermis has thinning of
overall appearance of aging skin. Application was well
stratum spinosum and flattening of the dermoepidermal
tolerated; an open-label extension of the trial showed that the
junction. Decrease in the numbers of melanocytes and
long-term application of DMAE gel for up to 1 year was
dysregulation of melanocyte density result in guttate hypo-
associated with a good safety profile. The benefits of DMAE
or hypermelanosis and a blotchy complexion. The number of
may include a potential anti-inflammatory effect and an
Langerhans cells also decreases, and the cells have less
increase in skin firmness with possible improvement in
dendrites. There are thickened, tangled, and degraded
nonfunctional fibers in the The interaction between
Ubiquinone (coenzyme 10) is present in almost all
collagen fibers and fibroblast is also decreased.In an
living cells, excluding some bacteria and fungi. It is a
experimental study, chronic UV-A irradiation of normal
strong antioxidant in cells. Ubiquinone can suppress UV-
human fibroblasts induced shortening of the cellular life span
A–induced production of collagenase in fibroblasts and,
and an increase of cellular diameter; MMP-1 was over-
thus, protect from the UV-A–induced degradation of
collagen. It can also retard loss of hyaluronic acid, increase
Photoaged skin has variable manifestations produced by
levels of glycosaminoglycan, and slowdown cell division.
changes of different cellular or noncellular components of
Ubiquinone can penetrate into the viable layers of the
the skin and caused by different mechanisms. It is difficult to
epidermis. Topical use of ubiquinone could reduce the
invent a cosmeceutical with multifunctions to meet all the
needs. Some of the aforementioned cosmeceuticals, such asdepigmenting, moisturizing, and antiwrinkle cosmeceuticals,have the potency to relieve part of photoaging signs. Thefollowing describes some agents that might be of potential
Sunscreens and antiphotoaging cosmeceuticals
Sesamol is a highly acclaimed antioxidant. An experiment
Exposure of skin to UV irradiation can cause acute
on mouse skin showed that it has a good effect on prevention
inflammatory changes, such as erythema, edema, and subse-
of photodamage, observed on biochemical and histopatho-
quently pigmentation or tanning, and chronic changes, such as
photoaging, immunosuppression, or photocarcinogenesis.
Several topically applied retinoids, such as tretinoin,
Sunscreens are intended to counteract these detrimental effects
isotretinoin, retinaldehyde, and tazarotene, have been proven
of UV through direct blocking of light or by absorbing UV
clinically and histologically effective for treating the
radiation. Many substances are commonly used in cosmetics,
appearance of photoaging. Adverse effects are also docu-
such as para-aminobenzoic acid derivatives, cinnamates,
mented as irritant reaction of variable intensity presenting
salicylates, octocrylene, and ensulizole as UV-B filter, and
with dryness, scaling, and Alitretinoin (9-cis-
benzophenones, butyl methoxydibenzoyl, and meradimate as
retinoic acid) is a naturally occurring endogenous retinoid. It
UV-A filter. Still, many other ingredients from different
has the ability to bind and activate all known intracellular
sources are tested as candidates in a cosmeceutical, including
retinoic acid receptors, which might promote the repair
calcitriol, caffeic acid, polyphenols compound, isoflavones,
mechanisms in damaged skin. A small-scale clinical trial
and so on, as excellently reviewed by Kullavanijaya and
showed that topical alitretinoin gel 0.1% was well tolerated
LimThe common adverse effects of sunscreens are irritant
by participants and showed improvement of benign skin
or allergic dermatitis and comedogenicity.
lesions (eg, seborrheic keratoses) and precancerous lesions
(eg, actinic keratoses).Large, blinded, controlled trials are
ascorbate (lipid soluble) in an anhydrous polysilicone gel
needed to investigate the role of this novel retinoid in the
base was tested to one half of the face and the inactive
polysilicone gel base to the opposite side. The effects were
Genistein is a soybean isoflavone with diverse biologic
evaluated clinically and histologically. A statistically
activities. It substantially inhibits skin carcinogenesis and
significant improvement of the vitamin C–treated side
cutaneous aging induced by UV light in mice and photo-
was seen in the decreased photoaging scores of the cheeks
damage in humans. The mechanisms of action involve
and the perioral area. Biopsies showed increased Grenz
protection of oxidatively and photodynamically damaged
zone collagen, as well as increased staining for messenger
DNA, down-regulation of UV-B–activated signal transduc-
RNA for type I collagen. No patients were found to have
tion cascades, and antioxidant Clinical trials are
any evidence of irritation and inflammation during the
required to further substantiate its clinical applications.
A newly formulated vitamin C complex having 10%
Green tea polyphenol inhibits the activity of collagenase
ascorbic acid (water soluble) and 7% tetrahexyldecyl
and increases collagen biosynthesis rate of human fibroblasts.
Examples of some cosmeceutical ingredients (in alphabetical order)
Fruit acids (glycolic acid, lactic acid,citric acid, titanic acid, pyruvic acid,maleic acid, etc)
Skin conditioning, increasing collagen production,
Smoothening, moisturizing, and protection
Linoleic, linolenic, and arachidonic acids
Antioxidants, smoothing, rejuvenation of skin
Supporting blood circulation, wound healing,
Skin whitening, antioxidant, antimicrobial,
Antioxidant, improving texture and integrity of skin
Smoothing, promoting cell renewal, and improving
compounds with similar mechanismsof action
Efficacy and safety of innovative cosmeceuticals
It can also inhibit tyrosinase activity. It was interesting to note
2. Dureja H, Kaushik D, Gupta M, et al. Cosmeceutical: an emerging
that after irradiation at 40 kGy by γ-ray, the abovementioned
concept. Indian J Pharmacol 2005;37:155-9.
3. Lee ES, Kim JH, Sungbin IM, et al. Application of computerized image
effects were all Green tea polyphenol or green
analysis in pigmentary skin diseases. Int J Dermatol 2001;40:45-9.
tea could protect UV-induced DNA damage in a variety of
4. Yoshimura K, Sato K, Aiba-Kojima E, et al. Repeated treatment
cell types, including skin fibroblasts and keratinocytes. When
protocols for melasma and acquired dermal melanocytosis. Dermatol
green tea was taken orally, it also showed photoprotective
effects manifested as low DNA damage of peripheral blood
5. Boissy RE, Visscher M, DeLong MA. DeoxyArbutin: a novel reversible
tyrosinase inhibitor with effective in vivo skin lightening potency. Exp
Orally taken green tea or green tea polyphenols
have mild adverse effects, such as excess gas, upset stomach,
6. Chakraborty AK, Funasaka Y, Komoto M, et al. Effect of arbutin on
nausea, heartburn, abdominal pain, dizziness, headache, and
melanogenic proteins in human melanocytes. Pigment Cell Res 1998;
muscle pain.Though it looks likely that green tea might be a
suitable candidate for antiaging, so far, there have been no
7. Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in
human melanocyte culture. J Pharmacol Exp Ther 1996;276:765-9.
convincing reports on the evaluation of topical use of green
8. Nakamura K, Yoshida M, Uchiwa H. Down-regulation of melanin
tea or its derivatives on skin. It should be kept in mind that
synthesis by a biphenyl derivative and its mechanism. Pigment Cell Res
green tea polyphenols are highly unstable and easily oxidized
in ambient environment. Formulary of green tea polyphenols
9. Usuki A, Ohashi A, Sato H, et al. The inhibitory effect of glycolic acid
as active ingredients in topicals, therefore, remains a
and lactic acid on melanin synthesis in melanoma cells. Exp Dermatol2003;12(Suppl 2):43-50.
challenge in the cosmeceutical industries.
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ALM I – Dermatology
Clinics in Dermatology (2008) 26, 367–374
Efficacy and safety of innovative cosmeceuticals☆
Xing-Hua Gao, MDa, Li Zhang, MDa, Huachen Wei, MDb, Hong-Duo Chen, MDa,⁎
aDepartment of Dermatology, No. 1 Hospital of China Medical University, Shenyang, ChinabDepartment of Dermatology, The Mount Sinai Medical Center, New York, USA
Abstract The research and development of cosmeceuticals is booming in recent years. Many substances,either from botanical, animal, or chemically synthesized sources, are tested or investigated as the activeingredients in cosmeceuticals. The interactions between cosmeceuticals and skin are complex,depending on the specific composites in cosmeceutical products, condition of the skin or general healthstatus of a subject, and the environment where the action occurs. As such, careful preclinical or clinicalevaluation of efficacy and safety is a prerequisite for the development of a specific cosmeceuticalproduct. This article reviews some of the ingredients that are currently in use or might be potentialcandidates in cosmeceuticals of different categories.